The Critical Role of Supply Chains in Preventing Human Immunodeficiency Virus Drug Resistance in Low- and Middle-Income Settings.

The functioning of the supply chain may be a driving factor behind the development of human immunodeficiency virus (HIV) drug resistance (HIVDR) in many low- and middle-income countries (LMICs). Additionally, the effectiveness of supply chains will likely impact the scale-up of both viral-load monitoring and HIVDR testing. This article describes the complexities of global supply chains relevant for LMICs and presents early data on stock-outs and drug substitutions in several countries supported by the US President's Emergency Plan for AIDS Relief. Supply chain systems will need to be strengthened to minimize interruptions as new antiretroviral therapy regimens are introduced and to facilitate adoption of new laboratory technologies.

Trends in the Uptake of Index Testing among Adolescents in USAID-Supported PEPFAR Programs, October 2017- September 2022.

INTRODUCTION: Adolescents 10-19 years account for a growing proportion of people living with HIV (PLHIV). In 2023, 140,000 adolescents were diagnosed with HIV, yet knowledge of HIV status and uptake of testing services remain critically low. Index testing - offering testing to contacts of PLHIV - is an important case-finding strategy. In 2021, PEPFAR expanded guidance to explicitly include older adolescents 15 to 19 years. We reviewed index testing data to assess uptake and case-finding trends among biological adolescent-aged children and siblings of PLHIV 10-19 years. METHODS: Routinely collected programmatic data from 27 USAID-supported PEPFAR country and regional programs were analyzed for fiscal years (FY) 2017 through FY2022 (October 2016 - September 2022). We compared the volume of index testing and subsequent new diagnoses across FYs and countries among biological adolescent-aged children and siblings of PLHIV, and disaggregated by age, 10-14 and 15-19 years, and sex. RESULTS: Index testing among adolescents 10-19 years increased from FY17 to FY22, nearly doubling from 147,088 to 291,534. Similarly, new diagnoses among adolescents increased between FY17 and FY22 (3,721 vs 10,730). Overall, across FYs, index testing uptake and case-finding were higher among females than males, and the gap in testing uptake between sexes was larger for older than younger adolescents. CONCLUSION: Index testing uptake has increased substantially among adolescents over time, with rebounded gains for adolescents 15-19 years noted beginning in FY21. However, uptake across age and sex remained uneven, highlighting an opportunity to ensure targeted testing strategies are employed to reach adolescents 15-19 years and males.

Trends in continuity of treatment among children and adolescents living with HIV in 14 districts in South Africa from 2018-2023: A retrospective program analysis.

Objectives: UNAIDS estimates 152,984 children under 15 years living with HIV (C/ALHIV) by 2022 in South Africa. Monitoring the continuity of antiretroviral treatment remains challenging without electronic health records. We explored treatment cohort growth and interruption trends in 14-USAID-PEPFAR-supported districts. Methods: We reviewed data from 2018 to 2023. We triangulated this data with NAOMI HIV estimates. We used Tableau version 2023.2 for analysis to understand heterogeneity in outcomes. Results: HIV incidence halved from 4.3 per 1000 in 2017 to 2.5 per 1000 in 2022. HIV testing doubled: 188,371 in FY19Q1 to 399,708 in FY23Q4 while testing positivity declined from 3.3% to 0.7%. Linkage to treatment increased from 67% to 102%, viral suppression increased from 79% to 84%. C/ALHIV treatment cohort started at 82,897 in FY19Q1 and increased to 105,107 in FY20Q2. Subsequently, the cohort decreased to 79,288 in FY23Q4 despite 42,498 initiations and 62,256 returns. Conclusions: The C/ALHIV treatment and viral suppression increased substantially commensurate with expected trends. Subsequent cohort decline was aligned to vertical transmission reduction, HIV incidence decline, and expected aging. We highlight the inadequacy of the information systems to quantify losses. We underscore a need for resources to enhance program monitoring and interventions to address this gap.

Are children of key population individuals at higher risk of HIV than other children? Results from a multi-country analysis of routine program data.

