Aetiology of vaginal discharge, urethral discharge, and genital ulcer in sub-Saharan Africa: A systematic review and meta-regression.

BACKGROUND: Syndromic management is widely used to treat symptomatic sexually transmitted infections in settings without aetiologic diagnostics. However, underlying aetiologies and consequent treatment suitability are uncertain without regular assessment. This systematic review estimated the distribution, trends, and determinants of aetiologies for vaginal discharge, urethral discharge, and genital ulcer in sub-Saharan Africa (SSA). METHODS AND FINDINGS: We searched Embase, MEDLINE, Global Health, Web of Science, and grey literature from inception until December 20, 2023, for observational studies reporting aetiologic diagnoses among symptomatic populations in SSA. We adjusted observations for diagnostic test performance, used generalised linear mixed-effects meta-regressions to generate estimates, and critically appraised studies using an adapted Joanna Briggs Institute checklist. Of 4,418 identified records, 206 reports were included from 190 studies in 32 countries conducted between 1969 and 2022. In 2015, estimated primary aetiologies for vaginal discharge were candidiasis (69.4% [95% confidence interval (CI): 44.3% to 86.6%], n = 50), bacterial vaginosis (50.0% [95% CI: 32.3% to 67.8%], n = 39), chlamydia (16.2% [95% CI: 8.6% to 28.5%], n = 50), and trichomoniasis (12.9% [95% CI: 7.7% to 20.7%], n = 80); for urethral discharge were gonorrhoea (77.1% [95% CI: 68.1% to 84.1%], n = 68) and chlamydia (21.9% [95% CI: 15.4% to 30.3%], n = 48); and for genital ulcer were herpes simplex virus type 2 (HSV-2) (48.3% [95% CI: 32.9% to 64.1%], n = 47) and syphilis (9.3% [95% CI: 6.4% to 13.4%], n = 117). Temporal variation was substantial, particularly for genital ulcer where HSV-2 replaced chancroid as the primary cause. Aetiologic distributions for each symptom were largely the same across regions and population strata, despite HIV status and age being significantly associated with several infection diagnoses. Limitations of the review include the absence of studies in 16 of 48 SSA countries, substantial heterogeneity in study observations, and impeded assessment of this variability due to incomplete or inconsistent reporting across studies. CONCLUSIONS: In our study, syndrome aetiologies in SSA aligned with World Health Organization guidelines without strong evidence of geographic or demographic variation, supporting broad guideline applicability. Temporal changes underscore the importance of regular aetiologic re-assessment for effective syndromic management. PROSPERO NUMBER: CRD42022348045.

Exploring Self-reported Adherence Measures to Screen for Elevated HIV Viral Load in Adolescents: A South African Cohort Study.

The timely identification of ART non-adherence among adolescents living with HIV presents a significant challenge, particularly in resource-limited settings where virologic monitoring is suboptimal. Using South African adolescent cohort data (N = 933, mean age 13.6 ± 2.89 years, 55.1% female, follow-up = 2014-2018), we examined the association between elevated viral load (VL ≥ 1000 copies/mL) and seven self-reported adherence measures on missed doses, and clinic appointments -with varying recall timeframes. The best performing measures, which were significantly associated with elevated viral load in covariate-adjusted models are: any missed dose -past 3 days (sensitivity = 91.6% [95%CI: 90.3-92.8], positive predictive value (PPV) = 78.8% [95%CI: 77.2-80.4]), -past week (sensitivity = 87% [95%CI: 85.4-88.6], PPV = 78.2% [95%CI: 76.5-79.9]), -past month (sensitivity = 79.5% [95%CI: 77.5-81.4], PPV = 78.2% [95%CI: 76.4-79.9]), any past-month days missed (sensitivity = 86.7% [95%CI: 85.1-88.3], PPV = 77.9% [95%CI:76.2-79.6]), and any missed clinic appointment (sensitivity = 88.3% [95%CI: 86.8-89.8], PPV = 78.4% [95%CI: 76.8-79.9]). Combining the three best performing measures missed dose -past 3 days, -past week, and any past-year missed clinic appointment increased sensitivity to 96.4% while maintaining a PPV of about 78%. The discriminatory power of simple and easy-to-administer self-reported adherence measures in detecting elevated viral load warrants consideration in resource-limited settings and may contribute to the aims of the new Global Alliance to End AIDS in children and adolescents by 2030.

