The epidemiology of adolescents living with perinatally acquired HIV: A cross-region global cohort analysis

Background Globally, the population of adolescents living with perinatally acquired HIV (APHs) continues to expand. In this study, we pooled data from observational pediatric HIV cohorts and cohort networks, allowing comparisons of adolescents with perinatally acquired HIV in “real-life” settings across multiple regions. We describe the geographic and temporal characteristics and mortality outcomes of APHs across multiple regions, including South America and the Caribbean, North America, Europe, sub-Saharan Africa, and South and Southeast Asia. Methods and findings Through the Collaborative Initiative for Paediatric HIV Education and Research (CIPHER), individual retrospective longitudinal data from 12 cohort networks were pooled. All children infected with HIV who entered care before age 10 years, were not known to have horizontally acquired HIV, and were followed up beyond age 10 years were included in this analysis conducted from May 2016 to January 2017. Our primary analysis describes patient and treatment characteristics of APHs at key time points, including first HIV-associated clinic visit, antiretroviral therapy (ART) start, age 10 years, and last visit, and compares these characteristics by geographic region, country income group (CIG), and birth period. Our secondary analysis describes mortality, transfer out, and lost to follow-up (LTFU) as outcomes at age 15 years, using competing risk analysis. Among the 38,187 APHs included, 51% were female, 79% were from sub-Saharan Africa and 65% lived in low-income countries. APHs from 51 countries were included (Europe: 14 countries and 3,054 APHs; North America: 1 country and 1,032 APHs; South America and the Caribbean: 4 countries and 903 APHs; South and Southeast Asia: 7 countries and 2,902 APHs; sub-Saharan Africa, 25 countries and 30,296 APHs). Observation started as early as 1982 in Europe and 1996 in sub-Saharan Africa, and continued until at least 2014 in all regions. The median (interquartile range [IQR]) duration of adolescent follow-up was 3.1 (1.5–5.2) years for the total cohort and 6.4 (3.6–8.0) years in Europe, 3.7 (2.0–5.4) years in North America, 2.5 (1.2–4.4) years in South and Southeast Asia, 5.0 (2.7–7.5) years in South America and the Caribbean, and 2.1 (0.9–3.8) years in sub-Saharan Africa. Median (IQR) age at first visit differed substantially by region, ranging from 0.7 (0.3–2.1) years in North America to 7.1 (5.3–8.6) years in sub-Saharan Africa. The median age at ART start varied from 0.9 (0.4–2.6) years in North America to 7.9 (6.0–9.3) years in sub-Saharan Africa. The cumulative incidence estimates (95% confidence interval [CI]) at age 15 years for mortality, transfers out, and LTFU for all APHs were 2.6% (2.4%–2.8%), 15.6% (15.1%–16.0%), and 11.3% (10.9%–11.8%), respectively. Mortality was lowest in Europe (0.8% [0.5%–1.1%]) and highest in South America and the Caribbean (4.4% [3.1%–6.1%]). However, LTFU was lowest in South America and the Caribbean (4.8% [3.4%–6.7%]) and highest in sub-Saharan Africa (13.2% [12.6%–13.7%]). Study limitations include the high LTFU rate in sub-Saharan Africa, which could have affected the comparison of mortality across regions; inclusion of data only for APHs receiving ART from some countries; and unavailability of data from high-burden countries such as Nigeria. Conclusion To our knowledge, our study represents the largest multiregional epidemiological analysis of APHs. Despite probable under-ascertained mortality, mortality in APHs remains substantially higher in sub-Saharan Africa, South and Southeast Asia, and South America and the Caribbean than in Europe. Collaborations such as CIPHER enable us to monitor current global temporal trends in outcomes over time to inform appropriate policy responses

HIV prevention programme with young women who sell sex in Mombasa, Kenya: learnings for scale-up

