Virologic response of adolescents living with perinatally acquired HIV receiving antiretroviral therapy in the period of early adolescence (10-14 years) in South Africa.

BACKGROUND AND OBJECTIVES: Adolescents living with perinatally acquired HIV (ALPHIV) on antiretroviral therapy (ART) have been noted to have poorer adherence, retention and virologic control compared to adolescents with non-perinatally acquired HIV, children or adults. We aimed to describe and examine factors associated with longitudinal virologic response during early adolescence. DESIGN: A retrospective cohort study. METHODS: We included ALPHIV who initiated ART before age 9.5 years in South African cohorts of the International epidemiology Database to Evaluate AIDS-Southern Africa (IeDEA-SA) collaboration (2004-2016); with viral load (VL) values <400 copies/ml at age 10 years and at least one VL measurement after age 10 years. We used a log-linear quantile mixed model to assess factors associated with elevated (75th quantile) VLs. RESULTS: We included 4396 ALPHIV, 50.7% were male, with median (interquartile range) age at ART start of 6.5 (4.5, 8.1) years. Of these, 74.9% were on a non-nucleoside reverse transcriptase inhibitor (NNRTI) at age 10 years. After adjusting for other patient characteristics, the 75th quantile VLs increased with increasing age being 3.13-fold (95% CI 2.66, 3.68) higher at age 14 versus age 10, were 3.25-fold (95% CI 2.81, 3.75) higher for patients on second-line protease-inhibitor and 1.81-fold for second-line NNRTI-based regimens (versus first-line NNRTI-based regimens). There was no difference by sex. CONCLUSIONS: As adolescents age between 10 and 14 years, they are increasingly likely to experience higher VL values, particularly if receiving second-line protease inhibitor or NNRTI-based regimens, which warrant adherence support interventions.

Characteristics and outcomes of adolescents living with perinatally acquired HIV within Southern Africa.

BACKGROUND: Using data from 15 International epidemiology Databases to Evaluate AIDS in Southern Africa sites, we compared the characteristics and outcomes of adolescents living with perinatally acquired HIV (ALPH). METHODS: We included ALPH entering care aged less than 13 years with at least one HIV care visit during adolescence (10-19 years). We compared the characteristics and cross-sectional outcomes: transfer out, loss to follow-up (no visit in the 12 months prior to database closure), mortality, and retention between those who entered care aged less than 10 vs. aged 10-13 years; and explored predictors of mortality after age 13 years using Cox Proportional Hazards models. RESULTS: Overall, 16 229 (50% female) ALPH who entered HIV care aged less than 10 years and 8897 (54% female) aged 10-13 years were included and followed for 152 574 person-years. During follow-up, 94.1% initiated antiretroviral therapy, with those who entered care aged less than 10 more likely to have initiated antiretroviral therapy [97.9%, 95% confidence interval (CI) 97.6; 98.1%] than those who presented aged 10-13 years (87.3%, 95% CI 86.6; 88.0%). At the end of follow-up, 3% had died (entered care aged <10 vs. 10-13 years; 1.4 vs. 5.1%), 22% were loss to follow-up (16.2 vs. 33.4%), and 59% (66.4 vs. 45.4%) were retained. There was no difference in the risk of dying after the age of 13 years between adolescents entering care aged less than 10 vs. 10-13 years (adjusted hazard ratio 0.72; 95% CI 0.36; 1.42). CONCLUSION: Retention outcomes for ALPH progressively worsened with increasing age, with these outcomes substantially worse among adolescents entering HIV care aged 10-13 vs. less than 10 years.

Long-term virologic responses to antiretroviral therapy among HIV-positive patients entering adherence clubs in Khayelitsha, Cape Town, South Africa: a longitudinal analysis.

