The early period of the COVID-19 pandemic limited access to HIV services for children and adolescents living with HIV (C/ALHIV). To determine progress in providing care and treatment services, we describe viral load coverage (VLC) and suppression (VLS) (<1000 copies/ mL) rates during the COVID-19 pandemic in 12 United States President's Emergency Plan for AIDS Relief (PEPFAR)-supported countries. Data for children (0-9 years) and adolescents (10-19 years) on VLC and VLS were analyzed for 12 sub-Saharan African (SSA) countries between 2019 (pre-COVID-19) and 2020 (during COVID-19). We report the number of viral load (VL) tests, and percent change in VLC and VLS for patients on ART. For 12 countries, 181,192 children had a VL test during the pre-COVID-19 period compared with 177,683 December 2020 during COVID-19. VLC decreased from 68.8% to 68.3% overall. However, 9 countries experienced an increase ranging from a 0.7%-point increase for Tanzania and Zimbabwe to a 15.3%-point increase for Nigeria. VLS increased for all countries from 71.2% to 77.7%. For adolescents the number with a VL test increased from 377,342 to 402,792. VLC decreased from 77.4% to 77.1%. However, 7 countries experienced an increase ranging from 1.8% for Mozambique to 13.8% for Cameroon. VLS increased for all countries from 76.8% to 83.8%. This analysis shows variation in HIV VLC across 12 SSA countries. VLS consistently improved across all countries demonstrating resilience of countries during 2020. Countries should continue to improve clinical outcomes from C/ALHIV despite service disruptions that may occur during pandemic response.

The number of children newly infected with HIV dropped by 50%, from 320 000 in 2010 to 160 000 in 2021. Despite progress, ongoing gaps persist in diagnosis, continuity of care, and treatment optimization. In response, the United States President's Emergency Plan for AIDS Relief created the Faith-based Action for Scaling-Up Testing and Treatment for Epidemic Response (FASTER). Faith-based Action for Scaling-Up Testing and Treatment for Epidemic Response addressed gaps in countries with the highest unmet need by working with government to operationalize innovative interventions and ensure alignment with national priorities and with communities living with HIV to ensure the change was community-led. Between 2019 and 2021, FASTER's interventions were incorporated into national policies, absorbed by Ministries of Health, and taken up in subsequent awards and country operating plans. Continued effort is needed to sustain gains made during the FASTER initiative and to continue scaling evidence-based interventions to ensure that children and adolescents are not left behind in the global HIV response.

Background: This manuscript aimed to examine treatment outcomes of HIV-positive children and adolescents. Methods: We retrospectively analyzed data of a sample of patients aged 0-19 years who initiated ART (October 2007-September 2016) in participating sites in 30 states and the Federal Capital Territory in Nigeria. Results: Among 4006 patients alive at the end of the follow up period, 138 (3.4%) were LTFU. Adolescents had a significantly higher risk of being LTFU than children aged 3-5 years (HR 2.47 [95% CI 1.40-4.34]). Patients with advanced disease had a significantly higher risk of being LTFU (Stage IV HR, 3.66 [95% CI: 2.00-6.68]). On average, optimal ART refill adherence was met by 67.3% of patients. Conclusion: Our findings suggest that focusing on preventing and managing advanced disease and interventions supporting adolescents when transferring to adult care is warranted.

