HIV Viral suppression following intensified adherence counseling among children on Antiretroviral therapy: Is it worth the wait?

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Faryad Muwabe, Diana Rutebarika, Christine Matama, Roy Basiimwa, and 5 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-6860769/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Background With the current UNAIDS strategy of attaining 95-95-95 by the year 2030, HIV positive children should not be left behind. However, statistics show that HIV diagnosis in children lags behind that of adult, the number of newly diagnosed babies initiated on treatment is much lower than that in adults. Even when initiated on ART, viral suppression among children is much lower than in adults. There is need for a call to action. Methods This study was nested within the DRIBS ( D rug R esistance testing among I nfants at B aseline S tudy), which enrolled 100 infants at the time of treatment initiation between 2017–2023. Infants were followed for two years. Viral load (VL) was measured every six months and after completion of the three sessions of intensified adherence counseling (IAC). Results At the end of the two-year follow-up period, 63% of the children and 85% of the mothers had achieved complete viral suppression. Among mother-infant pairs, 36% of the virally non-suppressing children belonged to non-suppressing mothers. 20% of all children in the study exhibited persistent viral non-suppression at more than three time points during the course of the study. Among mothers with viral loads > 1000 copies/ml, 40% experienced persistent non-suppression. Self-reported adherence at each study visit revealed that at least 15% of the mothers reported poor adherence (adherence < 95%) and this was not different between a lopinavir-based and a dolutegravir-based regimen (14% and 11% respectively). Children were more likely to miss doses than mothers (p = 0.031). A repeat viral load after IAC revealed that 67% of the mothers achieved complete viral suppression. On the other hand, 28% of the children achieved complete viral suppression and 42% were unsuppressed. Conclusion Within mother-infant pairs, children exhibit poor viral suppression. This non-suppression persists among pediatrics despite intensified adherence counseling. Biological sciences/Molecular biology Health sciences/Medical research mother-to-child transmission of HIV-1 antiretroviral therapy viral load viral suppression LLV and intensified adherence counseling Figures Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 Introduction As we strive to end the HIV epidemic by 2030, remarkable progress has been made in reducing pediatric HIV infections. Significant success has been documented in Eastern and Southern Africa, where the number of children aged 0–14 acquiring HIV has decreased by 73% between 2010 and 2023 [ 1 ]. Despite these advancements, Sub-Saharan Africa remains disproportionately affected, accounting for 86% of all new pediatric HIV infections [ 1 ]. While the Test-and-Treat approach has proven effective in the adult population, pediatric HIV test and treat following early infant diagnosis remains significantly lower than in adults [ 2 – 7 ]. Additionally, among children receiving antiretroviral therapy (ART), viral suppression rates are still much lower compared to adults [ 1 , 7 – 10 ]. This disparity presents two major challenges. First, it jeopardizes the goal of ending the HIV epidemic by 2030, as pediatric populations are being left behind [ 11 ]. Second, achieving this target will require a stronger focus on interventions to end pediatric HIV infections [ 12 – 14 ]. To bridge the gap, efforts must be intensified to further reduce new infections by eliminating mother-to-child transmission[ 12 – 14 ], improving early infant diagnosis to match adult rates (66% vs. 87% in adults) [ 1 , 15 – 18 ], ensuring all newly diagnosed infants are promptly initiated on ART (55% vs. 78% in adults) [ 1 , 19 , 20 ], and achieving viral suppression rates comparable to adults (48% vs. 73% in adults) [ 1 ]. For years, children taking lopinavir/ritonavir (LPV/r) faced significant challenges, particularly with the liquid formulation, which had a bitter taste that made it difficult to tolerate. Many children vomited after ingestion, leading to poor adherence and suboptimal treatment outcomes [ 21 ]. Additionally, the liquid formulation required refrigeration, which is not always available in low-and-middle-income countries (LMICs). To address these issues, the formulation was changed to pellets [ 21 , 22 ]; however, these were difficult for neonates and infants to swallow, often resulting in insufficient drug doses and poor viral suppression [ 23 , 24 ]. Children on LPV-containing regimens also experienced gastrointestinal side effects such as nausea, vomiting, and diarrhea, further discouraging caregivers from administering the medication regularly, which worsened viral suppression rates. Given these challenges, newer pediatric-friendly alternatives, such as dolutegravir (DTG)-based regimens, are currently in use. These regimens offer better tolerability, and fewer side effects, making them a more effective option for pediatric HIV treatment [ 25 – 27 ]. Methods This sub-study examined the impact of intensified adherence counseling on viral suppression. It was conducted within a larger study, whose design and methods have been described previously [ 28 ]. We enrolled and followed 100 newly diagnosed HIV-positive infants and their HIV-positive mothers in the D rug R esistance for I nfants at B aseline S tudy (DRIBS ) at the Joint Clinical Research Center (JCRC) in Kampala, Uganda. After obtaining informed consent from mothers, eligible infants aged six weeks to 12 months and their mothers were enrolled. This longitudinal study followed mother-infant pairs, with viral suppression as the primary endpoint and adherence as the secondary endpoint. At study initiation, all infants were placed on an LPV-containing regimen. However, during the study, children were transitioned to a DTG-containing regimen according to the National treatment guidelines. Since mothers had been on ART for varying durations, their viral load at enrollment was considered baseline, with some already achieving viral suppression. Ethical approval was granted by the JCRC Research and Ethics Committee (JC3617) and the National Council for Science and Technology (HS 2383). Patient enrollment and follow-up Infant demographics, as detailed in Nankya et al. [ 28 ] and Table 1, were collected at enrollment and each follow-up visit. Maternal demographics were also recorded. Mother-infant pairs were followed for two years, with study visits scheduled at weeks 8 and 12, then every 12 weeks until week 96. Key study interventions included ART initiation at enrollment, self-reported adherence assessments, viral load monitoring, intensified adherence counseling, and HIV drug resistance testing, all conducted per the National Treatment Guidelines. At each visit, infants were assessed by a pediatrician, and adherence was categorized as good (> 95%) or poor (< 95%) based on self-reports. The primary endpoint was viral suppression, while adherence was the secondary endpoint. Intensified adherence counseling Viral load assays for mother-infant pairs were conducted at enrollment and at six-month intervals throughout the study. If a viral load exceeding 1000 copies/ml was detected in the mother, infant, or both, the mother underwent a once a month session of intensified adherence counseling for three consecutive months. This was followed by a repeat viral load test, in accordance with National treatment guidelines. Additionally, self-reported adherence was evaluated for all mothers at every visit. In-depth interviews In addition to IAC, a subset of 17 mothers underwent in-depth interviews in order to clearly map out the factors contributing to viral non-suppression. Interviews were recorded and transcribed. Data analysis : Infant variables of interest including: age, sex, age at diagnosis, weight, head circumference, mid upper arm circumference, ART regimen, viral load, and CD4 cell count were extracted from the database. For the mother, the following were extracted: age, occupation, area of residence, parity, regimen, and viral load. Coded data with patient identification numbers were used. The primary endpoint for this sub-study was viral suppression following IAC. Results Participants and baseline characteristics Detailed demographics of the study have been described elsewhere [ 28 ] and as indicated in Fig. 1 . But briefly, 100 infants (60% female) and their mothers were enrolled and followed up for two years in the DRIBS study. Between August 2017 and October 2023, 100 infants (60% female) were enrolled and followed up for two years in the DRIBS study. 