Introduction: In 2018, the National AIDS and sexually transmitted infection (STI) Control Programme developed a national guidelines to facilitate the inclusion of young women who sell sex (YWSS) in the HIV prevention response in Kenya. Following that, a 1-year pilot intervention, where a package of structural, behavioural and biomedical services was provided to 1376 cisgender YWSS to address their HIV-related risk and vulnerability, was implemented. Methods: Through a mixed-methods, pre/post study design, we assessed the effectiveness of the pilot, and elucidated implementation lessons learnt. The three data sources used included: (1) monthly routine programme monitoring data collected between October 2019 and September 2020 to assess the reach and coverage; (2) two polling booth surveys, conducted before and after implementation, to determine the effectiveness; and (3) focus group discussions and key informant interviews conducted before and after intervention to assess the feasibility of the intervention. Descriptive analysis was performed to produce proportions and comparative statistics. Results: During the intervention, 1376 YWSS were registered in the programme, 28% were below 19 years of age and 88% of the registered YWSS were active in the last month of intervention. In the survey, respondents reported increases in HIV-related knowledge (61.7% vs. 90%, p <0.001), ever usage of pre-exposure prophylaxis (8.5% vs. 32.2%, p < 0.001); current usage of pre-exposure prophylaxis (5.3% vs. 21.1%, p<0.002); ever testing for HIV (87.2% vs. 95.6%, p <0.04) and any clinic visit (35.1 vs. 61.1, p <0.001). However, increase in harassment by family (11.7% vs. 23.3%, p<0.04) and discrimination at educational institutions (5.3% vs. 14.4%, p<0.04) was also reported. In qualitative assessment, respondents reported early signs of success, and identified missed opportunities and made recommendations for scale-up. Conclusions: Our intervention successfully rolled out HIV prevention services for YWSS in Mombasa, Kenya, and demonstrated that programming for YWSS is feasible and can effectively be done through YWSS peer-led combination prevention approaches. However, while reported uptake of treatment and prevention services increased, there was also an increase in reported harassment and discrimination requiring further attention. Lessons learnt from the pilot intervention can inform replication and scale-up of such interventions in Kenya

Measuring the performance of HIV self‐testing at private pharmacies in Kenya: a cross‐sectional study

Abstract Introduction HIV self‐testing (HIVST) has the potential to support daily oral pre‐exposure prophylaxis (PrEP) delivery in private pharmacies, but many national guidelines have not approved HIVST for PrEP dispensing. In Kenya, pharmacy providers are permitted to deliver HIVST, but often do not have the required certification to deliver rapid diagnostic testing (RDT). We estimated the performance of provider‐delivered HIVST compared to RDT, the standard of care for PrEP delivery, at private pharmacies in Kenya to inform decisions on the use of HIVST for PrEP scale‐up. Methods At 20 pharmacies in Kisumu County, we trained pharmacy providers (pharmacists and pharmaceutical technologists) on blood‐based HIVST use and client assistance (if requested). We recruited pharmacy clients purchasing sexual and reproductive health‐related products (e.g. condoms) and enrolled those ≥18 years with self‐reported behaviours associated with HIV risk. Enrolled clients received HIVST with associated provider counselling, followed by RDT by a certified HIV testing services (HTS) counsellor. Pharmacy providers and clients independently interpreted HIVST results prior to RDT (results interpreted only by the HTS counsellor). We calculated the sensitivity and specificity of pharmacy provider‐delivered HIVST compared to HTS counsellor‐administered RDT. Results Between March and June 2022, we screened 1691 clients and enrolled 1500; 64% (954/1500) were female and the median age was 26 years (IQR 22–31). We additionally enrolled 40 providers; 42% (17/40) were pharmacy owners and their median years of experience was 6 (IQR 4–10). The majority (79%, 1190/1500) of clients requested provider assistance with HIVST and providers spent a median of 20 minutes (IQR 15–43) with each HIVST client. The sensitivity of provider‐delivered HIVST at the pharmacy was high when interpreted by providers (98.5%, 95% CI 97.8%, 99.1%) and clients (98.8%, 95% CI 98.0%, 99.3%), as was the specificity of HIVST in this setting (provider‐interpretation: 96.9%, 95% CI 89.2%, 99.6%; client‐interpretation: 93.8%, 95% CI 84.8%, 98.3%). Conclusions When compared to the national HIV testing algorithm, provider‐delivered blood‐based HIVST at private pharmacies in Kenya performed well. These findings suggest that blood‐based HIVST may be a useful tool to support PrEP initiation and continuation at private pharmacies and potentially other community‐based delivery settings