Longitudinal Trajectories of Antiretroviral Treatment Adherence and Associations With Durable Viral Suppression Among Adolescents Living With HIV in South Africa.

BACKGROUND: Compared with other age groups, adolescents living with HIV (ALHIV) are estimated to have lower levels of adherence to antiretroviral treatment. Despite this, we lack evidence on adolescents' adherence patterns over time to inform the customization of intervention strategies. SETTING: Eastern Cape province, South Africa. METHODS: We analyzed data from a cohort of ALHIV (N = 1046, aged 10-19 years at baseline) recruited from 53 public health facilities. The cohort comprised 3 waves of data collected between 2014 and 2018 and routine viral load data from the National Institute for Communicable Disease data warehouse (2014-2019). Durable viral suppression was defined as having suppressed viral load (<1000 copies/mL) at ≥2 consecutive study waves. Group-based multitrajectory model was used to identify adherence trajectories using 5 indicators of self-reported adherence. Logistic regression modeling evaluated the associations between adherence trajectories and durable viral suppression. RESULTS: Overall, 933 ALHIV (89.2%) completed all 3 study waves (55.1% female, mean age: 13.6 years at baseline). Four adherence trajectories were identified, namely, "consistent adherence" (49.8%), "low start and increasing" (20.8%), "gradually decreasing" (23.5%), and "low and decreasing" (5.9%). Adolescents experiencing inconsistent adherence trajectories were more likely to be older, live in rural areas, and have sexually acquired HIV. Compared with the consistent adherence trajectory, the odds of durable viral suppression were lower among adolescents in the low start and increasing (adjusted odds ratio [aOR]: 0.62, 95% CI: 0.41 to 0.95), gradually decreasing (aOR: 0.40, 95% CI: 0.27 to 0.59), and the low and decreasing adherence (aOR: 0.25, 95% CI: 0.10 to 0.62) trajectories. CONCLUSIONS: Adherence to antiretroviral treatment remains a challenge among ALHIV in South Africa. Identifying adolescents at risk of nonadherence, based on their adherence trajectories may inform the tailoring of adolescent-friendly support strategies.

Are social protection and food security accelerators for adolescents to achieve the Global AIDS targets?

INTRODUCTION: Without effective, scalable interventions, we will fail to achieve the Global AIDS Targets of zero AIDS-related deaths, zero HIV transmission and zero discrimination. This study examines associations of social protection and food security among adolescents living with HIV (ALHIV), with three Global AIDS Targets aligned outcomes: antiretroviral treatment (ART) adherence and viral suppression, HIV transmission risk behaviour and enacted stigma. METHODS: We conducted three study visits over 2014-2018 with 1046 ALHIV in South Africa's Eastern Cape province. Standardized surveys provided information on receipt of government-provided cash transfers and past-week food security, alongside self-reported ART adherence, sexual debut and condom use, and enacted HIV-related stigma. Viral load (VL) data was obtained through data extraction from patient files and linkage with National Health Laboratory Service test results (2014-2020). We used a multivariable random-effects regression model to estimate associations between receiving government cash transfers and food security and three outcomes: ART adherence and viral suppression, delayed sexual debut or consistent condom use and no enacted stigma. We tested moderation by sex and age and fitted disaggregated models for each outcome. RESULTS: Among the 933 ALHIV completing all three study visits, 55% were female, and the mean age was 13.6 years at baseline. Household receipt of a government cash transfer was associated with improvements on all outcomes: ART adherence and viral suppression (aOR 2.03, 95% CI 1.29-3.19), delayed sexual debut or consistent condom use (aOR 1.62, 95% CI 1.16-2.27) and no enacted stigma (aOR 2.33, 95% CI 1.39-3.89). Food security was associated with improvements on all outcomes: ART adherence and viral suppression (aOR 1.73, 95% CI 1.30-2.30), delayed sexual debut or consistent condom use (aOR 1.30, 95% CI 1.03-1.64) and no enacted stigma (aOR 1.91, 95% CI 1.32-2.76). Receiving both cash transfers and food security increased the probability of ART adherence and VL suppression from 36% to 60%; delayed sexual debut or consistent condom use from 67% to 81%; and no enacted stigma from 84% to 96%. CONCLUSIONS: Government-provided cash transfers and food security, individually and in combination, are associated with improved outcomes for ALHIV aligned with Global AIDS Targets. They may be important, and underutilized, accelerators for achieving these targets.