INTRODUCTION: In South Africa, an estimated 4.6 million people were accessing antiretroviral therapy (ART) in 2018. As universal Test and Treat is implemented, these numbers will continue to increase. Given the need for lifelong care for millions of individuals, differentiated service delivery models for ART services such as adherence clubs (ACs) for stable patients are required. In this study, we describe long-term virologic outcomes of patients who have ever entered ACs in Khayelitsha, Cape Town. METHODS: We included adult patients enrolled in ACs in Khayelitsha between January 2011 and December 2016 with a recorded viral load (VL) before enrolment. Risk factors for an elevated VL (VL >1000 copies/mL) and confirmed virologic failure (two consecutive VLs >1000 copies/mL one year apart) were estimated using Cox proportional hazards models. VL completeness over time was assessed. RESULTS: Overall, 8058 patients were included in the analysis, contributing 16,047 person-years of follow-up from AC entry (median follow-up time 1.7 years, interquartile range [IQR]:0.9 to 2.9). At AC entry, 74% were female, 46% were aged between 35 and 44 years, and the median duration on ART was 4.8 years (IQR: 3.0 to 7.2). Among patients virologically suppressed at AC entry (n = 8058), 7136 (89%) had a subsequent VL test, of which 441 (6%) experienced an elevated VL (median time from AC entry 363 days, IQR: 170 to 728). Older age (adjusted hazard ratio [aHR] 0.64, 95% confidence interval [CI] 0.46 to 0.88), more recent year of AC entry (aHR 0.76, 95% CI 0.68 to 0.84) and higher CD4 count (aHR 0.67, 95% CI 0.54 to 0.84) were protective against experiencing an elevated VL. Among patients with an elevated VL, 52% (150/291) with a repeat VL test subsequently experienced confirmed virologic failure in a median time of 112 days (IQR: 56 to 168). Frequency of VL testing was constant over time (82 to 85%), with over 90% of patients remaining virologically suppressed. CONCLUSIONS: This study demonstrates low prevalence of elevated VLs and confirmed virologic failure among patients who entered ACs. Although ACs were expanded rapidly, most patients were well monitored and remained stable, supporting the continued rollout of this model.

Characterizing the double-sided cascade of care for adolescents living with HIV transitioning to adulthood across Southern Africa.

INTRODUCTION: As adolescents and young people living with HIV (AYLH) age, they face a "transition cascade," a series of steps associated with transitions in their care as they become responsible for their own healthcare. In high-income countries, this usually includes transfer from predominantly paediatric/adolescent to adult clinics. In sub-Saharan Africa, paediatric HIV care is mostly provided in decentralized, non-specialist primary care clinics, where "transition" may not necessarily include transfer of care but entails becoming more autonomous for one's HIV care. Using different age thresholds as proxies for when "transition" to autonomy might occur, we evaluated pre- and post-transition outcomes among AYLH. METHODS: We included AYLH aged <16 years at enrolment, receiving antiretroviral therapy (ART) within International epidemiology Databases to Evaluate AIDS Southern Africa (IeDEA-SA) sites (2004 to 2017) with no history of transferring care. Using the ages of 16, 18, 20 and 22 years as proxies for "transition to autonomy," we compared the outcomes: no gap in care (≥2 clinic visits) and viral suppression (HIV-RNA <400 copies/mL) in the 12 months before and after each age threshold. Using log-binomial regression, we examined factors associated with no gap in care (retention) in the 12 months post-transition. RESULTS: A total of 5516 AYLH from 16 sites were included at "transition" age 16 (transition-16y), 3864 at 18 (transition-18y), 1463 at 20 (transition-20y) and 440 at 22 years (transition-22y). At transition-18y, in the 12 months pre- and post-transition, 83% versus 74% of AYLH had no gap in care (difference 9.3 (95% confidence interval (CI) 7.8 to 10.9)); while 65% versus 62% were virally suppressed (difference 2.7 (-1.0 to 6.5%)). The strongest predictor of being retained post-transition was having no gap in the preceding year, across all transition age thresholds (transition-16y: adjusted risk ratio (aRR) 1.72; 95% CI (1.60 to 1.86); transition-18y: aRR 1.76 (1.61 to 1.92); transition-20y: aRR 1.75 (1.53 to 2.01); transition-22y: aRR 1.47; (1.21 to 1.78)). CONCLUSIONS: AYLH with gaps in care need targeted support to prevent non-retention as they take on greater responsibility for their healthcare. Interventions to increase virologic suppression rates are necessary for all AYLH ageing to adulthood.