12% of the infants had moderate to severe malnutrition at the time of enrollment and 64% had history of Nevirapine exposure. The median age at diagnosis was 79 (IQR, 57.75;140.75) days, with only 4% of patients diagnosed within 6 weeks after delivery, the majority (67%) were diagnosed between 6–12 weeks (Table 1). The median age at the initiation of ART was 110.5 (IQR, 87.0–162.0) days (table 1). Median age of the mothers was 26 (IQR,19;35) years with 40% of mothers having attained at least secondary level education. Viral suppression By the end of the two-year follow-up period, 63% and 83% of infants achieved viral loads (VL) < 50 copies/ml and < 1000 copies/ml, respectively. In contrast, mothers demonstrated higher rates of viral suppression, with 85% achieving VL < 50 copies/ml (Fig. 1 ). Among mother-infant pairs, 36% of non-suppressing children had mothers who were also virally non-suppressed during the study (Fig. 2 ). Further analysis revealed that 20% of all children in the study exhibited persistent viral non-suppression at more than three time points during the course of the study (Fig. 3 b). Among mothers with detectable viral loads > 1000 copies/ml, 40% experienced persistent non-suppression at two or more study visits, contributing to the 15% non-suppression observed at the study's conclusion (Fig. 3 a). Adherence and intensified adherence counseling Self-reported adherence at each study visit revealed that at least 10–20% of the mothers reported poor adherence (adherence < 95%) (Fig. 4 ). Since these children transitioned from a PI-based regimen to a DTG-based regimen during the course of the study, we compared adherence on these two regimens and found that the non-adherence levels were not significantly different between the PI-based regimen and the DTG-based regimen (14% and 11% respectively). When adherence was compared between mother and child, children were more likely to miss doses than mothers (p = 0.031) (and Fig. 5 ). A repeat viral load after IAC revealed that 67% of the mothers achieved complete viral suppression (viral load < 50 copies/ml) following AIC, and 15% had low level viremia (viral load between 50–999 copies/ml) (Fig. 6 a) On the other hand, 28% of the children achieved complete viral suppression, 42% unsuppressed (viral load > 1000 copies/ml) and 30% had low level viremia (Fig. 6 b). Discussion In order to eradicate HIV by 2030, there is need to fast track HIV infection control among the children. Although the adult population is showing evidence of progress, the pediatric population is still lagging behind. According to the UNAIDS report 2024, only 66% of the HIV positive babies are diagnosed within the first six weeks, of these, 55% are initiated on ART and of those on ART, viral suppression is about 50% [ 1 ]. It is evident that with this kind of progress, it will take much longer for the children to attain the 95-95-95 goal. One of the bottlenecks to achieving the third 95 in both adults and children is adherence. Children, especially infants struggled with ingestion of the LPV/r formulations that were either bitter, hard to swallow or nauseating resulting in vomiting [ 21 , 29 ]. This negatively impacted on viral suppression [ 24 ]. The roll out of DTG in the pediatric population saw an end to most of these struggles. However, even with the said roll out of DTG, we have shown that adherence is still a major challenge among children. Makonokaya et al showed that post-DTG transition viral suppression was associated with pre-DTG transition viral suppression implying that children who were previously suppressing while on a LPV/r containing regimen were more likely to maintain viral suppression when transitioned to a DTG-containing regimen [ 25 ]. Furthermore, in this pediatric study, adherence post-DTG transition was 52.5% [ 25 ] further indicating that the switch to DTG was not associated with improved adherence. The resulting viral non-suppression calls for a drug resistance test to ensure the patient is kept on a functional regimen. With the extreme lack of resources in the low to middle income countries, it is impossible to perform a drug resistance test for everyone failing with a detectable viral load. As a recommendation by WHO therefore, patients undergo three sessions of intense adherence counselling to ensure that the viral non-suppression is not as a result of poor adherence. This is then followed by a repeat viral load. Any viral load greater than 1000 copies/ml after these three sessions qualifies for a drug resistance test. In this study, we specifically focused on children who after diagnosis were initiated on ART, hence we focused on the third 95. We and others have previously shown that viral suppression among children initiated on ART is consistently lower than that seen in adults [ 28 ]. Furthermore, time to viral suppression is significantly different between adults and children [ 30 ]. This is also true for mother-infant pairs [ 28 , 30 ]. In this study, we focused on adherence as a secondary endpoint in the DRIBS study. Previously, we have shown that mothers who transmit to their babies do not have good adherence to ART for various reasons and these include: being in a discordant relationship, being involved in high risk behavior, not having a stable source of income, and moving from place to place looking for where to stay among family members [ 28 ]. All these have stigma implications. In this study mothers whose children missed doses indicated that stigma was the major reason for not giving the prescribed doses to their children. Spielman et al showed that caregivers who experienced HIV-related stigma, and those who lacked social support, were more likely not to give ART to their children regularly [ 31 ]. A review by Perger indicated that many Qualitative studies reported that stigma was a not only a barrier to ART adherence but also a barrier for engagement and retention in HIV care [ 32 ]. Although mothers who transmit to their babies have poor viral suppression, in this study, we show that these mothers had better viral suppression rates than their children. The poor viral suppression rates have previously been attributed to infants experiencing challenges with the LPV/r pellets which were very hard to swallow so mothers ended up skipping the children’s doses. Furthermore, mothers would open the pellet and give the child granules and sometimes they would not give a complete dose in the process. The taste of this granules was very unpleasant, this too resulted in missed doses. The liquid formulation that was developed following this had a bitter taste which did not make adherence better [ 33 ]. During the course of the study, there was a transition from LPV/r to DTG. This resulted in better viral suppression [ 28 ]. Viral non-suppression in both children and mothers was seen in two thirds (67%) of the mothers who were less than thirty years. About half of the mothers and children with viral non-suppression had persistent non-suppression (more than 1000 copies/ml at two or more time points). Self-reported adherence did not improve even with the transition to DTG. Children were more likely to miss pills than mothers. This was attributed to stigma where mothers due to being in a discordant relationship, lack of stable income, moving from place to place because of lack of a permanent place of residence were afraid to be seen giving their children ART [ 34 ]. Intensified adherence counseling resulted in viral in viral suppression in about 58% of the children. However, even those that suppressed below 1000 copies/ml, most of them had low-level viremia which has clinical implications on response to therapy [ 28 ]. During the period of intensified adherence counseling, it is evident that if there are drug resistant mutations, they are evolving. With the findings of low viral suppression following IAC, and the presence of LLV among those that suppress, the major question is, do the benefits of IAC outweigh the challenges? Is IAC effective among pediatrics especially those below two years of age bearing in mind the time it takes from performing the first viral load, getting the result back, having the three sessions of IAC, performing a repeat viral load and have the results back. Then finally, if the viral load is > 1000 copies/ml or between 200–999 copies/ml, the time it takes to perform a drug resistance test and have the report to guide treatment modification. In low to middle income countries, this whole sequence of events might take around six to eight months. Are we doing more damage during this time? How can we improve treatment outcomes in this age group? In order to address these questions, there is need for more studies to look at the dynamics of viral evolution during this time. Study Limitations Although viral load data was available for mother infant pairs during the time on the study, most of the mothers’ drug regimens were not captured for comparison with the child’s regimen. However, from the available data, most of these mothers had been diagnosed less than a year prior to enrollment into the study. They were initiated on the recommended regimen at the time. Those who enrolled before DTG roll out were on either an Efavirenz containing regimen or LPV-containing regimen. Then, with the roll-out of DTG, they were on a DTG containing regimen. Declarations Conflict of interest statement The authors declare that they have no competing interests. Authors’ contributions: IN designed the research study FM performed the lab work, CM, DR, RB, EN and PA, did the patient enrollment, follow-up, and counseling, and CO analyzed the data, IN wrote the paper and CK reviewed the paper. Ethic approval and consent to participate Ethical approval and approval from the Joint Clinical Research Centre Research and Ethics committee (JCRC REC) as well as from the National Council of Science and Technology were obtained (JC3617 and HS 2383, respectively). All research was performed in accordance with the JCRC REC guidelines/regulations. Informed consent was obtained from all partcipants’ legal guardians. Consent for Publication This was obtained under the consent to participate in the study Funding This study was fully funded by the European and Developing Countries Clinical Trials Partnership (EDCTP) under grant number TMA2015SF-1037. Acknowledgments This study was fully funded by the European and Developing Countries Clinical Trials Partnership (EDCTP) under grant number TMA2015SF-1037. Data Availability The dataset generated and analyzed during the current study is not publicly available due to the fact that more data analysis is still ongoing using the same dataset because this study was conducted to answer multiple questions. However, the data is available from the corresponding author on reasonable request. References UNAIDS, The Urgency of Now. 2024. Collins, I.J., et al., Cost-effectiveness of early infant HIV diagnosis of HIV-exposed infants and immediate antiretroviral therapy in HIV-infected children under 24 months in Thailand. PLoS One, 2014. 9 (3): p. e91004. Ciaranello, A.L., et al., Early infant HIV-1 diagnosis programs in resource-limited settings: opportunities for improved outcomes and more cost-effective interventions. BMC Med, 2011. 9 : p. 59. Ghadrshenas, A., et al., Improved access to early infant diagnosis is a critical part of a child-centric prevention of mother-to-child transmission agenda. Aids, 2013. 