Feasibility and acceptability of point of care testing for sexually transmitted infections in outpatient clinics offering integrated services in Eswatini.

BACKGROUND: Lack of point of care testing (POCT) for sexually transmitted infections (STIs) is a continuing missed opportunity in Sub-Saharan Africa. We assessed feasibility and acceptability of STI POCT in Eswatini. METHODS: STI POCT for Chlamydia trachomatis (CT) and Neisseria gonorrhoea (NG) was piloted among sexually active adults 18-45 years attending two urban outpatient clinics offering HIV services. Females were randomized 1:1 to provide urine or vaginal swab and all males provided urine samples for CT/NG testing using Cepheid CT/NG cartridges on existing GeneXpert platforms. Results were returned in-person or by telephone call. We assessed duration of procedures and participant and healthcare worker acceptability of services (5-point Likert scale), time spent on STI POCT services, and correlates of CT/NG infection. RESULTS: Of 250 adults triaged, 99% (248/250) accepted STI POCT, including 44% (109/248) people living with HIV. STI POCT procedures took a median of 3:22 hours. Most adults (90%, 224/248), received results within a day (61% same day, 29% next day). CT/NG was detected among 22% (55/248): 31/55 CT, 21/55 NG and 3/55 coinfections. Youth 18-25 years, history of any sexual intercourse, and condom-less sex within the previous 7 days were significantly associated with CT/NG detected (p < 0.05). Most adults with CT/NG were treated (51/55, 93%). Most participants were satisfied with STI POCT (217/241, 90%), and would accept again/recommend it. All 32 healthcare workers who participated were satisfied with STI POCT. CONCLUSION: STI POCT was feasible, acceptable, and identified a high prevalence of STIs, highlighting the urgent need for this testing.

Synthetic Controls for Implementation Science: Opportunities for HIV Program Evaluation Using Routinely Collected Data.

PURPOSE OF REVIEW: HIV service delivery programs are some of the largest funded public health programs in the world. Timely, efficient evaluation of these programs can be enhanced with methodologies designed to estimate the effects of policy. We propose using the synthetic control method (SCM) as an implementation science tool to evaluate these HIV programs. RECENT FINDINGS: SCM, introduced in econometrics, shows increasing utility across fields. Key benefits of this methodology over traditional design-based approaches for evaluation stem from directly approximating pre-intervention trends by weighting of candidate non-intervention units. We demonstrate SCM to evaluate the effectiveness of a public health intervention targeting HIV health facilities with high numbers of recent infections on trends in pre-exposure prophylaxis (PrEP) enrollment. This test case demonstrates SCM's feasibility for effectiveness evaluations of site-level HIV interventions. HIV programs collecting longitudinal, routine service delivery data for many facilities, with only some receiving a time-specified intervention, are well-suited for evaluation using SCM.

Risk Factors for Recent HIV Infections among Adults in 14 Countries in Africa Identified by Population-Based HIV Impact Assessment Surveys, 2015-2019.

Identifying persons who have newly acquired HIV infections is critical for characterizing the HIV epidemic direction. We analyzed pooled data from nationally representative Population-Based HIV Impact Assessment surveys conducted across 14 countries in Africa for recent infection risk factors. We included adults 15-49 years of age who had sex during the previous year and used a recent infection testing algorithm to distinguish recent from long-term infections. We collected risk factor information via participant interviews and assessed correlates of recent infection using multinomial logistic regression, incorporating each survey's complex sampling design. Compared with HIV-negative persons, persons with higher odds of recent HIV infection were women, were divorced/separated/widowed, had multiple recent sex partners, had a recent HIV-positive sex partner or one with unknown status, and lived in communities with higher HIV viremia prevalence. Prevention programs focusing on persons at higher risk for HIV and their sexual partners will contribute to reducing HIV incidence.

Cabotegravir for the prevention of HIV-1 in women: results from HPTN 084, a phase 3, randomised clinical trial.