Data_Sheet_1_Measuring the performance of computer vision artificial intelligence to interpret images of HIV self-testing results.docx

IntroductionHIV self-testing (HIVST) is highly sensitive and specific, addresses known barriers to HIV testing (such as stigma), and is recommended by the World Health Organization as a testing option for the delivery of HIV pre-exposure prophylaxis (PrEP). Nevertheless, HIVST remains underutilized as a diagnostic tool in community-based, differentiated HIV service delivery models, possibly due to concerns about result misinterpretation, which could lead to inadvertent onward transmission of HIV, delays in antiretroviral therapy (ART) initiation, and incorrect initiation on PrEP. Ensuring that HIVST results are accurately interpreted for correct clinical decisions will be critical to maximizing HIVST's potential. Early evidence from a few small pilot studies suggests that artificial intelligence (AI) computer vision and machine learning could potentially assist with this task. As part of a broader study that task-shifted HIV testing to a new setting and cadre of healthcare provider (pharmaceutical technologists at private pharmacies) in Kenya, we sought to understand how well AI technology performed at interpreting HIVST results.MethodsAt 20 private pharmacies in Kisumu, Kenya, we offered free blood-based HIVST to clients ≥18 years purchasing products indicative of sexual activity (e.g., condoms). Trained pharmacy providers assisted clients with HIVST (as needed), photographed the completed HIVST, and uploaded the photo to a web-based platform. In real time, each self-test was interpreted independently by the (1) client and (2) pharmacy provider, with the HIVST images subsequently interpreted by (3) an AI algorithm (trained on lab-captured images of HIVST results) and (4) an expert panel of three HIVST readers. Using the expert panel's determination as the ground truth, we calculated the sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) for HIVST result interpretation for the AI algorithm as well as for pharmacy clients and providers, for comparison.ResultsFrom March to June 2022, we screened 1,691 pharmacy clients and enrolled 1,500 in the study. All clients completed HIVST. Among 854 clients whose HIVST images were of sufficient quality to be interpretable by the AI algorithm, 63% (540/854) were female, median age was 26 years (interquartile range: 22–31), and 39% (335/855) reported casual sexual partners. The expert panel identified 94.9% (808/854) of HIVST images as HIV-negative, 5.1% (44/854) as HIV-positive, and 0.2% (2/854) as indeterminant. The AI algorithm demonstrated perfect sensitivity (100%), perfect NPV (100%), and 98.8% specificity, and 81.5% PPV (81.5%) due to seven false-positive results. By comparison, pharmacy clients and providers demonstrated lower sensitivity (93.2% and 97.7% respectively) and NPV (99.6% and 99.9% respectively) but perfect specificity (100%) and perfect PPV (100%).ConclusionsAI computer vision technology shows promise as a tool for providing additional quality assurance of HIV testing, particularly for catching Type II error (false-negative test interpretations) committed by human end-users. We discuss possible use cases for this technology to support differentiated HIV service delivery and identify areas for future research that is needed to assess the potential impacts—both positive and negative—of deploying this technology in real-world HIV service delivery settings.</p

The epidemiology of adolescents living with perinatally acquired HIV: A cross-region global cohort analysis

