Associations of inter-annual rainfall decreases with subsequent HIV outcomes for persons with HIV on antiretroviral therapy in Southern Africa: a collaborative analysis of cohort studies.

BACKGROUND: Periods of droughts can lead to decreased food security, and altered behaviours, potentially affecting outcomes on antiretroviral therapy (ART) among persons with HIV (PWH). We investigated whether decreased rainfall is associated with adverse outcomes among PWH on ART in Southern Africa. METHODS: Data were combined from 11 clinical cohorts of PWH in Lesotho, Malawi, Mozambique, South Africa, Zambia, and Zimbabwe, participating in the International epidemiology Databases to Evaluate AIDS Southern Africa (IeDEA-SA) collaboration. Adult PWH who had started ART prior to 01/06/2016 and were in follow-up in the year prior to 01/06/2016 were included. Two-year rainfall from June 2014 to May 2016 at the location of each HIV centre was summed and ranked against historical 2-year rainfall amounts (1981-2016) to give an empirical relative percentile rainfall estimate. The IeDEA-SA and rainfall data were combined using each HIV centre's latitude/longitude. In individual-level analyses, multivariable Cox or generalized estimating equation regression models (GEEs) assessed associations between decreased rainfall versus historical levels and four separate outcomes (mortality, CD4 counts < 200 cells/mm3, viral loads > 400 copies/mL, and > 12-month gaps in follow-up) in the two years following the rainfall period. GEEs were used to investigate the association between relative rainfall and monthly numbers of unique visitors per HIV centre. RESULTS: Among 270,708 PWH across 386 HIV centres (67% female, median age 39 [IQR: 32-46]), lower rainfall than usual was associated with higher mortality (adjusted Hazard Ratio: 1.18 [95%CI: 1.07-1.32] per 10 percentile rainfall rank decrease) and unsuppressed viral loads (adjusted Odds Ratio: 1.05 [1.01-1.09]). Levels of rainfall were not strongly associated with CD4 counts < 200 cell/mm3 or > 12-month gaps in care. HIV centres in areas with less rainfall than usual had lower numbers of PWH visiting them (adjusted Rate Ratio: 0.80 [0.66-0.98] per 10 percentile rainfall rank decrease). CONCLUSIONS: Decreased rainfall could negatively impact on HIV treatment behaviours and outcomes. Further research is needed to explore the reasons for these effects. Interventions to mitigate the health impact of severe weather events are required.

Prevalence and trends of advanced HIV disease among antiretroviral therapy-naïve and antiretroviral therapy-experienced patients in South Africa between 2010-2021: a systematic review and meta-analysis.

BACKGROUND: Despite the significant progress made in South Africa in getting millions of individuals living with HIV into care, many patients still present or re-enter care with Advanced HIV Disease (AHD). We aimed to estimate the prevalence of AHD among ART-naive and ART-experienced patients in South Africa using studies published between January 2010 and May 2022. METHODS: We searched for relevant data on PubMed, CINAHL, Scopus and other sources, with a geographical filters limited to South Africa, up to May 31, 2022. Two reviewers conducted all screening, eligibility assessment, data extraction, and critical appraisal. We synthesized the data using the inverse-variance heterogeneity model and Freeman-Tukey transformation. We assessed heterogeneity using the I2 statistic and publication bias using the Egger and Begg's test. RESULTS: We identified 2,496 records, of which 53 met the eligibility criteria, involving 11,545,460 individuals. The pooled prevalence of AHD among ART-naive and ART-experienced patients was 43.45% (95% CI 40.1-46.8%, n = 53 studies) and 58.6% (95% CI 55.7 to 61.5%, n = 2) respectively. The time trend analysis showed a decline of 2% in the prevalence of AHD among ART-naive patients per year. However, given the high heterogeneity between studies, the pooled prevalence should be interpreted with caution. CONCLUSION: Despite HIV's evolution to a chronic disease, our findings show that the burden of AHD remains high among both ART-naive and ART-experienced patients in South Africa. This emphasizes the importance of regular measurement of CD4 cell count as an essential component of HIV care. In addition, providing innovative adherence support and interventions to retain ART patients in effective care is a crucial priority for those on ART.