BACKGROUND: Oral pre-exposure prophylaxis has been introduced in more than 70 countries, including many in sub-Saharan Africa, but women experience considerable barriers to daily pill-taking, such as stigma, judgement, and the fear of violence. Safe and effective long-acting agents for HIV prevention are needed for women. We aimed to evaluate the safety and efficacy of injectable cabotegravir compared with daily oral tenofovir diphosphate plus emtricitabine (TDF-FTC) for HIV prevention in HIV-uninfected women. METHODS: HPTN 084 was a phase 3, randomised, double-blind, double-dummy, active-controlled, superiority trial in 20 clinical research sites in seven countries in sub-Saharan Africa. Participants were eligible for enrolment if they were assigned female sex at birth, were aged 18-45 years, reported at least two episodes of vaginal intercourse in the previous 30 days, were at risk of HIV infection based on an HIV risk score, and agreed to use a long-acting reversible contraceptive method. Participants were randomly assigned (1:1) to either active cabotegravir with TDF-FTC placebo (cabotegravir group) or active TDF-FTC with cabotegravir placebo (TDF-FTC group). Study staff and participants were masked to study group allocation, with the exception of the site pharmacist who was responsible for study product preparation. Participants were prescribed 5 weeks of daily oral product followed by intramuscular injections every 8 weeks after an initial 4-week interval load, alongside daily oral pills. Participants who discontinued injections were offered open-label daily TDF-FTC for 48 weeks. The primary endpoints of the study were incident HIV infection in the intention-to-treat population, and clinical and laboratory events that were grade 2 or higher in all women who had received at least one dose of study product. This study is registered with ClinicalTrials.gov, NCT03164564. FINDINGS: From Nov 27, 2017, to Nov 4, 2020, we enrolled 3224 participants (1614 in the cabotegravir group and 1610 in the TDF-FTC group). Median age was 25 years (IQR 22-30); 1755 (54·7%) of 3209 had two or more partners in the preceding month. 40 incident infections were observed over 3898 person-years (HIV incidence 1·0% [95% CI 0·73-1·40]); four in the cabotegravir group (HIV incidence 0·2 cases per 100 person-years [0·06-0·52]) and 36 in the TDF-FTC group (1·85 cases per 100 person-years [1·3-2·57]; hazard ratio 0·12 [0·05-0·31]; p<0·0001; risk difference -1·6% [-1·0% to -2·3%]. In a random subset of 405 TDF-FTC participants, 812 (42·1%) of 1929 plasma samples had tenofovir concentrations consistent with daily use. Injection coverage was 93% of the total number of person-years. Adverse event rates were similar across both groups, apart from injection site reactions, which were more frequent in the cabotegravir group than in the TDF-FTC group (577 [38·0%] of 1519 vs 162 [10·7%] of 1516]) but did not result in injection discontinuation. Confirmed pregnancy incidence was 1·3 per 100 person-years (0·9-1·7); no congenital birth anomalies were reported. INTERPRETATION: Although both products for HIV prevention were generally safe, well tolerated, and effective, cabotegravir was superior to TDF-FTC in preventing HIV infection in women. FUNDING: National Institute of Allergy and Infectious Diseases, ViiV Healthcare, and the Bill & Melinda Gates Foundation. Additional support was provided through the National Institute of Mental Health, the National Institute on Drug Abuse, and the Eunice Kennedy Shriver National Institute of Child Health and Human Development. ViiV Healthcare and Gilead Sciences provided pharmaceutical support.

Human Immunodeficiency Virus Infection in Adolescents and Mode of Transmission in Southern Africa: A Multinational Analysis of Population-Based Survey Data.

BACKGROUND: Adolescents aged 10-19 years living with human immunodeficiency virus (HIV) (ALHIV), both perinatally infected adolescents (APHIV) and behaviorally infected adolescents (ABHIV), are a growing population with distinct care needs. We characterized the epidemiology of HIV in adolescents included in Population-based HIV Impact Assessments (2015-2017) in Zimbabwe, Malawi, Zambia, Eswatini, and Lesotho. METHODS: Adolescents were tested for HIV using national rapid testing algorithms. Viral load (VL) suppression (VLS) was defined as VL <1000 copies/mL, and undetectable VL (UVL) as VL <50 copies/mL. Recent infection (within 6 months) was measured using a limiting antigen avidity assay, excluding adolescents with VLS or with detectable antiretrovirals (ARVs) in blood. To determine the most likely mode of infection, we used a risk algorithm incorporating recency, maternal HIV and vital status, history of sexual activity, and age at diagnosis. RESULTS: HIV prevalence ranged from 1.6% in Zambia to 4.8% in Eswatini. Of 707 ALHIV, 60.9% (95% confidence interval, 55.3%-66.6%) had HIV previously diagnosed, and 47.1% (41.9%-52.3%) had VLS. Our algorithm estimated that 72.6% of ALHIV (485 of 707) were APHIV, with HIV diagnosed previously in 69.5% of APHIV and 39.4% of ABHIV, and with 65.3% of APHIV and 33.5% of ABHIV receiving ARV treatment. Only 67.2% of APHIV and 60.5% of ABHIV receiving ARVs had UVL. CONCLUSIONS: These findings suggest that two-thirds of ALHIV were perinatally infected, with many unaware of their status. The low prevalence of VLS and UVL in those receiving treatment raises concerns around treatment effectiveness. Expansion of opportunities for HIV diagnoses and the optimization of treatment are imperative.

Low rates of prior HIV testing among HIV-positive adults accessing outpatient services in Eswatini.

Prior HIV testing and awareness of HIV-positive status were assessed among HIV-positive adults at 20 clinics in Eswatini. Of 2196 HIV-positive adults, 1183 (53.8%) reported no prior HIV testing, and 1948 (88.7%) were unaware of their HIV-positive status. Males [adjusted odds ratio, AOR, (95% confidence interval): 0.7 (0.5-0.9)], youth 18-25 years [AOR 0.6 (0.4-0.95)], adults ≥ 50 years [AOR 0.5 (0.3-0.9)], those needing family support [AOR 0.6 (0.5-0.8)], and those living ≥ 45 min from clinic [AOR 0.5 (0.4-0.8)] were less likely to know their HIV-positive status. More HIV testing is needed to achieve 95-95-95 targets, with targeted strategies for those less likely to test for HIV.