27 Suppl 2 : p. S197-205. Essajee, S., et al., Reducing mortality in HIV-infected infants and achieving the 90-90-90 target through innovative diagnosis approaches. J Int AIDS Soc, 2015. 18 (Suppl 6): p. 20299. Vojnov, L., et al., Same-day test and treat for infants with HIV infection: finally within reach. J Int AIDS Soc, 2022. 25 (9): p. e26016. Jani, I.V., et al., Impact of point-of-care birth test-and-treat on clinical outcomes among infants with HIV: A cluster randomized trial in Mozambique and Tanzania. Clin Infect Dis, 2024. Tayong, G.F.E., et al., HIV viral load suppression rates among adults and children living with HIV in the North West Region of Cameroon: A call for action! PLoS One, 2025. 20 (1): p. e0316399. Immaculate Nankya, E.N., Diana Rutebarika, Christine Matama, Roy Basiimwa Paul Arikod, Faryad Muwabe, Caroline Otike and Cissy Kityo, High prevalence of low-level viremia among infants initiated on antiretroviral drugs following mother-to-child transmission of HIV. Journal of AIDS Research and Therapy. in press . Walle, B.G., et al., Treatment failure among Sub-Sahara African children living with HIV: a systematic review and meta-analysis. Ital J Pediatr, 2024. 50 (1): p. 202. Harries, A.D., et al., Ending the HIV/AIDS epidemic in low- and middle-income countries by 2030: is it possible? F1000Res, 2016. 5 : p. 2328. Karthigeyan, K.P., et al., Research on Maternal Vaccination for HIV Prevention. Clin Perinatol, 2024. 51 (4): p. 769-782. Ruel, T., et al., Novel Approaches to Postnatal Prophylaxis to Eliminate Vertical Transmission of HIV. Glob Health Sci Pract, 2023. 11 (2). Penazzato, M., et al., Antiretroviral postnatal prophylaxis to prevent HIV vertical transmission: present and future strategies. J Int AIDS Soc, 2023. 26 (2): p. e26032. Webb, K., et al., Brief Report: Improving Early Infant Diagnosis Observations: Estimates of Timely HIV Testing and Mortality Among HIV-Exposed Infants. J Acquir Immune Defic Syndr, 2020. 83 (3): p. 235-239. Manasyan, A., et al., Differentiated community-based point-of-care early infant diagnosis to improve HIV diagnosis and ART initiation among infants and young children in Zambia: a quasi-experimental cohort study. BMJ Glob Health, 2025. 10 (2). Boeke, C.E., et al., Point-of-care testing can achieve same-day diagnosis for infants and rapid ART initiation: results from government programmes across six African countries. J Int AIDS Soc, 2021. 24 (3): p. e25677. le Roux, S.M., et al., Cost-effectiveness of point-of-care versus centralised, laboratory-based nucleic acid testing for diagnosis of HIV in infants: a systematic review of modelling studies. Lancet HIV, 2023. 10 (5): p. e320-e331. Migamba, S.M., et al., Rapid antiretroviral therapy initiation following rollout of point-of-care early infant diagnosis testing, Uganda, 2018-2021. AIDS Res Ther, 2024. 21 (1): p. 31. Chapuma, C.I.J., et al., Examining barriers to antiretroviral therapy initiation in infants living with HIV in sub-Saharan Africa despite the availability of point-of-care diagnostic testing: a narrative systematic review. J Int AIDS Soc, 2024. 27 Suppl 1 (Suppl 1): p. e26284. Kekitiinwa, A., et al., Acceptability of lopinavir/r pellets (minitabs), tablets and syrups in HIV-infected children. Antivir Ther, 2016. 21 (7): p. 579-585. Nebot Giralt, A., et al., Understanding the acceptability and adherence to paediatric antiretroviral treatment in the new formulation of pellets (LPV/r): the protocol of a realist evaluation. BMJ Open, 2017. 7 (3): p. e014528. Sliefert, M., et al., Challenges with pediatric antiretroviral therapy administration: Qualitative perspectives from caregivers and HIV providers in Kenya. PLoS One, 2024. 19 (1): p. e0296713. Musiime, V., et al., The pharmacokinetics and acceptability of lopinavir/ritonavir minitab sprinkles, tablets, and syrups in african HIV-infected children. J Acquir Immune Defic Syndr, 2014. 66 (2): p. 148-54. Makonokaya, L., et al., Early Effects of Scaling Up Dolutegravir-Based ARV Regimens Among Children Living with HIV in Malawi. AIDS Behav, 2024. 28 (6): p. 2148-2155. Devendra, A., et al., HIV viral suppression in children and adolescents 2 years after transition to dolutegravir: a multicentre cohort study. Aids, 2024. 38 (7): p. 1013-1023. Turkova, A., et al., Dolutegravir as First- or Second-Line Treatment for HIV-1 Infection in Children. N Engl J Med, 2021. 385 (27): p. 2531-2543. Immaculate Nankya, E.N., Diana Rutebarika, Christine Matama, Roy Basiimwa, Paul Arikod, Faryad Muwabe, Caroline Otike and Cissy Kityo, High prevalence of low-level viremia among infants initiated on antiretroviral drugs following mother-to-child transmission of HIV. AIDS Research and Therapy, 2025. 22 (34). Chupradit, S., et al., Population Pharmacokinetics of Pediatric Lopinavir/Ritonavir Oral Pellets in Children Living with HIV in Africa. Clin Pharmacol Ther, 2024. 115 (5): p. 1105-1113. Nankya, I., et al., High prevalence of low-level viremia among infants initiated on antiretroviral drugs following mother-to-child transmission of HIV. AIDS Research and Therapy, 2025. 22 (1): p. 34. Spielman, K.L., et al., Depressive symptoms, HIV-related stigma and ART adherence among caregivers of children in vulnerable households in rural southern Malawi. PLoS One, 2021. 16 (3): p. e0247974. Perger, T., et al., Impact of HIV-Related Stigma on Antiretroviral Therapy Adherence, Engagement and Retention in HIV Care, and Transition to Adult HIV Care in Pediatric and Young Adult Populations Living With HIV: A Literature Review. AIDS Behav, 2025. 29 (2): p. 497-516. Chen, S., et al., Anti-HIV drugs lopinavir/ritonavir activate bitter taste receptors. Chem Senses, 2023. 48 . Buh, A., et al., Barriers and facilitators for interventions to improve ART adherence in Sub-Saharan African countries: A systematic review and meta-analysis. PLoS One, 2023. 18 (11): p. e0295046. Table Table 1 . Patient demographics Variable Median IQR Age in months 4 (1;16) Age at diagnosis 79 (57.75;140.75) Age at initiation of ART 110.5 (87; 162) Weight in Kg 6.1 (3.9;9.5) CD4 count 2127.5 (447; 5011) Baseline viral load 4.44 (3.19;5.58) Mother's age 26 (19;35) Variable Frequency Percent Sex of the child Male 40 40 Female 60 60 Mother's education level No formal/primary education 60 60 Secondary/tertiary education 40 40 Mother's residence Urban 55 55 Rural 45 45 Nutrition assessment Red 3 3.3 Yellow 8 8.9 Green 79 87.8 Child birth order 1 30 30 2 to 4 61 61 ≥5 9 9 Chronic conditions in mother Yes 84 84 No 16 16 Nevirapine exposure Yes 64 64 No 36 36 Additional Declarations No competing interests reported. Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-6860769","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":497369438,"identity":"0b5bfd2e-0a85-46bb-a55e-f270f5a78144","order_by":0,"name":"Faryad Muwabe","email":"","orcid":"","institution":"Joint Clinical Research Centre","correspondingAuthor":false,"prefix":"","firstName":"Faryad","middleName":"","lastName":"Muwabe","suffix":""},{"id":497369439,"identity":"8a46e83c-d01e-442b-ba15-b615429cb9a1","order_by":1,"name":"Diana Rutebarika","email":"","orcid":"","institution":"Joint Clinical Research Centre","correspondingAuthor":false,"prefix":"","firstName":"Diana","middleName":"","lastName":"Rutebarika","suffix":""},{"id":497369440,"identity":"869f4fdc-dde5-4d41-9e59-a4fd1a2731b9","order_by":2,"name":"Christine Matama","email":"","orcid":"","institution":"Joint Clinical Research Centre","correspondingAuthor":false,"prefix":"","firstName":"Christine","middleName":"","lastName":"Matama","suffix":""},{"id":497369441,"identity":"f9945892-3694-4bd0-aaab-71ae3addd499","order_by":3,"name":"Roy Basiimwa","email":"","orcid":"","institution":"Joint Clinical Research Centre","correspondingAuthor":false,"prefix":"","firstName":"Roy","middleName":"","lastName":"Basiimwa","suffix":""},{"id":497369442,"identity":"5c7034b8-e62c-4d2f-adfd-ad35ef829dc8","order_by":4,"name":"Paul Arikod","email":"","orcid":"","institution":"Joint Clinical Research Centre","correspondingAuthor":false,"prefix":"","firstName":"Paul","middleName":"","lastName":"Arikod","suffix":""},{"id":497369443,"identity":"232c1054-94fb-4256-9734-6dfad57a7459","order_by":5,"name":"Eva Natukunda","email":"","orcid":"","institution":"Joint Clinical Research Centre","correspondingAuthor":false,"prefix":"","firstName":"Eva","middleName":"","lastName":"Natukunda","suffix":""},{"id":497369444,"identity":"6b7f882d-5566-4517-a4da-d9c0758e4c08","order_by":6,"name":"Caroline Otike","email":"","orcid":"","institution":"Joint Clinical Research Centre","correspondingAuthor":false,"prefix":"","firstName":"Caroline","middleName":"","lastName":"Otike","suffix":""},{"id":497369445,"identity":"08c1d5f6-8617-4b11-a61c-ef1d118a75ad","order_by":7,"name":"Cissy Kityo","email":"","orcid":"","institution":"Joint Clinical Research Centre","correspondingAuthor":false,"prefix":"","firstName":"Cissy","middleName":"","lastName":"Kityo","suffix":""},{"id":497369446,"identity":"76459106-fedf-4ee5-a62a-f6b742aea19c","order_by":8,"name":"Immaculate Nankya","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA3UlEQVRIiWNgGAWjYBACNiBmbGBgkAMRpGkxJl4LA1RLIvE6+KSbnz2c2WaX3tx+9uEHhop7dg0S6RfwO0zmmLnhxrbk3MaedGMJhjPFyQ0SOQX4tUgkmEk+bGPObZzBxsbA2JaQzCCRk0BAS/o3oJb6dEYStOSYSW5sO5wA02LHIJF+gJCWMskZ544bNvakMUsknElIYON5g1cHg/yM9G2SPWXV8obtxxg/fKhIsOdnT3+AXw8IMAIj1LAByAB6IrGNgceAsBaGP0DroEx7BgZ2ImwZBaNgFIyCkQQATUY/4Ejov6AAAAAASUVORK5CYII=","orcid":"","institution":"Joint Clinical Research Centre","correspondingAuthor":true,"prefix":"","firstName":"Immaculate","middleName":"","lastName":"Nankya","suffix":""}],"badges":[],"createdAt":"2025-06-10 08:23:26","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-6860769/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-6860769/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":88774862,"identity":"22f442d3-ad79-425b-84b4-9980c3b112e8","added_by":"auto","created_at":"2025-08-11 10:03:39","extension":"jpg","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":51716,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eViral suppression for mother and child\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eHIV viral loads were performed for both the mother (upper panel) and the child (lower panel). For the mother and child, viral loads were done every six months for the duration of the study (96 weeks). Viral load cut off for non-suppression was 1000 copies/ml and low-level viremia was considered for viral loads between 50 to 999 copies/ml and this was according to the standard of care guidelines.