Abacavir safety and effectiveness in young infants with HIV in South African observational cohorts.

BACKGROUND: WHO guidelines recommend abacavir in first-line antiretroviral treatment for children and neonates. However, there is no approved dose <3 months of age, and data in neonates are limited. METHODS: We included infants who initiated ART aged <3 months, between 2006 and 2019, in nine South African cohorts. In those who received abacavir or zidovudine, we described antiretroviral discontinuation rates; and 6- and 12-month viral suppression (<400 copies/mL). We compared infants aged <28 and ≥28 days, those weighing <3 and ≥3 kg. RESULTS: Overall 837/1643 infants (51%) received abacavir and 443 (27%) received zidovudine. Median (interquartile range, IQR) age was 52 days (23-71), CD4 percentage was 27.9 (19.2-38.0), and weight was 4.0 kg (3.0-4.7) at ART initiation. In those with ≥1 month's follow-up, 100/718 (14%) infants discontinued abacavir, at a median of 17.5 months (IQR 6.5-39.5). Abacavir discontinuations did not differ by age or weight category (p = 0.4 and 0.2, respectively); and were less frequent than zidovudine discontinuations (adjusted hazard ratio 0.14, 95% confidence interval 0.10-0.20). Viral suppression at 12 months occurred in 43/79 (54%) and 130/250 (52%) of those who started abacavir aged <28 and ≥28 days, respectively (p = 0.8); 11/19 (58%) and 31/60 (52%) in those who weighed <3 and ≥3 kg, respectively (p = 0.6); and 174/329 (53%) in those on abacavir versus 77/138 (56%) in those on zidovudine (adjusted odds ratio 1.8, 95% confidence interval 1.0-3.2). CONCLUSION: Our data suggest that abacavir may be used safely in infants <28 days old or who weigh <3 kg.

Economic evaluation of a cluster randomized, non-inferiority trial of differentiated service delivery models of HIV treatment in Zimbabwe.

About 85% of Zimbabwe's >1.4 million people living with HIV are on antiretroviral treatment (ART). Further expansion of its treatment program will require more efficient use of existing resources. Two promising strategies for reducing resource utilization per patient are multi-month medication dispensing and community-based service delivery. We evaluated the costs to providers and patients of community-based, multi-month ART delivery models in Zimbabwe. We used resource and outcome data from a cluster-randomized non-inferiority trial of three differentiated service delivery (DSD) models targeted to patients stable on ART: 3-month facility-based care (3MF), community ART refill groups (CAGs) with 3-month dispensing (3MC), and CAGs with 6-month dispensing (6MC). Using local unit costs, we estimated the annual cost in 2020 USD of providing HIV treatment per patient from the provider and patient perspectives. In the trial, retention at 12 months was 93.0% in the 3MF, 94.8% in the 3MC, and 95.5% in the 6MC arms. The total average annual cost of HIV treatment per patient was $187 (standard deviation $39), $178 ($30), and $167 ($39) in each of the three arms, respectively. The annual cost/patient was dominated by ART medications (79% in 3MF, 87% in 3MC; 92% in 6MC), followed by facility visits (12%, 5%, 5%, respectively) and viral load (8%, 8%, 2%, respectively). When costs were stratified by district, DSD models cost slightly less, with 6MC the least expensive in all districts. Savings were driven by differences in the number of facility visits made/year, as expected, and low uptake of annual viral load tests in the 6-month arm. The total annual cost to patients to obtain HIV care was $10.03 ($2) in the 3MF arm, $5.12 ($0.41) in the 3MC arm, and $4.40 ($0.39) in the 6MF arm. For stable ART patients in Zimbabwe, 3- and 6-month community-based multi-month dispensing models cost less for both providers and patients than 3-month facility-based care and had non-inferior outcomes.

Same-Day Antiretroviral Therapy Initiation as a Predictor of Loss to Follow-up and Viral Suppression Among People With Human Immunodeficiency Virus in Sub-Saharan Africa.