INTRODUCTION: Because of low pediatric HIV prevalence, more tests are needed to find 1 HIV-positive child compared with adults. In Uganda, the number needed to test (NNT) to find 1 new HIV-positive child was 64 in outpatient departments (OPDs) and 31 through index testing. We aimed to develop and validate a pediatric (1.5-14 years) screening tool to optimize testing approaches. METHODS: Phase 1 evaluated the performance of 10 screening questions in 14 OPDs using a variable selection algorithm to evaluate combinations of screening questions. Using logistic regression, we identified the number of screening questions with the best predictive accuracy using the receiver operation characteristic curve. Phase 2 validated the proposed tool in 15 OPDs and 7 orphan and vulnerable children programs. We estimated sensitivity, specificity, and NNT accounting for intercluster correlations. RESULTS: A total of 3482 children were enrolled. The optimal model included reported HIV-positive maternal status or 2/5 symptoms (sickly in the last 3 months, recurring skin problems, weight loss, not growing well, and history of tuberculosis). The proposed tool had sensitivity of 83.6% [95% confidence interval (CI): 68.1 to 92.4] and specificity of 62.5% (95% CI: 55.0 to 69.4). The tool was validated in a sample of 11,342 children; sensitivity was 87.8% (95% CI: 80.9 to 92.5) and specificity 62.6% (95% CI: 54.8 to 69.7) across OPDs and community sites. In OPDs, sensitivity was 88.1% (95% CI: 80.8 to 92.8) and specificity 69.0% (95% CI: 61.9 to 75.3). The NNT was 43 (95% CI: 28 to 67) across settings and 28 (95% CI: 20 to 38) for OPD. CONCLUSIONS: This HIV screening tool has high sensitivity and reasonable specificity, increasing testing efficiency and yield for children and adolescents.

BACKGROUND: Poor growth and metabolic disturbances remain concerns for children living with HIV (CLHIV). We describe the impact of viral load (VL) on growth and lipid outcomes in South African CLHIV <12 years initiating World Health Organization recommended first-line antiretroviral therapy (ART) from 2012 to 2015. METHODS: Z scores for length-for-age (LAZ), weight-for-age (WAZ) and body mass index-for-age were calculated. Lipids (total cholesterol, low-density lipoprotein and high-density lipoprotein) were measured. Hemoglobin A1C ≥5.8 was defined as at risk for type 2 diabetes. Mixed effects models were used to assess the association of VL at ART initiation with Z scores and lipids over time. RESULTS: Of 241 CLHIV, 151 (63%) were <3 years initiating LPV/r-based ART and 90 (37%) were ≥3 years initiating EFV-based ART. Among CLHIV <3 years, higher VL at ART initiation was associated with lower mean LAZ (ß: -0.30, P=0.03), WAZ (ß: -0.32, P=0.01) and low-density lipoprotein (ß: -6.45, P=0.03) over time. Among CLHIV ≥3, a log 10 increase in pretreatment VL was associated with lower mean LAZ (ß: -0.29, P=0.07) trending towards significance and lower WAZ (ß: -0.32, P=0.05) as well as with more rapid increases in LAZ (ß: 0.14 per year, P=0.01) and WAZ (ß: 0.19 per year, P=0.04). Thirty percent of CLHIV were at risk for type 2 diabetes at ART initiation. CONCLUSIONS: CLHIV initiating ART <3 years exhibited positive gains in growth and lipids, though high viremia at ART initiation was associated with persistently low growth and lipids, underscoring the need for early diagnosis and rapid treatment initiation. Future studies assessing the long-term cardiometabolic impact of these findings are warranted.

BACKGROUND: Children living with HIV (CLHIV) receiving antiretroviral treatment (ART) in resource limited settings are susceptible to high rates of acquired HIV drug resistance (HIVDR), but few studies include children initiating age-appropriate WHO-recommended first-line regimens. We report data from a cohort of ART-naïve South African children who initiated first-line ART. METHODS: ART-eligible CLHIV aged 0-12 years were enrolled from 2012 to 2014 at five public South African facilities and followed for up to 24 months. Enrolled CLHIV received standard of care WHO-recommended first-line ART. At the final study visit, a dried blood spot sample was obtained for viral load and genotypic resistance testing. RESULTS: Among 72 successfully genotyped CLHIV, 49 (68.1%) received ABC/3TC/LPV/r, and 23 (31.9%) received ABC/3TC/EFV. All but 2 children on ABC/3TC/LPV/r were <3 years and all CLHIV on ABC/3TC/EFV were ≥3 years. Overall, 80.6% (58/72) had at least one drug resistance mutation (DRM). DRMs to NNRTIs and NRTIs were found among 65% and 51% of all CLHIV, respectively, with no statistical difference by ART regimen. More CLHIV on ABC/3TC/EFV, 47.8% (11/23), were found to have 0 or only 1 effective antiretroviral drug remaining in their current regimen compared to 8.2% (4/49) on ABC/3TC/LPV/r. CONCLUSIONS: High levels of NNRTI and NRTI DRMs among CLHIV receiving ABC/3TC/LPV/r suggests a lasting impact of failed PMTCT interventions on DRMs. However, drug susceptibility analysis, reveals that CLHIV with detectable viremia on ABC/3TC/LPV/r are more likely to have maintained at least two effective agents on their current HIV regimen than those on ABC/3TC/EFV.