\u003c/p\u003e","description":"","filename":"1.jpg","url":"https://assets-eu.researchsquare.com/files/rs-6860769/v1/2be31892976f3bafaa8e55cc.jpg"},{"id":88779095,"identity":"b5a59a73-a0fb-4dcc-ad91-726d115e402a","added_by":"auto","created_at":"2025-08-11 10:27:39","extension":"jpg","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":84899,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eviral non-suppression\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eMother-infant pairs were selected for babies whose viral loads were above 1000 copies so that a viral load comparison can be made between mother and child. Child’s viral load is shown in blue while mother’s viral load is shown in orange.\u003c/p\u003e","description":"","filename":"2.jpg","url":"https://assets-eu.researchsquare.com/files/rs-6860769/v1/b60308304d7027855c0abe0f.jpg"},{"id":88774855,"identity":"b5582f12-141e-4a9e-bf1c-6018d7deabea","added_by":"auto","created_at":"2025-08-11 10:03:39","extension":"jpg","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":108255,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eViral load non-suppression over time\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eViral loads were measured every six months for the duration of the study to assess the response to therapy. Viral non-suppression over time was compared between mothers (3a: upper panel) and children (3b: lower panel)\u003c/p\u003e","description":"","filename":"3.jpg","url":"https://assets-eu.researchsquare.com/files/rs-6860769/v1/40c06c6181962acbf55b2fb7.jpg"},{"id":88777351,"identity":"276e9664-4bfd-43d2-8d65-e30b078d40bf","added_by":"auto","created_at":"2025-08-11 10:11:39","extension":"jpg","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":29882,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eSelf-reported adherence\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eSelf-reported adherence was assessed at every study visit for the duration of the study (every three months) and this was scored purely based on what the mother reported. Good adherence was graded as being adherent for more than 95% of the time while poor adherence was taken to represent adherence less than 95%.\u003c/p\u003e","description":"","filename":"4.jpg","url":"https://assets-eu.researchsquare.com/files/rs-6860769/v1/be49865c6e3331110c219a37.jpg"},{"id":88777346,"identity":"b5ebafe5-6af7-4712-aac9-c47a348d50fd","added_by":"auto","created_at":"2025-08-11 10:11:39","extension":"jpg","order_by":5,"title":"Figure 5","display":"","copyAsset":false,"role":"figure","size":27948,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eMissed doses\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAs a way to quantify missed doses as a cause of poor adherence, missed doses were compared between mother and child at each of the study visits.\u003c/p\u003e","description":"","filename":"5.jpg","url":"https://assets-eu.researchsquare.com/files/rs-6860769/v1/b727b26a647bb35b415bd604.jpg"},{"id":88777348,"identity":"d0ed5a3a-d0ab-42f7-aa4a-85b431703a16","added_by":"auto","created_at":"2025-08-11 10:11:39","extension":"jpg","order_by":6,"title":"Figure 6","display":"","copyAsset":false,"role":"figure","size":134944,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eViral suppression following IAC\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eSince viral non-suppression was seen in both mothers and children as evidenced by viral loads greater than 1000 copies/ml, IAC was performed for the mother either whose child had a viral greater than 1000 copies, a mother who together with her child had a detectable viral load \u0026gt;1000 copies/ml or a mother whose viral load was greater than 1000 copies/ml. Following three sessions (a session every month) of IAC, a repeat viral load was done to assess whether IAC resulted in effective viral suppression. A comparison of viral suppression was done between mother (6a: upper panel) and child (6b: lower panel).\u003c/p\u003e","description":"","filename":"6.jpg","url":"https://assets-eu.researchsquare.com/files/rs-6860769/v1/cf88fd4bbfdf5287919aac91.jpg"},{"id":96250572,"identity":"6dcfe518-1dc8-479d-b486-36092cf53791","added_by":"auto","created_at":"2025-11-19 07:38:40","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1312015,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-6860769/v1/d30b9c79-25fd-4a26-b76c-02bfe2b250e9.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"HIV Viral suppression following intensified adherence counseling among children on Antiretroviral therapy: Is it worth the wait?","fulltext":[{"header":"Introduction","content":"\u003cp\u003eAs we strive to end the HIV epidemic by 2030, remarkable progress has been made in reducing pediatric HIV infections. Significant success has been documented in Eastern and Southern Africa, where the number of children aged 0–14 acquiring HIV has decreased by 73% between 2010 and 2023 [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. Despite these advancements, Sub-Saharan Africa remains disproportionately affected, accounting for 86% of all new pediatric HIV infections [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. While the Test-and-Treat approach has proven effective in the adult population, pediatric HIV test and treat following early infant diagnosis remains significantly lower than in adults [\u003cspan additionalcitationids=\"CR3 CR4 CR5 CR6\" citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e–\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]. Additionally, among children receiving antiretroviral therapy (ART), viral suppression rates are still much lower compared to adults [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan additionalcitationids=\"CR8 CR9\" citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e–\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]. This disparity presents two major challenges. First, it jeopardizes the goal of ending the HIV epidemic by 2030, as pediatric populations are being left behind [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]. Second, achieving this target will require a stronger focus on interventions to end pediatric HIV infections [\u003cspan additionalcitationids=\"CR13\" citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e–\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e]. To bridge the gap, efforts must be intensified to further reduce new infections by eliminating mother-to-child transmission[\u003cspan additionalcitationids=\"CR13\" citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e–\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e], improving early infant diagnosis to match adult rates (66% vs. 87% in adults) [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan additionalcitationids=\"CR16 CR17\" citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e–\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e], ensuring all newly diagnosed infants are promptly initiated on ART (55% vs. 78% in adults) [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e, \u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e], and achieving viral suppression rates comparable to adults (48% vs. 73% in adults) [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eFor years, children taking lopinavir/ritonavir (LPV/r) faced significant challenges, particularly with the liquid formulation, which had a bitter taste that made it difficult to tolerate. Many children vomited after ingestion, leading to poor adherence and suboptimal treatment outcomes [\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e]. Additionally, the liquid formulation required refrigeration, which is not always available in low-and-middle-income countries (LMICs). To address these issues, the formulation was changed to pellets [\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e, \u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e]; however, these were difficult for neonates and infants to swallow, often resulting in insufficient drug doses and poor viral suppression [\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e, \u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e]. Children on LPV-containing regimens also experienced gastrointestinal side effects such as nausea, vomiting, and diarrhea, further discouraging caregivers from administering the medication regularly, which worsened viral suppression rates. Given these challenges, newer pediatric-friendly alternatives, such as dolutegravir (DTG)-based regimens, are currently in use. These regimens offer better tolerability, and fewer side effects, making them a more effective option for pediatric HIV treatment [\u003cspan additionalcitationids=\"CR26\" citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e–\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e].\u003c/p\u003e"},{"header":"Methods","content":"\u003cp\u003eThis sub-study examined the impact of intensified adherence counseling on viral suppression. It was conducted within a larger study, whose design and methods have been described previously [\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e]. We enrolled and followed 100 newly diagnosed HIV-positive infants and their HIV-positive mothers in the \u003cb\u003eD\u003c/b\u003erug \u003cb\u003eR\u003c/b\u003eesistance for \u003cb\u003eI\u003c/b\u003enfants at \u003cb\u003eB\u003c/b\u003easeline \u003cb\u003eS\u003c/b\u003etudy (DRIBS\u003cb\u003e)\u003c/b\u003e at the Joint Clinical Research Center (JCRC) in Kampala, Uganda. After obtaining informed consent from mothers, eligible infants aged six weeks to 12 months and their mothers were enrolled. This longitudinal study followed mother-infant pairs, with viral suppression as the primary endpoint and adherence as the secondary endpoint. At study initiation, all infants were placed on an LPV-containing regimen. However, during the study, children were transitioned to a DTG-containing regimen according to the National treatment guidelines. Since mothers had been on ART for varying durations, their viral load at enrollment was considered baseline, with some already achieving viral suppression. Ethical approval was granted by the JCRC Research and Ethics Committee (JC3617) and the National Council for Science and Technology (HS 2383).