BACKGROUND: Treat-All guidelines recommend initiation of antiretroviral therapy (ART) for all people with HIV (PWH) on the day of diagnosis when possible, yet uncertainty exists about the impact of same-day ART initiation on subsequent care engagement. We examined the association of same-day ART initiation with loss to follow-up and viral suppression among patients in 11 sub-Saharan African countries. METHODS: We included ART-naive adult PWH from sites participating in the International epidemiology Databases to Evaluate AIDS (IeDEA) consortium who enrolled in care after Treat-All implementation and prior to January 2019. We used multivariable Cox regression to estimate the association between same-day ART initiation and loss to follow-up and Poisson regression to estimate the association between same-day ART initiation and 6-month viral suppression. RESULTS: Among 29 017 patients from 63 sites, 18 584 (64.0%) initiated ART on the day of enrollment. Same-day ART initiation was less likely among those with advanced HIV disease versus early-stage disease. Loss to follow-up was significantly lower among those initiating ART ≥1 day of enrollment, compared with same-day ART initiators (20.6% vs 27.7%; adjusted hazard ratio: .66; 95% CI .57-.76). No difference in viral suppression was observed by time to ART initiation (adjusted rate ratio: 1.00; 95% CI: .98-1.02). CONCLUSIONS: Patients initiating ART on the day of enrollment were more frequently lost to follow-up than those initiating later but were equally likely to be virally suppressed. Our findings support recent World Health Organization recommendations for providing tailored counseling and support to patients who accept an offer of same-day ART.

Effect of antiretroviral therapy care interruptions on mortality in children living with HIV.

OBJECTIVE: To evaluate the characteristics and outcomes of HIV-infected children that have care interruptions, during which the child's health status and use of medication is unknown. DESIGN: We included data on children initiating ART between 2004 and 2016 at less than 16 years old at 16 International Epidemiologic Databases to Evaluate AIDS Southern Africa cohorts. Children were classified as loss to follow up (LTFU) if they had not attended clinic for more than 180 days. Children had a care interruption if they were classified as LTFU, and subsequently returned to care. Children who died within 180 days of ART start were excluded. METHODS: The main outcome was all cause mortality. Two exposed groups were considered: those with a first care interruption within the first 6 months on ART, and those with a first care interruption after 6 months on ART. Adjusted hazard ratios were determined using a Cox regression model. RESULTS: Among 53 674 children included, 23 437 (44%) had a care interruption, of which 10 629 (20%) had a first care interruption within 6 months on ART and 12 808 (24%) had a first care interruption after 6 months on ART. Increased mortality was associated with a care interruption within 6 months on ART [adjusted hazard ratio (AHR) = 1.52, 95% CI 1.12-2.04] but not with a care interruption after 6 months on ART (AHR = 1.05, 95% CI 0.77-1.44). CONCLUSION: The findings suggest that strengthening retention of children in care in the early period after ART initiation is critical to improving paediatric ART outcomes.

Benefits and challenges of community-based multi-month dispensing of antiretroviral treatment in Zimbabwe: A qualitative study from a cluster randomized trial.

Sub-Saharan Africa carries the highest burden of HIV, with approximately 70% of all people living with HIV (PLWH) globally living in this region. The provision of antiretroviral treatment (ART) significantly affects already overburdened health systems, which need to accommodate large volumes of ART patients while facing a shortage of professional health workers, infrastructure challenges and medical resources. Finding alternative ways to provide routine services to PLWH has become significantly more urgent. Multi-month dispensing (MMD) of ART aims to improve access to treatment for PLWH, while also improving the efficiency of the health system. This study explores the experienced benefits and challenges of community-based MMD in order to make recommendations for future implementation efforts. Twenty focus group discussions were conducted with members of community ART refill groups (CARGs) who received 3-monthly or 6-monthy MMD. Individual interviews were also conducted with health providers. All interviews and focus group discussions took place between April and June 2019 conducted by research nurses in English, Shona or Ndebele. Multiple benefits of community-based MMD were reported, including decreased congestion in health facilities, improved service delivery, decline in staff burnout and increased time availability for CARG members due to less time spent at clinics, improved ART adherence and social support experienced amongst members of CARGs. Identified challenges included the possibility of being exposed to HIV-related stigma when belonging to a CARG, and low levels of medical supplies and ART stock at clinics. Recommendations were made by CARG members and health care workers on how CARGs could be improved and sustained in the future. Results from this study show that the implementation of community-based MMD holds multiple benefits at an individual and health facility level. Future recommendations include evaluating the feasibility of MMD among other vulnerable populations.

