Windhoek joined the Fast-Track Cities Initiative in 2017 to optimize HIV service delivery for adolescents, promoting adherence and sustaining viral suppression. Recent surveys and programmatic data show that the treatment gap remains greatest among children and adolescents living with HIV. A retrospective cohort analysis of adolescents living with HIV (ALHIV) receiving antiretroviral therapy (ART) at Windhoek healthcare facilities was conducted. Routine clinical data were extracted from the electronic Patient Monitoring System (ePMS). The SPSS statistical package was used to determine viral non-suppression and perform inferential statistics. 695 ALHIV were analysed with median age of 16 years (IQR = 13–18). Viral non-suppression at 1000 copies/mL threshold was 12%. Viral non-suppression was associated with age at ART initiation, duration on ART, current ART regimen and WHO Clinical Stage. In multivariate analysis, longer duration on ART was a protective factor for viral non-suppression , while being on third line regimen (vs. first line) was protective against viral non-suppression . A significant treatment gap is evident for ALHIV with high viral non-suppression levels. Interventions are required to counter treatment fatigue to keep adolescents engaged in ART, and timely switching to rescue regimens for failing adolescents. The Fast-Track Cities Initiative, which was launched at the occasion of the 2014 World AIDS day, positioned cities as a critical component playing an essential role in the HIV response worldwide [Adolescents present an increasing population of people living with HIV (PLWHIV) across the world, with an estimated 1.75 million 1.16–2.3 million) adolescents living with HIV (ALHIV) in 2020  million . GloballAccording to the Namibia Population-based HIV Impact Assessment (NAMPHIA), there were an estimated 11,057 ALHIV in Namibia in 2017, with an HIV prevalence of 3.7% in the older adolescents (15–19 years) and 1.9% prevalence in the younger 10–14 years age group . The repGlobally, considerable advancements have been made in the development of biomedical interventions for individuals living with HIV and in expanding access to antiretroviral therapy (ART) . The maiAdolescents living with HIV and receiving ART reportedly have an increased likelihood of poorer treatment adherence and viral suppression compared to adults receiving ART, who achieve higher rates of viral suppression ,16,17. CThe Windhoek district is the only district in the Khomas region of Namibia. The Khomas region hosts the capital city, Windhoek, and is located in the central part of Namibia, home to an estimated 431,000 residents. According to the 2017 NAMPHIA report, Namibia had achieved 86–96–91% of the 90–90–90 UNAIDS and WHO targets with an overall 4.0% prevalence of HIV among young people (15–24 years) and 1.7% among young adolescents (10–14 years) [A quantitative, retrospective cohort analysis was conducted of routine clinical data of adolescents aged 10–19 years registered at the 13 public healthcare facilities in the Windhoek district between January 2019 and December 2021. We extracted individual patient-level data for all ALHIV from the standard routine patient-monitoring data system used at all public healthcare facilities in Namibia, the electronic Patient Monitoring System (ePMS). Data extraction was conducted on the 25th of February 2022, and it consisted of anonymized data with unique patient identifiers, sociodemographic variables, and the linked clinical and treatment outcomes data recorded at routine clinic visits. Facility-based data clerks enter patient data into the ePMS from all clinic visits and the services provided during the visit as documented by clinicians in the patient files, the Patient Care Booklets (PCB). However, the electronic system only provides the last viral load test conducted on the line list report. Patient Care Booklets for patients with incomplete records in the electronic database were retrieved, and the missing information was updated in the electronic database.The primary focus of this study was viral load non-suppression—which was defined as a viral load ≥ 1000 RNA copies/mL after at least six months of HIV treatment as recommended by WHO . The Namp < 0.05.Extracted data were merged into a Microsoft Excel  spreadsheet, matching patient data from the ePMS and PCBs using the unique ART numbers allocated as unique patient identifiers at each clinic. The complete extracted anonymized data was saved into a password-protected Excel file to ensure that the data could not be altered. The complete Excel spreadsheet was imported into the SPSS statistical software  for analysis. Descriptive statistics were performed to describe the clinical and demographic characteristics of the adolescents included in the study. Bivariate analysis was performed using the Chi-square test to determine the significance of associations between viral non-suppression and the demographic and clinical variables . The variables which were significant at the 10% level were fed into the multivariate logistic regression model to determine risk factors for viral non-suppression. Fisher’s exact test was used as an alternative to the Chi-square test in instances of sparse data (<5 in any cell). A multivariate logistic regression model was performed, and odds ratios were used to determine predictors of viral non-suppression among adolescents on ART, with the significance level of association set at The ethical clearance was obtained from the University of the Western Cape Biomedical Research Ethics Committee (ref. no. BM21/5/7) in Cape Town, South Africa, and the Namibia Research Management Committee (ref. no. 17/3/3/FKM) based at the Ministry of Health and Social Services (MoHSS). We also obtained permission from the MoHSS to access the Patient Care Booklets (PCB) and electronic databases. To ensure confidentiality and respect for the privacy and dignity of the participants, no personal identifying information such as patient name/surname or identity number was extracted from the database or during the review of individual PCBs. This study was conducted in compliance with the 1964 Declaration of Helsinki guidelines and its subsequent amendments.A total of 695 adolescents aged 10–19 years accessing ART services between January 2019 and December 2021 at the 13 Windhoek district facilities were included in this analysis. The total number of ALHIV in this study was all-inclusive of all adolescents receiving ART in Windhoek district during the study period. The median age of the participants was 16 years (IQR = 13–18). The majority of adolescents included in this study were older adolescents (15–19 years) (62%), female (56.7%), had started taking ART between the ages of 0–9 years (73.5%), and were on ART for more than 24 months (85%). Namibia adopted the test-and-treat approach, also known as treat-all, whereby all individuals diagnosed HIV-positive are immediately initiated on ART . Approxip = 0.079); duration on ART (p < 0.001); current ART regimen (p < 0.001); and WHO clinical stage at ART initiation (p < 0.001). There were no significant associations between viral non-suppression status and sex, age-group, ART regimen at initiation, HIV disclosure status, TB screening results, type of facility, and retention in care (p > 0.10).The results of the bivariate analysis of viral non-suppression (≥1000 copies/mL) by demographic and clinical characteristics of the adolescents on ART in Windhoek are summarized in p > 0.05) when accounting for the duration on ART and the current ART regimen.After controlling for possible confounders, unsuppressed viral loads were significantly associated with duration on ART and the current ART regimen . PatientOur study reports viral non-suppression levels among adolescents at 12%, which is comparable to what a previous study in Windhoek reported  ,25,26. HAdolescents who had been on ART for longer durations were less likely to be unsuppressed than those who had been on treatment for a shorter duration. Similar findings were reported in Kenya where adolescents who were on treatment for more than ten years were 1.75 times more likely to have suppressed viral loads compared to those on treatment for less than two years, although the association was not statistically significant . This isIt is apparent from the findings of this study that the majority of adolescents were “treatment experienced adolescents” in the ‘older adolescents’ category, with most of them having been initiated on ART at an age of less than 9 years and the majority having been on treatment for a median duration of approximately 8.8 years. The higher percentage of older adolescents in this cohort may indicate the successes of the HIV program and service delivery in Namibia, i.e., the implementation of more effective treatment options and strengthening of the elimination of Mother-to-Child Transmission (eMTCT) program in Namibia, which may be resulting in substantial decreases in perinatally acquired infections. In addition, many perinatally infected adolescents are growing into older adolescents. The NAMPHIA study also reported a comparatively higher incidence of HIV in adolescents and young girls compared to the rest of the population, which could also be contributing to the higher proportions of older adolescents living with HIV .Our study showed significant differences in proportions of unsuppressed viral loads according to the age of the adolescents at the time they were initiated on ART. Adolescents who were aged 10–14 years and 0–9 years when they started ART had comparatively higher levels of non-suppression  than adolescents who were initiated on ART at ages 15–19 years (8.3%). Similar findings were reported in Kenya where adolescents who were diagnosed and initiated on ART at age 10–14 years had higher proportions of viral non-suppression compared to the adolescents who started ART at 15–19 years of age (27.6% vs. 9.6%) . A studyThe type of regimen  for children and younger adolescents, combined with transmitted resistance and possible acquired drug resistance from factors associated with appropriate dose adjustments by weight in children and changes in the metabolism of medication with age, have been associated with higher odds of virologic failure in younger population subgroups ,28. PoorAs expected, the majority of adolescents on ART were initiated on an NNRTI-based regimen as prescribed in the National ART Guidelines. The proportion of adolescents with viral non-suppression was highest among adolescents who were initiated on an NNRTI-based regimen compared to a protease inhibitor (PI)- or dolutegravir (DTG)-based regimen, but the differences did not significantly affect viral suppression. This finding can be attributed to the very small numbers of adolescents started on non-NNRTI-based regimens. It is also interesting to note that none of the eleven adolescents who were initiated on a DTG-based regimen were virally unsuppressed and only three of forty-eight adolescents who started on a PI-based regimen were unsuppressed. The WHO recommended DTG as the preferred HIV treatment option due to having greater effectiveness, fewer side effects, and a high genetic barrier to developing drug resistance . A largeMost of the adolescents remained on a first-line regimen and achieved and maintained viral suppression with a 9.7% proportion of non-suppression, whilst those who were switched to a second-line regimen had a higher proportion of viral non-suppression at 46.3%. However, neither of the two adolescents currently on a third-line regimen were virally unsuppressed and there was no significant difference in viral non-suppression between adolescents on second-line regimens compared to those on a first-line regimen. On the other hand, findings from two South African studies reported higher viral non-suppression levels among adolescents on second-line ART compared to those on first-line regimens ,24. A stThis study was a retrospective cohort study that relied on routinely collected patient data during clinical interactions at clinic visits. The completeness and accuracy of the available data were dependent on the data collection and capturing of patient records by the clinicians and data clerks; this meant that we could not control the selection of variables of interest outside of those routinely collected and could not account for other unmeasured clinical and socioeconomic factors as covariates. Other variables, such as CD4 count, alcohol use, and pregnancy status for female adolescents, were poorly and inconsistently captured and could not be reliably included in the analyses. The amount of missing HIV disclosure, TB screening, WHO clinical stage at ART initiation, and viral load data could have potentially affected the findings of this study. The ePMS has limitations in obtaining longitudinal data and only the last viral load results could be obtained from the system; thus, we could not obtain consecutive viral load results, so virally unsuppressed adolescents may have had viral blips. On the other hand, the analysis of routinely collected clinical data provides a real-life lens into the HIV service delivery’s strengths and gaps for the study population, including the information gaps, as reflected by the incomplete data. Our study sample was also all-inclusive of all adolescents, reducing biases such as sampling or selection bias.Our study demonstrates comparatively high rates of viral non-suppression among the adolescent population living with HIV in Windhoek, Namibia. Viral suppression is close to the previous 90% target but requires reinvigoration to reach the new 95% threshold. The remaining gap towards the achievement of the revised UNAIDS and WHO targets for epidemic control calls for urgent attention to the implementation of targeted interventions to improve adherence to treatment among adolescents. The study also confirms that the longer we can keep adolescents engaged in treatment, the lesser risk of viral non-suppression. Regular viral load monitoring is essential to identify virologic failure and switch failing adolescents to more potent rescue regimens appropriately. Potentially perinatally infected ALHIV who enter later adolescence, which coincides with the transition to adult care, are at the greatest risk for viral non-suppression, and thus require intensive intervention to combat treatment fatigue as well as psychosocial issues emanating from long-term adherence requirements and lifestyle and development changes. Leveraging successful evidence-based strategies and new innovations will be key in closing the treatment gap among ALHIV and can potentially reduce rates of viral non-suppression.