\u003c/p\u003e\u003cp\u003e\u003cstrong\u003ePatient enrollment and follow-up\u003c/strong\u003e\u003c/p\u003e\u003cp\u003eInfant demographics, as detailed in Nankya et al. [\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e] and Table\u0026nbsp;1, were collected at enrollment and each follow-up visit. Maternal demographics were also recorded. Mother-infant pairs were followed for two years, with study visits scheduled at weeks 8 and 12, then every 12 weeks until week 96. Key study interventions included ART initiation at enrollment, self-reported adherence assessments, viral load monitoring, intensified adherence counseling, and HIV drug resistance testing, all conducted per the National Treatment Guidelines. At each visit, infants were assessed by a pediatrician, and adherence was categorized as good (\u0026gt; 95%) or poor (\u0026lt; 95%) based on self-reports. The primary endpoint was viral suppression, while adherence was the secondary endpoint.\u003c/p\u003e\u003cp\u003e\u003cstrong\u003eIntensified adherence counseling\u003c/strong\u003e\u003c/p\u003e\u003cp\u003eViral load assays for mother-infant pairs were conducted at enrollment and at six-month intervals throughout the study. If a viral load exceeding 1000 copies/ml was detected in the mother, infant, or both, the mother underwent a once a month session of intensified adherence counseling for three consecutive months. This was followed by a repeat viral load test, in accordance with National treatment guidelines. Additionally, self-reported adherence was evaluated for all mothers at every visit.\u003c/p\u003e\u003cp\u003e\u003cstrong\u003eIn-depth interviews\u003c/strong\u003e\u003c/p\u003e\u003cp\u003eIn addition to IAC, a subset of 17 mothers underwent in-depth interviews in order to clearly map out the factors contributing to viral non-suppression. Interviews were recorded and transcribed.\u003c/p\u003e\u003cp\u003e\u003cb\u003eData analysis\u003c/b\u003e: Infant variables of interest including: age, sex, age at diagnosis, weight, head circumference, mid upper arm circumference, ART regimen, viral load, and CD4 cell count were extracted from the database. For the mother, the following were extracted: age, occupation, area of residence, parity, regimen, and viral load. Coded data with patient identification numbers were used. The primary endpoint for this sub-study was viral suppression following IAC.\u003c/p\u003e"},{"header":"Results","content":"\u003cp\u003e\u003cb\u003eParticipants and baseline characteristics\u003c/b\u003e\u003c/p\u003e\u003cp\u003eDetailed demographics of the study have been described elsewhere [\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e] and as indicated in Fig.\u0026nbsp;\u003cspan refid=\"Fig6\" class=\"InternalRef\"\u003e1\u003c/span\u003e. But briefly, 100 infants (60% female) and their mothers were enrolled and followed up for two years in the DRIBS study. Between August 2017 and October 2023, 100 infants (60% female) were enrolled and followed up for two years in the DRIBS study. 12% of the infants had moderate to severe malnutrition at the time of enrollment and 64% had history of Nevirapine exposure. The median age at diagnosis was 79 (IQR, 57.75;140.75) days, with only 4% of patients diagnosed within 6 weeks after delivery, the majority (67%) were diagnosed between 6\u0026ndash;12 weeks (Table\u0026nbsp;1). The median age at the initiation of ART was 110.5 (IQR, 87.0\u0026ndash;162.0) days (table 1). Median age of the mothers was 26 (IQR,19;35) years with 40% of mothers having attained at least secondary level education.\u003c/p\u003e\u003cp\u003e\u003cb\u003eViral suppression\u003c/b\u003e\u003c/p\u003e\u003cp\u003eBy the end of the two-year follow-up period, 63% and 83% of infants achieved viral loads (VL)\u0026thinsp;\u0026lt;\u0026thinsp;50 copies/ml and \u0026lt;\u0026thinsp;1000 copies/ml, respectively. In contrast, mothers demonstrated higher rates of viral suppression, with 85% achieving VL\u0026thinsp;\u0026lt;\u0026thinsp;50 copies/ml (Fig.\u0026nbsp;\u003cspan refid=\"Fig6\" class=\"InternalRef\"\u003e1\u003c/span\u003e). Among mother-infant pairs, 36% of non-suppressing children had mothers who were also virally non-suppressed during the study (Fig.\u0026nbsp;\u003cspan refid=\"Fig7\" class=\"InternalRef\"\u003e2\u003c/span\u003e). Further analysis revealed that 20% of all children in the study exhibited persistent viral non-suppression at more than three time points during the course of the study (Fig.\u0026nbsp;\u003cspan refid=\"Fig8\" class=\"InternalRef\"\u003e3\u003c/span\u003eb). Among mothers with detectable viral loads\u0026thinsp;\u0026gt;\u0026thinsp;1000 copies/ml, 40% experienced persistent non-suppression at two or more study visits, contributing to the 15% non-suppression observed at the study's conclusion (Fig.\u0026nbsp;\u003cspan refid=\"Fig8\" class=\"InternalRef\"\u003e3\u003c/span\u003ea).\u003c/p\u003e\u003cp\u003e\u003cb\u003eAdherence and intensified adherence counseling\u003c/b\u003e\u003c/p\u003e\u003cp\u003eSelf-reported adherence at each study visit revealed that at least 10\u0026ndash;20% of the mothers reported poor adherence (adherence\u0026thinsp;\u0026lt;\u0026thinsp;95%) (Fig.\u0026nbsp;\u003cspan refid=\"Fig9\" class=\"InternalRef\"\u003e4\u003c/span\u003e). Since these children transitioned from a PI-based regimen to a DTG-based regimen during the course of the study, we compared adherence on these two regimens and found that the non-adherence levels were not significantly different between the PI-based regimen and the DTG-based regimen (14% and 11% respectively). When adherence was compared between mother and child, children were more likely to miss doses than mothers (p\u0026thinsp;=\u0026thinsp;0.031) (and Fig.\u0026nbsp;\u003cspan refid=\"Fig10\" class=\"InternalRef\"\u003e5\u003c/span\u003e).\u003c/p\u003e\u003cp\u003eA repeat viral load after IAC revealed that 67% of the mothers achieved complete viral suppression (viral load\u0026thinsp;\u0026lt;\u0026thinsp;50 copies/ml) following AIC, and 15% had low level viremia (viral load between 50\u0026ndash;999 copies/ml) (Fig.\u0026nbsp;\u003cspan refid=\"Fig11\" class=\"InternalRef\"\u003e6\u003c/span\u003ea) On the other hand, 28% of the children achieved complete viral suppression, 42% unsuppressed (viral load\u0026thinsp;\u0026gt;\u0026thinsp;1000 copies/ml) and 30% had low level viremia (Fig.\u0026nbsp;\u003cspan refid=\"Fig11\" class=\"InternalRef\"\u003e6\u003c/span\u003eb).\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eIn order to eradicate HIV by 2030, there is need to fast track HIV infection control among the children. Although the adult population is showing evidence of progress, the pediatric population is still lagging behind. According to the UNAIDS report 2024, only 66% of the HIV positive babies are diagnosed within the first six weeks, of these, 55% are initiated on ART and of those on ART, viral suppression is about 50% [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. It is evident that with this kind of progress, it will take much longer for the children to attain the 95-95-95 goal.\u003c/p\u003e\u003cp\u003eOne of the bottlenecks to achieving the third 95 in both adults and children is adherence. Children, especially infants struggled with ingestion of the LPV/r formulations that were either bitter, hard to swallow or nauseating resulting in vomiting [\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e, \u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e]. This negatively impacted on viral suppression [\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e]. The roll out of DTG in the pediatric population saw an end to most of these struggles. However, even with the said roll out of DTG, we have shown that adherence is still a major challenge among children. Makonokaya et al showed that post-DTG transition viral suppression was associated with pre-DTG transition viral suppression implying that children who were previously suppressing while on a LPV/r containing regimen were more likely to maintain viral suppression when transitioned to a DTG-containing regimen [\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e]. Furthermore, in this pediatric study, adherence post-DTG transition was 52.5% [\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e] further indicating that the switch to DTG was not associated with improved adherence. The resulting viral non-suppression calls for a drug resistance test to ensure the patient is kept on a functional regimen. With the extreme lack of resources in the low to middle income countries, it is impossible to perform a drug resistance test for everyone failing with a detectable viral load. As a recommendation by WHO therefore, patients undergo three sessions of intense adherence counselling to ensure that the viral non-suppression is not as a result of poor adherence. This is then followed by a repeat viral load. Any viral load greater than 1000 copies/ml after these three sessions qualifies for a drug resistance test. In this study, we specifically focused on children who after diagnosis were initiated on ART, hence we focused on the third 95. We and others have previously shown that viral suppression among children initiated on ART is consistently lower than that seen in adults [\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e]. Furthermore, time to viral suppression is significantly different between adults and children [\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e]. This is also true for mother-infant pairs [\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e, \u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e]. In this study, we focused on adherence as a secondary endpoint in the DRIBS study. Previously, we have shown that mothers who transmit to their babies do not have good adherence to ART for various reasons and these include: being in a discordant relationship, being involved in high risk behavior, not having a stable source of income, and moving from place to place looking for where to stay among family members [\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e]. All these have stigma implications. In this study mothers whose children missed doses indicated that stigma was the major reason for not giving the prescribed doses to their children. Spielman et al showed that caregivers who experienced HIV-related stigma, and those who lacked social support, were more likely not to give ART to their children regularly [\u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e]. A review by Perger indicated that many Qualitative studies reported that stigma was a not only a barrier to ART adherence but also a barrier for engagement and retention in HIV care [\u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eAlthough mothers who transmit to their babies have poor viral suppression, in this study, we show that these mothers had better viral suppression rates than their children. The poor viral suppression rates have previously been attributed to infants experiencing challenges with the LPV/r pellets which were very hard to swallow so mothers ended up skipping the children\u0026rsquo;s doses. Furthermore, mothers would open the pellet and give the child granules and sometimes they would not give a complete dose in the process. The taste of this granules was very unpleasant, this too resulted in missed doses. The liquid formulation that was developed following this had a bitter taste which did not make adherence better [\u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e]. During the course of the study, there was a transition from LPV/r to DTG. This resulted in better viral suppression [\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e]. Viral non-suppression in both children and mothers was seen in two thirds (67%) of the mothers who were less than thirty years. About half of the mothers and children with viral non-suppression had persistent non-suppression (more than 1000 copies/ml at two or more time points).\u003c/p\u003e\u003cp\u003eSelf-reported adherence did not improve even with the transition to DTG. Children were more likely to miss pills than mothers. This was attributed to stigma where mothers due to being in a discordant relationship, lack of stable income, moving from place to place because of lack of a permanent place of residence were afraid to be seen giving their children ART [\u003cspan citationid=\"CR34\" class=\"CitationRef\"\u003e34\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eIntensified adherence counseling resulted in viral in viral suppression in about 58% of the children. However, even those that suppressed below 1000 copies/ml, most of them had low-level viremia which has clinical implications on response to therapy [\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e]. During the period of intensified adherence counseling, it is evident that if there are drug resistant mutations, they are evolving. With the findings of low viral suppression following IAC, and the presence of LLV among those that suppress, the major question is, do the benefits of IAC outweigh the challenges? Is IAC effective among pediatrics especially those below two years of age bearing in mind the time it takes from performing the first viral load, getting the result back, having the three sessions of IAC, performing a repeat viral load and have the results back. Then finally, if the viral load is \u0026gt;\u0026thinsp;1000 copies/ml or between 200\u0026ndash;999 copies/ml, the time it takes to perform a drug resistance test and have the report to guide treatment modification. In low to middle income countries, this whole sequence of events might take around six to eight months. Are we doing more damage during this time? How can we improve treatment outcomes in this age group? In order to address these questions, there is need for more studies to look at the dynamics of viral evolution during this time.\u003c/p\u003e\u003cp\u003e\u003cb\u003eStudy Limitations\u003c/b\u003e\u003c/p\u003e\u003cp\u003eAlthough viral load data was available for mother infant pairs during the time on the study, most of the mothers\u0026rsquo; drug regimens were not captured for comparison with the child\u0026rsquo;s regimen. However, from the available data, most of these mothers had been diagnosed less than a year prior to enrollment into the study. They were initiated on the recommended regimen at the time. Those who enrolled before DTG roll out were on either an Efavirenz containing regimen or LPV-containing regimen. Then, with the roll-out of DTG, they were on a DTG containing regimen.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cem\u003e\u003cstrong\u003eConflict of\u0026nbsp;\u003c/strong\u003e\u003c/em\u003e\u003cem\u003e\u003cstrong\u003einterest statement\u003c/strong\u003e\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare that they have no competing interests.\u003c/p\u003e\n\u003cp\u003e\u003cem\u003e\u003cstrong\u003eAuthors\u0026rsquo; contributions:\u0026nbsp;\u003c/strong\u003e\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003e\u003c/em\u003e\u003c/strong\u003eIN designed the research study FM performed the lab work, CM, DR, RB, EN and PA, did the patient enrollment, follow-up, and counseling, and CO analyzed the data, IN wrote the paper and CK reviewed the paper.\u003c/p\u003e\n\u003cp\u003e\u003cem\u003e\u003cstrong\u003eEthic approval and consent to participate\u003c/strong\u003e\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eEthical approval and approval from the Joint Clinical Research Centre Research and Ethics committee (JCRC REC) as well as from the National Council of Science and Technology were obtained (JC3617 and HS 2383, respectively). All research was performed in accordance with the JCRC REC guidelines/regulations. Informed consent was obtained from all partcipants\u0026rsquo; legal guardians.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003eConsent for Publication\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eThis was obtained under the consent to participate in the study\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003eFunding\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis study was fully funded by the European and Developing Countries Clinical Trials Partnership (EDCTP) under grant number TMA2015SF-1037.\u003c/p\u003e\n\u003cp\u003e\u003cem\u003e\u003cstrong\u003eAcknowledgments\u003c/strong\u003e\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eThis study was fully funded by the European and Developing Countries Clinical Trials Partnership (EDCTP) under grant number TMA2015SF-1037.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eData Availability\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe dataset generated and analyzed during the current study is not publicly available due to the fact that more data analysis is still ongoing using the same dataset because this study was conducted to answer multiple questions. However, the data is available from the corresponding author on reasonable request.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eUNAIDS, \u003cem\u003eThe Urgency of Now.\u003c/em\u003e 2024.\u003c/li\u003e\n\u003cli\u003eCollins, I.J., et al., \u003cem\u003eCost-effectiveness of early infant HIV diagnosis of HIV-exposed infants and immediate antiretroviral therapy in HIV-infected children under 24 months in Thailand.\u003c/em\u003e PLoS One, 2014. \u003cstrong\u003e9\u003c/strong\u003e(3): p. e91004.\u003c/li\u003e\n\u003cli\u003eCiaranello, A.L., et al., \u003cem\u003eEarly infant HIV-1 diagnosis programs in resource-limited settings: opportunities for improved outcomes and more cost-effective interventions.\u003c/em\u003e BMC Med, 2011. \u003cstrong\u003e9\u003c/strong\u003e: p. 59.\u003c/li\u003e\n\u003cli\u003eGhadrshenas, A., et al., \u003cem\u003eImproved access to early infant diagnosis is a critical part of a child-centric prevention of mother-to-child transmission agenda.\u003c/em\u003e Aids, 2013. \u003cstrong\u003e27 Suppl 2\u003c/strong\u003e: p. S197-205.\u003c/li\u003e\n\u003cli\u003eEssajee, S., et al., \u003cem\u003eReducing mortality in HIV-infected infants and achieving the 90-90-90 target through innovative diagnosis approaches.\u003c/em\u003e J Int AIDS Soc, 2015. \u003cstrong\u003e18\u003c/strong\u003e(Suppl 6): p. 20299.\u003c/li\u003e\n\u003cli\u003eVojnov, L., et al., \u003cem\u003eSame-day test and treat for infants with HIV infection: finally within reach.\u003c/em\u003e J Int AIDS Soc, 2022. \u003cstrong\u003e25\u003c/strong\u003e(9): p. e26016.\u003c/li\u003e\n\u003cli\u003eJani, I.V., et al., \u003cem\u003eImpact of point-of-care birth test-and-treat on clinical outcomes among infants with HIV: A cluster randomized trial in Mozambique and Tanzania.\u003c/em\u003e Clin Infect Dis, 2024.\u003c/li\u003e\n\u003cli\u003eTayong, G.F.E., et al., \u003cem\u003eHIV viral load suppression rates among adults and children living with HIV in the North West Region of Cameroon: A call for action!\u003c/em\u003e PLoS One, 2025. \u003cstrong\u003e20\u003c/strong\u003e(1): p. e0316399.\u003c/li\u003e\n\u003cli\u003eImmaculate Nankya, E.N., Diana Rutebarika, Christine Matama, Roy Basiimwa Paul Arikod, Faryad Muwabe, Caroline Otike and Cissy Kityo, \u003cem\u003eHigh prevalence of low-level viremia among infants initiated on antiretroviral drugs following mother-to-child transmission of HIV.\u003c/em\u003e Journal of AIDS Research and Therapy. \u003cstrong\u003ein press\u003c/strong\u003e.\u003c/li\u003e\n\u003cli\u003eWalle, B.G., et al., \u003cem\u003eTreatment failure among Sub-Sahara African children living with HIV: a systematic review and meta-analysis.