BACKGROUND: In 2012, Rwanda introduced a Treat All approach for HIV-infected children younger than 5 years. We compared antiretroviral therapy (ART) initiation, outcomes, and retention, before and after this change. METHODS: We conducted a retrospective study of children enrolled into care between June 2009 and December 2011 [Before Treat All (BTA) cohort] and between July 2012 and April 2015 [Treat All (TA) cohort]. SETTING: Medical records of a nationally representative sample were abstracted for all eligible aged 18-60 months from 100 Rwandan public health facilities. RESULTS: We abstracted 374 medical records: 227 in the BTA and 147 in the TA cohorts. Mean (SD) age at enrollment was [3 years (1.1)]. Among BTA, 59% initiated ART within 1 year, vs. 89% in the TA cohort. Median time to ART initiation was 68 days (interquartile range 14-494) for BTA and 9 days (interquartile range 0-28) for TA (P < 0.0001), with 9 (5%) undergoing same-day initiation in BTA compared with 50 (37%) in TA (P < 0.0001). Before ART initiation, 59% in the BTA reported at least one health condition compared with 35% in the TA cohort (P < 0.0001). Although overall loss to follow-up was similar between cohorts (BTA: 13%, TA: 8%, P = 0.18), loss to follow-up before ART was significantly higher in the BTA (8%) compared with the TA cohort (2%) (P = 0.02). CONCLUSIONS: Nearly 90% of Rwandan children started on ART within 1 year of enrollment, most within 1 month, with greater than 90% retention after implementation of TA. TA was also associated with fewer morbidities.

We report data from an observational cohort of South African children living with HIV <12 years of age eligible for fast track ART (rapid) initiation. We found that less than half those eligible for rapid ART initiation based on immunologic and disease status started treatment within one week.

We report data from an observational cohort of South African children living with HIV <12 years of age eligible for fast track ART (rapid) initiation. We found that less than half those eligible for rapid ART initiation based on immunologic and disease status started treatment within one week.

INTRODUCTION: There are limited data on viral suppression (VS) in children with HIV receiving antiretroviral therapy (ART) in routine care in low-resource settings. We examined VS in a cohort of children initiating ART in routine HIV care in Eastern Cape Province, South Africa. METHODS: The Pediatric Enhanced Surveillance Study enrolled HIV-infected ART eligibility children zero to twelve years at five health facilities from 2012 to 2014. All children received routine HIV care and treatment services and attended quarterly study visits for up to 24 months. Time to VS among those starting treatment was measured from ART start date to first viral load (VL) result <1000 and VL <50 copies/mL using competing risk estimators (death as competing risk). Multivariable sub-distributional hazards models examined characteristics associated with VS and VL rebound following suppression among those with a VL >30 days after the VS date. RESULTS: Of 397 children enrolled, 349 (87.9%) started ART: 118 (33.8%) children age <12 months, 122 (35.0%) one to five years and 109 (31.2%) six to twelve years. At study enrolment, median weight-for-age z-score (WAZ) was -1.7 (interquartile range (IQR):-3.1 to -0.4) and median log VL was 5.6 (IQR: 5.0 to 6.2). Cumulative incidence of VS <1000 copies/mL at six, twelve and twenty-four months was 57.6% (95% CI 52.1 to 62.7), 78.7% (95% CI 73.7 to 82.9) and 84.0% (95% CI 78.9 to 87.9); for VS <50 copies/mL: 40.3% (95% CI 35.0 to 45.5), 63.9% (95% CI 58.2 to 69.0) and 72.9% (95% CI 66.9 to 78.0). At 12 months only 46.6% (95% CI 36.6 to 56.0) of children <12 months had achieved VS <50 copies/mL compared to 76.9% (95% CI 67.9 to 83.7) of children six to twelve years (p < 0.001). In multivariable models, children with VL >1 million copies/mL at ART initiation were half as likely to achieve VS <50 copies/mL (adjusted sub-distributional hazards 0.50; 95% CI 0.36 to 0.71). Among children achieving VS <50 copies/mL, 37 (19.7%) had VL 50 to 1000 copies/mL and 31 (16.5%) had a VL >1000 copies/mL. Children <12 months had twofold increased risk of VL rebound to VL >1000 copies/mL (adjusted relative risk 2.03, 95% CI: 1.10 to 3.74) compared with six to twelve year olds. CONCLUSIONS: We found suboptimal VS among South African children initiating treatment and high proportions experiencing VL rebound, particularly among younger children. Greater efforts are needed to ensure that all children achieve optimal outcomes.

