Second-line virologic failure and elevated bilirubin as a potential surrogate marker of ART adherence among people living with HIV in Eastern Uganda.

Second-line antiretroviral therapy (ART) based on ritonavir-boosted protease inhibitors (bPIs) represents the only available option after first-line failure for the majority of individuals living with human immunodeficiency virus (HIV) worldwide. Maximizing their effectiveness is imperative. This cohort study was nested within the French National Agency for AIDS and Viral Hepatitis Research (ANRS) 12249 Treatment as Prevention (TasP) cluster-randomized trial in rural KwaZulu-Natal, South Africa. We prospectively investigated risk factors for virological failure (VF) of bPI-based ART in the combined study arms. VF was defined by a plasma viral load >1000 copies/mL ≥6 months after initiating bPI-based ART. Cumulative incidence of VF was estimated and competing risk regression was used to derive the subdistribution hazard ratio (SHR) of the associations between VF and patient clinical and demographic factors, taking into account death and loss to follow-up. One hundred one participants contributed 178.7 person-years of follow-up. Sixty-five percent were female; the median age was 37.4 years. Second-line ART regimens were based on ritonavir-boosted lopinavir, combined with zidovudine or tenofovir plus lamivudine or emtricitabine. The incidence of VF on second-line ART was 12.9 per 100 person-years (n = 23), and prevalence of VF at censoring was 17.8%. Thirteen of these 23 (56.5%) virologic failures resuppressed after a median of 8.0 months (interquartile range, 2.8-16.8 months) in this setting where viral load monitoring was available. Tuberculosis treatment was associated with VF (SHR, 11.50 [95% confidence interval, 3.92-33.74]; P < .001). Second-line VF was frequent in this setting. Resuppression occurred in more than half of failures, highlighting the value of viral load monitoring of second-line ART. Tuberculosis was associated with VF; therefore, novel approaches to optimize the effectiveness of PI-based ART in high-tuberculosis-burden settings are needed. NCT01509508.

Virological failure on first-line antiretroviral therapy (ART) remains a major challenge in the management of HIV/AIDS in resource-limited settings, including Ethiopia. However, the prevalence of virological failure and its associated factors among adult patients on first-line ART in West Hararghe, Ethiopia, are not well documented. Therefore, this study aimed to assess virological treatment failure and its determinants among people living with HIV (PWH) in West Hararghe, Eastern Ethiopia. A retrospective cohort study was conducted using routine HIV-related data from a health facility providing services in West Hararghe between 01 January 2017 and 31 December 2020. Sociodemographic, behavioral, clinical, and HIV-related data were collected through medical chart reviews. Virological treatment failure was defined as a plasma viral load above 1,000 copies/mL based on two consecutive viral load measurements. A logistic regression model was used to identify factors associated with virological treatment failure. A total of 257 records of PWH were reviewed and included in this analysis. Of these, 11.67% experienced virological failure while on first-line ART. Baseline undernutrition (AOR = 3.717: 1.051, 13.139), non-disclosure of serostatus (AOR = 4.453: 1.340, 14.793), early (≤ 30 days) ART initiation (AOR = 0.235: 0.064, 0.859), a history of missed daily ART doses (AOR = 3.156: 1.007, 9.891), and the use of a dolutegravir (DTG)-based regimen (AOR = 0.275: 0. 085, 0.895) were statistically associated with virological failure on first-line ART. Virological failure on first-line ART was found to be significantly high in West Hararghe. Factors such as undernutrition, non-disclosure of serostatus, interruption of ART doses, and the use of DTG-based regimens were identified as significant predictors of virological treatment failure. Healthcare providers should focus on the accelerated initiation of ART (preferably with a DTG-based regimen) and supplemental nutritional therapy for patients with undernutrition.