Treatment management after repeated failure of antiretroviral therapy (ART) is difficult due to resistance and adherence challenges. For people who have failed non-nucleoside reverse transcriptase inhibitor-(NNRTI-) and protease inhibitor-(PI-) based regimens with no or limited resistance, remaining on PI-based ART is an option. Using data from an ART strategy trial (A5288) in low/middle-income countries which included this option, we explored whether predictors can be identified distinguishing those who experienced further virologic failure from those who achieved and maintained virologic suppression.A5288 enrolled people with confirmed HIV-1 RNA ≥ 1000 copies/mL after ≥ 24 weeks of PI-based ART and prior failure on NNRTI-based ART. This analysis focused on the 278 participants with no resistance to the PI being taken and no or limited nucleoside reverse transcriptase inhibitor (NRTI) resistance, who continued their PI with flexibility to change NRTIs. Proportional hazards models were used to evaluate predictors of virologic failure during follow-up (VF: confirmed HIV-1 RNA ≥ 1000 copies/mL at ≥ 24 weeks of follow-up).3, HIV-1 RNA 20,444 copies/mL; and 37% had NRTI resistance. The estimated proportion experiencing VF increased from 39% at week 24 to 60% at week 96. In multivariable analysis, significant predictors at study entry of VF were higher HIV-1 RNA , lower age (1.96 for < 30 versus ≥ 30 years), NRTI resistance (1.74 for present versus absent), lower CD4 count (1.73 for < 200 versus ≥ 200 cells/mm3), and shorter ART duration (1.62 for < 10 versus ≥ 10 years). There was a strong trend in proportion with VF at week 96 with the number of these five risk factors that a participant had, varying from 8% for zero, to 31%, 40%, 73%, and 100% for one, two, three, and four/five. Only 13% of participants developed new NRTI or PI resistance mutations.56% of participants were female. At study entry, median age was 40 years, time on ART 7.8 years, CD4 count 169 cells/mmA simple count of five predictors might have value for identifying risk of continued VF. Novel antiretroviral and adherence support interventions are needed to improve virologic outcomes for higher risk individuals.The online version contains supplementary material available at 10.1186/s12981-022-00494-9. Even with the advent of dolutegravir-based antiretroviral therapy (ART), increasing numbers of people living with HIV in low- and middle-income countries (LMICs) will receive ART including a protease inhibitor (PI) following virologic failure on ART which included a non-nucleoside reverse transcriptase inhibitor (NNRTI) , 2. PeopThe AIDS Clinical Trials Group (ACTG) conducted a clinical trial of a treatment strategy for individuals failing second-line PI-based ART in LMICs , Latin America  and Asia (India and Thailand). The design has previously been described in detail , 8. Key Ethical approvals were obtained from the institution review boards at all the participating clinical sites, as follows: Case Western Reserve University, Instituto Nacional de Infectologia Evandro Chagas, Harvard Longwood Campus (HLC) Institutional Review Board, University of Washington, Joint Clinical Research Centre, University of Pennsylvania Perelman School of Medicine, National Institutes of Health, YR Gaitonde Center for AIDS Research and Education, University of North Carolina, National Commission for Science and Technology Malawi, University of Pittsburgh, and the National Health Research Ethics Council (NHREC) (South Africa). Written informed consent was obtained from participants before undertaking study procedures.Real-time HIV genotype resistance results, treatment history and, if available, any historical resistance results, were used to assign participants to one of four treatment cohorts  . Site inAll participants were followed until the last enrolled participant reached 48 weeks of follow-up. Study visits occurred at weeks 4, 12, 24 and every 12 weeks thereafter, with HIV-1 RNA measurements at weeks 12, 24 and every 24 weeks thereafter. Participants with HIV-1 RNA ≥ 1000 copies/mL during follow-up had an additional HIV-1 RNA test as soon as possible  and collection of a plasma sample for possible genotyping. In the event of confirmed virologic failure (two consecutive HIV-1 RNA ≥ 1000 copies/mL at or after 24 weeks), a genotype resistance test was performed, and participants were assigned to an ART regimen using the same approach as at study entry. Adherence counseling by site staff occurred at study pre-entry and entry visits, and then adherence support followed the site’s standard of care (SOC). Except in Peru, participants at all sites were randomized to receive either a cellphone adherence support intervention (CPI) in addition to SOC adherence support (CPI + SOC) or SOC adherence support. The CPI was used for the first 48 weeks of follow-up. Results comparing virologic and other outcomes for CPI + SOC versus SOC have been previously reported and showed no significant effect of CPI [This report focuses on the key secondary outcome measure in the A5288 study of time from study entry to confirmed virologic failure, defined as the time to the first of two successive HIV-1 RNA measurements ≥ 1000 copies/mL at or after 24 weeks from study entry. One participant who died following an HIV-1 RNA measurement ≥ 1000 copies/mL at 24 weeks without confirmation was considered as having confirmed virologic failure. Among those experiencing virologic failure during follow-up, we further considered whether or not the resistance genotype obtained at virologic failure showed new resistance-associated mutations according to the Stanford HIV Database algorithm version 6.2 , 9 compa3), duration of time since first starting ART  any level of resistance using the Stanford HIV Database algorithm version 6.2 to any NRTI commonly used at the time in LMICs , and the randomized adherence support intervention . Kaplan-Meier estimates and proportional hazards models were used to evaluate associations of these variables with time to confirmed virologic failure, with Gray’s test used to test associations involving the competing risks of virologic failure with, and without, new resistance mutations. Analysis was on an intent to continue treatment basis, i.e. ignoring any changes in antiretroviral treatment. For participants not experiencing virologic failure, follow-up was censored at the last available HIV-1 RNA measurement. Associations were considered significant if p < 0.05.This is an exploratory analysis of predictors of time to confirmed virologic failure. The following variables assessed at study entry were considered as possible predictors: sex, age , HIV-1 RNA at study entry , CD4 count  had HIV-1 RNA < 1000 copies/mL at study entry despite having confirmed HIV-1 RNA ≥ 1000 copies/mL during screening.A total of 287 participants were enrolled into Cohort A between 2013 and 2015, representing 53% of the overall A5288 study population [The PI continued was LPV/r for 173 participants (62%) and ATV/ritonavir (ATV/r) for 103 (37%); for two other participants it was ATV (because of intolerance to ritonavir) or saquinavir (SQV). All participants took either 3TC or FTC. The second NRTI was TDF for 256 participants (92%), ZDV for 20 participants (7%), and ABC for one participant (< 1%); the remaining participant (< 1%) took both TDF and ZDV (plus FTC). Of the 278 participants, 104 (37%) had NRTI resistance based on the genotype obtained at screening including 89 (32%) with resistance to one NRTI in the regimen taken during follow-up (or to two NRTIs for the participant who took both TDF and ZDV plus FTC). Thus 189 participants (68%) had virus susceptible to both the two NRTIs and the PI taken. Among those with resistance to the NRTI component on the regimen taken, 80 participants (29% of the study population of 278 participants) had high-level resistance to 3TC/FTC (due to the M184V mutation), two (< 1%) had intermediate-level resistance to 3TC/FTC , and seven (3%) had low-level resistance or potential low-level resistance to the other NRTI  , only 6 participants (2%) were lost to follow-up without first experiencing virologic failure. Only 12 (4%) of participants had a change in their ART regimen prior to virologic failure or prior to their last HIV-1 RNA measurement if they did not experience virologic failure. Six changed due to adverse events, four due to noncompliance or participant decision to stop ART, one due to a drug supply issue, and one due to a potential drug interaction with tuberculosis treatment.Of the 278 participants, 139 (50%) experienced confirmed virologic failure at or after week 24 of follow-up. Figure 3; and for duration of ART, < 10 versus ≥ 10 years. Using these revised categories, Table 3), and shorter duration of ART (aHR 1.62 for < 10 versus ≥ 10 years). Female participants had somewhat higher risk of virologic failure than male participants (aHR: 1.30) though this was not statistically significant (p = 0.16). Although the estimated hazard ratio for CPI + SOC versus SOC was in the direction of a small benefit of CPI (aHR: 0.80), it was not statistically significant (p = 0.45). We further evaluated whether there was effect modification between each possible pair of variables included in the multivariable model and found no significant evidence . We also found no significant evidence that the PI taken (LPV or ATV) was predictive when added to the model or that any of the associations were modified by which PI was taken. Similarly, with the caveat of limited power, there was no significant evidence that country was predictive of virologic failure when added to the multivariable model or that any of the associations varied among countries. Sensitivity analyses using thresholds of ≥ 50 copies/mL and ≥ 200 copies/mL instead of ≥ 1000 copies/mL to define virologic failure showed the same five variables as the strongest predictors though the hazard ratios for both HIV-1 RNA and CD4 count at study entry showed weaker associations as the threshold used decreased from 1000 to 50 copies/mL  experienced virologic failure. In comparison, among the 98 participants reporting taking < 90% of their doses at either or both of weeks 12 and 24, 51 (52%) experienced virologic failure. The difference was not statistically significant in univariable analysis (p = 0.15) or when added to the multivariable model (p = 0.17).Of the 139 participants who experienced virologic failure, 134 had a resistance genotype available at virologic failure, including 36 who developed new NRTI or PI resistance mutations compared with the genotype obtained during screening for study entry  who might be able to successfully achieve and maintain re-suppression on their PI-based ART.Given the importance of maintaining virologic suppression for