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AbstractIntroductionThe Spectrum/AIM model is used by national HIV programs and UNAIDS to prepare annual estimates of key HIV indicators. This article describes key updates to paediatric and adult models for the 2021 round of HIV estimates.MethodsPotential updates to Spectrum arise due to newly available data, new analyses of existing data, and the need for new issues to be addressed. Updates are guided by experts through the UNAIDS Reference Group on Estimates, Modelling and Projections. Changes are tested and assessed for impact before being accepted into the final model.ResultsSpectrum tracks children living with HIV by CD4% for ages 0–4 and CD4 count for ages 5–14. Data from IeDEA treatment sites have been used to map the transition from CD4% to CD4 count at age 5. Breastfeeding patterns in sub‐Saharan Africa have been updated with the latest survey data and estimates of continuation on antiretroviral therapy (ART) with breastfeeding have been revised based on recent studies. Model assumptions about the CD4 counts of people who drop out of ART have been revised to account for CD4 count increases while on treatment. If available, monthly data on numbers on ART can now be used to estimate the effects of COVID‐19‐related disruptions during 2020.ConclusionsThese changes are intended to provide more accurate estimates of HIV burden. The effects of these changes on paediatric indicators are small except in countries with new surveys that might have updated patterns of breastfeeding. Changes to the adult model have little effect on total new infections. AIDS‐related deaths will be somewhat lower in countries that have data on ART drop out but might be increased by HIV care disruptions due to COVID‐19. The updated model uses newly available data to improve the estimation of paediatric and adult HIV indicators.

AbstractIntroductionMonitoring mother‐infant pairs with HIV exposure is needed to assess the effectiveness of vertical transmission (VT) prevention programmes and progress towards VT elimination.MethodsWe used routinely collected data on infants with HIV exposure, born May 2018–April 2021 in the Western Cape, South Africa, with follow‐up through mid‐2022. We assessed the proportion of infants diagnosed with HIV at birth (≤7 days), 10 weeks (>1 to 14 weeks) and >14 weeks as proxies for intrauterine, intrapartum/early breastfeeding and late breastfeeding transmission, respectively. We used mixed‐effects Poisson regression to assess factors associated with VT in mothers known with HIV by delivery.ResultsWe included 50,461 infants born to mothers known with HIV by delivery. HIV was diagnosed in 894 (1.8%) infants. Among mothers, 51% started antiretroviral treatment (ART) before and 27% during pregnancy; 17% restarted during pregnancy after ≥6 months interruption; and 6% had no recorded ART during pregnancy. Most pregnancy ART regimens included non‐nucleoside reverse transcriptase inhibitors (83%). Of mothers with available results (90% with viral load [VL]; 70% with CD4), VL nearest delivery was <100 copies/ml in 78% and CD4 count ≥350 cells/μl in 62%. HIV‐PCR results were available for 86%, 67% and 48% of eligible infants at birth, 10 weeks and >14 weeks. Among these infants, 0.9%, 0.4% and 1.5% were diagnosed positive at birth, 10 weeks and >14 weeks, respectively. Among infants diagnosed with HIV, 43%, 16% and 41% were diagnosed at these respective time periods. Among mothers with VL<100, 100–999, 1000–99,000 and ≥100,000 copies/ml nearest delivery, infant HIV diagnosis incidence was 0.4%, 2.3%, 6.6% and 18.4%, respectively. Increased VT was strongly associated with recent elevated maternal VL with a seven‐fold increased rate with even modestly elevated VL (100–999 vs. <100 copies/ml). VT was also associated with unknown/low maternal CD4, maternal age <20 years, no antenatal ART, later maternal ART start/restart in pregnancy and ART gaps.ConclusionsDespite high maternal ART coverage and routine postnatal prophylaxis, ongoing VT remains a concern. Timing of infant HIV diagnoses suggests intrapartum and/or breastfeeding transmission in nearly 60%. Interventions to ensure retention on ART and sustained maternal viral suppression are needed to reduce VT.