\u003c/em\u003e Ital J Pediatr, 2024. \u003cstrong\u003e50\u003c/strong\u003e(1): p. 202.\u003c/li\u003e\n\u003cli\u003eHarries, A.D., et al., \u003cem\u003eEnding the HIV/AIDS epidemic in low- and middle-income countries by 2030: is it possible?\u003c/em\u003e F1000Res, 2016. \u003cstrong\u003e5\u003c/strong\u003e: p. 2328.\u003c/li\u003e\n\u003cli\u003eKarthigeyan, K.P., et al., \u003cem\u003eResearch on Maternal Vaccination for HIV Prevention.\u003c/em\u003e Clin Perinatol, 2024. \u003cstrong\u003e51\u003c/strong\u003e(4): p. 769-782.\u003c/li\u003e\n\u003cli\u003eRuel, T., et al., \u003cem\u003eNovel Approaches to Postnatal Prophylaxis to Eliminate Vertical Transmission of HIV.\u003c/em\u003e Glob Health Sci Pract, 2023. \u003cstrong\u003e11\u003c/strong\u003e(2).\u003c/li\u003e\n\u003cli\u003ePenazzato, M., et al., \u003cem\u003eAntiretroviral postnatal prophylaxis to prevent HIV vertical transmission: present and future strategies.\u003c/em\u003e J Int AIDS Soc, 2023. \u003cstrong\u003e26\u003c/strong\u003e(2): p. e26032.\u003c/li\u003e\n\u003cli\u003eWebb, K., et al., \u003cem\u003eBrief Report: Improving Early Infant Diagnosis Observations: Estimates of Timely HIV Testing and Mortality Among HIV-Exposed Infants.\u003c/em\u003e J Acquir Immune Defic Syndr, 2020. \u003cstrong\u003e83\u003c/strong\u003e(3): p. 235-239.\u003c/li\u003e\n\u003cli\u003eManasyan, A., et al., \u003cem\u003eDifferentiated community-based point-of-care early infant diagnosis to improve HIV diagnosis and ART initiation among infants and young children in Zambia: a quasi-experimental cohort study.\u003c/em\u003e BMJ Glob Health, 2025. \u003cstrong\u003e10\u003c/strong\u003e(2).\u003c/li\u003e\n\u003cli\u003eBoeke, C.E., et al., \u003cem\u003ePoint-of-care testing can achieve same-day diagnosis for infants and rapid ART initiation: results from government programmes across six African countries.\u003c/em\u003e J Int AIDS Soc, 2021. \u003cstrong\u003e24\u003c/strong\u003e(3): p. e25677.\u003c/li\u003e\n\u003cli\u003ele Roux, S.M., et al., \u003cem\u003eCost-effectiveness of point-of-care versus centralised, laboratory-based nucleic acid testing for diagnosis of HIV in infants: a systematic review of modelling studies.\u003c/em\u003e Lancet HIV, 2023. \u003cstrong\u003e10\u003c/strong\u003e(5): p. e320-e331.\u003c/li\u003e\n\u003cli\u003eMigamba, S.M., et al., \u003cem\u003eRapid antiretroviral therapy initiation following rollout of point-of-care early infant diagnosis testing, Uganda, 2018-2021.\u003c/em\u003e AIDS Res Ther, 2024. \u003cstrong\u003e21\u003c/strong\u003e(1): p. 31.\u003c/li\u003e\n\u003cli\u003eChapuma, C.I.J., et al., \u003cem\u003eExamining barriers to antiretroviral therapy initiation in infants living with HIV in sub-Saharan Africa despite the availability of point-of-care diagnostic testing: a narrative systematic review.\u003c/em\u003e J Int AIDS Soc, 2024. \u003cstrong\u003e27 Suppl 1\u003c/strong\u003e(Suppl 1): p. e26284.\u003c/li\u003e\n\u003cli\u003eKekitiinwa, A., et al., \u003cem\u003eAcceptability of lopinavir/r pellets (minitabs), tablets and syrups in HIV-infected children.\u003c/em\u003e Antivir Ther, 2016. \u003cstrong\u003e21\u003c/strong\u003e(7): p. 579-585.\u003c/li\u003e\n\u003cli\u003eNebot Giralt, A., et al., \u003cem\u003eUnderstanding the acceptability and adherence to paediatric antiretroviral treatment in the new formulation of pellets (LPV/r): the protocol of a realist evaluation.\u003c/em\u003e BMJ Open, 2017. \u003cstrong\u003e7\u003c/strong\u003e(3): p. e014528.\u003c/li\u003e\n\u003cli\u003eSliefert, M., et al., \u003cem\u003eChallenges with pediatric antiretroviral therapy administration: Qualitative perspectives from caregivers and HIV providers in Kenya.\u003c/em\u003e PLoS One, 2024. \u003cstrong\u003e19\u003c/strong\u003e(1): p. e0296713.\u003c/li\u003e\n\u003cli\u003eMusiime, V., et al., \u003cem\u003eThe pharmacokinetics and acceptability of lopinavir/ritonavir minitab sprinkles, tablets, and syrups in african HIV-infected children.\u003c/em\u003e J Acquir Immune Defic Syndr, 2014. \u003cstrong\u003e66\u003c/strong\u003e(2): p. 148-54.\u003c/li\u003e\n\u003cli\u003eMakonokaya, L., et al., \u003cem\u003eEarly Effects of Scaling Up Dolutegravir-Based ARV Regimens Among Children Living with HIV in Malawi.\u003c/em\u003e AIDS Behav, 2024. \u003cstrong\u003e28\u003c/strong\u003e(6): p. 2148-2155.\u003c/li\u003e\n\u003cli\u003eDevendra, A., et al., \u003cem\u003eHIV viral suppression in children and adolescents 2 years after transition to dolutegravir: a multicentre cohort study.\u003c/em\u003e Aids, 2024. \u003cstrong\u003e38\u003c/strong\u003e(7): p. 1013-1023.\u003c/li\u003e\n\u003cli\u003eTurkova, A., et al., \u003cem\u003eDolutegravir as First- or Second-Line Treatment for HIV-1 Infection in Children.\u003c/em\u003e N Engl J Med, 2021. \u003cstrong\u003e385\u003c/strong\u003e(27): p. 2531-2543.\u003c/li\u003e\n\u003cli\u003eImmaculate Nankya, E.N., Diana Rutebarika, Christine Matama, Roy Basiimwa, Paul Arikod, Faryad Muwabe, Caroline Otike and Cissy Kityo, \u003cem\u003eHigh prevalence of low-level viremia among infants initiated on antiretroviral drugs following mother-to-child transmission of HIV.\u003c/em\u003e AIDS Research and Therapy, 2025. \u003cstrong\u003e22\u003c/strong\u003e(34).\u003c/li\u003e\n\u003cli\u003eChupradit, S., et al., \u003cem\u003ePopulation Pharmacokinetics of Pediatric Lopinavir/Ritonavir Oral Pellets in Children Living with HIV in Africa.\u003c/em\u003e Clin Pharmacol Ther, 2024. \u003cstrong\u003e115\u003c/strong\u003e(5): p. 1105-1113.\u003c/li\u003e\n\u003cli\u003eNankya, I., et al., \u003cem\u003eHigh prevalence of low-level viremia among infants initiated on antiretroviral drugs following mother-to-child transmission of HIV.\u003c/em\u003e AIDS Research and Therapy, 2025. \u003cstrong\u003e22\u003c/strong\u003e(1): p. 34.\u003c/li\u003e\n\u003cli\u003eSpielman, K.L., et al., \u003cem\u003eDepressive symptoms, HIV-related stigma and ART adherence among caregivers of children in vulnerable households in rural southern Malawi.\u003c/em\u003e PLoS One, 2021. \u003cstrong\u003e16\u003c/strong\u003e(3): p. e0247974.\u003c/li\u003e\n\u003cli\u003ePerger, T., et al., \u003cem\u003eImpact of HIV-Related Stigma on Antiretroviral Therapy Adherence, Engagement and Retention in HIV Care, and Transition to Adult HIV Care in Pediatric and Young Adult Populations Living With HIV: A Literature Review.\u003c/em\u003e AIDS Behav, 2025. \u003cstrong\u003e29\u003c/strong\u003e(2): p. 497-516.\u003c/li\u003e\n\u003cli\u003eChen, S., et al., \u003cem\u003eAnti-HIV drugs lopinavir/ritonavir activate bitter taste receptors.\u003c/em\u003e Chem Senses, 2023. \u003cstrong\u003e48\u003c/strong\u003e.\u003c/li\u003e\n\u003cli\u003eBuh, A., et al., \u003cem\u003eBarriers and facilitators for interventions to improve ART adherence in Sub-Saharan African countries: A systematic review and meta-analysis.\u003c/em\u003e PLoS One, 2023. \u003cstrong\u003e18\u003c/strong\u003e(11): p. e0295046.\u003c/li\u003e\n\u003c/ol\u003e"},{"header":"Table","content":"\u003ctable border=\"0\" cellspacing=\"0\" cellpadding=\"0\" width=\"513\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 61.5984%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eTable 1\u003c/strong\u003e. Patient demographics\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 16.9591%;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 21.4425%;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 61.5984%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eVariable\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16.9591%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eMedian\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 21.4425%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eIQR\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 61.5984%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eAge in months\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16.9591%;\"\u003e\n \u003cp\u003e4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 21.4425%;\"\u003e\n \u003cp\u003e(1;16)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 61.5984%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eAge at diagnosis\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16.9591%;\"\u003e\n \u003cp\u003e79\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 21.4425%;\"\u003e\n \u003cp\u003e(57.75;140.75)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 61.5984%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eAge at initiation of ART\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16.9591%;\"\u003e\n \u003cp\u003e110.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 21.4425%;\"\u003e\n \u003cp\u003e(87; 162)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 61.5984%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eWeight in Kg\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16.9591%;\"\u003e\n \u003cp\u003e6.1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 21.4425%;\"\u003e\n \u003cp\u003e(3.9;9.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 61.5984%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eCD4 count\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16.9591%;\"\u003e\n \u003cp\u003e2127.