reducing risk of HIV disease progression and transmission, we undertook an exploratory analysis to evaluate whether there might be factors predictive of virologic failure among people failing second-line ART with limited NRTI resistance who continued on their PI-based regimen. We identified five factors that were strong and statistically significant predictors of increased risk in both univariable and multivariable modeling: HIV-1 RNA ≥ 10,000 copies/mL, age < 30 years, NRTI resistance, CD4 count < 200 cells/mm3 might reflect uncontrolled HIV disease due to long-term incomplete adherence, particularly in environments in which HIV-1 RNA monitoring may not have been present or may have been limited. Treatment guidelines recognize adherence challenges in young adults [Among the five factors identified, several might reflect issues with adherence to ART. Both HIV-1 RNA ≥ 10,000 copies/mL and CD4 count < 200 cells/mmg adults . ExperieIn a systematic review, the value of self-reported adherence for predicting virologic outcome was mixed across studies . In our Compared with men, women in our study also had a significantly increased risk of virologic failure when continuing their second-line regimen in univariable analysis but the association was reduced and not statistically significant in multivariable analysis. This is consistent with our previous findings in the broader A5288 study population, which may have been associated with increased issues with tolerability to PI-based regimens in women than men, though there may be other factors such as reduced drug availability in women than men .Continuation of second-line ART following virologic failure raises the possibility of development of new resistance mutations. During a median 72 weeks of follow-up, 13% of the study population developed new resistance mutations. We found that the risk of virologic failure with new resistance mutations was also associated with our simple scoring based on the five risk factors identified. Development of new NRTI resistance mutations was more common than new PI resistance mutations, and the latter were generally observed among those with pre-existing NRTI resistance at screening for entry into the study. Not all new resistance mutations observed at virologic failure were mutations indicative of resistance to the drugs being taken, suggesting naturally occurring polymorphisms or re-emergence of mutations conferring resistance to drugs a participant had previously taken (or transmitted resistant virus).A strength of this study was large number of enrolled participants from diverse urban sites in 10 LMICs. On the other hand, our findings come from a clinical trial and so may not generalize to general clinical practice or to rural populations. In particular, retention in care was very high in our study and potentially higher than might be achieved in practice. The clinical trial included enrollment between 2013 and 2015 and so it is possible that predictors of outcome have changed with time. Participants in our study remained on LPV/r- or ATV/r-based regimens which, though still widely used, may not be as well tolerated as newer generation NNRTIs, PIs (including ritonavir-boosted darunavir) and integrase inhibitors  as indicIn conclusion, in this analysis, we identified factors that predict whether further virologic failure is likely or whether virologic re-suppression may be achieved and maintained when continuing PI-based ART among participants experiencing failure on that regimen with no PI resistance and no or limited NRTI resistance. The simple scoring system based on these factors merits further evaluation to assess whether its use coupled with novel adherence support strategies and newer antiretroviral regimens might enhance outcomes in this population.Additional file 1: Fig. S1. Flow Chart Describing the Construction of the Study Population for this Report. Table S1. Resistance Profiles of Participants in the Study Population at Screening to Study Entry. Table S2. Results from Proportional Hazards Model When Virological Failure is Defined as Having Two Successive HIV-1 RNA Measurements ≥50 Copies/mL At or After Week 24 (Instead of Two Successive HIV-1 RNA Measurements ≥1000 Copies/mL As in Table 2 of the Manuscript). Table S3. Results from Proportional Hazards Model When Virological Failure is Defined as Having Two Successive HIV-1 RNA Measurements ≥200 Copies/mL At or After Week 24 (Instead of Two Successive HIV-1 RNA Measurements ≥1000 Copies/mL As in Table 2 of the Manuscript). Table S4. Changes in Nucleoside Reverse Transcriptase Inhibitor (NRTI) and Protease Inhibitor (PI) Resistance Profiles Between Study Screening and Virologic Failure for the 36 Participants with New NRTI- and/or PI-Associated Resistance Mutations at Virologic Failure.


Few studies have analysed the effect of HIV universal test and treat (UTT) on retention and mortality among people living with HIV (PLHIV) in routine care. We examined six-month retention and mortality at 11 health facilities (HFs) run by a large NGO, The AIDS Support Organisation (TASO), before and after UTT.We used a quasi-experimental study using patient data extracted from 11 TASO HFs. Two periods, one before UTT (2015–2016) and the other during UTT (2017–2018) were compared. The primary outcome was six-month retention defined as the proportion of PLHIV who were alive and in care at six months from enrolment. The secondary outcome was six-month mortality defined as the proportion of PLHIV who died within six months from enrolment. We performed an interrupted time series analysis using graphical aids to study trends in six-month retention and mortality and a segmented regression to evaluate the effect of UTT. We used a generalized linear mixed model (GLMM) and generalized estimating equations (GEE) to account for facility-level clustering.Of the 20,171 PLHIV registered between 2015 and 2018 and included in the analysis, 12,757 (63.2%) were enrolled during the UTT period. 5256/7414 (70.9%) of the pre-UTT period compared to 12239/12757 (95.9%) of the UTT were initiated on ART treatment with 6 months from enrolment. The median time from enrolment to initiating ART was 14 (interquartile range (IQR): 0–31) days for the pre-UTT compared to 0 (IQR: 0–0) days for the UTT period. The median age at enrolment was 32.5 years for the pre-UTT and 35.0 years for the UTT period. Overall, the six-month retention just after scale-up of UTT, increased by 9.2 percentage points (p = 0.002) from the baseline value of 82.6% (95% CI: 77.6%-87.5%) but it eventually decreased at a rate 1.0 percentage point (p = 0.014) for cohorts recruited each month after UTT. The baseline six-month mortality was 3.3% (95% CI: 2.4%-4.2%) and this decreased by 1.6 percentage points (p = 0.003) immediately after UTT. The six-month mortality continued decreasing at a rate of 0.1 percentage points (p = 0.002) for cohorts enrolled each month after UTT. Retention differed between some health facilities with Rukungiri HF having the highest and Soroti the lowest retention. Retention was slightly higher among males and younger people. Mortality was highest among people aged 50 years and more. The effect of UTT on retention and mortality was similar across sex and age groups.Overall, UTT significantly led to an immediate increase in retention and decrease in mortality among PLHIV enrolled in HIV care from 11 HFs run by TASO in Uganda. However, retention  significantly decreased for cohorts enrolled each month after UTT. Retention was highest in Rukungiri and lowest in Soroti HFs and slightly higher in males and younger people. Mortality was highest in older patients and lowest in adolescents. We recommend for innovative interventions to improve the overall retention particularly in facilities reporting low retention in order to achieve the UNAIDS 2030 target of 95-95-95. Screening populations at risk for HIV-infection and offering rapid treatment with antiretroviral therapy (ART) in those who are diagnosed as HIV positive ) is standard practice and a key strategy of the World Health Organization (WHO), geared towards ending the HIV epidemic . We refeUTT has been scaled up actively in high HIV-burden countries since around 2014–2015 –6, decreIn Uganda, it is estimated that 84% of HIV-infected persons know their status, and of these 72% are on antiretroviral therapy and of these 64% are virally suppressed .For countries in Africa to achieve the epidemic control, retention in care of those tested and started on antiretroviral therapy is critical. Factors documented to facilitate retention in care include older age, decreased time between testing and ART initiation, higher CD4 count at ART initiation (among men), maintaining physical health, a patient-centered treatment environment, supportive partnerships, few negative consequences to disclosure, and the ability to seek care in facilities outside of their community of residence . Lack ofDespite the above information on improvement in retention following UTT, the strategies to increase HIV yield and starting patients on treatment while in communities  without In this paper, we aimed to determine the effect of UTT strategy on retention and mortality among PLHIV receiving care from 11 health facilities (HFs) in Uganda. We hypothesize that UTT could have negatively affected retention which the ART programmes had achieved in TASO HFs prior to UTT policy.We used a quasi-experimental study to compare two periods, that is, before and after UTT. We extracted and used secondary data for PLHIV registered between 2015 and 2018 at TASO-Uganda using a pre-existing cohort electronic database. TASO is one of the pioneer nongovernmental organizations in HIV service delivery in Uganda that has provided HIV services, health systems strengthening, community and economic strengthening activities for PLHIV since its inception in 1987 (34 years). It is located within the Mulago National Referral Hospital complex, approximately 5 kilometers north-east of Kampala’s central business district. TASO serves over 36 districts of Uganda through its 11 regional service delivery centers  funded mainly by PEPFAR and CDC. TASO has provided HIV prevention, care and treatment services to over 180,000 PLHIV since its inception. In addition to trained health workers , TASO practices meaningful involvement of PLHIV in their own chronic care to ensure ownership. In this case, HIV patients, known as expert clients or peer educators, are actively involved in HIV service delivery through a peer-to-peer approach by providing peer-to-peer support to fellow PLHIV. For one to qualify to be an expert client or peer educator, he/she should be exemplary by having high adherence and be virally suppressed. The newly initiated patients attend clinics and pick their ART drugs nearly