Virologic non-suppression and early loss to follow up among pregnant and non-pregnant adolescents aged 15-19 years initiating antiretroviral therapy in South Africa: a retrospective cohort study.

INTRODUCTION: Older adolescents aged 15-19 years continue to have high rates of loss to follow up (LTFU), and high rates of virologic non-suppression (VNS) compared to younger adolescents and adults. Adolescent females are at risk of pregnancy, which puts those living with HIV at a dual vulnerability. Our study assessed the factors associated with VNS and LTFU in older adolescents (including pregnant females) who initiated antiretroviral therapy (ART) in South Africa. METHODS: We included adolescents aged 15-19 years initiating ART between 2004 and 2019, with ≥ one viral load (VL) measurement between 4 and 24.5 months, and ≥ 6 months follow-up, from six South African cohorts of the International epidemiology Databases to Evaluate AIDS-Southern Africa (IeDEA-SA). We defined VNS as VL ≥400 copies/ml and LTFU as not being in care for ≥180 days from ART start and not known as transferred out of the clinic or dead in the first 24 months on ART. We examined factors associated with VNS and LTFU using Fine&Gray competing risk models. RESULTS: We included a total of 2733 adolescents, 415 (15.2%) males, median (IQR) age at ART start of 18.6 (17.3, 19.4) years. Among females, 585/2318 (25.2%) were pregnant. Over the 24-month follow-up, 424 (15.5%) of all adolescents experienced VNS: range (11.1% pregnant females and 20.5% males). Over half of all adolescents were LTFU before any other event could occur. The hazard of VNS reduced with increasing age and CD4 count above 200 cells/µl at ART initiation among all adolescents having adjusted for all measured patient characteristics [adjusted sub-distribution hazard ratio (aSHR) 19 vs. 15 years: 0.50 (95% CI: 0.36, 0.68), aSHR: >500 vs. ≤200 cells/µl: 0.22 (95% CI: 0.16, 0.31)]. The effect of CD4 count persisted in pregnant females. Increasing age and CD4 count >200 cells/µl were risk factors for LTFU among all adolescents. CONCLUSIONS: Older adolescents had a high risk of LTFU shortly after ART start and a low risk of VNS, especially those initiating treatment during pregnancy. Interventions addressing adherence and retention should be incorporated into adolescent-friendly services to prevent VNS and LTFU and endeavour to trace lost adolescents as soon as they are identified.

Community-based differentiated service delivery models incorporating multi-month dispensing of antiretroviral treatment for newly stable people living with HIV receiving single annual clinical visits: a pooled analysis of two cluster-randomized trials in southern Africa.

INTRODUCTION: Differentiated service delivery (DSD) models for HIV treatment decrease health facility visit frequency and limit healthcare facility-based exposure to severe acute respiratory syndrome coronavirus 2. However, two important evidence gaps include understanding DSD effectiveness amongst clients commencing DSD within 12 months of antiretroviral treatment (ART) initiation and amongst clients receiving only single annual clinical consultations. To investigate these, we pooled data from two cluster-randomized trials investigating community-based DSD in Zimbabwe and Lesotho. METHODS: Individual-level participant data of newly stable adults enrolled between 6 and 12 months after ART initiation were pooled. Both trials (conducted between August 2017 and July 2019) had three arms: Standard-of-care three-monthly ART provision at healthcare facilities (SoC, control); ART provided three-monthly in community ART groups (CAGs) (3MC) and ART provided six-monthly in either CAGs or at community-distribution points (6MC). Clinical visits were three-monthly in SoC and annually in intervention arms. The primary outcome was retention in care and secondary outcomes were viral suppression (VS) and number of unscheduled facility visits 12 months after enrolment. Individual-level regression analyses were conducted by intention-to-treat specifying for clustering and adjusted for country. RESULTS AND DISCUSSION: A total of 599 participants were included; 212 (35.4%), 128 (21.4%) and 259 (43.2%) in SoC, 3MC and 6MC, respectively. Few participants aged <25 years were included (n = 32). After 12 months, 198 (93.4%), 123 (96.1%) and 248 (95.8%) were retained in SoC, 3MC and 6MC, respectively. Retention in 3MC was superior versus SoC, adjusted risk difference (aRD) = 4.6% (95% CI: 0.7%-8.5%). Retention in 6MC was non-inferior versus SoC, aRD = 1.7% (95% CI: -2.5%-5.9%) (prespecified non-inferiority aRD margin -3.25%). VS was similar between arms, 99.3, 98.6 and 98.1% in SoC, 3MC and 6MC, respectively. Adjusted risk ratio's for VS were 0.98 (95% CI: 0.92-1.03) for 3MC versus SoC, and 0.98 (CI: 0.95-1.00) for 6MC versus SoC. Unscheduled clinic visits were not increased in intervention arms: incidence rate ratio = 0.53 (CI: 0.16-1.80) for 3MC versus SoC; and 0.82 (CI: 0.25-2.79) for 6MC versus SoC. CONCLUSIONS: Community-based DSD incorporating three- and six-monthly ART refills and single annual clinical visits were at least non-inferior to standard facility-based care amongst newly stable ART clients aged ≥25 years. ClinicalTrials.gov: NCT03238846 & NCT03438370.