To investigate whether an unrecognised diagnosis of tuberculosis (TB) at the start of antiretroviral therapy (ART) influences subsequent CD4+ T cell (CD4) count recovery in an urban HIV clinic in Uganda. In a retrospective cohort study, a multivariable polynomial mixed effects model was used to estimate CD4 recovery in the first 96 weeks of ART in two groups of patients: prevalent TB (started ART while on TB treatment), unrecognised TB (developed TB within 6 months after start ART). Included were 511 patients with a median baseline CD4 count of 57 cells/mm(3) (interquartile range: 22-130), of whom 368 (72%) had prevalent TB and 143 (28%) had unrecognised TB. Compared with prevalent TB, unrecognised TB was associated with lower CD4 count recovery at 96 weeks: -22.3 cells/mm(3) (95% confidence interval -43.2 to -1.5, P = 0.036). These estimates were adjusted for gender, age, baseline CD4 count and the use of zidovudine-based regimen. Unrecognised TB at the time of ART initiation resulted in impaired CD4 recovery compared with TB treated before ART initiation. More vigilant screening with more sensitive and rapid TB diagnostics prior to ART initiation is needed to decrease the risk of ART-associated TB and sub-optimal immune reconstitution.

Background: The growing number of people on antiretroviral therapy in Kenya has led to a decrease in HIV morbidity and mortality. However, virologic failure (VF) threatens to reverse these gains. In Makueni County, existing data indicate challenges in achieving viral load (VL) suppression among persons living with HIV (PLHIV). Few studies have been carried out investigating VF in the region despite its high incidence of HIV infections. Methods: An analytical cross-sectional study was conducted among PLHIV in Makueni County to investigate the determinants and estimate the prevalence of VF. The prevalence of VF and its associated 95% exact binomial confidence interval was estimated, and a mixed-effects logistic regression model used to evaluate the relationship between the predictors and VF. Results: The estimated period prevalence of VF between October 2018 and June 2019 was 13.2% (95% CI: 12.7%–13.8%). Being 15 years or older (aOR=0.53; 95% CI: 0.44 – 0.645) and having blood samples tested for reasons other than baseline VL measurement was associated with lower odds of VF: breastfeeding mothers (aOR=0.1; 95% CI: 0.01 – 0.97); clinical failure (aOR=0.08; 95% CI: 0.01 – 0.44); confirmation of VF (aOR=0.2; 95% CI: 0.07 – 0.62); no VL data (aOR=0.06; 95% CI: 0.01 – 0.31); routine VL (aOR=0.04; 95% CI: 0.01 – 0.12); drug substitution (aOR=0.03; 95% CI: 0.01 – 0.08). Taking ABC-based, AZT-based, or other non-TDF-Based regimens increased the odds of VF (aOR=1.61; 95% CI: 1.34 – 1.94), (aOR=1.75; 95% CI: 1.52 - 2.01), and (aOR=1.55; 95% CI: 0.99 - 2.44) respectively. Conclusion: This study showed that over 13% of HIV patients on ART in Makueni County had VF between October 2018 and June 2019. The significant risk factors associated with VF were found to be age lower than 15 years, taking a non-TDF-based ART regimen, and blood sampling for baseline VL measurements.

<i>Introduction: </i>Even though first-line antiretroviral therapy (ART) has led to a profound reduction in the incidence of opportunistic infections (OIs) and AIDS related deaths, it is challenged by virologic failure, which predisposes patients to a new or recurrent clinical condition and, as a result, affects their quality of life and increases HIV-associated mortality. Therefore, understanding the burden of virologic failure and its determinants helps with early prevention and improvement of the quality of life. However, the prevalence of virologic failure and its associated factors among adult patients on first-line ART at Debre Tabor Comprehensive Specialized Hospital is not well understood. <i>Objective: </i>This study was aimed at determining the prevalence of virologic failure and identifying its contributing factors among HIV-positive adults receiving first-line ART at Debre Tabor Comprehensive Specialized Hospital in Northwest Ethiopia. <i>Methods: </i>An institutional-based cross-sectional study was conducted on 376 adults who had started ART from February 8, 2017, to February 7, 2022. After selecting a computer-generated simple random sampling technique, data on patients' socio-demographic, behavioral, clinical, and ART-related factors were collected through a review of medical charts. A binary logistic regression model was used to identify associated factors with virologic failure, and an AOR with a 95% CI at P less than or equal to 0.05 was used to declare the association. <i>Results: </i>The prevalence of virologic failure was 13.6% (95% CI: 10.4%- 17.2%). Significant associated factors for virological failure were smoking cigarettes (AOR 4.76, 95% CI: 1.06-21.38), HIV non-disclosure (AOR 4.56, 95% CI: 1.6- 2.46), presence of stigma and discrimination (AOR 2.91, 95% CI: 1.14-7.39), having baseline OIs (AOR 6.66, 95% CI: 1.94-22.90), not taking CPT (AOR 3.21, 95% CI: 1.12-9.18), treatment interruption (AOR 2.97, 95% CI: 1.11-7.94), loss to follow-up (AOR 9.03, 95% CI: 3.08-26.47), fair or poor adherence status for ART (AOR 3.409, 95% CI: 1.26-9.24). <i>Conclusion and recommendation: </i>The prevalence of virologic failure was in line with the national prevalence. Smoking cigarettes, HIV non-disclosure, baseline OIs, suboptimal adherence, loss to follow-up, treatment interruption, not taking CPT, and taking additional medication were significantly associated with virological failure. Therefore, special attention should be given to those individuals who have the above factors to minimize and prevent virologic failure.