INTRODUCTION: Children of key population individuals (CPK) often face the same stigma and discrimination as their parents, limiting their access to HIV services. The Meeting Targets and Maintaining Epidemic Control project analyzed pediatric HIV testing data from project-supported sites to better understand risk among CKP and improve comprehensive prevention, testing, and treatment for KP families. METHODS: We conducted a retrospective analysis of routine program data collected October 1, 2021-September 30, 2022, in project-supported sites in Burundi, Côte d'Ivoire, Democratic Republic of Congo, Tanzania, and Togo. We compared HIV case finding (defined as the percentage of children diagnosed with HIV among those who were tested) and treatment initiation (defined as the percentage of children diagnosed with HIV who were initiated on antiretroviral therapy) data for children <15 years disaggregated by index versus non-index testing and CKP versus children of non-KP individuals (non-CKP). RESULTS: A total of 5,651 children were tested (n = 2,974 index testing; n = 2,677 non-index testing). Of those diagnosed with HIV, 33% (181/541) were CKP, with case finding 17% (181 positive/1,070 tested) among CKP and 8% among non-CKP (360 positive/4,581 tested). Almost half of CKP diagnosed were ages 1-4 years. Among the 2,974 (53%) reached through index testing, overall case finding was higher among CKP (17%; 178 positive/1,052 tested) than non-CKP (11%; 219 positive/1,922 tested). Treatment initiation was 97% among CKP and 94% among non-CKP. DISCUSSION: CKP were identified primarily through index testing which, although considered a priority strategy to identify children at high risk, has not been widely used within KP family networks. Most CKP reached were children of female sex workers, but those of other KPs should also be prioritized. CONCLUSIONS: KP-focused programs have often excluded children, but the case-finding approaches in the project's KP programs were effective in reaching CKP. Comprehensive, family-centered KP programming is needed that includes family planning, prevention of vertical transmission, early infant diagnosis, and other maternal and child health services to reduce the impact of HIV on families and achieve an HIV-free generation.

Pediatric Antiretroviral Therapy Coverage and AIDS Deaths in the "Treat All" Era.

OBJECTIVES: In 2015, CD4-based clinical staging criteria for antiretroviral therapy (ART) initiation were removed, expanding ART eligibility ("Treat All") for children, who shoulder an outsized burden of HIV-related deaths. To quantify the impact of "Treat All" on pediatric HIV outcomes, we examined shifts in pediatric ART coverage and AIDS mortality before and after "Treat All" implementation. METHODS: We abstracted country-level ART coverage (proportion of children <15 years on ART) and AIDS mortality (deaths per 100 000 population) estimates over 11 years. For 91 countries, we also abstracted the year "Treat All" was incorporated into national guidelines. We used multivariable 2-way fixed effects negative binomial regression to estimate changes in pediatric ART coverage and AIDS mortality potentially attributable to "Treat All" expansion, reported as adjusted incidence rate ratios (adj.IRR) with 95% confidence intervals (95% CI). RESULTS: From 2010 to 2020, pediatric ART coverage tripled (16% to 54%), and AIDS-related deaths were halved (240 000 to 99 000). Compared with the pre-implementation period, observed ART coverage continued increasing after "Treat All" adoption, but this rate of increase declined by 6% (adj.IRR = 0.94, 95% CI: 0.91-0.98). AIDS mortality continued declining after "Treat All" adoption, but this rate of decline decreased by 8% (adj.IRR = 1.08, 95% CI: 1.05-1.11) in the post-implementation period. CONCLUSIONS: Although "Treat All" called for increased HIV treatment equity, ART coverage continues lagging in children and comprehensive approaches that address structural issues, including family-based services and intensified case-finding, are needed to close pediatric HIV treatment gaps.

Considerations to Improve Pediatric HIV Testing and Close the Treatment Gap in 16 African Countries.