Out-of-Facility Multimonth Dispensing of Antiretroviral Treatment: A Pooled Analysis Using Individual Patient Data From Cluster-Randomized Trials in Southern Africa.

BACKGROUND: Out-of-facility multi-month dispensing (MMD) is a differentiated service delivery model which provides antiretroviral treatment (ART) at intervals of up to 6 monthly in the community. Limited randomized evidence investigating out-of-facility MMD is available. We evaluated participant outcomes and compared out-of-facility MMD models using data from cluster-randomized trials in Southern Africa. SETTING: Eight districts in Zimbabwe and Lesotho. METHODS: Individual-level participant data from 2 cluster-randomized trials that included stable adults receiving ART at 60 facilities were pooled. Both trials had 3 arms: ART collected 3-monthly at healthcare facilities (3MF, control); ART provided three-monthly in community ART groups (CAGs) (3MC); and ART provided 6-monthly in either CAGs or on an individual provider-patient basis (6MC). Participant retention, viral suppression and incidence of unscheduled facility visits were compared. RESULTS: Ten thousand one hundred thirty-six participants were included, 3817 (37.7%), 2893 (28.5%) and 3426 (33.8%) in arms 3MF, 3MC and 6MC, respectively. After 12 months, retention was non-inferior for 3MC (95.7%) vs. 3MF (95.0%) {adjusted risk difference (aRD) = 0.3 [95% confidence interval (CI): -0.8 to 1.4]}; and 6MC (95.1%) vs. 3MF [aRD = -0.2 (95% CI: -1.4 to 1.0)]. Retention was greater amongst intervention arm participants in CAGs versus 6MC participants not in CAGs, aRD = 1.5% (95% CI: 0.2% to 2.9%). Viral suppression was excellent (≥98%) and unscheduled facility visits were not increased in the intervention arms. CONCLUSIONS: Three and 6-monthly out-of-facility MMD was non-inferior versus facility-based care for stable ART patients. Out-of-facility 6-monthly MMD should incorporate small group peer support whenever possible. CLINICALTRIAL REGISTRATION: ClinicalTrials.gov NCT03238846 and NCT03438370.

Delivering an integrated sexual reproductive health and rights and HIV programme to high-school adolescents in a resource-constrained setting.

Southern Africa remains the epicentre of the human immunodeficiency virus (HIV) epidemic with AIDS the leading cause of death amongst adolescents. Poor policy translation, inadequate programme implementation and fragmentation of services contribute to adolescents' poor access to sexual and reproductive health and rights (SRHR) services. This study assessed an integrated, school-based SRHR and HIV programme, modelled on the South African Integrated School Health Policy in a rural, high HIV-prevalence district. A retrospective cohort study of 1260 high-school learners was undertaken to assess programme uptake, change in HIV knowledge and behaviour and the determinants of barrier-methods use at last sexual intercourse. Programme uptake increased (2%-89%; P�<�0.001) over a 16-month period, teenage-pregnancy rates declined (14%-3%; P�<�0.050) and accurate knowledge about HIV transmission through infected blood improved (78.3%-93.8%; P�<�0.050), a year later. Post-intervention, attending a clinic perceived as adolescent-friendly increased the odds of barrier-methods use during the last sexual encounter (aOR=1.85; 95% CI: 1.31-2.60), whilst being female (aOR=0.69; 95% CI: 0.48-0.99), <15 years (aOR=0.44; 95% CI: 0.24-0.80), or having >5 sexual partners in the last year (aOR=0.59; 95% CI: 0.38-0.91) reduced the odds. This study shows that the unmet SRHR needs of under-served adolescents can be addressed through integrated, school-based SRHR programmes.