Healthcare worker experiences with Option B+ for prevention of mother-to-child HIV transmission in eSwatini: findings from a two-year follow-up study.

BACKGROUND: Prevention of mother-to-child transmission (PMTCT) across sub-Saharan Africa has rapidly shifted towards Option B+, an approach in which all HIV+ pregnant and breastfeeding women initiate lifelong antiretroviral therapy (ART) independent of CD4+ count. Healthcare workers (HCW) are critical to the success of Option B+, yet little is known regarding HCW acceptability of Option B+, particularly over time. METHODS: Ten health facilities in the Manzini and Lubombo regions of eSwatini transitioned from Option A to Option B+ between 2013 and 2014 as part of the Safe Generations study examining PMTCT retention. Fifty HCWs (5 per facility) completed questionnaires assessing feasibility and acceptability: (1) prior to transitioning to Option B+, (2) two months post transition, and (3) approximately 2 years post Option B+ transition. This analysis describes HCW perceptions and experiences two years after transitioning to Option B+. RESULTS: Two years after transition, 80% of HCWs surveyed reported that Option B+ was easy for HCWs, noting that it was particularly easy to explain and coordinate. Immediate ART initiation also reduced delays by eliminating need for laboratory tests prior to ART initiation. Additionally, HCWs reported ease of patient follow-up (58%), documentation (56%), and counseling (58%) under Option B+. Findings also indicate that a majority of HCWs reported that their workloads increased under Option B+. Sixty-eight percent of HCWs at two years post-transition reported more work under Option B+, specifically noting increased involvement in adherence counseling, prescribing/monitoring medications, and appointment scheduling/tracking. Some HCWs attributed their higher workloads to increased client loads, now that all HIV-positive women were initiated on ART. New barriers to patient uptake, and issues related to retention, adherence, and follow-up were also noted as challenges face by HCW when implementing Option B+. CONCLUSIONS: Overall, HCWs found Option B+ to be acceptable and feasible while providing critical insights into the practical issues of universal ART. Further strengthening of the healthcare system may be necessary to alleviate worker burden and to ensure effective monitoring of client retention and adherence. HCW perceptions and experiences with Option B+ should be considered more broadly as countries implement Option B+ and consider universal treatment for all HIV+ individuals. TRIAL REGISTRATION: http://clinicaltrials.gov NCT01891799 , registered on July 3, 2013.

Effectiveness of a combination strategy for linkage and retention in adult HIV care in Swaziland: The Link4Health cluster randomized trial.

BACKGROUND: Gaps in the HIV care continuum contribute to poor health outcomes and increase HIV transmission. A combination of interventions targeting multiple steps in the continuum is needed to achieve the full beneficial impact of HIV treatment. METHODS AND FINDINGS: Link4Health, a cluster-randomized controlled trial, evaluated the effectiveness of a combination intervention strategy (CIS) versus the standard of care (SOC) on the primary outcome of linkage to care within 1 month plus retention in care at 12 months after HIV-positive testing. Ten clusters of HIV clinics in Swaziland were randomized 1:1 to CIS versus SOC. The CIS included point-of-care CD4+ testing at the time of an HIV-positive test, accelerated antiretroviral therapy (ART) initiation for treatment-eligible participants, mobile phone appointment reminders, health educational packages, and noncash financial incentives. Secondary outcomes included each component of the primary outcome, mean time to linkage, assessment for ART eligibility, ART initiation and time to ART initiation, viral suppression defined as HIV-1 RNA < 1,000 copies/mL at 12 months after HIV testing among patients on ART ≥6 months, and loss to follow-up and death at 12 months after HIV testing. A total of 2,197 adults aged ≥18 years, newly tested HIV positive, were enrolled from 19 August 2013 to 21 November 2014 (1,096 CIS arm; 1,101 SOC arm) and followed for 12 months. The median participant age was 31 years (IQR 26-39), and 59% were women. In an intention-to-treat analysis, 64% (705/1,096) of participants at the CIS sites achieved the primary outcome versus 43% (477/1,101) at the SOC sites (adjusted relative risk [RR] 1.52, 95% CI 1.19-1.96, p = 0.002). Participants in the CIS arm versus the SOC arm had the following secondary outcomes: linkage to care regardless of retention at 12 months (RR 1.08, 95% CI 0.97-1.21, p = 0.13), mean time to linkage (2.5 days versus 7.5 days, p = 0.189), retention in care at 12 months regardless of time to linkage (RR 1.48, 95% CI 1.18-1.86, p = 0.002), assessment for ART eligibility (RR 1.20, 95% CI 1.07-1.34, p = 0.004), ART initiation (RR 1.16, 95% CI 0.96-1.40, p = 0.12), mean time to ART initiation from time of HIV testing (7 days versus 14 days, p < 0.001), viral suppression among those on ART for ≥6 months (RR 0.97, 95% CI 0.88-1.07, p = 0.55), loss to follow-up at 12 months after HIV testing (RR 0.56, 95% CI 0.40-0.79, p = 0.002), and death (N = 78) within 12 months of HIV testing (RR 0.80, 95% CI 0.46-1.35, p = 0.41). Limitations of this study include a small number of clusters and the inability to evaluate the incremental effectiveness of individual components of the combination strategy. CONCLUSIONS: A combination strategy inclusive of 5 evidence-based interventions aimed at multiple steps in the HIV care continuum was associated with significant increase in linkage to care plus 12-month retention. This strategy offers promise of enhanced outcomes for HIV-positive patients. TRIAL REGISTRATION: ClinicalTrials.gov NCT01904994.