The identification and management of first-line antiretroviral therapy (ART) failure is a key challenge for HIV programs in resource-limited settings. In 2008, the National AIDS Control Organisation, India piloted a national strategy to provide second-line ART. We assessed the National AIDS Control Organisation second-line ART evaluation algorithm. Adult patients who had received 6 months or more of standard first-line ART were referred for second-line ART evaluation if they demonstrated CD4 decline to pre-ART values, CD4 drop to less than 50% of peak on-treatment value, failure to achieve CD4 greater than 100 c/mm(3), or development of a new World Health Organization Stage 3 or 4 AIDS-defining illness. Patients received HIV RNA testing, and those with HIV RNA 10,000 c/mL or greater qualified to switch to second-line ART. World Health Organization-defined clinical and CD4 criteria for ART failure were compared against virologic failure criteria. Between January and June 2008, 154 patients met criteria for evaluation. Of 122 (79%) patients who had HIV RNA testing, 87 (71%) had viral load 10,000 c/mL or greater and were recommended to start second-line ART, 29 (24%) had viral load less than 400 c/mL, and six (5%) had viral load between 400 and 10,000 c/mL. The positive predictive value of World Health Organization clinical/immunologic criteria to detect virologic failure was 71% (95% confidence interval, 63% to 79%). Second-line ART was initiated in the public sector in India using an approach combining clinical and immunologic evaluation with confirmation of virologic failure. Almost 25% of patients who met clinical/immunologic failure criteria demonstrated virologic suppression. Inclusion of targeted HIV RNA testing in the evaluation of treatment failure can prevent unnecessary switches to second-line ART.

Despite several interventions to eradicate HIV/AIDS globally, virological failure continues to threaten the goals of antiretroviral therapies (ART) and quality of life (QoL) of people with HIV/AIDS (PWHA). This study aimed to assess the prevalence and predictors of virological failure and determine the QoL of PWHA. A cross-sectional study was conducted at the ART clinic of a Municipal Hospital, from June to August 2023, to assess the socio-demographic, medical data, and QoL of PWHA receiving therapy at the clinic. Participants were randomly selected and interviewed: their weight and height were taken and their clinic folders examined to assess virological failure status. Both self-developed structured questionnaire and the WHOQOL-HIV BREF scale (Cronbach alpha = 0.84) were used to assess participants' data. Bivariate and multiple logistic regression analysis were conducted to determine predictors of virological failure. Also, multiple linear regression was conducted to determine factors influencing QoL of study participants. A total of 398 participants comprising of 328 (82.41%) females, and with a mean age of 48.2 years (SD ± 11.71 years), were recruited into the study. The prevalence of virological failure was 6.03%. Factors such as forgetting to take ART (Adjusted Odds Ratio (AOR) = 2.87, 95% Confidence Interval (CI) = 1.02, 7.51; p = 0.04), being classified as baseline WHO clinical staging II (AOR = 6.20, 95% CI = 1.91, 20.04; p = 0.002), and HIV stigmatization (AOR = 3.97, 95% C.I. = 1.1, 14.25; p = 0.035) were associated with virological failure. The overall QoL was good (75.35%). Having no comorbidities (Coefficient of Determination (β) = -2.7, p < 0.0001), having social support (β = 3.94, p < 0.0001) and receiving an average monthly income (β = 2.03, p = 0.002) contributed to good QoL. Virological failure in the municipality exceeded the 5.0% target set by the Joint United Nations Programme, despite majority of the study participants presenting with good QoL. The National AIDS Control Programme should consider long-acting injectable therapy for PWHA struggling to adhere to medication.