Economic evaluation of differentiated service delivery models for HIV treatment in Lesotho: costs to providers and patients.

INTRODUCTION: Lesotho, the country with the second-highest HIV/AIDS prevalence (23.6%) in the world, has made considerable progress towards achieving the "95-95-95" UNAIDS targets, but recent success in improving treatment access to all known HIV positive individuals has severely strained existing healthcare infrastructure, financial and human resources. Lesotho also faces the challenge of a largely rural population who incur a significant time and financial burden to visit healthcare facilities. Using data from a cluster-randomized non-inferiority trial conducted between August 2017 and July 2019, we evaluated costs to providers and costs to patients of community-based differentiated models of multi-month delivery of antiretroviral therapy (ART) in Lesotho. METHODS: The trial of multi-month dispensing compared 12-month retention in care among three arms: conventional care, which required quarterly facility visits and ART dispensation (3MF); three-month community adherence groups (CAGs) (3MC) and six-month community ART distribution (6MCD). We first estimated the average total annual cost of providing HIV care and treatment followed by the total cost per patient retained 12 months after entry for each arm, using resource utilization data from the trial and local unit costs. We then estimated the average annual cost to patients in each arm with self-reported questionnaire data. RESULTS: The average total annual cost of providing HIV care and treatment per patient was the highest in the 3MF arm ($122.28, standard deviation [SD] $23.91), followed by 3MC ($114.20, SD $23.03) and the 6MCD arm ($112.58, SD $21.44). Per patient retained in care, the average provider cost was $125.99 (SD $24.64) in the 3MF arm and 6% to 8% less for the other two arms ($118.38, SD $23.87 and $118.83, SD $22.63 for the 3MC and 6MCD respectively). There was a large reduction in patient costs for both differentiated service delivery arms: from $44.42 (SD $12.06) annually in the 3MF arm to $16.34 (SD $5.11) annually in the 3MC (63% reduction) and $18.77 (SD $8.31) annually in 6MCD arm (58% reduction). CONCLUSIONS: Community-based, multi-month models of ART in Lesotho are likely to produce small cost savings to treatment providers and large savings to patients in Lesotho. Patient cost savings may support long-term adherence and retention in care.

A mechanistic model for long-term immunological outcomes in South African HIV-infected children and adults receiving ART.

Long-term effects of the growing population of HIV-treated people in Southern Africa on individuals and the public health sector at large are not yet understood. This study proposes a novel 'ratio' model that relates CD4+ T-cell counts of HIV-infected individuals to the CD4+ count reference values from healthy populations. We use mixed-effects regression to fit the model to data from 1616 children (median age 4.3 years at ART initiation) and 14,542 adults (median age 36 years at ART initiation). We found that the scaled carrying capacity, maximum CD4+ count relative to an HIV-negative individual of similar age, and baseline scaled CD4+ counts were closer to healthy values in children than in adults. Post-ART initiation, CD4+ growth rate was inversely correlated with baseline CD4+ T-cell counts, and consequently higher in adults than children. Our results highlight the impacts of age on dynamics of the immune system of healthy and HIV-infected individuals.