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 21.4425%;\"\u003e\n \u003cp\u003e(447; 5011)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 61.5984%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eBaseline viral load\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16.9591%;\"\u003e\n \u003cp\u003e4.44\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 21.4425%;\"\u003e\n \u003cp\u003e(3.19;5.58)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 61.5984%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eMother\u0026apos;s age\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16.9591%;\"\u003e\n \u003cp\u003e26\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 21.4425%;\"\u003e\n \u003cp\u003e(19;35)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 61.5984%;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 16.9591%;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 21.4425%;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 61.5984%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eVariable\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16.9591%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eFrequency\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 21.4425%;\"\u003e\n \u003cp\u003e\u003cstrong\u003ePercent\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 61.5984%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eSex of the child\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 16.9591%;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 21.4425%;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 61.5984%;\"\u003e\n \u003cp\u003eMale\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16.9591%;\"\u003e\n \u003cp\u003e40\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 21.4425%;\"\u003e\n \u003cp\u003e40\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 61.5984%;\"\u003e\n \u003cp\u003eFemale\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16.9591%;\"\u003e\n \u003cp\u003e60\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 21.4425%;\"\u003e\n \u003cp\u003e60\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 61.5984%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eMother\u0026apos;s education level\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 16.9591%;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 21.4425%;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 61.5984%;\"\u003e\n \u003cp\u003eNo formal/primary education\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16.9591%;\"\u003e\n \u003cp\u003e60\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 21.4425%;\"\u003e\n \u003cp\u003e60\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 61.5984%;\"\u003e\n \u003cp\u003eSecondary/tertiary education\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16.9591%;\"\u003e\n \u003cp\u003e40\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 21.4425%;\"\u003e\n \u003cp\u003e40\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 61.5984%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eMother\u0026apos;s residence\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 16.9591%;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 21.4425%;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 61.5984%;\"\u003e\n \u003cp\u003eUrban\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16.9591%;\"\u003e\n \u003cp\u003e55\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 21.4425%;\"\u003e\n \u003cp\u003e55\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 61.5984%;\"\u003e\n \u003cp\u003eRural\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16.9591%;\"\u003e\n \u003cp\u003e45\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 21.4425%;\"\u003e\n \u003cp\u003e45\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 61.5984%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eNutrition assessment\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 16.9591%;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 21.4425%;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 61.5984%;\"\u003e\n \u003cp\u003eRed\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16.9591%;\"\u003e\n \u003cp\u003e3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 21.4425%;\"\u003e\n \u003cp\u003e3.3\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 61.5984%;\"\u003e\n \u003cp\u003eYellow\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16.9591%;\"\u003e\n \u003cp\u003e8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 21.4425%;\"\u003e\n \u003cp\u003e8.9\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 61.5984%;\"\u003e\n \u003cp\u003eGreen\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16.9591%;\"\u003e\n \u003cp\u003e79\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 21.4425%;\"\u003e\n \u003cp\u003e87.8\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 61.5984%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eChild birth order\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 16.9591%;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 21.4425%;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 61.5984%;\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16.9591%;\"\u003e\n \u003cp\u003e30\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 21.4425%;\"\u003e\n \u003cp\u003e30\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 61.5984%;\"\u003e\n \u003cp\u003e2 to 4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16.9591%;\"\u003e\n \u003cp\u003e61\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 21.4425%;\"\u003e\n \u003cp\u003e61\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 61.5984%;\"\u003e\n \u003cp\u003e\u0026ge;5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16.9591%;\"\u003e\n \u003cp\u003e9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 21.4425%;\"\u003e\n \u003cp\u003e9\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"3\" style=\"width: 100%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eChronic conditions in mother\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 61.5984%;\"\u003e\n \u003cp\u003eYes\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16.9591%;\"\u003e\n \u003cp\u003e84\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 21.4425%;\"\u003e\n \u003cp\u003e84\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 61.5984%;\"\u003e\n \u003cp\u003eNo\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16.9591%;\"\u003e\n \u003cp\u003e16\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 21.4425%;\"\u003e\n \u003cp\u003e16\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 61.5984%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eNevirapine exposure\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 16.9591%;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 21.4425%;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 61.5984%;\"\u003e\n \u003cp\u003eYes\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16.9591%;\"\u003e\n \u003cp\u003e64\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 21.4425%;\"\u003e\n \u003cp\u003e64\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 61.5984%;\"\u003e\n \u003cp\u003eNo\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16.9591%;\"\u003e\n \u003cp\u003e36\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 21.4425%;\"\u003e\n \u003cp\u003e36\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"mother-to-child transmission of HIV-1, antiretroviral therapy, viral load, viral suppression, LLV, and intensified adherence counseling","lastPublishedDoi":"10.21203/rs.3.rs-6860769/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-6860769/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground\u003c/h2\u003e\u003cp\u003eWith the current UNAIDS strategy of attaining 95-95-95 by the year 2030, HIV positive children should not be left behind. However, statistics show that HIV diagnosis in children lags behind that of adult, the number of newly diagnosed babies initiated on treatment is much lower than that in adults. Even when initiated on ART, viral suppression among children is much lower than in adults. There is need for a call to action.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e\u003cp\u003eThis study was nested within the DRIBS (\u003cb\u003eD\u003c/b\u003erug \u003cb\u003eR\u003c/b\u003eesistance testing among \u003cb\u003eI\u003c/b\u003enfants at \u003cb\u003eB\u003c/b\u003easeline \u003cb\u003eS\u003c/b\u003etudy), which enrolled 100 infants at the time of treatment initiation between 2017\u0026ndash;2023. Infants were followed for two years. Viral load (VL) was measured every six months and after completion of the three sessions of intensified adherence counseling (IAC).\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e\u003cp\u003eAt the end of the two-year follow-up period, 63% of the children and 85% of the mothers had achieved complete viral suppression. Among mother-infant pairs, 36% of the virally non-suppressing children belonged to non-suppressing mothers. 20% of all children in the study exhibited persistent viral non-suppression at more than three time points during the course of the study. Among mothers with viral loads\u0026thinsp;\u0026gt;\u0026thinsp;1000 copies/ml, 40% experienced persistent non-suppression. Self-reported adherence at each study visit revealed that at least 15% of the mothers reported poor adherence (adherence\u0026thinsp;\u0026lt;\u0026thinsp;95%) and this was not different between a lopinavir-based and a dolutegravir-based regimen (14% and 11% respectively). Children were more likely to miss doses than mothers (p\u0026thinsp;=\u0026thinsp;0.031). A repeat viral load after IAC revealed that 67% of the mothers achieved complete viral suppression. On the other hand, 28% of the children achieved complete viral suppression and 42% were unsuppressed.\u003c/p\u003e\u003ch2\u003eConclusion\u003c/h2\u003e\u003cp\u003eWithin mother-infant pairs, children exhibit poor viral suppression. This non-suppression persists among pediatrics despite intensified adherence counseling.\u003c/p\u003e","manuscriptTitle":"HIV Viral suppression following intensified adherence counseling among children on Antiretroviral therapy: Is it worth the wait?","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-08-11 10:03:34","doi":"10.21203/rs.3.rs-6860769/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"9a258bff-6eab-4bd5-935f-2870c8fc3375","owner":[],"postedDate":"August 11th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[{"id":52835659,"name":"Biological sciences/Molecular biology"},{"id":52835660,"name":"Health sciences/Medical research"}],"tags":[],"updatedAt":"2025-11-18T07:38:12+00:00","versionOfRecord":[],"versionCreatedAt":"2025-08-11 10:03:34","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-6860769","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-6860769","identity":"rs-6860769","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}