Background:Virological failure in second-line antiretroviral therapy (ART) occurs when HIV patients have a viral load exceeding 1000 copies/ml, presenting significant public health challenges, including increased risk of transmission of HIV, heightened morbidity and mortality rates, and the risk of developing drug resistance. The extent of virological failure among second-line ART patients in the Harari region and Dire Dawa city of Eastern Ethiopia has not been thoroughly investigated. This study aimed to determine the prevalence of virological failure and its influencing factors from January 1 to December 31, 2023.Design and methods:A cross-sectional study was conducted among 478 adult second-line antiretroviral therapy users at an institution-based setting. A census was employed to recruit the study participants. Data was collected using a semi-structured data extraction checklist entered into EpiData version 4.6 and exported to SPSS version 26 for analysis. Descriptive statistics, along with bivariable and multivariable logistic regression analyses, were performed to determine the associations between virological failure and independent variables, using adjusted odds ratios with 95% confidence intervals. A p-value less than 0.05 was used to declare the statistical significance.Results:The overall prevalence of virological failure among adult second-line ART users was 12.76% (95% CI = 10.05–16.07). Smoking (AOR = 2.81), BMI status (AOR = 6.97), TB-HIV co-infection (AOR = 0.20), history of INH prophylaxis (AOR = 4.25), and enhanced ART adherence counseling (AOR = 7.02) were found to be significantly associated with virological failure among second-line ART users.Conclusion:Nearly 1 in 10 adults on second-line ART experienced virological failure. Factors such as smoking, nutritional status, TB-HIV co-infection, and adherence counseling significantly influenced outcomes. Continuous monitoring and clinical interventions are crucial to reduce virological failures in this population.