AbstractIntroductionThere is an urgent need for more efficient models of differentiated antiretroviral therapy (ART) delivery for people living with HIV (PLHIV), with the World Health Organization calling for evidence to guide whether annual ART prescriptions and consultations (12M scripts) should be recommended in global guidelines. We assessed the association between 12M scripts (allowed temporarily during the COVID‐19 pandemic) versus standard 6‐month prescriptions and consultations (6M scripts) and clinical outcomes.MethodsWe performed a retrospective cohort study using routine, de‐identified data from 59 public clinics in KwaZulu‐Natal, South Africa. We included PLHIV aged ≥18 years with a recent suppressed viral load (VL) who had been referred for community ART delivery with 6M or 12M scripts. We used modified Poisson regression to compare 12‐month retention‐in‐care (≤90 days late for all visits) and viral suppression (<50 copies/ml) between prescription groups.ResultsAmong 27,148 PLHIV referred for community ART during Jun–Dec 2020, 57.4% received 12M scripts. The median age was 39 years and 69.4% were women. Age, sex, prior community ART use and time on ART were similar across groups. However, more of the 12M script group had dolutegravir‐based regimens (60.0% vs. 46.3%). The median (interquartile range) number of clinic visits in the year of follow‐up was 1(1‐1) in the 12M group and 2(2‐3) in the 6M group. Retention was 94.6% (95% confidence interval [CI]: 94.2%–94.9%) among those receiving 12M scripts and 91.8% (95% CI: 91.3%–92.3%) among those with 6M scripts. 17.1% and 16.9% of clients in the 12M and 6M groups were missing follow‐up VL data, respectively. Among those with VLs, 92.4% (95% CI: 92.0%–92.9%) in the 12M group and 91.4% (95% CI: 90.8%–92.0%) in the 6M group were suppressed. After adjusting for age, sex, ART regimen, time on ART, prior community ART use and calendar month, retention (adjusted risk ratio [aRR]: 1.03, 95% CI: 1.01–1.05) and suppression (aRR: 1.00, 95% CI: 0.99–1.01) were similar across groups.ConclusionsAmong PLHIV referred for community ART with a recent suppressed VL, the use of 12M scripts reduced clinic visits without impacting short‐term clinical outcomes. 12M scripts should be considered for differentiated service delivery programmes.

AbstractIntroductionThere is little data on long‐term implementation and outcomes for people living with HIV (PLHIV) in differentiated antiretroviral therapy (ART) delivery programmes. We aimed to analyse usage patterns of and associated treatment outcomes in a community ART programme, within the Centralized Chronic Medicines Dispensing and Distribution programme, in South Africa over 3.5 years.MethodsWe performed a retrospective cohort study among PLHIV on first‐line ART who were eligible for community ART delivery between October 2016 and March 2019, from 56 urban clinics in KwaZulu‐Natal, South Africa. Follow‐up ended in March 2020. We measured referral rates and, among those referred, we characterized patterns of community ART usage using group‐based trajectory modelling following referral. We used survival analysis to measure the association between community ART usage and loss‐to‐care (no visit for ≥365 days) and logistic regression to measure the association between community ART usage and viraemia (≥50 copies/ml).ResultsAmong the 80,801 patients eligible for community ART, the median age was 36 years, 69.8% were female and the median (interquartile range [IQR]) follow‐up time was 22 (13–31) months. In total, 49,961 (61.8%) were referred after a median of 6 (IQR 2–13) months from first eligibility. After referral, time spent in community ART varied; 42% remained consistently in community ART, 15% returned to consistent clinic‐based care and the remaining 43% oscillated between community ART and clinic‐based care. Following referral, the incidence of loss‐to‐care was 3.93 (95% confidence interval [CI]: 3.71–4.15) per 100 person‐years during periods of community ART usage compared to 5.75 (95% CI: 5.28–6.25) during clinic‐based care. In multivariable models, community ART usage was associated with a 36% reduction in the hazards of loss‐to‐care (adjusted hazard ratio: 0.64 [95% CI: 0.57–0.72]). The proportion of patients who became viraemic after first community ART referral was 5.2% and a 10% increase in time in community ART was associated with a 3% reduction in odds of viraemia (adjusted odds ratio: 0.97 [95% CI: 0.95–0.99]).ConclusionsCommunity ART usage patterns vary considerably, while clinical outcomes were good. Promoting consistent community ART usage may reduce clinic burden and the likelihood of patients being lost to care, while sustaining viral suppression.

AbstractIntroductionIn recent years, the expansion of HIV treatment eligibility has resulted in an increase in people with antiretroviral therapy (ART) experience prior to pregnancy but little is known about postpartum engagement in care in this population. We examined differences in disengagement from HIV care after delivery by maternal ART history before conception.MethodsWe analysed data from people living with HIV (aged 15–49) in Khayelitsha, South Africa, with ≥1 live birth between April 2013 and March 2019. We described trends over time in ART history prior to estimated conception, classifying ART history groups as: (A) on ART with no disengagement (>270 days with no evidence of HIV care); (B) returned before pregnancy following disengagement; (C) restarted ART in pregnancy after disengagement; and (D) ART new start in pregnancy. We used Kaplan–Meier curves and proportional‐hazards models (adjusted for maternal age, number of pregnancy records and year of delivery) to examine the time to disengagement from delivery to 2 years postpartum.ResultsAmong 7309 pregnancies (in 6680 individuals), the proportion on ART (A) increased from 19% in 2013 to 41% in 2019. The proportions of those who returned (B) and restarted (C) increased from 2% to 13% and from 2% to 10%, respectively. There was a corresponding decline in the proportion of new starts (D) from 77% in 2013 to 36% in 2019. In the first recorded pregnancy per person in the study period, 26% (95% CI 25–27%) had disengaged from care by 1 year and 34% (95% CI 33–36%) by 2 years postpartum. Individuals who returned (B: aHR 2.10, 95% CI 1.70–2.60), restarted (C: aHR 3.32, 95% CI 2.70–4.09) and newly started ART (D: aHR 2.41, 95% CI 2.12–2.74) had increased hazards of postpartum disengagement compared to those on ART (A).ConclusionsThere is a growing population of people with ART experience prior to conception and postpartum disengagement varies substantially by ART history. Antenatal care presents an important opportunity to understand prior ART experiences and an entry into interventions for strengthened engagement in HIV care.