on a monthly basis and subsequently every after 3 to 6 months for the virally suppressed patients. TASO rolled out UTT across all its 11 health facilities in 2017 at the same time as the national policy.cells/μL with exception of pregnant women, children below 15 years and key populations who were started on ART regardless of their CD4 count [We evaluated two periods, one pre-UTT 2015–2016) and the other post-UTT (2017–2018). During the pre-UTT period, HIV positive patients were being initiated on ART when their CD4 count was less than 500 –2016 andWe included all PLHIV enrolled in care between 2015 and 2018. We excluded children below 15 years, pregnant mothers and key populations sub-groups to avoid bias in comparing the two periods since these were initiated on ART regardless of their CD4 count by TASO before and after UTT [The primary outcome of interest was six-month retention defined as proportion of PLHIV who were alive and in care at six months from enrolment. In this study, enrolment in care refers to getting registered in TASO as HIV patient after or before initiating ART treatment. The secondary outcome was six-month mortality defined as proportion of PLHIV who died from all causes not necessarily linked to HIV within six months from enrolment. Patients not seen more than 3 months from their next appointment date were considered as LTFU. Both retention and mortality were binary outcomes.We generated a consort chart showing the number of PLHIV enrolled at the 11 TASO HFs between 2015 and 2018, number excluded and number experiencing study outcomes stratified by the two study periods. Six-month retention was calculated considering different cohorts of PLHIV enrolled each month from January 2015 through December 2018 resulting in six-month retention trend data. This implies that the first time series data point refers to six-month retention for the cohort enrolled in January 2015, the second six-month retention data point refers to the cohort enrolled in Feb 2015 and so on. For each month cohort, the denominator for retention equals to the number of PLHIV enrolled in that month (after exclusions) and followed for six months, and the numerator equals to the number that remained in care at the end of 6 months from enrolment. We also analysed for trend in six-month mortality. In this case, the numerator equals to the number known to have died within 6 months from enrolment and the denominator is as described for retention. We used interrupted time series analysis to evaluate the effect of UTT on retention and mortality using the six-month rates.Yt is six-month retention ; Time is a continuous variable for time in months starting from January 2015; Period is an indicator for the study period ; Time after UTT is a continuous variable counting the number of months from when UTT was fully scaled-up (January 2017 which is month 25 in the series) with values starting from 1 for the UTT period and with value 0 everywhere during the pre-UTT period; β0 estimates the baseline retention  (intercept): baseline refers to the first month time point, which is January 2015; β1 estimates change in retention  that occurs for each month cohort before UTT; β2 estimates the level change just after UTT; β3 estimates the change in retention  after introduction of UTT; and et is an error term representing the random variability not explained by the model. We used a generalized linear mixed model (GLMM) to account for facility-level clustering and to be able to predict facility-specific retention rates. For mortality, we used generalized estimating equations (GEE) because the GLMM failed to converge possibly due to very few or no death in some facilities for patients enrolled in some months. We fitted both the GLMM and the GEE models to binary data representing retention and death considering a Gaussian family distribution, an identity link function and robust standard errors. The choice for the Gaussian family distribution with robust standard errors (over the commonly used logistic regression), enabled us to directly estimate the retention and mortality rates (proportions) and difference in rates [Line graphs were used to show trends in six-month retention and six-month mortality comparing the two periods. We used segmented regression analysis to evaluate the effect of UTT on retention and mortality. The segmented regression model was fitted as follows ;Yt=β0+in rates  and R soin rates .The study received a waiver for the requirement to obtain informed consent from the TASO Institutional Review Board because it used fully anonymized and already existing data (TASOREC/096/19-UG-REC-009).There were 26,255 PLHIV enrolled into 11 TASO health facilities between 2015 and 2018 of whom 16,244 (61.9%) were enrolled during the UTT period. After applying the exclusion criteria, 20,171 PLHIV were included in the analysis with 12,757 (63.2%) enrolled during the UTT period. Of those enrolled during the pre-UTT period and included in the analysis, 5256/7414 (70.9%) were started on ART within 6 months from enrolment with a median time of 14 (interquartile range (IQR): 0–31) days compared to 12239/12757 (95.9%) started on ART within a median of 0 (IQR: 0–0) days for those enrolled during the UTT period. The median duration on ART in 6 months from enrolment was 5.5 (IQR: 4.9–6.0) months for those enrolled during pre-UTT period and 6 (IQR: 6–6) months for the UTT period.In When analysed separately for males and females accounting for facility differences, the baseline retention was 79.8% (95% CI: 71.0%-88.6%) among females and 81.0% (95% CI: 75.0%-87.0%) among males. When analysed separately for age groups accounting for facility differences, the baseline retention was 89.0% (95% CI: 80.8%-97.3%) for adolescents (15–17 years); 81.9% (95% CI: 75.4%-88.3%) for 15–24 years; 80.7% (95% CI: 75.7%-85.8%) for 25–49 years; and 81.4% (95% CI: 73.7%-89.2%) for 50 years and more. The increase in retention just after the scale-up of UTT as well as the rates of decrease in retention after UTT were similar cross sex and age groups and were equal to the overall rates shown in Our study has shown that UTT for PLHIV in routine care in Uganda had a significant effect on both retention and mortality. Overall, there was no significant month-to-month change in retention and mortality before UTT. The six-month retention and six-month mortality were respectively rather stationary at 82.6% and 3.3% for the period before UTT. However, after scale up of UTT, there was a sudden increase in retention and later a decrease in month-to-month trend in retention. Mortality suddenly decreased after UTT and the trend continued decreasing each month. The effect of UTT on both retention and mortality was similar across sex and age groups.et al. who showed in a study conducted in Uganda that delays in starting on ART treatment was associated with non-retention [The sudden increase in retention of 9.2 percentage points just after UTT agrees with the study conducted in Malawi which reported a 6% higher 12-months retention among UTT patients compared to the standard of care [etention , 20.et al. who reported higher ART discontinuation rates and hence poor retention among males and patients aged 18–35 years [The decrease in retention each month after full scale-up of UTT in our study setting could be attributed to the increased number of patients started on ART and enrolled in care which could have burdened the available resources. In addition, during UTT many patients were being enrolled in TASO from communities  without 35 years .Our findings further indicated that the effect of UTT on retention differed between health facilities where patients get HIV care. This could be due to increased number of PLHIV enrolled in care during UTT with limited resources in some facilities which could have affected service delivery and consequently the retention. Moreover, the campaign to increase HIV yield during the period of UTT by testing people from communities and start those who test positive on treatment without proper referral and close monitoring could also have increased LTFU and hence affect retention.Overall, our study shows higher rates of retention for PLHIV compared to other studies conducted elsewhere –24. For The baseline mortality estimated in this study is comparable to that from a similar study conducted in Ethiopia which estimated an incidence of death of 3 per-100 person years . In addiThe reduction in mortality following UTT could be attributed to the benefits of starting treatment in early stages of the infection . Early tet al in Uganda is that we used interrupted time series analysis using six-month rates generated from cohorts of PLHIV enrolled each month and followed for at least six months other than simply comparing the pre-UTT and UTT as ordinary cohorts. In addition, we used data from multi-sites enabling us to account for site differences using GLMM and GEE, hence producing more robust estimates. However, our study had some limitations. First, the study excluded children aged below 15 years, the pregnant women and key populations. This means that the findings presented in this paper cannot be generalized to these sub-populations. Second, the analysis for the secondary outcome, mortality, did not account for the competing risk of loss to follow up, which could result in underestimation. An interrupted time series analysis where mortality and LTFU are considered as competing risks would help to improve our results on mortality. Third, we could not analyse the influence of CD4 count on retention and mortality because during UTT period, CD4 count was not obtained from many patients since this was no longer a requirement to initiate ART.The strength of our study over that of Malawi and that by Brown In summary, our study has shown that, overall, UTT had an effect on retention and mortality among PLHIV enrolled and receiving HIV care from 11 HFs managed by TASO in Uganda. There was a marked reduction in retention over time after UTT was introduced with little to moderate reductions in mortality. Retention differed between some health facilities and it was highest in Rukungiri and lowest in Soroti. Retention was slightly higher in males than females as well as among younger people compared to the older ones. Mortality was higher among males and patients aged 50 years and above. We recommend that additional research be undertaken to understand factors facilitating or hindering success of UTT. The declining trend in retention reported in this paper has negative policy implications especially if we must attain the UNAIDS 2030 target of 95-95-95. We therefore recommend innovative interventions to check the declining trend in retention following the test and treat policy.S1 Data(ZIP)Click here for additional data file.