ODYSSEY showed superior efficacy for dolutegravir-based antiretroviral therapy (ART) versus standard of care (SOC) in children living with HIV starting first-line or second-line ART aged 4 weeks or older. Here, we aim to compare virological outcomes and resistance in the dolutegravir group versus SOC for first-line and second-line ART up to 96 weeks. ODYSSEY was an open-label, multicentre, randomised, non-inferiority trial done in 29 centres in seven countries (Germany, Spain, South Africa, Thailand, the UK, Uganda, and Zimbabwe). ODYSSEY recruited children living with HIV aged at least 28 days and younger than 18 years, weighing at least 3 kg, starting first-line ART (ODYSSEY A), or switching to second-line therapy after treatment failure (ODYSSEY B). Children were randomly assigned (1:1) to dolutegravir plus two nucleoside or nucleotide reverse transcriptase inhibitors (NRTIs; dolutegravir group) versus the SOC group (non-nucleoside reverse transcriptase inhibitor [NNRTI], boosted protease inhibitor, or non-dolutegravir integrase strand-transfer inhibitor, plus two NRTIs). Two randomised cohorts were combined in this exploratory analysis: children weighing at least 14 kg were enrolled between Sept 20, 2016, and June 22, 2018, and children weighing less than 14 kg were enrolled between July 5, 2018, and Aug 26, 2019. Virological failure was defined as an inadequate virological response at week 24 with an ART switch or confirmed HIV-1 RNA viral load of at least 400 copies per mL after week 36. Virological suppression was defined as two consecutive viral loads of less than 400 copies per mL and was compared between groups, including an ART switch and death as competing risks. Children with virological failure were tested for post-failure genotypic resistance, with baseline results used to identify emergent resistance. Development of emergent resistance was a secondary trial outcome and all other outcomes are exploratory. ODYSSEY was registered with ClinicalTrials.gov (NCT02259127), EUDRACT (2014-002632-14), and ISRCTN (ISRCTN91737921). In ODYSSEY at enrolment, 381 participants started first-line ART (ODYSSEY A: 189 in the dolutegravir group and 192 in the SOC group) and 407 participants started second-line ART (ODYSSEY B: 202 in the dolutegravir group and 205 in the SOC group). 72 participants in ODYSSEY A and 13 participants in ODYSSEY B weighed less than 14 kg. 401 (51%) of 788 participants were female and 387 (49%) were male. Virological suppression occurred significantly earlier in the dolutegravir group (adjusted [cause-specific] hazard ratio [HR] 1·57 [95% CI 1·35 to 1·83]; p<0·0001). Overall, 51 (13%) participants had virological failure by 96 weeks in the dolutegravir group versus 86 (22%) in the SOC group (including 18 [10%] vs 43 [22%] in ODYSSEY A and in 33 [16%] vs 43 [21%] in ODYSSEY B; adjusted HR 0·56 [0·40 to 0·79]; p=0·0011). Among ODYSSEY B participants starting dolutegravir, virological failure was higher in children starting zidovudine (HR 2·22 [1·01 to 4·88]; p=0·048) and similar in those starting tenofovir disoproxil fumarate (1·19 [0·50 to 2·83]; p=0·70) compared with abacavir. Time to virological suppression was marginally faster in participants receiving second-line dolutegravir and abacavir with high-level abacavir resistance at baseline compared with those with no, low-level, intermediate-level resistance (cause-specific HR 1·70 [1·01 to 2·85]; p=0·046); and failure rates by week 96 were similar (HR 0·90 [0·23 to 3·61]; p=0·88). An estimated 1% (95% CI 0 to 2) of participants in the dolutegravir group versus 20% (14 to 26) in the SOC group in ODYSSEY A had emergent resistance to at least one drug-class within their first-line regimen (risk difference -20% [-25 to -14]; p<0·0001); 4% (1 to 6) versus 5% (2 to 8) had resistance to drug within their initial second-line regimen (risk difference -1% [-5 to 3]; p=0·60). 3% (0 to 5) of participants in the dolutegravir group had emergent integrase strand-transfer inhibitors resistance compared with 3% (1 to 6) of participants in the SOC group who had emergent resistance to the anchor drug (risk difference 0% [-4 to 3]; p=0·78). Dolutegravir led to faster virological suppression and lower risk of virological failure than NNRTIs and boosted protease inhibitor-based SOC. Participants starting second-line dolutegravir-based ART with an abacavir or tenofovir backbone were at lower risk of virological failure than those starting zidovudine. During first-line therapy, dolutegravir protected against emergent resistance; starting second-line therapy, the risk of emergent resistance to nucleoside reverse transcriptase inhibitor backbone, and anchor drugs, was similar among participants starting dolutegravir within their second-line regimen and those starting mainly boosted protease inhibitor-based SOC. Penta Foundation, ViiV Healthcare, and UK Medical Research Council.

BackgroundMalawi’s national antiretroviral therapy program provides atazanavir/ritonavir–based second line regimens which cause concentration-dependent rise in indirect bilirubin. We sought to determine if elevated bilirubin, as a surrogate of atazanavir/ritonavir adherence, can aid in the evaluation of second line virological failure in Malawi.MethodsWe conducted a cross-sectional study of HIV-infected patients ≥15 years who were on boosted protease inhibitor-based second line antiretroviral therapy for at least 6 months in two urban HIV clinics in Lilongwe, Malawi. Antiretroviral therapy history and adherence data were extracted from the electronic medical records and blood was drawn for viral load, complete blood count, total bilirubin, and CD4 cell count at a clinic visit. Factors associated with virological failure were assessed using multivariate logistic regression model.ResultsOut of 376 patients on second line antiretroviral therapy evaluated, 372 (98.9%) were on atazanavir/ritonavir-based therapy and 142 (37.8%) were male. Mean age was 40.9 years (SD ± 10.1), mean duration on second line antiretroviral therapy was 41.9 months (SD ± 27.6) and 256 patients (68.1%) had elevated bilirubin >1.3 mg/dL. Overall, 35 (9.3%) patients had viral load >1000 copies/ml (virological failure). Among the virologically failing vs. non-failing patients, bilirubin was elevated in 34.3% vs. 72.0% respectively (p < 0.001), although adherence by pill count was similar (62.9% vs. 60.7%, p = 0.804). The odds of virological failure were higher for adults aged 25–40 years (adjusted odds ratio (aOR) 2.5, p = 0.048), those with CD4 cell count <100 (aOR 17.5, p < 0.001), and those with normal bilirubin levels (aOR 5.4, p < 0.001); but were lower for the overweight/obese patients (aOR 0.3, p = 0.026). Poor pill count adherence (aOR 0.7, p = 0.4) and male gender (aOR 1.2, p = 0.698) were not associated with second line virological failure.ConclusionsAmong patients receiving atazanavir/ritonavir-based second line antiretroviral therapy, bilirubin levels better predicted virological failure than pill count adherence. Therefore, strategic use of bilirubin and viral load testing to target adherence counseling and support may be cost-effective in monitoring second line antiretroviral therapy adherence and virological failure. Drug resistance testing targeted for patients with virological failure despite elevated bilirubin levels would facilitate timely switch to third line antiretroviral regimens whenever available.