textabstractBackground: Globally, the population of adolescents living with perinatally acquired HIV (APHs) continues to expand. In this study, we pooled data from observational pediatric HIV cohorts and cohort networks, allowing comparisons of adolescents with perinatally acquired HIV in “real-life” settings across multiple regions. We describe the geographic and temporal characteristics and mortality outcomes of APHs across multiple regions, including South America and the Caribbean, North America, Europe, sub-Saharan Africa, and South and Southeast Asia. Methods and findings: Through the Collaborative Initiative for Paediatric HIV Education and Research (CIPHER), individual retrospective longitudinal data from 12 cohort networks were pooled. All children infected with HIV who entered care before age 10 years, were not known to have horizontally acquired HIV, and were followed up beyond age 10 years were included in this analysis conducted from May 2016 to January 2017. Our primary analysis describes patient and treatment characteristics of APHs at key time points, including first HIV-associated clinic visit, antiretroviral therapy (ART) start, age 10 years, and last visit, and compares these characteristics by geographic region, country income group (CIG), and birth period. Our secondary analysis describes mortality, transfer out, and lost to follow-up (LTFU) as outcomes at age 15 years, using competing risk analysis. Among the 38,187 APHs included, 51% were female, 79% were from sub-Saharan Africa and 65% lived in low-income countries. APHs from 51 countries were included (Europe: 14 countries and 3,054 APHs; North America: 1 country and 1,032 APHs; South America and the Caribbean: 4 countries and 903 APHs; South and Southeast Asia: 7 countries and 2,902 APHs; sub-Saharan Africa, 25 countries and 30,296 APHs). Observation started as early as 1982 in Europe and 1996 in sub-Saharan Africa, and continued until at least 2014 in all regions. The median (interquartile range [IQR]) duration of adolescent follow-up was 3.1 (1.5–5.2) years for the total cohort and 6.4 (3.6–8.0) years in Europe, 3.7 (2.0–5.4) years in North America, 2.5 (1.2–4.4) years in South and Southeast Asia, 5.0 (2.7–7.5) years in South America and the Caribbean, and 2.1 (0.9–3.8) years in sub-Saharan Africa. Median (IQR) age at first visit differed substantially by region, ranging from 0.7 (0.3–2.1) years in North America to 7.1 (5.3–8.6) years in sub-Saharan Africa. The median age at ART start varied from 0.9 (0.4–2.6) years in North America to 7.9 (6.0–9.3) years in sub-Saharan Africa. The cumulative incidence estimates (95% confidence interval [CI]) at age 15 years for mortality, transfers out, and LTFU for all APHs were 2.6% (2.4%–2.8%), 15.6% (15.1%–16.0%), and 11.3% (10.9%–11.8%), respectively. Mortality was lowest in Europe (0.8% [0.5%–1.1%]) and highest in South America and the Caribbean (4.4% [3.1%–6.1%]). However, LTFU was lowest in South America and the Caribbean (4.8% [3.4%–6.7%]) and highest in sub-Saharan Africa (13.2% [12.6%–13.7%]). Study limitations include the high LTFU rate in sub-Saharan Africa, which could have affected the comparison of mortality across regions; inclusion of data only for APHs receiving ART from some countries; and unavailability of data from high-burden countries such as Nigeria. Conclusion: To our knowledge, our study represents the largest multiregional epidemiological analysis of APHs. Despite probable under-ascertained mortality, mortality in APHs remains substantially higher in sub-Saharan Africa, South and Southeast Asia, and South America and the Caribbean than in Europe. Collaborations such as CIPHER enable us to monitor current global temporal trends in outcomes over time to inform appropriate policy responses

Profile of geographic regions included in the CIPHER global cohort adolescent analysis (<i>N</i> = 38,187 adolescents).

<p>Profile of geographic regions included in the CIPHER global cohort adolescent analysis (<i>N</i> = 38,187 adolescents).</p

Adolescent characteristics at first visit, ART start, age 10 years, and last visit and cumulative incidence of outcomes (mortality, transferred out, LTFU), compared by CIG.

<p>Adolescent characteristics at first visit, ART start, age 10 years, and last visit and cumulative incidence of outcomes (mortality, transferred out, LTFU), compared by CIG.</p

Comparison by CIG of characteristics at first visit, ART start, age 10 years, and last visit of adolescents living with perinatally acquired HIV.

<p>ART, antiretroviral therapy; CIG, country income group; IQR, interquartile range; WHO, World Health Organization.</p

Comparison by geographic region of characteristics at first visit, ART start, age 10 years, and last visit of adolescents living with perinatally acquired HIV.

<p>ART, antiretroviral therapy; IQR, interquartile range; S&SE Asia, South and Southeast Asia; WHO, World Health Organization.</p

Flow diagram of inclusion of adolescents living with perinatally acquired HIV (<i>N</i> = 38,187).

<p>CIPHER, Collaborative Initiative for Paediatric HIV Education and Research.</p