Lower Levels of Antiretroviral Therapy Enrollment Among Men with HIV Compared with Women - 12 Countries, 2002-2013.

Equitable access to antiretroviral therapy (ART) for men and women with human immunodeficiency virus (HIV) infection is a principle endorsed by most countries and funding bodies, including the U.S. President's Emergency Plan for AIDS (acquired immunodeficiency syndrome) Relief (PEPFAR) (1). To evaluate gender equity in ART access among adults (defined for this report as persons aged ≥15 years), 765,087 adult ART patient medical records from 12 countries in five geographic regions* were analyzed to estimate the ratio of women to men among new ART enrollees for each calendar year during 2002-2013. This annual ratio was compared with estimates from the Joint United Nations Programme on HIV/AIDS (UNAIDS)(†) of the ratio of HIV-infected adult women to men in the general population. In all 10 African countries and Haiti, the most recent estimates of the ratio of adult women to men among new ART enrollees significantly exceeded the UNAIDS estimates for the female-to-male ratio among HIV-infected adults by 23%-83%. In six African countries and Haiti, the ratio of women to men among new adult ART enrollees increased more sharply over time than the estimated UNAIDS female-to-male ratio among adults with HIV in the general population. Increased ART coverage among men is needed to decrease their morbidity and mortality and to reduce HIV incidence among their sexual partners. Reaching more men with HIV testing and linkage-to-care services and adoption of test-and-treat ART eligibility guidelines (i.e., regular testing of adults, and offering treatment to all infected persons with ART, regardless of CD4 cell test results) could reduce gender inequity in ART coverage.

Advanced HIV disease at entry into HIV care and initiation of antiretroviral therapy during 2006-2011: findings from four sub-saharan African countries.

BACKGROUND: Timely antiretroviral therapy (ART) initiation requires early diagnosis of human immunodeficiency virus (HIV) infection with prompt enrollment and engagement in HIV care. METHODS: We examined programmatic data on 334 557 adults enrolling in HIV care, including 149 032 who initiated ART during 2006-2011 at 132 facilities in Kenya, Mozambique, Rwanda, and Tanzania. We examined trends in advanced HIV disease (CD4+ count <100 cells/µL or World Health Organization disease stage IV) and determinants of advanced HIV disease at ART initiation. RESULTS: Between 2006-2011, the median CD4+ count at ART initiation increased from 125 to 185 cells/µL an increase of 10 cells/year. Although the proportion of patients initiating ART with advanced HIV disease decreased from 42% to 29%, sex disparities widened. In 2011, the odds of advanced disease at ART initiation were higher among men (adjusted odds ratio [AOR], 1.4; 95% CI, 1.3-1.5), those on tuberculosis treatment (AOR, 1.6; 95% CI, 1.3-2.0), and those with a ≥ 12 month gap in pre-ART care (AOR, 2.0; 95% CI, 1.6-2.6). CONCLUSIONS: Intensified efforts are needed to identify and link HIV-infected individuals to care earlier and to retain them in continuous pre-ART care to facilitate more timely ART initiation.

Antiretroviral therapy enrollment characteristics and outcomes among HIV-infected adolescents and young adults compared with older adults--seven African countries, 2004-2013.

Although scale-up of antiretroviral therapy (ART) since 2005 has contributed to declines of about 30% in the global annual number of human immunodeficiency (HIV)-related deaths and declines in global HIV incidence, estimated annual HIV-related deaths among adolescents have increased by about 50% and estimated adolescent HIV incidence has been relatively stable. In 2012, an estimated 2,500 (40%) of all 6,300 daily new HIV infections occurred among persons aged 15-24 years. Difficulty enrolling adolescents and young adults in ART and high rates of loss to follow-up (LTFU) after ART initiation might be contributing to mortality and HIV incidence in this age group, but data are limited. To evaluate age-related ART retention challenges, data from retrospective cohort studies conducted in seven African countries among 16,421 patients, aged ≥15 years at enrollment, who initiated ART during 2004-2012 were analyzed. ART enrollment and outcome data were compared among three groups defined by age at enrollment: adolescents and young adults (aged 15-24 years), middle-aged adults (aged 25-49 years), and older adults (aged ≥50 years). Enrollees aged 15-24 years were predominantly female (81%-92%), commonly pregnant (3%-32% of females), unmarried (54%-73%), and, in four countries with employment data, unemployed (53%-86%). In comparison, older adults were more likely to be male (p<0.001), employed (p<0.001), and married, (p<0.05 in five countries). Compared with older adults, adolescents and young adults had higher LTFU rates in all seven countries, reaching statistical significance in three countries in crude and multivariable analyses. Evidence-based interventions to reduce LTFU for adolescent and young adult ART enrollees could help reduce mortality and HIV incidence in this age group.