BACKGROUND: In 2019, South Africa, Nigeria, Tanzania, Democratic Republic of Congo, Uganda, Mozambique, Zambia, Angola, Cameroon, Zimbabwe, Ghana, Ethiopia, Malawi, Kenya, South Sudan and Côte d'Ivoire accounted for 80% of children living with HIV (CLHIV) not receiving HIV treatment. This manuscript describes pediatric HIV testing to inform case-finding strategies. METHODS: We analyzed US President's Emergency Plan for AIDS Relief monitoring, evaluation, and reporting data (October 1, 2018 to September 30, 2019) for these 16 countries. Number of HIV tests and positive results were reported by age band, country, treatment coverage and testing modality. The number needed to test (NNT) to identify 1 new CLHIV 1-14 years was measured by testing modality and country. The pediatric testing gap was estimated by multiplying the estimated number of CLHIV unaware of their status by NNT per country. RESULTS: Among children, 6,961,225 HIV tests were conducted, and 101,762 CLHIV were identified (NNT 68), meeting 17.6% of the pediatric testing need. Index testing accounted for 13.0% of HIV tests (29.7% of positive results, NNT 30), provider-initiated testing and counseling 65.9% of tests (43.6% of positives, NNT 103), and universal testing at sick entry points 5.3% of tests (6.5% of positives, NNT 58). CONCLUSIONS: As countries near HIV epidemic control for adults, the need to increase pediatric testing continues. Each testing modality - PITC, universal testing at sick entry points, and index testing - offers unique benefits. These results illustrate the comparative advantages of including a strategic mix of testing modalities in national programs to increase pediatric HIV case finding.

Adapting HIV services for pregnant and breastfeeding women, infants, children, adolescents and families in resource-constrained settings during the COVID-19 pandemic.

INTRODUCTION: The COVID-19 pandemic has impacted global health service delivery, including provision of HIV services. Countries with high HIV burden are balancing the need to minimize interactions with health facilities to reduce the risk of COVID-19 transmission, while delivering uninterrupted essential HIV prevention, testing and treatment services. Many of these adaptations in resource-constrained settings have not adequately accounted for the needs of pregnant and breastfeeding women, infants, children and adolescents. We propose whole-family, tailored programme adaptations along the HIV clinical continuum to protect the programmatic gains made in services. DISCUSSION: Essential HIV case-finding services for pregnant and breastfeeding women and children should be maintained and include maternal testing, diagnostic testing for infants exposed to HIV, index testing for children whose biological parents or siblings are living with HIV, as well as for children/adolescents presenting with symptoms concerning for HIV and comorbidities. HIV self-testing for children two years of age and older should be supported with caregiver and provider education. Adaptations include bundling services in the same visit and providing testing outside of facilities to the extent possible to reduce exposure risk to COVID-19. Virtual platforms can be used to identify vulnerable children at risk of HIV infection, abuse, harm or violence, and link them to necessary clinical and psychosocial support services. HIV treatment service adaptations for families should focus on family based differentiated service delivery models, including community-based ART initiation and multi-month ART dispensing. Viral load monitoring should not be a barrier to transitioning children and adolescents experiencing treatment failure to more effective ART regimens, and viral load monitoring for pregnant and breastfeeding women and children should be prioritized and bundled with other essential services. CONCLUSIONS: Protecting pregnant and breastfeeding women, infants, children and adolescents from acquiring SARS-CoV-2 while sustaining essential HIV services is an immense global health challenge. Tailored, family friendly programme adaptations for case-finding, ART delivery and viral load monitoring for these populations have the potential to limit SARS-CoV-2 transmission while ensuring the continuity of life-saving HIV case identification and treatment efforts.

Pursuing use of optimal formulations for paediatric HIV epidemic control - a look at the use of LPV/r oral pellets and oral granules.

INTRODUCTION: Despite a significant reduction in mother-to-child transmission of HIV, an estimated 180,000 children were infected with HIV in 2017, and only 52% of children under 15 years of age living with HIV (CLHIV) are on life-saving antiretroviral therapy (ART). Without effective treatment, half of CLHIV die before the age of two years and only one in five survives to five years of age. DISCUSSION: Over the past four years, the United States Food and Drug Administration tentatively approved new formulations of lopinavir/ritonavir (LPV/r) in the form of oral pellets and oral granules. However, the slow uptake of the aforementioned formulations in the low- and middle-income countries with the highest paediatric HIV burden is largely due to three challenges: limited manufacturing capacity; current unit cost of the pellets and granules; and slow uptake of these new formulations by policy makers and health care workers. CONCLUSIONS: Solutions to overcome these barriers include ensuring availability of an adequate supply of LPV/r oral pellets and oral granules, considering all programmatic and clinical factors when selecting paediatric ART formulations, and leveraging current resources to decrease paediatric HIV morbidity and mortality.

Boosting ART uptake and retention among HIV-infected pregnant and breastfeeding women and their infants: the promise of innovative service delivery models.