BackgroundSouth African HIV treatment guidelines call for patients who fail first-line antiretroviral therapy (ART) to be switched to second-line ART, yet logistical issues, clinician decisions and patient preferences make delay in switching to second-line likely. We explore the impact of delaying second-line ART after first-line treatment failure on rates of death and virologic failure.MethodsWe include patients with documented virologic failure on first-line ART from an observational cohort of 9 South African clinics. We explored predictors of delayed second-line switch and used marginal structural models to analyze rates of death following first-line failure by categorical time to switch to second-line. Cox proportional hazards models were used to examine virologic failure on second-line ART among patients who switched to second-line.Results5895 patients failed first-line ART, and 63% switched to second-line. Among patients who switched, median time to switch was 3.4 months (IQR: 1.1–8.7 months). Longer time to switch was associated with higher CD4 counts, lower viral loads and more missed visits prior to first-line failure. Worse outcomes were associated with delay in second-line switch among patients with a peak CD4 count on first-line treatment ≤100 cells/mm3. Among these patients, marginal structural models showed increased risk of death (adjusted HR for switch in 6–12 months vs. 0–1.5 months = 1.47 (95% CI: 0.94–2.29), and Cox models showed increased rates of second-line virologic failure despite the presence of survivor bias (adjusted HR for switch in 3–6 months vs. 0–1.5 months = 2.13 (95% CI: 1.01–4.47)).ConclusionsEven small delays in switch to second-line ART were associated with increased death and second-line failure among patients with low CD4 counts on first-line. There is opportunity for healthcare providers to switch patients to second-line more quickly.

IntroductionHIV-1 resistance data to inform treatment sequencing are limited for children with virological failure on first- and second-line antiretroviral therapy (ART) in Sub-Saharan Africa.MethodsHIV-1-infected children aged ≤15 years were retrospectively identified from an ART cohort in Cape Town, South Africa (2003 to 2010). First-line ART was either non-nucleoside reverse transcriptase inhibitor (NNRTI) or lopinavir/ritonavir-based (with the exception of children <6 months old who received full-dose ritonavir as the sole protease inhibitor (PI) from 2004 to 2007). Second-line ART was the alternative regimen. Treatment outcomes, including virological failure, loss to care, death or remaining in care, were determined. Genotypic resistance testing was conducted on stored serum from children at first- or second-line virological failure (two consecutive HIV-1 RNA levels >1000 copies/ml). International AIDS Society criteria defined resistance mutations.ResultsOf 472 children starting first-line ART, 352 (75%) remained in care, 45 (9%) were lost and 4 (1%) died on first-line treatment. Seventy-one (15%) had observed virological failure, and 37 of these children had specimens available for genotype testing. Eight children (22%) had wild-type virus, seven (19%) had thymidine analog mutations (TAMs), 24 (65%) had NNRTI resistance and two (5.4%) had multiple protease resistance (PR). Of the 78 children who received second-line ART, 54 (71%) remained in care, 6 (8%) were lost and 1 (1%) died during second-line treatment. Fifteen (20%) had observed virological failure; 13 had samples available for genotype. Three (23%) had wild-type virus, eight (62%) had TAMs, nine (69%) had NNRTI resistance, and five (38%) had multiple PI resistance all of whom had received full-dose ritonavir.ConclusionAlthough virological failure was infrequent in children on first- and second-line ART, rates of observed resistance including multiple PR resistance after failure were high. Reasons for high rates of resistance include use of full-dose ritonavir and continued viremia. Wild-type virus was common, suggesting poor adherence or challenges in correct dosing. Genotype resistance testing in children with virological failure may optimize selection of subsequent regimens and inform recommendations for sequencing of existing ART.