Low risk of attrition among adults on antiretroviral therapy in the Rwandan national program: a retrospective cohort analysis of 6, 12, and 18 month outcomes.

BACKGROUND: We report levels and determinants of attrition in Rwanda, one of the few African countries with universal ART access. METHODS: We analyzed data abstracted from health facility records of a nationally representative sample of adults [≥ 18 years] who initiated ART 6, 12, and 18 months prior to data collection; and collected facility characteristics with a health facility assessment questionnaire. Weighted proportions and rates of attrition [loss to follow-up or death] were calculated, and patient- and health facility-level factors associated with attrition examined using Cox proportional hazard models. RESULTS: 1678 adults initiated ART 6, 12 and 18 months prior to data collection, with 1508 person-years [PY] on ART. Attrition was 6.8% [95% confidence interval [CI] 6.0-7.8]: 2.9% [2.4-3.5] recorded deaths and 3.9% [3.4-4.5] lost to follow-up. Population attrition rate was 7.5/100 PY [6.1-9.3]. Adjusted hazard ratio [aHR] for attrition was 4.2 [3.0-5.7] among adults enrolled from in-patient wards [vs 2.2 [1.6-3.0] from PMTCT, ref: VCT]. Compared to adults who initiated ART 18 months earlier, aHR for adults who initiated ART 12 and 6 months earlier was 1.8 [1.3-2.5] and 1.3 [0.9-1.9] respectively. Male aHR was 1.4 [1.0-1.8]. AHR of adults enrolled at urban health facilities was 1.4 [1.1-1.8, ref: rural health facilities]. AHR for adults with CD4+ ≥ 200 cells/µL vs <200 cells/µL was 0.8 [0.6-1.0]; and adults attending facilities with performance-based financing since 2004-2006 [vs. 2007-2008] had aHR 0.8 [0.6-0.9]. CONCLUSIONS: Attrition was low in the Rwandan national program. The above patient and facility correlates of attrition can be the focus of interventions to sustain high retention.

Prevalence of monoclonal gammopathy of undetermined significance in eswatini: a Population-Based study in africa.

PURPOSE: Although monoclonal gammopathy of undetermined significance (MGUS) and multiple myeloma disproportionately affect Black individuals, few epidemiologic studies have been conducted on these plasma cell disorders in Africa. Here we describe the prevalence of MGUS in Eswatini and compare our results to the landmark Olmsted County, USA study. METHODS: Between 2016 and 2017, 13,339 residents of Eswatini participated in the Swaziland HIV Incidence Measurement Survey, from which a nationally-representative biorepository was created. Plasma samples were then randomly selected and analyzed for MGUS. MGUS prevalence in Eswatini was compared to that of Olmsted County. Additionally, demographic and HIV-related associations with MGUS were assessed. RESULTS: Of the 515 samples randomly selected, the median age was 50 years (range 35-80) and 60% were female; 38.6% were HIV-positive, of whom 82.4% were on antiretroviral therapy. We found that 68 had evidence of MGUS for a prevalence of 13.2%. HIV status was not significantly associated with MGUS (OR, 1.05; 95%CI, 0.62-1.77), but among HIV-positive individuals, MGUS was less frequent for those on antiretroviral therapy (adjusted OR, 0.31; 95%CI, 0.11-0.82). The prevalence of conventional MGUS was similar between Eswatini and Olmsted County (3.4% vs 3.2-3.4%), while light-chain MGUS was significantly greater in Eswatini (12.3% vs 0.8%). CONCLUSION: Our study suggests that the incidence of MGUS is similar between ethnicities and raises the question of whether the current definition of light-chain MGUS reliably reflects a true monoclonal protein precursor state. Perhaps the current definition of light-chain MGUS may be capturing alternate etiologies, such as untreated HIV infection.

Brief Report: Self-Reported HIV-Positive Status but Subsequent HIV-Negative Test Results in Population-Based HIV Impact Assessment Survey Participants-11 Sub-Saharan African Countries, 2015-2018.

