BACKGROUND: During the COVID-19 pandemic, the US President's Emergency Plan for AIDS Relief supported oral caregiver-assisted HIV self-testing (CG-HIVST) to address the gap in HIV diagnosis of children. We aimed to investigate caregiver uptake, results return, acceptability, and potential social harms of CG-HIVST. METHODS: This prospective, interventional, study was done at 32 health facilities in Uganda and 15 health facilities in Zambia. Caregivers aged 18 years and older (plus emancipated minors aged 15-17 years in Uganda) living with HIV who were currently accessing HIV care and considered index cases, with no positive responses to an intimate partner violence screen, and with one or more children aged 18 months to 14 years with unknown HIV status were eligible to participate. Eligible caregivers were offered oral HIVST kits to screen their children and primary outcomes were described by caregiver and child characteristics. Following HIVST kit administration, caregivers were surveyed using a standardised questionnaire to document their perceptions, adverse events, and social harm. Primary outcomes were the uptake of HIVST and the number and proportion of returned screening test results, reactive results, reactive screens with confirmatory HIV testing, confirmatory testing with a positive result, and children who were confirmed HIV-positive who were linked to treatment. This study was registered with ClinicalTrials.gov, NCT04774666 and NCT04754386, and is completed. FINDINGS: From Feb 1 to Oct 31, 2021, 12 998 interested caregivers were screened for eligibility, 4023 of whom were eligible. 3903 (97·0%) accepted HIVST kits to screen their child for HIV (1609 [41·2%] in Zambia and 2294 [58·8%] in Uganda). Among caregivers, 3094 (79·3%) of 3903 were female, and 809 (20·7%) were male. 7601 children were enrolled (3779 [49·7%] were female and 3822 [50·3%] were male). 4766 (97·9%) of 4866 test results were returned in Uganda and 2647 (96·8%) of 2735 in Zambia. 119 (1·6%) of 7413 children had reactive HIVST results, requiring confirmatory testing. Of 116 children with confirmatory testing, 43 were confirmed HIV-positive (HIV prevalence 0·7% [n=32] in Uganda and 0·4% [n=11] in Zambia) and 100% were linked to antiretroviral therapy. Adverse events were rare (11 [0·4%] of 2720) and minor, and there were no reports of social harm or violence. Caregivers surveyed reported the HIVST kit was easy to use (2637 [97·0%] of 2718), they would use it again (2650 [99·1%] of 2674), and they would recommend it to other parents (2615 [97·8%] of 2674). INTERPRETATION: Our findings suggest that oral CG-HIVST is acceptable, feasible, and safe, with no reports of social harm, and has the potential to expand access to HIV testing for children while reducing the service delivery burden on health facilities. FUNDING: US President's Emergency Plan for AIDS Relief and Wellcome Trust.

BACKGROUND: In 2019, WHO recommended dolutegravir (DTG) as a backbone for first- and second-line antiretroviral therapy (ART) regimens for people living with HIV (PLHIV). According to the 2018 Uganda's HIV treatment guidelines, patients with viral non-suppression (≥1,000 copies/mL) should receive intensive adherence counseling (IAC) with repeat viral load (VL) within 6 months. This analysis focused on the prevalence and factors associated with viral suppression following IAC among PLHIV on DTG-based regimens (DBRs) with an initial episode of viral non-suppression (VNS) in Uganda. METHODS: We conducted a retrospective analysis for PLHIV on DBRs with an initial episode of VNS (≥1,000 copies/mL) in Uganda during October 2019-September 2020 who had a follow up VL test result during September 2020-July 2021. Data were abstracted from the Central Public Health Laboratory (CPHL) database, including patient demographics and VL results. Viral non-suppression (VNS) was defined as a VL test result of ≥1,000 copies/mL. We characterized PLHIV on DBRs and used logistic regression models to determine factors associated with VL suppression after an initial episode of VNS. RESULTS: A total of 564 PLHIV on DBRs with an initial episode of VNS were followed up and 43 were excluded due to missing data. Of the 521, 220 (42.2%) were children (<15 years) and 231 (44.3%) were female. Median age was 28 years (interquartile range [IQR]: 12-43 years), and median duration on DBRs was 12 months (IQR: 6-15 months). Overall, 80.8% (421/521) PLHIV had a suppressed viral load at first follow up testing (children = 74.5% [164/220]; adults = 85.4% [257/301]). Children with initial VL results ≥5,000 copies/mL were less likely to achieve viral suppression at follow up testing compared to those with <5,000 copies/mL (AOR: 0.38; 95% CI: 0.20-0.71; p = 0.002). CONCLUSIONS: In a programmatic setting, most adults and children suppressed following an initial episode of VNS on DBRs. High rates of suppression after VNS suggest adherence challenges, rather than drug resistance. Continuation of DBRs should be considered before regimen switch.

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.

HIV-positive children and adolescents face gaps in viral load (VL) testing. To understand trends in pediatric/adolescent VL testing, 7 countries collected data from Laboratory Information Management Systems. Results showed increasing proportion of VL tests done through dried blood spot (DBS) and decreased sample rejection rates for DBS compared with plasma, supporting use of DBS VL when skilled phlebotomy is unavailable.