INTRODUCTION: With the rapid scale-up of antiretroviral treatment (ART) in the "Treat All" era, there has been increasing emphasis on using differentiated models of HIV service delivery. The gaps within the clinical cascade for mothers and their infants suggest that current service delivery models are not meeting families' needs and prompt re-consideration of how services are provided. This article will explore considerations for differentiated care and encourage the ongoing increase of ART coverage through innovative strategies while also addressing the unique needs of mothers and infants. DISCUSSION: Service delivery models should recognize that the timing of the mother's HIV diagnosis is a critical aspect of determining eligibility. Women newly diagnosed with HIV require a more intensive approach so that adequate counselling and monitoring of ART initiation and response can be provided. Women already on ART with evidence of virologic failure are also at high risk of transmitting HIV to their infants and require close follow-up. However, women stable on ART with a suppressed viral load before conception have a very low likelihood of HIV transmission and thus are strong candidates for multi-month ART dispensing, community-based distribution of ART, adherence clubs, community adherence support groups and longer intervals between clinical visits. A number of other factors should be considered when defining eligibility of mothers and infants for differentiated care, including location of services, viral load monitoring and duration on ART. To provide differentiated care that is client-centred and driven while encompassing a family-based approach, it will be critical to engage mothers, families and communities in models that will optimize client satisfaction, retention in care and quality of services. CONCLUSIONS: Differentiated care for mothers and infants represents an opportunity to provide client-centred care that reduces the burden on clients and health systems while improving the quality and uptake of services for families. However, with decreasing funding, stable HIV incidence, and aspirations for sustainability, it is critical to consider efficient, customized and cost-effective models of care for these populations as we aspire to eliminate mother-to-child transmission of HIV.

The time is now: closing the pediatric treatment gap and building resilience among female sex workers and their children.

: Motherhood is common among female sex workers (FSWs) and many have at least one biological child. Preventable mother-to-child transmission of HIV can occur given poor uptake of contraception coupled with high rates of unintended pregnancies among FSWs. Globally, there are 2.1 million children living with HIV, and antiretroviral treatment coverage is dismally low at 43%. Without timely diagnosis and treatment, half of all children born with HIV will die by the age of 2 years. By integrating services for key populations and their children, prevention of mother-to-child transmission of HIV uptake among FSW mothers and early infant diagnosis can improve and therefore reduce transmission of HIV. This field note addresses the needs of FSWs and their children, and advocates for programs to develop and scale up comprehensive, integrated, stigma-free services for this vulnerable population. Sensitive, confidential, child-friendly, tailored services that protect FSWs while addressing their children are essential to saving these young lives and breaking the transmission cycle of the virus. By siloing programs that neglect children of FSWs, we are missing opportunities and existing entry points to take an innovative, holistic, family approach to care, support, and treatment services that could improve outcomes. Given the high prevalence of HIV in FSWs and other stigmatizing factors which affect access to services, children of FSWs can no longer afford to be left behind and the time is now to prioritize them in current and future HIV programming.

Community-Based Interventions to Reach 95-95-95 for Children and Adolescents: An Exploratory Programmatic Review From Lesotho.

BACKGROUND: Viral suppression is the desired outcome for children and adolescents with HIV. In this article, data from districts supporting community interventions (implementation districts) were reviewed and compared with data from districts without community interventions (nonimplementation districts) to explore a potential correlation between community interventions and clinical outcomes. SETTING: The study was based on data collected from facilities in 6 districts in Lesotho. METHODS: Twelve-month retention, viral load coverage, and viral suppression data from patients with ART between ages 5 and 24 from facilities in both district types were collected retrospectively. RESULTS: Implementation districts showed retention rates of 75%, with 5365 patients (47% of all patients on ART) having documented viral load results and 4641 (87%) being virally suppressed. Retention comparison demonstrated significantly higher rates in implementation districts (73%) as compared to (63%) in nonimplementation districts (P = 0.023). Viral load coverage and suppression comparison found that implementation district hospitals reported 632 (37% of total on ART) patients with a documented viral load, with 539 (85%) virally suppressed, whereas nonimplementation district hospitals reported 220 (31%) patients with viral load results, of whom 181 (82%) were suppressed. CONCLUSIONS: Overall, retention rates in the implementation districts were reasonable and were significantly better than the rates in the nonimplementation districts.