AbstractIntroductionWhile a large proportion of people with HIV (PWH) have experienced SARS‐CoV‐2 infections, there is uncertainty about the role of HIV disease severity on COVID‐19 outcomes, especially in lower‐income settings. We studied the association of mortality with characteristics of HIV severity and management, and vaccination, among adult PWH.MethodsWe analysed observational cohort data on all PWH aged ≥15 years experiencing a diagnosed SARS‐CoV‐2 infection (until March 2022), who accessed public sector healthcare in the Western Cape province of South Africa. Logistic regression was used to study the association of mortality with evidence of antiretroviral therapy (ART) collection, time since first HIV evidence, CD4 cell count, viral load (among those with evidence of ART collection) and COVID‐19 vaccination, adjusting for demographic characteristics, comorbidities, admission pressure, location and time period.ResultsMortality occurred in 5.7% (95% CI: 5.3,6.0) of 17,831 first‐diagnosed infections. Higher mortality was associated with lower recent CD4, no evidence of ART collection, high or unknown recent viral load and recent first HIV evidence, differentially by age. Vaccination was protective. The burden of comorbidities was high, and tuberculosis (especially more recent episodes of tuberculosis), chronic kidney disease, diabetes and hypertension were associated with higher mortality, more strongly in younger adults.ConclusionsMortality was strongly associated with suboptimal HIV control, and the prevalence of these risk factors increased in later COVID‐19 waves. It remains a public health priority to ensure PWH are on suppressive ART and vaccinated, and manage any disruptions in care that occurred during the pandemic. The diagnosis and management of comorbidities, including for tuberculosis, should be optimized.

AbstractIntroductionThe Joint United Nations Programme on HIV/AIDS (UNAIDS) projections of paediatric HIV prevalence and deaths rely on the International epidemiology Databases to Evaluate AIDS (IeDEA) consortium for mortality estimates among children living with HIV (CHIV) receiving antiretroviral therapy (ART). Previous estimates, based on data through 2014, may no longer be accurate due to expanded paediatric HIV care and treatment eligibility, and the possibility of unreported deaths in CHIV considered lost to follow‐up (LTFU). We therefore estimated all‐cause mortality and its trends in CHIV (<15 years old) on ART using extended and new IeDEA data.MethodsWe analysed (i) IeDEA observational data from CHIV in routine care globally, and (ii) novel data from an IeDEA tracing study that determined outcomes in a sample of CHIV after being LTFU in southern Africa. We included 45,711 CHIV on ART during 2004 to 2017 at 72 programmes in Africa, Asia‐Pacific and Latin America. We used mixed effects Poisson regression to estimate mortality by age, sex, CD4 at ART start, time on ART, region and calendar year. For Africa, in an adjusted analysis that accounts for unreported deaths among those LTFU, we first modified the routine data by simulating mortality outcomes within six months after LTFU, based on a Gompertz survival model fitted to the tracing data (n = 221).ResultsObserved mortality rates were 1.8 (95% CI: 1.7 to 1.9) and 9.4 (6.3 to 13.4) deaths per 100 person‐years in the routine and tracing data, respectively. We found strong evidence of higher mortality at shorter ART durations, lower CD4 values, and in infancy. Averaging over covariate patterns, the adjusted mortality rate was 54% higher than the unadjusted rate. In unadjusted analyses, mortality reduced by an average 60% and 73% from 2005 to 2017, within and outside of Africa, respectively. In the adjusted analysis for Africa, this temporal reduction was 42%.ConclusionsMortality rates among CHIV have decreased substantially over time. However, when accounting for worse outcomes among those LTFU, mortality estimates increased and temporal improvements were slightly reduced, suggesting caution in interpreting analyses based only on programme data. The improved and updated IeDEA estimates on mortality among CHIV on ART support UNAIDS efforts to accurately model global HIV statistics.