During 2020, an estimated 150,000 persons aged 0-14 years acquired HIV globally (1). Case identification is the first step to ensure children living with HIV are linked to life-saving treatment, achieve viral suppression, and live long, healthy lives. Successful interventions to optimize pediatric HIV testing during the COVID-19 pandemic are needed to sustain progress toward achieving Joint United Nations Programme on HIV/AIDS (UNAIDS) 95-95-95 targets.* Changes in HIV testing and diagnoses among persons aged 1-14 years (children) were assessed in 22 U.S. President's Emergency Plan for AIDS Relief (PEPFAR)-supported countries during October 1, 2019-September 30, 2020. This period corresponds to the two fiscal quarters before the COVID-19 pandemic (i.e., Q1 and Q2) and the two quarters after the pandemic began (i.e., Q3 and Q4). Testing was disaggregated by age group, testing strategy, and fiscal year quarter. During October 2019-September 2020, PEPFAR supported 4,312,343 HIV tests and identified 74,658 children living with HIV (CLHIV). The number of HIV tests performed was similar during Q1 and Q2, decreased 40.1% from Q2 to Q3, and increased 19.7% from Q3 to Q4. The number of HIV cases identified among children aged 1-14 years (cases identified) increased 7.4% from Q1 to Q2, decreased 29.4% from Q2 to Q3, and increased 3.3% from Q3 to Q4. Although testing in outpatient departments decreased 21% from Q1 to Q4, testing from other strategies increased during the same period, including mobile testing by 38%, facility-based index testing (offering an HIV test to partners and biological children of persons living with HIV) by 8%, and testing children with signs or symptoms of malnutrition within health facilities by 7%. In addition, most tests (61.3%) and cases identified (60.9%) were among children aged 5-14 years (school-aged children), highlighting the need to continue offering HIV testing to older children. These findings provide important information on the most effective strategies for identifying CLHIV during the COVID-19 pandemic. HIV testing programs should continue to use programmatic, surveillance, and financial data at both national and subnational levels to determine the optimal mix of testing strategies to minimize disruptions in pediatric case identification during the COVID-19 pandemic.

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: WHO revised their HIV drug resistance (HIVDR) monitoring strategy in 2014, enabling countries to generate nationally representative HIVDR prevalence estimates from surveys conducted using this methodology. In 2016, we adopted this strategy in Uganda and conducted an HIVDR survey among adults initiating or reinitiating ART. METHODS: A cross-sectional survey of adults aged ≥18 years initiating or reinitiating ART was conducted at 23 sites using a two-stage cluster design sampling method. Participants provided written informed consent prior to enrolment. Whole blood collected in EDTA vacutainer tubes was used for preparation of dried blood spot (DBS) specimens or plasma. Samples were shipped from the sites to the Central Public Health Laboratory (CPHL) for temporary storage before transfer to the Uganda Virus Research Institute (UVRI) for genotyping. Prevalence of HIVDR among adults initiating or reinitiating ART was determined. RESULTS: Specimens from 491 participants (median age 32 years and 61.5% female) were collected between August and December 2016. Specimens from 351 participants were successfully genotyped. Forty-nine had drug resistance mutations, yielding an overall weighted HIVDR prevalence of 18.2% with the highest noted for NNRTIs at 14.1%. CONCLUSIONS: We observed a high HIVDR prevalence for NNRTIs among adults prior to initiating or reinitiating ART in Uganda. This is above WHO's recommended threshold of 10% when countries should consider changing from NNRTI- to dolutegravir-based first-line regimens. This recommendation was adopted in the revised Ugandan ART guidelines. Dolutegravir-containing ART regimens are preferred for first- and second-line ART regimens.

BACKGROUND: With the scale-up of antiretroviral therapy (ART), monitoring programme performance is needed to maximize ART efficacy and limit HIV drug resistance (HIVDR). METHODS: We implemented a WHO HIVDR prospective survey protocol at three treatment centers between 2012 and 2013. Data were abstracted from patient records at ART start (T1) and after 12 months (T2). Genotyping was performed in the HIV pol region at the two time points. RESULTS: Of the 425 patients enrolled, at T2, 20 (4.7%) had died, 66 (15.5%) were lost to follow-up, 313 (73.6%) were still on first-line, 8 (1.9%) had switched to second-line, 17 (4.0%) had transferred out and 1 (0.2%) had stopped treatment. At T2, 272 out of 321 on first and second line (84.7%) suppressed below 1000 copies/ml and the HIV DR prevention rate was 70.1%, just within the WHO threshold of ≥70%. The proportion of participants with potential HIVDR was 20.9%, which is higher than the 18.8% based on pooled analyses from African studies. Of the 35 patients with mutations at T2, 80% had M184V/I, 65.7% Y181C, and 48.6% (54.8% excluding those not on Tenofovir) had K65R mutations. 22.9% had Thymidine Analogue Mutations (TAMs). Factors significantly associated with HIVDR prevention at T2 were: baseline viral load (VL) <100,000 copies/ml [Adjusted odds ratio (AOR) 3.13, 95% confidence interval (CI): 1.36-7.19] and facility. Independent baseline predictors for HIVDR mutations at T2 were: CD4 count <250 cells/mul (AOR 2.80, 95% CI: 1.08-7.29) and viral load ≥100,000 copies/ml (AOR 2.48, 95% CI: 1.00-6.14). CONCLUSION: Strengthening defaulter tracing, intensified follow-up for patients with low CD4 counts and/or high VL at ART initiation together with early treatment initiation above 250 CD4 cells/ul and adequate patient counselling would improve ART efficacy and HIVDR prevention. The high rate of K65R and TAMs could compromise second line regimens including NRTIs.