BACKGROUND: HIV testing is a critical step to accessing antiretroviral therapy (ART) because early diagnosis can facilitate earlier initiation of ART. This study presents aggregated data of individuals who self-reported being HIV-positive but subsequently tested HIV-negative during nationally representative Population-Based HIV Impact Assessment surveys conducted in 11 countries from 2015 to 2018. METHOD: Survey participants aged 15 years or older were interviewed by trained personnel using a standard questionnaire to determine HIV testing history and self-reported HIV status. Home-based HIV testing and counseling using rapid diagnostic tests with return of results were performed by survey staff according to the respective national HIV testing services algorithms on venous blood samples. Laboratory-based confirmatory HIV testing for all participants identified as HIV-positives and self-reported positives, irrespective of HIV testing results, was conducted and included Geenius HIV-1/2 and DNA polymerase chain reaction if Geenius was negative or indeterminate. RESULTS: Of the 16,630 participants who self-reported as HIV-positive, 16,432 (98.6%) were confirmed as HIV-positive and 198 (1.4%) were HIV-negative by subsequent laboratory-based testing. Participants who self-reported as HIV-positive but tested HIV-negative were significantly younger than 30 years, less likely to have received ART, and less likely to have received a CD4 test compared with participants who self-reported as HIV-positive with laboratory-confirmed infection. CONCLUSIONS: A small proportion of self-reported HIV-positive individuals could not be confirmed as positive, which could be due to initial misdiagnosis, deliberate wrong self-report, or misunderstanding of the questionnaire. As universal ART access is expanding, it is increasingly important to ensure quality of HIV testing and confirmation of HIV diagnosis before ART initiation.

HIV risk behaviour, viraemia, and transmission across HIV cascade stages including low-level viremia: Analysis of 14 cross-sectional population-based HIV Impact Assessment surveys in sub-Saharan Africa.

As antiretroviral treatment (ART) coverage for people living with HIV (PLHIV) increases, HIV programmes require up-to-date information about evolving HIV risk behaviour and transmission risk, including those with low-level viremia (LLV; >50 to ≤1000 copies/mL), to guide prevention priorities. We aimed to assess differences in sexual risk behaviours, distribution of viral load (VL) and proportion of transmission across PLHIV subgroups. We analysed data from Population-based HIV Impact Assessment surveys in 14 sub-Saharan African countries during 2015-2019. We estimated adjusted prevalence ratios (aPR) of self-reported HIV high-risk behaviour (multiple partners and condomless sex) across cascade stages via generalised estimation equations. We modelled the proportions of transmission from each subgroup using relative self-reported sexual risk, a Hill function for transmission rate by VL, and proportions within cascade stages from surveys and UNAIDS country estimates for 2010-2020. Compared to PLHIV with undetectable VL (≤50 copies/mL), undiagnosed PLHIV (aPR women: 1.28 [95% CI: 1.08-1.52]; men: 1.61 [1.33-1.95]) and men diagnosed but untreated (2.06 [1.52-2.78]) were more likely to self-report high-risk sex. High-risk behaviour was not significantly associated with LLV. Mean VL was similar among undiagnosed, diagnosed but untreated, and on ART but non-suppressed sub-groups. Across surveys, undiagnosed and diagnosed but untreated contributed most to transmission (40-91% and 1-41%, respectively), with less than 1% from those with LLV. Between 2010 and 2020, the proportion of transmission from individuals on ART but non-suppressed increased. In settings with high ART coverage, effective HIV testing, ART linkage, and retention remain priorities to reduce HIV transmission. Persons with LLV are an increasing share of PLHIV but their contribution to HIV transmission was small. Improving suppression among PLHIV on ART with VL ≥1000 copies/mL will become increasingly important.

Reviewing progress: 7 year trends in characteristics of adults and children enrolled at HIV care and treatment clinics in the United Republic of Tanzania.

BACKGROUND: To evaluate the on-going scale-up of HIV programs, we assessed trends in patient characteristics at enrolment and ART initiation over 7 years of implementation. METHODS: Data were from Optimal Models, a prospective open cohort study of HIV-infected (HIV+) adults (≥15 years) and children (<15 years) enrolled from January 2005 to December 2011 at 44 HIV clinics in 3 regions of mainland Tanzania (Kagera, Kigoma, Pwani) and Zanzibar. Comparative statistics for trends in characteristics of patients enrolled in 2005-2007, 2008-2009 and 2010-2011 were examined. RESULTS: Overall 62,801 HIV + patients were enrolled: 58,102(92.5%) adults, (66.5% female); 4,699(7.5%) children.Among adults, pregnant women enrolment increased: 6.8%, 2005-2007; 12.1%, 2008-2009; 17.2%, 2010-2011; as did entry into care from prevention of mother-to-child HIV transmission (PMTCT) programs: 6.6%, 2005-2007; 9.5%, 2008-2009; 12.6%, 2010-2011. WHO stage IV at enrolment declined: 27.1%, 2005-2007; 20.2%, 2008-2009; 11.1% 2010-2011. Of the 42.5% and 29.5% with CD4+ data at enrolment and ART initiation respectively, median CD4+ count increased: 210 cells/µL, 2005-2007; 262 cells/µL, 2008-2009; 266 cells/µL 2010-2011; but median CD4+ at ART initiation did not change (148 cells/µL overall). Stavudine initiation declined: 84.9%, 2005-2007; 43.1%, 2008-2009; 19.7%, 2010-2011.Among children, median age (years) at enrolment decreased from 6.1(IQR:2.7-10.0) in 2005-2007 to 4.8(IQR:1.9-8.6) in 2008-2009, and 4.1(IQR:1.5-8.1) in 2010-2011 and children <24 months increased from 18.5% to 26.1% and 31.5% respectively. Entry from PMTCT was 7.0%, 2005-2007; 10.7%, 2008-2009; 15.0%, 2010-2011. WHO stage IV at enrolment declined from 22.9%, 2005-2007, to 18.3%, 2008-2009 to 13.9%, 2010-2011. Proportion initiating stavudine was 39.8% 2005-2007; 39.5%, 2008-2009; 26.1%, 2010-2011. Median age at ART initiation also declined significantly. CONCLUSIONS: Over time, the proportion of pregnant women and of adults and children enrolled from PMTCT programs increased. There was a decline in adults and children with advanced HIV disease at enrolment and initiation of stavudine. Pediatric age at enrolment and ART initiation declined. Results suggest HIV program maturation from an emergency response.