Many children living with HIV in resource-limited settings remain undiagnosed and at risk for HIV-related mortality and morbidity. This article describes 5 key strategies for strengthening HIV case finding and linkage to treatment for infants, children, and adolescents. These strategies result from lessons learned during the Accelerating Children's HIV/AIDS Treatment Initiative, a public-private partnership between the President's Emergency Plan for AIDS Relief (PEPFAR) and the Children's Investment Fund Foundation (CIFF). The 5 strategies include (1) implementing a targeted mix of HIV case finding approaches (eg, provider-initiated testing and counseling within health facilities, optimization of early infant diagnosis, index family testing, and integration of HIV testing within key population and orphan and vulnerable children programs); (2) addressing the unique needs of adolescents; (3) collecting and using data for program improvement; (4) fostering a supportive political and community environment; and (5) investing in health system-strengthening activities. Continued advocacy and global investments are required to eliminate AIDS-related deaths among children and adolescents.

Children living with human immunodeficiency virus (HIV) in low- and middle-income countries (LMICs) experience higher rates of virologic failure than adults. Human immunodeficiency virus drug resistance (HIVDR) plays a major role in pediatric HIV treatment failure because nonsuppressive maternal antiretroviral therapy (ART) during pregnancy and breastfeeding as well as infant antiretroviral prophylaxis lead to high rates of pretreatment drug resistance to regimens most commonly used in children living with HIV. Lack of availability of durable, potent drugs in child-friendly formulations in LMICs and adherence difficulties contribute to acquired drug resistance during treatment. Optimizing drugs available for treating children living with HIV in LMICs, providing robust adherence support, and ensuring virologic monitoring for children receiving ART are essential for reducing HIVDR and improving treatment outcomes for children living with HIV in LMICs.

A survey of 461 HIV-infected Kenyan children receiving antiretroviral therapy found 143 (31%) failing virologically. Drug resistance mutations were found in 121; 37 had L74V/I mutations, with 95% receiving abacavir-containing regimens. L74V/I was associated with current abacavir usage (p=0.0001). L74V/I may be more prevalent than previously realized in children failing abacavir-containing regimens, even when time on treatment has been short. Ongoing rigorous pediatric drug resistance surveillance is needed.

BACKGROUND: Early antiretroviral therapy (ART) initiation in HIV-infected infants significantly improves survival but is often delayed in resource-limited settings. Adding HIV testing of infants at birth to the current recommendation of testing at age 4-6 weeks may improve testing rates and decrease time to ART initiation. We modeled the benefit of adding HIV testing at birth to the current 6-week testing algorithm. METHODS: Microsoft Excel was used to create a decision-tree model of the care continuum for the estimated 1,400,000 HIV-infected women and their infants in sub-Saharan Africa in 2012. The model assumed average published rates for facility births (42.9%), prevention of mother-to-child HIV transmission utilization (63%), mother-to-child-transmission rates based on prevention of mother-to-child HIV transmission regimen (5%-40%), return of test results (41%), enrollment in HIV care (52%), and ART initiation (54%). We conducted sensitivity analyses to model the impact of key variables and applied the model to specific country examples. RESULTS: Adding HIV testing at birth would increase the number of infants on ART by 204% by age 18 months. The greatest increase is seen in early ART initiations (543% by age 3 months). The increase would lead to a corresponding increase in survival at 12 months of age, with 5108 fewer infant deaths (44,550, versus 49,658). CONCLUSION: Adding HIV testing at birth has the potential to improve the number and timing of ART initiation of HIV-infected infants, leading to a decrease in infant mortality. Using this model, countries should investigate a combination of HIV testing at birth and during the early infant period.