Viral suppression remains the most desired outcome in the management of patients with Human Immunodeficiency Virus/Acquired Immune Deficiency Syndrome (HIV/AIDS) and this can be achieved by an effective Antiretroviral Therapy (ART). However, some patients who achieve viral suppression may experience viral rebound with dire consequence. We evaluated viral suppression and rebound and their associated factors among adult patients on ART in Kumasi, Ghana.p < 0.05 was considered statistically significant.This hospital-based retrospective study was conducted at the Komfo Anokye Teaching Hospital in Ghana. We reviewed the medical records of 720 HIV patients on ART. Statistical analyses were performed using SPSS Version 26.0 and GraphPad prism version 8.0. p < 0.0001], having good adherence to ART , taking Nevirapine-based regimen  and increasing duration of treatment (p < 0.0001) were independently associated with higher odds of viral suppression. However, being diagnosed at WHO stage II  and stage III , having poor adherence , recording baseline suppression value of 20–49 copies/mL  and being treated with Zidovudine/Lamivudine/Efavirenz  and Zidovudine/Lamivudine/Nevirapine  were independently associated with higher odds of viral rebound.Proportions of patients with viral suppression and viral rebound were 76.1% and 21.0% respectively. Being diagnosed at WHO stage I [aOR = 11.40, 95% CI (3.54–36.74), Approximately 76% viral suppression rate among HIV patients on ART in Kumasi falls below the WHO 95% target by the year 2030. Choice of ART combination, drug adherence, WHO clinical staging and baseline viral load are factors associated with suppression or rebound. These clinical characteristics of HIV patients must be monitored concurrently with the viral load. Human immunodeficiency virus/acquired immune deficiency syndrome (HIV/AIDS) is the leading cause of death and morbidity in the world . In 2015In response to the global HIV/AIDS mortality and morbidity, the Joint United Nations Programme on HIV/AIDS (UNAIDS) launched the “90–90–90” targets in 2014, to help eradicate HIV as part of Sustainable Development Goals (SDGs) . By 2020The adopted ART regimen in Ghana includes first line, second line and third line ART regimens. First line ART regimen include; Tenofovir + Lamivudine (or Emtricitabine) + Efavirenz second alternate as Tenofovir + Lamivudine (or Emtricitabine) + Nevirapine. The second line regimen is used when there is evidence of treatment failure with the first line regimen. This is confirmed by viral load monitoring. Second line ART regimen include; Zidovudine + Lamivudine (or Emtricitabine) + Lopinavir/r (or Atazanavir/r) with second alternate as Tenofovir + Lamivudine (or Emtricitabine) + Lopinavir/r (or Atazanavir/r). A third line therapy is recommended for those who have failed for second line treatment. Baseline investigation include laboratory testing for immunological function (CD4 + count) or patient’s viral load. Third line ART regimen includes; Darunavir/r + Dolutegravir or Raltegravir ± 1 or 2 NRTI with second alternate as DRV/r + 2NRTIs ± NNRTI .The key focus on the fight against HIV/AIDS has been on the sustained antiretroviral therapy (ART), which has increased the success of viral suppression and continuous reduction in HIV/AIDS-related death . EpidemiViral rebound increases vulnerability to other illnesses, treatment failure, ART resistance , and theStudies from other countries have related HIV viral suppression and viral rebound to numerous factors including adherence , 12, actThis hospital-based retrospective study was conducted at the Komfo Anokye Teaching Hospital (KATH). Participants’ data were retrieved from hospital archives and patients’ folders. KATH is the second major tertiary Hospital in Ghana. The facility has over 1000 bed capacity and serves as a referral center for other hospitals in the middle and northern belts of Ghana.The study population included registered HIV patients receiving ART at KATH from 2016 to 2020. Records of a total number of 5000 HIV patients over a five-year period were reviewed. Of the 5000 patients, 4280 were excluded for not meeting inclusion criteria. Finally, 720 participants met the inclusion criteria and were included in the study. Of the 720 participants, 548 had achieved viral suppression and 172 did not achieve viral suppression. Of the 548 participants that achieved viral suppression, 115 experienced viral rebound and the remaining 433 maintained viral suppression . Where total population of 5000 registered HIV patients accessing the ART clinics of the three study sites from 2016 to 2020 with 95% confidence level, 50% response distribution, and 5% margin of error were employed. Substituting these values, the minimum sample size required in this study was 357. To increase statistical power, a total of 720 HIV patients were included in the study.The sample size was calculated using the online Calculator.net sample size calculator . A thorough explanation of the study protocol and assurance of anonymity was made to the subjects. Written informed consent was also sought from participants and healthcare management before data and sample collection. All methods were carried out in accordance with relevant guidelines and regulations.Medical files of study participants were inspected and information on age, gender, religion, level of education, occupation and marital status, history of co-infections, opportunistic infections, type of HIV infection, ART regimens, adherence to treatment, and WHO stages of HIV/AIDS abstracted. The date and time patients were diagnosed and started ART were recorded. The date and results of the first viral load test (6 months after diagnosis) was taken as the baseline viral load. Date and results of subsequent viral load tests  were recorded.Viral suppression was defined as recording at least one viral load less than 50 copies/mL after commencement of treatment –20 whilswww.graphpad.com). Data collected in this study were categorical data and were therefore presented as frequencies and percentages. A bar chart was used to illustrate the prevalence of viral suppression among study participants. Univariate logistic regression analysis was performed to screen for potential clinical and socio-demographic characteristics associated with viral suppression and viral rebound. Multivariate logistic regression model was used to determine independent predictors of viral suppression and viral rebound among HIV patients on treatment. p-values less than 0.05 (p < 0.05) were considered statistically significant.Collected data obtained were entered, coded, edited, and cleaned in Microsoft Excel 2016. All statistical analyses were performed using the Statistical Package for Social Sciences (SPSS) Version 26.0  and GraphPad Prism version 8.0  or 40–49 years (32.5%). The majority of the patients in this study were females (74.4%), married (44.6%), have had junior high school (33.2%) or primary school education (22.1%), were working in the informal sector (73.2%) or were Christians (85.4%) (Table .8% or 40Majority of the patients were infected with HIV-1 (96.0%), were diagnosed at WHO stage I (38.8%) or stage III (35.8%) or had no past antiretroviral (ARV) experience (97.9%). More than half (51.8%) of the patients had good adherence to ART. A few participants had other co-morbidities  (11.1%), opportunistic infections (10.8%), or had ever stopped or changed ARV (7.6%). The majority of the patients were on the Efavirenz-based regimen (79.7%) and a few participants were on Lopinavir (PI)-based regimen (5.0%). Again, more than half of the participants were taking TDF/3TC/EFV (69.6%) as the specific ARV combination Table .Table 2COf 720 participants that were analyzed in this study, the proportion of participants that achieved viral suppression  was 548 representing 76.1% , p < 0.0001], being treated with TDF/3TC/EFV , AZT/3TC/EFV  or AZT/3TC/NVP  and increasing duration of treatment were independently associated with increased odds of viral suppression. However, ever stopping or changing ARV  was significantly associated with lower odds of viral suppression , .54–36.74p < 0.0001) and WHO stage III , having fair , or poor adherence , recording a baseline viral suppression value of 20–49 copies/mL , being treated with AZT/3TC/EFV  or AZT/3TC/NVP , obtaining durability of ARVs viral suppression for up to 24 months ; p < 0.0001) were independently associated with higher odds of viral rebound.In a multivariate logistic regression model, being diagnosed at WHO stage II  is a leading cause of death worldwide. The fight against HIV/AIDS is hinged on initiation and adherence to an effective Antiretroviral Therapy (ART), and this has increased the attainment of viral suppression and reduction in HIV/AIDS-related death. Unfortunately, some people who achieve viral suppression are unable to maintain it and experience viral rebound, increasing their risk of treatment failure and the potential for transmission.The United Nation's principal goal for eradicating HIV/AIDS by 2030 involves expanding access to and coverage of ART across the globe and viral suppression –26. HoweWe explored the factors associated with viral suppression among patients on ART. We observed that being diagnosed with WHO stage I, having good adherence to ART, being on a Nevirapine-based regimen and increasing duration of treatment with ARV were independently associated with higher chances of viral suppression. However, stopping or changing ARVs was associated with lower chances of viral suppression. Our findings are comparable to those observed by Maina et al. , who repIn our study, increasing duration of treatment was associated with higher chances of viral suppression, consistent with a study by Kiselinova et al.  in the UViral rebound increases vulnerability to illness, treatment failure, ART resistance, and the potential for HIV transmission , 36. In We evaluated a number of putative factors associated with viral rebound. In the current study, we observed that patients diagnosed at WHO stage II and stage III had higher chances of viral rebound compared to those diagnosed at WHO stage I. Our study finding is in harmony with a study by Maina et al. , who repNotably, we observed that poor adherence was associated with higher viral rebound. Consistent with our study findings, Bulage et al.  reportedMoreover, we observed that patients on Zidovudine based-regimen (AZT/3TC/EFV and AZT/3TC/NVP) had higher chances of viral rebound compared to patients on Tenofovir based-regimen (TDF/3TC/EFV). This is in line with a study by Mania et al. , who obsOur study provides useful findings to guide HIV clinicians and policy makers in the fight against the infection. However, it is limited by the fact that it was a retrospective study and single-centered. We relied on available hospital data, especially patients’ viral load results, which posed a challenge to completeness of data. Moreover, some variable such as duration of treatment had larger confidence intervals for predicting viral suppression and rebound indicating less power and therefore a larger study is needed to generate enough evidence of the estimates.The viral suppression rate among HIV patients on ART in Kumasi (76%) do not meet the WHO target (90%). Good adherence to ART, being on Nevirapine-based regimen and increasing duration of treatment with ARV independently leads to viral suppression. However, being diagnosed at WHO stage II and stage III, having bad to fair adherence, recording baseline suppression value of 20–49 copies/ml and being treated with AZT/3TC/EFV and AZT/3TC/NVP leads to viral rebound. These clinical characteristics of HIV patients, associated with viral suppression and viral rebound must be monitored concurrently with the viral load.