"Our parents kiss in front of us": Reasons for early sexual debut among in-school youth in the Manzini Region in Eswatini.

BACKGROUND: Early sexual debut (i.e., sex before the age of 15 years), especially if it is unprotected, may increase the risk of acquiring HIV, sexually transmitted infections, and unwanted pregnancies. We investigated the reasons for early sexual debut among in-school youth in Eswatini, a setting with high HIV incidence among youth. METHODS: This was a qualitative, exploratory-descriptive study whereby data were collected from 81 sexually active in-school youth through seven focus group discussions (FGDs) in four purposively selected public high schools (two urban and two rural) in the Manzini region, Eswatini. In each school, except one, two FGDs (one for boys and one for girls) were conducted. Qualitative data were coded and analyzed thematically in Dedoose version 8.2.14. RESULTS: Nearly 40% of the participants reported having initiated sexual activity before 18 years. Six major themes emerged from the data: i) Intrapersonal factors (feeling mature, religiosity, nutritional or dietary patterns); ii) Parenting and household factors (living arrangement, lack of sexuality education, working parents, negative role-modeling from adults); iii) Peer and partner pressure (pressure from friends, threats from sexual partners, intergenerational sexual partnerships and transactional sex, testing sexual prowess, desire to fit in); iv) Contextual factors (neighborhood, location); v) Mass media (cell phone ownership, social media, and television shows or movies); and vi) Cultural factors (attending traditional ceremonies, loss of cultural norms, values, and traditions, and dress code). CONCLUSION AND RECOMMENDATIONS: The poor monitoring and negative role-modeling by elders highlight the importance of involving parents or guardians as key stakeholders when designing interventions targeting risky sexual behavior among youth. The multifaceted nature of the cited reasons for early sexual debut calls for interventions aimed at curbing risky sexual behavior to be culturally sensitive and responsive to the themes identified in this study.

Male partner age, viral load, and HIV infection in adolescent girls and young women: evidence from eight sub-Saharan African countries.

OBJECTIVE: We aimed to elucidate the role of partnerships with older men in the HIV epidemic among adolescent girls and young women (AGYW) aged 15-24 years in sub-Saharan Africa. DESIGN: Analysis of Population-based HIV Impact Assessments in Eswatini, Lesotho, Malawi, Namibia, Tanzania, Uganda, Zambia, and Zimbabwe. METHODS: We examined associations between reported partner age and recent HIV infection among AGYW, incorporating male population-level HIV characteristics by age-band. Recent HIV infection was defined using the LAg avidity assay algorithm. Viremia was defined as a viral load of more than 1000 copies/ml, regardless of serostatus. Logistic regression compared recent infection in AGYW with older male partners to those reporting younger partners. Dyadic analysis examined cohabitating male partner age, HIV status, and viremia to assess associations with AGYW infection. RESULTS: Among 17 813 AGYW, increasing partner age was associated with higher odds of recent infection, peaking for partners aged 35-44 (adjusted odds ratio = 8.94, 95% confidence interval: 2.63-30.37) compared with partners aged 15-24. Population-level viremia was highest in this male age-band. Dyadic analyses of 5432 partnerships confirmed the association between partner age-band and prevalent HIV infection (male spousal age 35-44-adjusted odds ratio = 3.82, 95% confidence interval: 2.17-6.75). Most new infections were in AGYW with partners aged 25-34, as most AGYW had partners in this age-band. CONCLUSION: These results provide evidence that men aged 25-34 drive most AGYW infections, but partners over 9 years older than AGYW in the 35-44 age-band confer greater risk. Population-level infectiousness and male age group should be incorporated into identifying high-risk typologies in AGYW.

The epidemiology of HIV population viral load in twelve sub-Saharan African countries.