The global commitment to reach the United Nations 90-90-90 targets will require a tremendous effort to almost double the number of HIV-infected individuals receiving antiretroviral treatment (ART), from 15.8 to 29.9 million, in the next 4 years [1]. In sub-Saharan Africa alone, ART initiation for an additional 6.2 million persons will be needed to reach this target. Given the infrastructure constraints and healthcare worker shortages in many resource-limited settings, there is increasing recognition that traditional facility-based models of clinician-led HIV service delivery will not be feasible with the increase in patient volume. In response, multiple proposed alternative service delivery models have been developed that center on transitioning at least some aspects of care out of health facilities into the community to decongest clinics and maximize the use of limited healthcare worker resources [2]. | Several commonly employed service delivery modifications have documented success in improving patient outcomes. One of the most common focuses on multimonth prescribing in which pharmacies dispense more than a month's supply of ART, requiring fewer patient visits to collect medications [2]. Another employs alternative ART delivery points; for example, HIV-infected patients can collect their ART at a community pharmacy/drug delivery site or have ART delivered to their homes by a cadre of lay workers [3]. A third model reduces the number of required follow-up visits for certain patients, most often those considered ‘stable’ by criteria such as time on ART and/or viral load suppression. These patients are seen at the facility by medical staff only once or twice per year [4]. Other models employ community adherence clubs, where groups of HIV-infected individuals receive all of their medication and care in the community on a particular day [5]. Finally, community ART groups rely on the member of the group to collect monthly antiretrovirals (ARVs) for all members while visiting the health facility for their yearly/biyearly visit [6]. This list is not exhaustive, and new strategies ideally suited for specific populations are continuing to be implemented. However, one commonality among most alternative models of ART service delivery is that children have almost uniformly been excluded.

Antiretroviral treatment coverage for children living with HIV is low, and new efforts are underway to expand eligibility so that all children and adolescents qualify for treatment regardless of immune suppression or clinical stage. While recent trials provide direct evidence of the benefit of this approach in adults, no such studies have been performed in children. This paper examines the available body of evidence regarding universal HIV treatment for children and adolescents. The benefits and challenges for individual patient health, as well as programmatic-level outcomes, are assessed. Universal treatment eligibility for children with HIV has great potential for improved growth and neurodevelopment and fewer morbidities for children, and treatment coverage would be expected to increase though guideline simplification. However, concerns regarding toxicities, drug resistance, and costs require careful planning. Successful implementation will depend on effective strategies for case-finding, treatment adherence support, and program monitoring that will contribute to the growing evidence base for this pivotal pediatric HIV policy shift.

BACKGROUND: During 2004-2009, >12,000 children (<15 years old) initiated antiretroviral therapy (ART) in Mozambique. Nationally representative outcomes and temporal trends in outcomes were investigated. METHODS: Rates of death, loss to follow-up (LTFU), and attrition (death or LTFU) were evaluated in a nationally representative sample of 1,054 children, who initiated ART during 2004-2009 at 25 facilities randomly selected using probability-proportional-to-size sampling. RESULTS: At ART initiation during 2004-2009, 50% were male, median age was 3.3 years, median CD4% was 13%, median CD4 count was 375 cells/microL, and median weight-for-age z-score was -2.1. During 2004-2009, median time from HIV diagnosis to care initiation declined from 33 to 0 days (p=0.001), median time from care to ART declined from 93 to 62 days (p=0.004), the percentage aged <2 at ART initiation increased from 16% to 48% (p=0.021), the percentage of patients with prior tuberculosis declined from 50% to 10% (p=0.009), and the percentage with prior lymphocytic interstitial pneumonia declined from 16% to 1% (p<0.001). Over 2,652 person-years of ART, 183 children became LTFU and 26 died. Twelve-month attrition was 11% overall, but increased from 3% to 22% during 2004-2009, due mainly to increases in 12-month LTFU (from 3% to 18%). CONCLUSION: Declines in the prevalence of markers of advanced HIV disease at ART initiation probably reflect increasing ART access. However, 12-month LTFU increased during program expansion, and this negated any program improvements in outcomes that might have resulted from earlier ART initiation.