Healthcare provisions associated with multiple HIV-related outcomes among adolescent girls and young women living with HIV in South Africa: a cross-sectional study.

INTRODUCTION: Adolescent girls and young women (AGYW) living with HIV experience poor HIV outcomes and high rates of unintended pregnancy. Little is known about which healthcare provisions can optimize their HIV-related outcomes, particularly among AGYW mothers. METHODS: Eligible 12- to 24-year-old AGYW living with HIV from 61 health facilities in a South African district completed a survey in 2018-2019 (90% recruited). Analysing surveys and medical records from n = 774 participants, we investigated associations of multiple HIV-related outcomes (past-week adherence, consistent clinic attendance, uninterrupted treatment, no tuberculosis [TB] and viral suppression) with seven healthcare provisions: no antiretroviral therapy (ART) stockouts, kind and respectful providers, support groups, short travel time, short waiting time, confidentiality, and safe and affordable facilities. Further, we compared HIV-related outcomes and healthcare provisions between mothers (n = 336) and nulliparous participants (n = 438). Analyses used multivariable regression models, accounting for multiple outcomes. RESULTS: HIV-related outcomes were poor, especially among mothers. In multivariable analyses, two healthcare provisions were "accelerators," associated with multiple improved outcomes, with similar results among mothers. Safe and affordable facilities, and kind and respectful staff were associated with higher predicted probabilities of HIV-related outcomes (p<0.001): past-week adherence (62% when neither accelerator was reported to 87% with both accelerators reported), clinic attendance (71%-89%), uninterrupted ART treatment (57%-85%), no TB symptoms (49%-70%) and viral suppression (60%-77%). CONCLUSIONS: Accessible and adolescent-responsive healthcare is critical to improving HIV-related outcomes, reducing morbidity, mortality and onward HIV transmission among AGYW. Combining these provisions can maximize benefits, especially for AGYW mothers.

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.

Impacts of intimate partner violence and sexual abuse on antiretroviral adherence among adolescents living with HIV in South Africa.

OBJECTIVE: We are failing to reach 95-95-95 for adolescents living with HIV (ALHIV). Sexual abuse and intimate partner violence (IPV) may impact antiretroviral therapy (ART) adherence, with high rates of 17.4 and 29.7%, respectively, across the southern sub-Saharan African region. However, evidence on their associations with adolescent ART adherence remains limited, with only three cross-sectional studies globally. DESIGN: A prospective cohort of ALHIV (sample N = 980, 55% female individuals, baseline mean age 13.6 years) were recruited from 53 health facilities in South Africa's Eastern Cape Province and responded to a structured questionnaire at 18-month and 36-month follow-up (2015-2016, 2017-2018). METHODS: A repeated-measures random effects model assessed multivariable associations of self-reported sexual abuse and IPV with past-week ART adherence, controlling for individual, socioeconomic, and HIV-related factors. Past-week adherence was defined based on currently taking ART and not having missed any doses in the past 7 days (including weekends). We further fitted a moderation model by sex. RESULTS: Fifty-one percent of adolescents reported consistent ART adherence at both time points. Exposure to IPV was associated with lower odds of self-reported ART adherence (aOR 0.39, 95% CI 0.21-0.72, P = 0.003), as was sexual abuse (aOR 0.54, 95% CI 0.29-0.99, P = 0.048). The marginal predicted probability of ART adherence for adolescents with no exposure to either IPV or sexual abuse was 72% (95% CI 70-74%) compared with 38% (95% CI 20-56%) for adolescents with exposure to both IPV and sexual abuse. Moderation results showed similar associations between sexual violence and ART adherence by sex. CONCLUSION: Sexual violence prevention and postviolence care may be essential components of supporting adolescent ART adherence. Integration of HIV and violence prevention services will require accessible services and simple referral systems.

Predictors and consequences of HIV status disclosure to adolescents living with HIV in Eastern Cape, South Africa: a prospective cohort study.