In 2016 Rwanda adopted “treat all” where all patients with HIV are immediately eligible for ART regardless of disease progression. Despite widespread availability of treatment, it is unknown whether presentation with advanced HIV persists.3 or WHO stage 3 or 4, and compared baseline characteristics of patients with and without advanced HIV. We compared cumulative incidences and time to events using Chi squared tests and Cox proportional hazards models, respectively, for (a) viral load tests; (b) viral suppression; (c) death; and (d) treatment failure .We conducted a retrospective cohort among patients aged ≥ 15 who enrolled in care between July 2016 and July 2018 in three rural Rwandan districts. We estimated the prevalence of advanced HIV, defined as presenting with CD4 count < 200 cells/mmAmong 957 patients, 105 (11.0%) presented with advanced HIV. These patients were significantly more likely to have low body mass index, come from Burera district, be older, and be identified through inpatient settings rather than through voluntary or prenatal testing. Patients with advanced HIV had significantly higher risks of death at 12-months  and 18-months  and significantly higher risk of treatment failure at 12-months . After adjusting for confounders, patients with advanced HIV had still higher rates of death  and treatment failure , but no difference in viral load testing  or viral suppression . When allowing for the hazard ratio to vary over time, patients with advanced HIV experienced elevated rates of treatment failure in the first six of enrollment, but not after nine months.Presenting with advanced HIV remains common and is still associated with poor patient outcomes. Sensitization of the community to the benefits of early ART initiation, identification of patients with advanced HIV, and holistic support programs for the first 6 months of treatment may be needed to improve outcomes. In 2016, the World Health Organization’s (WHO) guidelines changed from antiretroviral treatment (ART) initiation based on CD4 count thresholds to a “treat all” strategy in which patients are eligible to initiate ART regardless of their CD4 count –8. HowevIn Rwanda, the national HIV program has successfully decentralized access to free HIV services and by 2013 had created a national network of over 450 health facilities, almost all of which (97%) offered HIV testing and the vast majority of which (89%) offered ART with no cost required from patients . SubsequThe study was conducted in the catchment areas of Rwinkwavu, Kirehe and Butaro district hospitals, which include 43 affiliated health centers. Rwinkwavu and Kirehe are in rural Eastern province while Butaro is in the rural Northern Province of Rwanda. The HIV program in these areas is implemented by the Rwandan Ministry of Health (MoH) through Rwanda Biomedical Center (RBC) and receives technical and financial support from Partners In Health/Inshuti Mu Buzima (PIH/IMB), which is an international nongovernmental organization.In accordance with the current Rwandan national guidelines, patients with HIV are eligible to receive free ART regardless of their baseline CD4 count or WHO stage and are enrolled in the Differentiated Service Delivery Model (DSDM) . ThroughWe conducted a retrospective cohort study to compare patients with HIV who presented for treatment with advanced HIV to those who presented without advanced HIV in PIH/IMB-supported health facilities. We included all patients with HIV aged 15 years and above who entered the HIV program between July 1st 2016 and July 31st 2018. Patients with neither a baseline CD4 count nor a baseline WHO stage reported could not be classified as presenting with or without advanced HIV and were excluded from the study.We used routinely collected data extracted from electronic medical record (EMR). Variables extracted or derived from the EMR included district; age; sex; distance to health facility; Body Mass Index (BMI) at baseline categorized as < 16, 16–18.5, and > 18.5; WHO stage at baseline, CD4 count at baseline, and method of enrolment into the HIV program, categorized as voluntary counselling and testing (VCT), PMTCT, inpatient and tuberculosis patients, and outpatient patients. For BMI, WHO stage, and CD4 count, the earliest measurement within 180 days of enrollment was considered the baseline measurement. Additional data extracted from the EMR included date of enrollment into the program, date of ART initiation, dates of scheduled and observed patient visits, viral load results, dates of collection for viral load results, and date of death or exit from the HIV program.3 at enrollment or WHO stage 3 and 4 at enrollment were classified as presenting with advanced HIV [3 and baseline WHO stage 1 or 2, or (b) baseline CD4 count > 200 cells/mm3 at enrollment and no documentation of WHO stage 3 or 4, or (c) baseline WHO stage 1 or 2 and no documentation of CD4 count.Because our analysis used existing medical records, many patients were missing information on either CD4 count or WHO stage. Consequently, patients presenting with CD4 count < 200 cells/mmnced HIV . The remIn Rwanda, treatment guidelines recommend to provide same-day treatment initiation for HIV when possible and within the two weeks of diagnosis for almost all patients and viral load testing 6- and 18-months after treatment initiation. As a conservative measure of adherence to these guidelines, we assessed the proportion of patients who initiated ART within 14 days of presentation and the proportion of patient who received an initial viral load test within 9 months (270 days) of presentation. Among patients who received an initial viral load test within 270 days of enrollment, we also reported the proportion who were virally suppressed, defined as < 200 copies/ml. We also reported the 12- and 18-month cumulative incidence of death; loss to follow-up and virological failure, and treatment failure. Lost to follow-up was assumed to occur on the last observed visit date if the patient had no recorded clinical visits for > 3 months following their last scheduled appointment or > 7 months after the last visit date. Virological failure was defined as observing viral load ≥ 200 copies/ml among those who had previously achieved viral suppression. We defined treatment failure as a composite outcome that included death, loss to follow-up, or virological failure. In rural Rwanda, where patients rely almost exclusively on the local public hospitals and health centers for access to HIV treatment and deaths are sometimes unreported in the EMR, these outcomes are closely correlated. For example, patients who have become loss to follow up are unlikely to be accessing any HIV treatment at all, are at risk of virologic failure, and may be dead. Our composite outcome of treatment failure reflects the fact that any of these events are of clinical concern.We also calculated four time-to-event outcomes: time to viral load test, time to viral suppression, time to death, and time to treatment failure. Time to first viral load test and time to viral suppression, which was defined as the time to the first viral load measurement < 200 copies/ml, were both censored by death, loss to follow-up, or transferring out of the program. Time to death was censored by loss to follow-up or transferring out of the program. Time to treatment failure was defined the earliest occurrence of death, loss to follow-up, or virological failure and was censored by transfer out of the program. If a patient experienced an event of interest or a censoring event on their day of enrollment, we set the time to event to 0.5 days to ensure that these individuals were not excluded from analysis. All time to event outcomes were administratively censored at 21 months (630 days). This time frame was chosen to allow patients a reasonable opportunity to complete their second viral load test, which should occur approximately 18 months after treatment initiation according to national guidelines but is often delayed in practice.We described and compared demographic characteristics, clinical characteristics, and clinical outcomes of patients presenting with advanced and non-advanced HIV using frequencies and Chi-squared tests or Fisher’s exact tests for variables with cell counts < 5. Due to small cell counts, the VCT and PMTCT categories were collapsed in regression analyses. We created missing indicator categories to account for missing data. We compared time to event for our four main outcomes among patients presenting with and without advanced HIV using Kaplan–Meier curves and log-rank tests. For each outcome, we fit three Cox proportional hazards models to estimate hazard ratios and corresponding 95% confidence intervals (CIs) for the association between presenting with advanced HIV and experiencing the outcome of interest. The first model was unadjusted. The second model adjusted for baseline demographic characteristics, including district, age, sex, and distance from the health facility, that could be common causes of both presenting with advanced HIV and experiencing treatment failures and were therefore considered to be potential confounders . Two varFor each outcome and each model, we assessed whether the proportional hazards assumption held using a global test of Schoenfeld residuals. If we observed a significant association on the global test, we assessed the association between each covariate’s residuals and time to identify which covariates violated the proportional hazards assumptions. The global test of Schoenfeld residuals was only observed to be statistically significant for one model, which was the unadjusted association between presentation with advanced HIV and time to treatment failure. Despite the violation of proportional hazards, we present this unadjusted hazard ratio as it is still interpretable as an approximation for the average incidence rate ratio comparing treatment failure among patients presenting for care with and without advanced HIV over 630 days of follow-up . However3. Although the majority (51.6%) of non-advanced HIV were identified through VCT or PMTCT, only 20.0% of advanced HIV were identified through these venues.Of the 1129 patients aged 15 years or older who enrolled in care for HIV at a PIH-IMB supported site between July 2016 and July 2018, 957 participants had data on baseline CD4 or WHO stage. Among these 957 patients, 105 (11.0%) presented with advanced HIV and 852 (89.0%) presented with non-advanced HIV , South Africa (22%-26%) and Botswana (24.7%) , 11, 27.3 [Surprisingly, in our unadjusted analyses we observed time to viral load testing and viral suppression were faster among patients presenting with advanced HIV. This finding is likely the result of selection bias due to competing risks of death as death was associated with advanced HIV and because death was substantially more likely to occur among patients with advanced HIV in the first six months of treatment. Consequently, the sickest advanced HIV patients would have exited the cohort through death before becoming eligible for viral load testing. However, this association did not persist after adjusting for confounders, and ultimately our results suggest that patients with advanced HIV who survive and remain and treatment experience similar virologic outcomes as patients without advanced HIV. However, in both groups we observed suboptimal adherence to Rwanda’s national guidelines: Less than 70% of patients initiated care within two weeks of enrollment and less than 50% received their initial viral load test within 9 months of treatment. It was reported that newly-diagnosed PLWH in Rwanda, initiating ART rapidly under Treat All presents logistical and emotional challenges despite the perceived benefits  and vira3 . In geneOur findings suggest multiple opportunities to improve HIV services. First, although Rwanda has decentralized HIV testing, there is a need to increase patient engagement with existing HIV testing services, which could include strategies such as expanded self-testing options, provision of HIV tests through the workplace or at the community, and increasing community awareness of that Undetectable = Untransmitable (“U = U)” among others . Second,Our study had some limitations: First, we used routinely collected data from EMR and some variable of interest, including cause of death and markers of socioeconomic status, were commonly missing from the EMR. Due COVID-related movement restrictions, we were unable to supplement the EMR with data from patients’ chart. In particular, missing CD4 and WHO stage information led us to use a definition of non-advanced HIV that was vulnerable to misclassification. We would have expected this bias would be expected to underestimate the true prevalence of advanced HIV disease and bias associations between advanced HIV disease and poor clinical outcomes towards the null. However, missing data could have also caused us to underreport timely ART initiation or timely viral load testing and over-report loss to follow-up. Second, our time-to-event analyses for death does not account for potential competing risks due to loss to follow-up, which is likely associated with death. If loss to follow-up were associated with advanced HIV, the analyses for these outcomes could have underestimated the associated between death and advanced HIV. However, we did not observe any associations between advanced HIV and loss to follow-up. Furthermore, the composite outcome of treatment failure included, viral suppression, death, and loss to follow-up, and is consequently not vulnerable to bias from competing events. Similarly, our time-to-event analyses for time to viral testing and time to viral suppression do not account for the competing risks of death, which, as previously discussed, could account for the surprising finding that time to viral load testing and viral suppression were faster among patients presenting with advanced HIV. Third, our analysis focuses on three rural districts that receive substantial support from an international NGO, so our results might not be generalizable elsewhere in the country. However, because of the additional support provided to these facilities, we would generally expect better HIV-related outcomes, including lower proportion of patients presenting for care with advanced HIV and lower rates of death and treatment failure, than in other rural Rwandan settings, suggesting this problem could be more widespread elsewhere.Despite adoption of the treat all, presentation for care with advanced HIV disease is still common in Rwanda and is still associated with poor treatment outcome. There is need for enhanced sensitization around the benefit of early HIV testing and availability of ART for all. In addition, patients presenting with advanced HIV may require additional support improve their treatment outcomes. More studies are needed to identify the specific causes of death among late presenters to help identity and prevent common causes of deaths.