Background Virological failure (VF) significantly threatens the efficacy of antiretroviral therapy (ART) programs in East Africa. This systematic review and meta-analysis assess the prevalence and predictors of VF among individuals living with HIV. Methods We searched PubMed, Web of Science, African Journals Online, and EMBASE for relevant studies. Heterogeneity was assessed using the I 2 statistic, and random-effects models addressed between-study variability. Publication bias was examined through funnel plots, Egger’s regression, and Begg’s tests. Subgroup analyses and meta-regression explored heterogeneity sources and potential VF predictors. Analyses were conducted using MedCalc version 20.010, adhering to PRISMA 2020 guidelines. Results Twenty-five records were included, with a sample size of 29,829 people living with HIV on ART. The pooled prevalence of VF in East Africa was 19.4% (95% CI: 15.2%–24.0%), with substantial heterogeneity across studies. Sociodemographic predictors of VF included male sex (30.9%, p < .001), unmarried status (28.2%, p < .001), lower educational attainment (33.0%, p < .001), non-formal employment (47.2%, p < .001), and urban residence (51.2%, p < .001). Clinical factors associated with higher VF rates were ambulatory status (44.7%, p < .001), low CD4 count (35.1%, p < .001), low haemoglobin (52.2%, p < .001), advanced HIV stage III/IV (44.2%, p < .001), HIV/TB co-infection (24.3%, p < .001), and other opportunistic infections (20.5%, p = .008). Treatment-related factors associated with VF were first-line nevirapine-based regimen (27.7%, p = .009) and poor ART adherence (41.76%, p < .001). Conclusion Sociodemographic factors, advanced HIV disease, co-morbidities, poor adherence, and specific first-line ART regimens are key predictors of virological failure. Targeted, multidisciplinary interventions focusing on routine viral load monitoring, adherence support, and addressing socioeconomic barriers are essential to improve ART outcomes in East Africa.

Two-way mobile phone intervention compared with standard-of-care adherence support after second-line antiretroviral therapy failure: a multinational, randomised controlled trial

BackgroundIn Uganda, 20% (19,073/94,579) of children and adolescents (0-19 years) living with HIV (CALHIV) were receiving second-line antiretroviral therapy (ART) by the end of March 2020. Data on incidence and predictors of virological failure among these CALHIV on second-line ART is limited. Lack of this information and limited access to HIV drug resistance testing prevents early identification of CALHIV at risk of virological failure on second-line ART. The aim of this study was to determine the incidence and predictors of virological failure among CALHIV on second-line ART in Uganda.MethodologyThis was a retrospective cohort study of all CALHIV aged 0-19 years who were switched to second-line ART regimen between June 2010 and June 2019 at the Baylor Uganda Centre of Excellence clinic. Data was analysed using STATA 14. Cumulative incidence curves were used to assess incidence of virological failure. Factors associated with virological failure were identified using sub-distributional hazard regression analysis for competing risks considering death, transfer out and loss to follow-up as competing risks.ResultsOf 1104 CALHIV, 53% were male. At switch to Protease Inhibitor (PI) based second-line ART, majority (47.7%) were aged 5 – 9 years,56.2% had no/mild immune suppression for age while 77% had viral load copies < 100,000 copies/mL. The incidence of virological failure on second-line ART regimen among CALHIV was 3.9 per 100 person-years (PY) with a 10-year cumulative incidence rate of 32%. Factors significantly associated with virological failure were age 10 – 19 years (HR 3.2, 95% 1.6 – 6.2, p < 0.01) and HIV viral load count > 100,000 copies/mL (HR 2.2, 95% CI 1.5 – 3.1), p < 0.01) prior to second-line ART switch.ConclusionTreatment outcomes for children and adolescents on second-line ART are favourable with one third of them developing virological failure at 10 years of follow up. Adolescent age group and high HIV viral load at the start of second-line ART were significantly associated with virological failure on second-line ART. There is need to determine optimal strategies to improve ART treatment outcomes among adolescents with high viral load counts at second-line ART switch.