BACKGROUND: We examined the epidemiology and transmission potential of HIV population viral load (VL) in 12 sub-Saharan African countries. METHODS: We analyzed data from Population-based HIV Impact Assessments (PHIAs), large national household-based surveys conducted between 2015 and 2019 in Cameroon, Cote d'Ivoire, Eswatini, Kenya, Lesotho, Malawi, Namibia, Rwanda, Tanzania, Uganda, Zambia, and Zimbabwe. Blood-based biomarkers included HIV serology, recency of HIV infection, and VL. We estimated the number of people living with HIV (PLHIV) with suppressed viral load (<1,000 HIV-1 RNA copies/mL) and with unsuppressed viral load (viremic), the prevalence of unsuppressed HIV (population viremia), sex-specific HIV transmission ratios (number female incident HIV-1 infections/number unsuppressed male PLHIV per 100 persons-years [PY] and vice versa) and examined correlations between a variety of VL metrics and incident HIV. Country sample sizes ranged from 10,016 (Eswatini) to 30,637 (Rwanda); estimates were weighted and restricted to participants 15 years and older. RESULTS: The proportion of female PLHIV with viral suppression was higher than that among males in all countries, however, the number of unsuppressed females outnumbered that of unsuppressed males in all countries due to higher overall female HIV prevalence, with ratios ranging from 1.08 to 2.10 (median: 1.43). The spatial distribution of HIV seroprevalence, viremia prevalence, and number of unsuppressed adults often differed substantially within the same countries. The 1% and 5% of PLHIV with the highest VL on average accounted for 34% and 66%, respectively, of countries' total VL. HIV transmission ratios varied widely across countries and were higher for male-to-female (range: 2.3-28.3/100 PY) than for female-to-male transmission (range: 1.5-10.6/100 PY). In all countries mean log10 VL among unsuppressed males was higher than that among females. Correlations between VL measures and incident HIV varied, were weaker for VL metrics among females compared to males and were strongest for the number of unsuppressed PLHIV per 100 HIV-negative adults (R2 = 0.92). CONCLUSIONS: Despite higher proportions of viral suppression, female unsuppressed PLHIV outnumbered males in all countries examined. Unsuppressed male PLHIV have consistently higher VL and a higher risk of transmitting HIV than females. Just 5% of PLHIV account for almost two-thirds of countries' total VL. Population-level VL metrics help monitor the epidemic and highlight key programmatic gaps in these African countries.

Estimates of the prevalence of undiagnosed HIV among children living with HIV in Eswatini, Lesotho, Malawi, Namibia, Tanzania, Zambia, and Zimbabwe from 2015 to 2017: an analysis of data from the cross-sectional Population-based HIV Impact Assessment surveys.

BACKGROUND: In 2020, there were an estimated 1·7 million children younger than 15 years living with HIV worldwide, but there are few data on the proportion of children living with HIV who are undiagnosed. We aimed to estimate the prevalence of undiagnosed HIV among children living with HIV in Eswatini, Lesotho, Malawi, Namibia, Tanzania, Zambia, and Zimbabwe. METHODS: We conducted an analysis of data from the cross-sectional Population-based HIV Impact Assessment (PHIA) surveys from 2015 to 2017. PHIAs are nationally representative surveys measuring HIV outcomes. HIV rapid test data (with PCR confirmatory testing for children aged <18 months) were used to measure HIV prevalence among children in each country (Eswatini, Lesotho, Malawi, Namibia, Tanzania, Zambia, and Zimbabwe). Mothers or guardians reported previous HIV testing of children and previous results. Detection of antiretroviral medications was done using dried blood spots. Children who tested positive in the PHIA with previous negative or unknown HIV test results and without detectable antiretroviral medication blood concentrations were considered previously undiagnosed; all other children who tested positive were considered previously diagnosed. Survey weights with jackknife variance were used to generate national estimates of HIV prevalence and undiagnosed HIV in children aged 1-14 years. We also report the prevalence (weighted proportions) of antiretroviral therapy coverage and viral load suppression (<400 copies per mL). FINDINGS: Between 2015 and 2017, 42 248 children aged 1-14 years were included in the surveys, of whom 594 were living with HIV. Across the seven countries, the estimated weighted HIV prevalence was 0·9% (probability band 0·7-1·1) and we estimated that there were 425 000 (probability band 365 000-485 000) children living with HIV. Among all children living with HIV, 61·0% (n=259 000 [probability band 216 000-303 000]) were previously diagnosed and 39·0% (n=166 000 [128 000-204 000]) had not been previously diagnosed with HIV. Among previously diagnosed children living with HIV, 88·4% had detectable antiretroviral medication blood concentrations and 48·3% had viral load suppression. Among all children living with HIV (regardless of previous diagnosis status), 54·7% had detectable antiretroviral medication blood concentrations and 32·6% had viral load suppression. INTERPRETATION: Our findings show the uneven coverage of paediatric HIV testing across these seven countries and underscore the urgent need to address gaps in diagnosis and treatment for all children living with HIV. FUNDING: None.