In Zimbabwe, children, adolescents and young adults living with HIV (CALWH) who are on public health antiretroviral therapy (ART) have inadequate viral load (VL) suppression. We assessed whether a clinic-based VL monitoring could decrease 12-month virologic failure rates among these CALWH.The study was registered on ClinicalTrials.gov: NCT03986099. CALWH in care at Chidamoyo Christian Hospital (CCH) and 8 rural outreach sites (ROS) on long-term community-based ART were randomized (1:1) to 6 monthly VL monitoring by COBAS®Ampliprep®/Taqman48® HIV-1 at the provincial referral laboratory (PRL) as per standard of care (SOC) or by the clinic-based SAMBA II assay, Diagnostics for the Real World, at CCH. VL suppression, turn-around-time (TAT) for VL results, drug switching and drug resistance in second-line failure were assessed at 12 months.Of 390 CALWH enrolled 347 (89%) completed 12 months follow-up. Median (IQR) age and ART duration were 14.1 (9.7–18.2) and 6.4 (3.7–7.9) years, respectively. Over half (57%) of the participants were female. At enrolment, 78 (20%) had VL ≥1,000 copies/ml and VL suppression of 80% was unchanged after 12 months, with no significant difference between the SOC (81%) and the clinic-based (80%) arms (p = 0.528). Median (IQR) months to confirmatory VL result at CCH vs PRL was 4.0 (2.1–4.4) vs 4.5 (3.5–6.3) respectively; p = 0.027 at 12 months. Drug switching was documented among 26/347 (7%) participants with no difference between the median (IQR) time to switch in SOC vs clinic-based arms (5.1 (3.9–10.0) months vs 4.4 (2.5–8.4) respectively; p = 0.569). Out of 24 confirmed second-line failures, only 4/19 (21%) had protease inhibitor resistance.In rural Zimbabwe, the clinic-based SAMBA II assay was able to provide confirmatory VL results faster than the SOC VL assay at the PRL. However, this rapid TAT did not allow for a more efficient drug switch among these CALWH. The World Health Organization (WHO) recommends regular viral load (VL) monitoring for people living with HIV (PLHIV) on antiretroviral therapy (ART) . In the Standard of care (SOC) VL monitoring with central laboratory Nucleic Acid Assay Testing (NAAT) , 10 in mWe hypothesized that a clinic-based VL testing could improve care in achieving VL suppression for children and adolescents receiving care through an established community program provided in a remote rural district.We performed a randomized trial of central laboratory compared to clinic-based VL testing in a community treatment program at Chidamoyo Christian Hospital (CCH) and rural outreach sites (ROS) in Hurungwe district in Mashonaland West province in North West, Zimbabwe. The study compared virologic outcomes, drug switching and drug resistance mutations (DRMs) among children, adolescents and young adults. The aim of this study was to reduce virologic failure rates among children, adolescents and young adults in HIV care through implementation of a package of interventions that includes digital data collection, clinic-based VL monitoring and lower cost genotyping for persistently viraemic individuals.The primary objective was to determine whether the Simplified Amplification-based Assays (SAMBA), a clinic-based VL monitoring vs SOC VL monitoring decreased 12-month virologic failure rates among children, adolescents and young adults living with HIV (CALWH) in rural Zimbabwe. The secondary outcomes included rates of lost to follow up, drug switching, TAT for VL results and DRMs among these CALWH.Chidamoyo Christian Hospital (CCH) is a mission hospital which serves a dispersed rural community, providing ART to over 2,500 patients in Hurungwe district, Mashonaland West, Zimbabwe. The service delivery model is a nurse-run program providing bimonthly ART drug refills and adherence counselling at either the hospital clinic or through eight ROS, 22.5 to 47 km by poor gravel roads (mean 32.8 km) from CCH . Clinic This study was approved by the Institutional Review Board of the Biomedical Research and Training Institute (AP143/2018) and the Medical Research Council of Zimbabwe (MRCZ/A/2269). The study was registered as community-based ART (CBART) on clinical trial.gov (NCT03986099). Guardian consent was obtained for those < 7 years. Assent was obtained from 7 to 17-year old with guardian consent and those aged ≥18 years provided written consent at enrolment into the study.We estimated the required sample based on the primary outcome of VL suppression at 48 weeks. Under usual care, viral suppression rate was about 60%. We hypothesized that the clinic-based VL testing SAMBA intervention would improve care to achieve viral suppression to 90% after 12 months. We estimated that, with a total of 356 CALWH on ART, we could detect at least a 15% increase in virologic suppression with 90% power at 0.05 significance level, assuming a 10% lost to follow up.This was a prospective randomized open label trial of two strategies for VL differentiated care monitoring of virologic outcome among CALWH receiving ART at 8 treatment ROS near their homes provided by CCH. Between February 2018 and July 2019, 451 CALWH (ages 3–24) who had been on ART for more than 1 year at CCH or at ROS were enrolled and randomized. This was a parallel group randomized trial where only participants were blinded and assigned (1:1) to either SAMBA or SOC VL testing. The random allocation was not concealed and allocation sequences were generated by the data team, who also assigned the participants to the interventions. All study procedures and enrolment were integrated into routine care from existing clinic and outreach site staff (clinicians/nurses) as part of routine service delivery. Nurses and clinicians recruited the participants and were not blinded to the randomization. There were no anticipated risks associated with clinic-based VL differentiated care since all study procedures were consistent with the National SOC VL. Participants were seen bimonthly either through the CBART program at ROS or at youth clinics at the CCH. We abstracted data from medical records to a structured data retrieval form. Information collected included age, gender, weight, clinical and laboratory data (VL and CD4 count), ART regimen, ART initiation and cotrimoxazole prophylaxis dates, primary caregiver and site of HIV care (CCH versus ROS). Treatment dispensed, drug switching and VL measures were captured into a MS Access database.Participants enrolled in the study were assigned (1:1) to the SOC VL testing at the PRL using Roche COBAS® Ampliprep®/COBAS Taqman48® HIV-1 v 2.0 or to the intervention, a clinic-based VL assay, the SAMBA II semi-Q assay   at CCH.Whole blood was collected in ethylenediaminetetraacetic acid (EDTA) tubes and plasma was prepared by centrifugation at 1,000g for 10 mins and stored at -20°C within 6 hours of collection. In the laboratory, plasma samples for SOC testing were dispatched weekly to the PRL (200 km in Chinhoyi) and a quantitative VL result with a detection range of 20 copies/ml to 10,000,000 copies/ml  at 6 months and 4(2.1–4.4) vs 4.5(3.5–6.3) months at 12 months, respectively [p = 0.027]).Of the 78 study participants with virological failure (VF) at enrolment, 26 (33%) switched regimens after confirmation of VL ≥1,000 copies/ml. At enrolment, 37/237 (16%) of NNRTI-based first-line ART recipients had a VL ≥1,000 copies/ml and 21/237 (9%) of the participants who were on NNRTI-based ART were switched to PI-based second-line ART. In contrast, of the participants on a PI-based second-line regimen, 41/153 (27%) had confirmed VF, but only 5/153 (3%) switched to integrase strand transfer inhibitor (InSTI)-based third-line ART. The median (IQR) time to switch regimens from the first VL ≥1,000 copies/ml was 5.1 (3.9–10.0) months in SOC VL testing arm compared to 4.4 (2.5–8.4) months by the clinic-based SAMBA VL testing, (p = 0.569).Genotypic resistance testing was carried out among 24 participants (15 participants in the SOC arm vs 9 participants in the clinic-based assay arm) persistently failing a PI-based second-line regimen: atazanavir/ritonavir in 12, lopinavir/ritonavir in 11. One participant, who did not have PI or InSTI resistance mutations, was on darunavir + raltegravir + lamivudine/tenofovir disoproxil fumarate. Altogether, DRMs were identified in 19 of 24 (79%) participants, with 87% (13/15) in the SOC arm versus 67% (6/9) in the clinic-based SAMBA assay arm .Major DRMs to PIs were identified in only 4/19 (21%). Resistance to NNRTIs was found in 17/19 (89%) of the participants, with G190A being the most common mutation, found in 8 (42%) participants. The most common NRTI mutation was M184V in 12/19 (63%). Dual class resistance to NRTIs and NNRTIs was detected in 10 (53%) participants, and 3/19 (16%) had multiclass drug resistance to PIs, NRTIs, and NNRTIs. Thymidine analogue mutations were less common in these 3 participants: Two had only a T215Y mutation and the other had the M41L and T215Y mutations.Children, adolescents and young adults living with HIV (CALWH) in sub-Saharan Africa have high rates of mortality and morbidity due to disproportionately lower rates of VL suppression, reduced adherence and low rates of switching to second and third-line regimens , 26. NewClinic-based assays and point of care (POC) VL testing may result in more efficient and rapid drug switching. A recent study by Nicholas, et al (2019) in rural clinics in Malawi demonstrated that POC testing with SAMBA, reduced TAT for VL results and time to drug switching . The autAlthough the OR point estimate for the weighted model is slightly greater than 1, and less than 1 in the ITT missing VL = failure model, the overall result is the same, there is no significant difference in VL suppression between the two arms. The main reason for the different direction of the effect of SAMBA compared to SOC might be because of the assumption of treating all missing VL as failure. Since SOC has a higher proportion of missing 12 month VL compared to SAMBA (13% vs. 9% per protocol and 25% vs 21% per ITT), the suppression rate in the SOC arm is almost the same compared to the SAMBA arm (81% vs. 80% respectively). However, this assumption does not effectively change the conclusions of the study. Studies of assays of lower level VL thresholds (>20–999 copies/ml) suggest that the WHO-recommended ≥1,000 copies/ml threshold may underestimate virologic failure , 28. HerWe found that the SAMBA-II semi quantitative assay is well suited to identifying VL failure at the ≥ 1,000 copies/ml threshold and was simple to manage in a rural hospital setting with limited power, internet access and telecommunication. New clinic-based assays and POC technologies offering rapid quantitative POC VL at lower thresholds  may furtAccess to InSTI-based-third-line treatment has been restricted by the requirement for genotyping and the demonstration of major PI resistance mutations as prerequisites for consideration of InSTI-based, third-line treatment and darunavir-based regimens. Here we found that only 4/24 (17%) second-line failures had major PI resistance despite persistent VF as described in urban Zimbabwe , 35. AltCare at Chidamoyo provides long-term retention and support through community-based counselling and ART . InteresStrengths of our study include the use of relatively large sample of participant data from a largely decentralized HIV programme in Zimbabwe and that the clinic-based SAMBA VL testing was successfully performed by the clinic medical team at the Chidamoyo clinic. Sustaining long-term ART and VL testing in rural Zimbabwe in CALWH requires innovative approaches to DSD to improve adherence, retention in care and faster drug switch .The major limitation of our study includes the fact that, the clinic-based SAMBA VL testing did not help in rapidly facilitating adherence counselling and faster regimen switch after identifying VF, due to the bimonthly visit programme at CCH. Another limitation includes the high lost to follow up resulting in only 89% (347/390) of VL tests being used in the final analysis, possibly underestimating VL testing coverage. The power of the study to be able to determine a difference between the clinic-based SAMBA assay and SOC VL testing was also limited due to relatively good rates of viral suppression at baseline and limited duration of follow-up.We found that in rural Zimbabwe, the clinic-based SAMBA II assay for VL testing can achieve high testing coverage in rural Zimbabwe and reduced TAT for VL results. However, the rapid TAT did not allow for a more efficient drug switch constrained by the bimonthly visit schedules. Despite access to VL monitoring, VL suppression among these CALWH did not reach 90%. A study-adapted visit schedule is recommended in future trial. This study design would help ascertain the effectiveness of clinic-based VL testing in reducing TAT for VL results and drug switch and consequently improving VL suppression among CALWH in rural Zimbabwe.VL testing remains important to identify those with adherence and access issues to mitigate the selection of drug resistance. Monitoring VL using a mixture of clinic-based assays and central laboratory testing, adapted to HIV programs serving vulnerable populations, will simplify ART with the widespread use of more effective drug regimens to end the HIV pandemic.S1 Appendix(DOCX)Click here for additional data file.S2 Appendix(DOC)Click here for additional data file.S1 Data(XLSX)Click here for additional data file.