The human immunodeficiency virus (HIV) remains an ongoing global pandemic. There is currently no cure for HIV, but antiretroviral therapies can keep the virus in check and allow individuals with HIV to live longer, healthier lives. These drugs work in two ways. They block the ability of the virus to multiply and they allow numbers of an important type of infection-fighting cell called CD4+ T cells to rebound. As more patients with HIV survive and transition from one life stage to the next, it is critical to understand how long-term antiretroviral therapies will affect normal age-related changes in their immune systems. The health of an immune system can be evaluated by looking at the number of CD4+ T cells an individual has, though this will vary by age and location. Clinicians use the same metrics to assess the immune health of individuals with HIV, however, as they age, it becomes a challenge to identify if a patient's immune system recovers normally or insufficiently. Thus, learning more about age-related differences in CD4+ T cells in people living with HIV may help improve their care. Using data from 1,616 children and 14,542 adults from South Africa, Ujeneza et al. created a simple mathematical model that can compare the immune system of person with HIV with the immune system of a similarly aged healthy individual. The model shows that among individuals with HIV receiving antiretroviral therapies, children have CD4+ T-cell numbers that are closest to the numbers seen in healthy individuals of the same age. This suggests that children may be more able to recover immune system function than adults after beginning treatment. Children also start antiretroviral therapies before their immune system has been severely damaged, while adults tend to start treatment much later when they have fewer CD4+ T cells left. Ujeneza et al. show that the fewer CD4+ T cells a person has when they start treatment, the faster the number of these cells grows after starting treatment. This suggests that the more damaged the immune system is, the harder it works to recover. This reinforces the need to identify people infected with HIV as soon as possible through testing and to begin treatment promptly. The new model may help clinicians and policy makers develop screening and treatment protocols tailored to the specific needs of children and adults living with HIV.

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.

From Easing Lockdowns to Scaling Up Community-based Coronavirus Disease 2019 Screening, Testing, and Contact Tracing in Africa-Shared Approaches, Innovations, and Challenges to Minimize Morbidity and Mortality.

The arrival of coronavirus disease 2019 (COVID-19) on the African continent resulted in a range of lockdown measures that curtailed the spread of the infection but caused economic hardship. African countries now face difficult choices regarding easing of lockdowns and sustaining effective public health control measures and surveillance. Pandemic control will require efficient community screening, testing, and contact tracing; behavioral change interventions; adequate resources; and well-supported, community-based teams of trained, protected personnel. We discuss COVID-19 control approaches in selected African countries and the need for shared, affordable, innovative methods to overcome challenges and minimize mortality. This crisis presents a unique opportunity to align COVID-19 services with those already in place for human immunodeficiency virus, tuberculosis, malaria, and non communicable diseases through mobilization of Africa's interprofessional healthcare workforce. By addressing the challenges, the detrimental effect of the COVID-19 pandemic on African citizens can be minimized.

Recording of HIV viral loads and viral suppression in South African patients receiving antiretroviral treatment: a multicentre cohort study.

BACKGROUND: Viral suppression in patients on antiretroviral treatment (ART) is critical to reducing HIV transmission and HIV-related mortality. Although many studies have evaluated factors associated with viral suppression, few have assessed the extent to which missing viral load data may bias results. METHODS: We included data on all patients starting ART from 2005 to 2019 in eight South African cohorts participating in the International epidemiology Databases to Evaluate AIDS (IeDEA) collaboration. Multivariable logistic regression models were used to determine factors associated with having a viral load measurement within 2 months of a scheduled testing date and having a viral load <400 RNA copies/ml ('viral suppression'). In a sensitivity analysis, missing viral loads were imputed based on patients' clinical and demographic characteristics and outcomes. RESULTS: Viral load tests were scheduled in 603,549 and 77,423 intervals in adults and children, respectively, but test results were recorded in only 40.7% and 41.2%, respectively. The proportion of recorded results suppressed was 85.7% in adults and 72.4% in children. After imputation of missing viral load measurements, viral suppression reduced slightly in adults (85.3%) and increased in children (73.2%). Predictors of virological suppression in adults, which included female sex, older age, higher baseline CD4+ T-cell count and recent testing year, were similar in the main analysis and after imputing missing viral loads. CONCLUSIONS: Although viral load information was frequently missing in the South African setting, estimates of viral suppression and predictors of viral suppression did not change substantially after adjusting for missing data.

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.

Twelve-Month Outcomes of Community-Based Differentiated Models of Multimonth Dispensing of ART Among Stable HIV-Infected Adults in Lesotho: A Cluster-Randomized Noninferiority Trial.