BACKGROUND: During 2004-2008, >2,000 children (<15 years old) initiated antiretroviral therapy (ART) in Cote d'Ivoire. Nationally representative outcomes, temporal trends in outcomes during 2004-2008, and site-level outcome determinants have not been investigated. METHODS: Incidence rates of death, loss to follow-up (LTFU), and attrition (death or LTFU) were evaluated in a nationally representative, retrospective cohort study among 2,110 children, who initiated ART at 29 facilities in Cote d'Ivoire during 2004-2008. RESULTS: At ART initiation, 54% were male, 1% were HIV-2-infected, and median age was 5.1 years. Median CD4% was 11%, and 61% had weight-for-age z-score (WAZ) ≤-2. Vaccination completion was documented for 9% of children. Eleven of 29 facilities had an integrated nutrition program. Over 4,585 person-years of ART, 237 children died and 427 became LTFU. Twelve-month attrition was 22% overall, but increased from 4-34% during 2004-2008, due to increases in 12-month mortality (from 3-11%) and 12-month LTFU (from 2-23%). In adjusted analysis, compared with enrollees in 2004, enrollees in 2008 had nearly four-fold higher mortality and eight-fold higher LTFU. World Health Organization stage III/IV, CD4% <10%, WAZ ≤2, and hemoglobin <8g/dL, were predictive of mortality. Incomplete vaccination was predictive of mortality and LTFU. Facilities with nutrition programs had lower LTFU and mortality rates. Clinics reporting nurse dissatisfaction with working conditions had higher LTFU rates. CONCLUSION: Investigation of causes of increasing mortality and LTFU is needed. Ensuring earlier ART initiation, vaccination completion, scale-up of site-level nutrition programs, and nurse work-environment satisfaction, could improve pediatric ART program outcomes.

BACKGROUND: Child-to-Breastfeeding-Woman Transmission (CBWT) of HIV occurs when an HIV-infected infant transmits the virus to an HIV-uninfected woman through breastfeeding. Transmission likely occurs as a result of breastfeeding contact during a period of epithelial disruption, such as maternal skin fissures and/or infant stomatitis. Despite extensive epidemiologic and phylogenetic evidence, however, CBWT of HIV continues to be overlooked. OBJECTIVE: This paper summarizes the available evidence for CBWT from nosocomial outbreaks, during which nosocomially HIV-infected infants transmitted the virus to their mothers through breastfeeding. This paper also explores the CBWT risk associated with HIV-infected orphans and their female caretakers, and the lack of guidance regarding CBWT prevention in infant feeding recommendations. METHODS: We searched online databases including PubMed and ScienceDirect for English language articles published from January 1975 to January 2011 using the search terms "HIV", "perinatal", "child-to-mother", and "breastfeeding". The citations from all selected articles were reviewed for additional studies. RESULTS: We identified five studies documenting cases of CBWT. Two studies contained data on the number of HIV-infected women, as well as the proportion breastfeeding. Rates of CBWT ranged from 40 - 60% among women reporting breastfeeding after their infants were infected. CONCLUSIONS: Poor infection control practices, especially in areas of high HIV prevalence, have resulted in pediatric HIV infections and put breastfeeding women at risk for CBWT. Current infant feeding guidelines and HIV prevention messages do not address CBWT, and fail to provide strategies to help women reduce their risk of acquiring HIV during breastfeeding.