Medical records of pregnant and postpartum women living with HIV and their infants attending a large referral facility in Kenya from 2015 to 2019 were analyzed to identify characteristics associated with retention in care and viral suppression. Women were stratified based on the timing of HIV care enrollment: known HIV-positive  and newly HIV-positive . Associations with retention at 18 months postpartum and viral suppression (< 1000 copies/mL) were determined. Among 856 women (20% NHP), retention was 83% for KHPs and 53% for NHPs. Viral suppression was 88% for KHPs and 93% for NHPs, but 19% of women were missing viral load results. In a competing risk model, viral suppression increased by 18% for each additional year of age but was not associated with other factors. Overall, 1.9% of 698 infants with ≥ 1 HIV test result were HIV-positive. Tailored interventions are needed to promote retention and viral load testing, particularly for NHPs, in the PMTCT continuum.The online version contains supplementary material available at 10.1007/s10461-022-03666-w. In the prevention of mother-to-child transmission of HIV (PMTCT) cascade in Eastern and Southern Africa, the global regions most affected by HIV, an estimated 95% of pregnant women living with HIV (WLHIV) accessed antiretroviral therapy (ART) for PMTCT in 2019 . Viral nTo date, a variety of factors influencing retention and viral suppression in the PMTCT continuum have been identified. Among them, diagnosis of HIV and ART initiation during pregnancy is a pervasive theme, with one study finding that women who initiated ART during pregnancy were five times more likely to disengage from care compared to women who initiated ART because of advanced HIV disease , 21. YouKenya has one of the largest HIV burdens in the world with an HIV prevalence of 6.1% among women of reproductive age . Kenya iThis retrospective cohort study used electronic medical record data from WLHIV who received HIV care during pregnancy at Moi Teaching and Referral Hospital (MTRH) in western Kenya, from 2015 to 2019. The study was approved by the Institutional Research and Ethics Committee at Moi University and MTRH in Kenya. A waiver of informed consent was obtained because the data were routinely collected clinical data that were de-identified prior to analysis. The study was also exempt from IRB review at Indiana University in the United States because the data were de-identified prior to analysis. The reporting of this study follows the STROBE guidelines  .MTRH is the largest public referral hospital in western Kenya. Within MTRH are antenatal clinics (ANC) and postnatal clinics (PNC) that offer integrated HIV services provided by dedicated nurses, clinical officers, and peer counsellors . Routine viral load testing is also available on site. MTRH is the headquarters of the Academic Model Providing Access to Healthcare (AMPATH). AMPATH is a USAID-funded HIV care and treatment program and a participating site in the International Epidemiology Databases to Evaluate AIDS East Africa consortium , 48. SinWLHIV were included in the study if they were pregnant or postpartum on or after September 1, 2015 (study start date), had one or more HIV or integrated ANC visits at MTRH during pregnancy, and had a delivery date (or estimated delivery date [EDD] if delivery date was not available) that occurred at least 18 months prior to March 6, 2019 (database closure). All HIV-exposed infants born to eligible WLHIV were also included.At the time of the study, WHO and Kenyan HIV treatment guidelines recommended efavirenz-based first-line ART for adults ≥ 15 years of age, including women of childbearing age , 42. SecWe used clinical and viral load data available in the AMPATH electronic medical record that was collected by clinicians during routine care, initially on paper forms which were back-entered into the electronic medical record by a data clerk, and from 2019 by point-of-care data entry .Eligible women were delineated based on the timing of enrollment in HIV care: newly HIV-positive  and known HIV-positive . Patient-level, independent variables at the time of enrollment in ANC or pregnancy identification included: age, gestational age, time on ART, antiretroviral base class, viral load (with window of 6 months before or after), CD4 at ART initiation (closest within 90 days before and 7 days after ART initiation), and WHO stage at ART initiation. For the latter, the maximum WHO stage prior to ART initiation was taken to be the WHO stage at ART initiation. If the WHO stage at ART initiation was missing and the next available WHO stage was 1 or 2, then the WHO stage at ART initiation was assumed to be stage 1 or 2. Otherwise, the WHO stage at ART initiation was recorded as missing.Independent variables following enrollment through 18 months postpartum included: age at delivery, time from ART initiation to delivery, delivery method, pregnancy outcome, duration of breastfeeding, tuberculosis treatment, repeat pregnancy, and viral suppression  , 52. PerRetention in care was defined as attending clinic +/- 90 days of four time points: delivery, and 6, 12 and 18 months postpartum. These timepoints align with the infant HIV testing schedule in Kenya and are frequently used as retention endpoints in the PMTCT literature . This apWomen who transferred out or died were also enumerated. A threshold of 30 days was selected based on the observed timing of scheduled return visits at the clinic (next paragraph). To analyze the prevalence of gaps in each period, subjects could transition from the ‘gap’ to ‘no gap’ states (or vice versa) across periods, based on the absence or presence of a gap in care, respectively. Women who died or transferred out were not included in subsequent time periods, and women who became LTFU, defined as missing the last scheduled visit by > 30 days and not returning by 18 months postpartum, remained in the ‘gap’ state.To understand the retention data in the context of routine care at MTRH, we determined the timing and frequency of routine clinic visits to MTRH during pregnancy and the postpartum periods. We calculated the median number of attended visits during these periods, where HIV services were accessed , and the timing of scheduled return visits during PMTCT follow-up. We also calculated the weeks post-delivery at the first postpartum visit, censoring at 90 days postpartum for women who did not have any postpartum visit unless they died or transferred out beforehand. NHPs and KHPs were compared using the log rank test.Logistic regression models were used to calculate unadjusted and adjusted odds ratios (aOR) and 95% confidence intervals (CI) for independent variables to assess their associations with non-retention  and gaps in care, respectively. Independent variables of age and gestational age were measured at the time of ANC enrollment or pregnancy identification. Other independent variables included WHO stage prior to ART initiation, NHP status and ART base class. The gaps-in-care analysis was set up similar to the non-retention analysis, with the exception that the dependent variable was defined as the occurrence of a gap in care at any point in time from pregnancy to 18 months postpartum.To examine factors associated with viral suppression during pregnancy, we selected for analysis the subset of women who were KHP, ≥ 6 months post-ART initiation, and had at least one viral load within the period from pregnancy through two weeks post-delivery. If two or more viral load measures were available within this period, the viral load closest to the delivery date was selected. This analysis excluded women who were NHP because Kenya HIV treatment guidelines recommend that an initial viral load test be performed six months after ART initiation . Viral sFinally, we used a semiparametric proportional odds regression approach for interval-censored competing risk data to analyze the cumulative incidence of viral suppression from two weeks to 18 months post-delivery (censoring event), and ≥ 6 months post-ART initiation . This apA total of 967 pregnant and postpartum WLHIV enrolled in care on or after September 1, 2015 and had a delivery date that occurred at least 18 months prior to database closure. Of these, 111 were excluded because they had no HIV or integrated ANC visits at MTRH during pregnancy, resulting in 856 pregnant WLHIV eligible for analysis along with their HIV-exposed infants. Among the eligible women, 167 (20%) were NHPs and 689 (80%) were KHPs . However, 40–65% of all infants known to be alive did not have a documented HIV test result at each of the 6 week and 6, 12 and 18 month time points. Among infants retained in care at 18 months, 95% had stopped breastfeeding and of these, 39% were missing an HIV test after stopping breastfeeding.Older age was associated with a slightly lower adjusted odds of experiencing a gap in care . Older age was associated with a slightly higher adjusted odds of viral suppression (aOR = 1.10). Those with WHO stages 3 or 4 pre-ART initiation had lower adjusted odds of being virally suppressed during pregnancy compared to those with WHO stages 1 or 2 (aOR = 0.45).In the competing risk model for time to viral suppression following delivery, the adjusted odds of viral suppression increased by 18% for each additional year of age at delivery . Missing data, particularly maternal viral loads and infant HIV tests, may also limit extrapolation of our findings to broader populations. For example, missing viral load and HIV test results may indicate missed appointments, potentially implying that patients with test results had higher levels of engagement in care and ART adherence compared to those without test results. Missing viral loads may also be more prevalent in patients with a history of poor ART adherence, as clinicians may have deferred viral load testing until their adherence was optimized. The proportion of preterm births was also lower than expected in our retrospective cohort at 0.5%, compared to 10–20% among prospective cohorts in the region , 77. It Retention in care during the ‘Treat All’ era was suboptimal at a large referral facility in Kenya providing integrated HIV and maternal and child health services. Retention among NHPs was substantially lower than retention among KHPs, underscoring the need for interventions tailored to this vulnerable population.The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.List of abbreviations.AMPATH, Academic Model Providing Access to Healthcare; ANC, antenatal clinic; aOR, adjusted Odds Ratio; ART, antiretroviral therapy; ARV, antiretroviral; CI, confidence interval; IQR, interquartile range; KHP; Known HIV-positive; MTRH, Moi Teaching and Referral Hospital; NHP; Newly HIV-positive; PNC, postnatal clinic; WHO, World Health Organization; WLHIV, women living with HIV.Below is the link to the electronic supplementary material.Supplementary Material 1Supplementary Material 2