BACKGROUND: Lesotho adopted the test-and-treat approach for HIV treatment in June 2016, which increased antiretroviral treatment (ART) clinic volume. We evaluated community-based vs. facility-based differentiated models of multimonth dispensing of ART among stable HIV-infected adults in Lesotho. METHODS: Thirty facilities were randomized to 3 arms, facility 3-monthly ART (3MF) (control), community ART groups (3MC), and 6-monthly community distribution points (6MCD). We estimated risk differences (RDs) between arms using population-averaged generalized estimating equations, controlling for baseline imbalances and specifying for clustering. The primary outcome was retention in ART care by intention-to-treat and virologic suppression as a secondary outcome (ClinicalTrials.gov: NCT03438370). RESULTS: A total of 5,336 participants were enrolled, with 1898, 1558, and 1880 in 3MF, 3MC, and 6MCD, respectively. Retention in ART care was not different across arms and achieved the prespecified noninferiority limit (-3.25%) between 3MC vs. 3MF (control); 6MCD vs. 3MF; and 6MCD vs. 3MC, adjusted RD = -0.1% [95% confidence interval (CI): -1.6% to 1.5%], adjusted RD = -1.3% (95% CI: -3.0% to 0.5%), and adjusted RD = -1.2% (95% CI: -2.9% to 0.5%), respectively. After 12 months, 98.6% (n = 1503), 98.1% (n = 1126), and 98.3% (n = 1285) were virally load (VL) suppressed in 3MF, 3MC, and 6MCD, respectively. There were no differences in VL between 3MC vs. control and 6MCD vs. control, risk ratio (RR) = 1.00 (95% CI: 0.98 to 1.01) and RR = 1.00 (95% CI: 0.98 to 1.01), respectively. CONCLUSIONS: There were no differences in retention and VL suppression for stable HIV-infected participants receiving multimonth dispensing of ART within community-based differentiated models when compared with the facility-based standard-of-care model.

Trends in CD4 and viral load testing 2005 to 2018: multi-cohort study of people living with HIV in Southern Africa.

INTRODUCTION: The World Health Organization (WHO) recommends a CD4 cell count before starting antiretroviral therapy (ART) to detect advanced HIV disease, and routine viral load (VL) testing following ART initiation to detect treatment failure. Donor support for CD4 testing has declined to prioritize access to VL monitoring. We examined trends in CD4 and VL testing among adults (≥15 years of age) starting ART in Southern Africa. METHODS: We analysed data from 14 HIV treatment programmes in Lesotho, Malawi, Mozambique, South Africa, Zambia and Zimbabwe in 2005 to 2018. We examined the frequency of CD4 and VL testing, the percentage of adults with CD4 or VL tests, and among those having a test, the percentage starting ART with advanced HIV disease (CD4 count <200 cells/mm3 ) or failing to suppress viral replication (>1000 HIV-RNA copies/mL) after ART initiation. We used mixed effect logistic regression to assess time trends adjusted for age and sex. RESULTS: Among 502,456 adults, the percentage with CD4 testing at ART initiation decreased from a high of 78.1% in 2008 to a low of 38.0% in 2017; the probability declined by 14% each year (odds ratio (OR) 0.86; 95% CI 0.86 to 0.86). Frequency of CD4 testing also declined. The percentage starting ART with advanced HIV disease declined from 83.3% in 2005 to 23.5% in 2018; each year the probability declined by 20% (OR 0.80; 95% CI 0.80 to 0.81). VL testing after starting ART varied; 61.0% of adults in South Africa and 10.7% in Malawi were tested, but fewer than 2% were tested in the other four countries. The probability of VL testing after ART start increased only modestly each year (OR 1.06; 95% CI 1.05 to 1.06). The percentage with unsuppressed VL was 8.6%. There was no evidence of a decrease in unsuppressed VL over time (OR 1.00; 95% CI 0.99 to 1.01). CONCLUSIONS: CD4 cell counting declined over time, including testing at the start of ART, despite the fact that many patients still initiated ART with advanced HIV disease. Without CD4 testing and expanded VL testing many patients with advanced HIV disease and treatment failure may go undetected, threatening the effectiveness of ART in sub-Saharan Africa.