INTRODUCTION: The World Health Organization recommends full disclosure of HIV-positive status to adolescents who acquired HIV perinatally (APHIV) by age 12. However, even among adolescents (aged 10-19) already on antiretroviral therapy (ART), disclosure rates are low. Caregivers often report the child being too young and fear of disclosure worsening adolescents' mental health as reasons for non-disclosure. We aimed to identify the predictors of disclosure and the association of disclosure with adherence, viral suppression and mental health outcomes among adolescents in sub-Saharan Africa. METHODS: Analyses included three rounds (2014-2018) of data collected among a closed cohort of adolescents living with HIV in Eastern Cape, South Africa. We used logistic regression with respondent random-effects to identify factors associated with disclosure, and assess differences in ART adherence, viral suppression and mental health symptoms between adolescents by disclosure status. We also explored differences in the change in mental health symptoms and adherence between study rounds and disclosure groups with logistic regression. RESULTS: Eight hundred and thirteen APHIV were interviewed at baseline, of whom 769 (94.6%) and 729 (89.7%) were interviewed at the second and third rounds, respectively. The proportion aware of their HIV-positive status increased from 63.1% at the first round to 85.5% by the third round. Older age (adjusted odds ratio [aOR]: 1.27; 1.08-1.48) and living in an urban location (aOR: 2.85; 1.72-4.73) were associated with disclosure between interviews. There was no association between awareness of HIV-positive status and ART adherence, viral suppression or mental health symptoms among all APHIV interviewed. However, among APHIV not aware of their status at baseline, adherence decreased at the second round among those who were disclosed to (N = 131) and increased among those not disclosed to (N = 151) (interaction aOR: 0.39; 0.19-0.80). There was no significant difference in the change in mental health symptoms between study rounds and disclosure groups. CONCLUSIONS: Awareness of HIV-positive status was not associated with higher rates of mental health symptoms, or lower rates of viral suppression among adolescents. Disclosure was not associated with worse mental health. These findings support the recommendation for timely disclosure to APHIV; however, adherence support post-disclosure is important.

Risk scores for predicting HIV incidence among adult heterosexual populations in sub-Saharan Africa: a systematic review and meta-analysis.

INTRODUCTION: Several HIV risk scores have been developed to identify individuals for prioritized HIV prevention in sub-Saharan Africa. We systematically reviewed HIV risk scores to: (1) identify factors that consistently predicted incident HIV infection, (2) review inclusion of community-level HIV risk in predictive models and (3) examine predictive performance. METHODS: We searched nine databases from inception until 15 February 2021 for studies developing and/or validating HIV risk scores among the heterosexual adult population in sub-Saharan Africa. Studies not prospectively observing seroconversion or recruiting only key populations were excluded. Record screening, data extraction and critical appraisal were conducted in duplicate. We used random-effects meta-analysis to summarize hazard ratios and the area under the receiver-operating characteristic curve (AUC-ROC). RESULTS: From 1563 initial search records, we identified 14 risk scores in 13 studies. Seven studies were among sexually active women using contraceptives enrolled in randomized-controlled trials, three among adolescent girls and young women (AGYW) and three among cohorts enrolling both men and women. Consistently identified HIV prognostic factors among women were younger age (pooled adjusted hazard ratio: 1.62 [95% confidence interval: 1.17, 2.23], compared to above 25), single/not cohabiting with primary partners (2.33 [1.73, 3.13]) and having sexually transmitted infections (STIs) at baseline (HSV-2: 1.67 [1.34, 2.09]; curable STIs: 1.45 [1.17; 1.79]). Among AGYW, only STIs were consistently associated with higher incidence, but studies were limited (n = 3). Community-level HIV prevalence or unsuppressed viral load strongly predicted incidence but was only considered in 3 of 11 multi-site studies. The AUC-ROC ranged from 0.56 to 0.79 on the model development sets. Only the VOICE score was externally validated by multiple studies, with pooled AUC-ROC 0.626 [0.588, 0.663] (I2 : 64.02%). CONCLUSIONS: Younger age, non-cohabiting and recent STIs were consistently identified as predicting future HIV infection. Both community HIV burden and individual factors should be considered to quantify HIV risk. However, HIV risk scores had only low-to-moderate discriminatory ability and uncertain generalizability, limiting their programmatic utility. Further evidence on the relative value of specific risk factors, studies populations not restricted to "at-risk" individuals and data outside South Africa will improve the evidence base for risk differentiation in HIV prevention programmes. PROSPERO NUMBER: CRD42021236367.