A public health approach to addressing and preventing misdiagnosis in the scale-up of HIV rapid testing programmes.

The global impact of the scale-up HIV testing and treatment has been impressive. In 2015, approximately 60% of people with HIV worldwide were aware of their status [1]. As a result by the end of 2015, 17 million people with HIV were on treatment, and global treatment coverage reached 46% [1]. HIV testing and treatment have reduced AIDS-related deaths by 43% since 2003 [1,2]. In order to further increase impact and improve health outcomes, in 2016 the World Health Organization (WHO) recommended antiretroviral therapy (ART) for all people with HIV regardless of disease status [3]. These calls to continue scale-up of testing and treatment and to achieve the United Nation’s (UN) “90-90-90” targets remain a global priority. Achieving the “first 90” by reaching people with HIV who have yet to be diagnosed, and linking them to treatment as early as possible, is a critical first step. Degrees of uncertainty exist with all medical testing and diagnoses; in the field of HIV, advances in diagnostic test technology have made testing accurate and reliable. WHO prequalified HIV rapid diagnostic tests all have a sensitivity of ≥99% and specificity ≥98% and are accurate when used correctly in a validated national algorithm. A large number of tests are conducted every year. Although a degree of error and misdiagnosis can be expected, very few cases of false negative and false positive diagnoses have been reported [4–12]. This lack of reporting on testing error and misdiagnoses is not unique to HIV [13–16]. Publication bias and concerns about programme reputation may have contributed to low reporting of misdiagnosis and limit the open discussion required to address errors systematically [16]. To further investigate diagnostic error, determine common causes, and identify potential ways to address misdiagnosis, particularly in resource-limited settings, WHO, Liverpool School of Tropical Medicine and Médecins Sans Frontières (MSF) held a symposium to address the social, public health, human rights, ethical and legal implications of misdiagnosis of HIV status [17]. This special issue of the Journal of the International AIDS Society follows this symposium by focusing on the individual and public health implications of HIV misdiagnosis

Improving HIV test uptake and case finding with assisted partner notification services.

OBJECTIVE: Despite the enormous expansion of HIV testing services (HTS), an estimated 40% of people with HIV infection remain undiagnosed. To enhance the efficiency of HTS, new approaches are needed. The WHO conducted a systematic review on the effectiveness of assisted partner notification in improving HIV test uptake and diagnosis, and the occurrence of adverse events, to inform the development of normative guidelines. METHODS: We systematically searched five electronic databases through June 2016. We also contacted experts in the field and study authors for additional information where needed. Eligible studies compared assisted HIV partner notification services to passive or no notification. Where multiple studies reported comparable outcomes, meta-analysis was conducted using a random-effects model to produce relative risks (RRs) or risk ratios and 95% confidence intervals (CIs). RESULTS: Of 1742 citations identified, four randomized controlled trials and six observational studies totalling 5150 index patients from eight countries were included. Meta-analysis of three individually randomized trials showed that assisted partner notification services resulted in a 1.5-fold increase in HTS uptake among partners compared with passive referral (RR = 1.46; 95% CI: 1.22-1.75; I = 0%). The proportion of HIV-positive partners was 1.5 times higher with assisted partner notification than with passive referral (RR = 1.47; 95% CI: 1.12-1.92; I = 0%). Few instances of violence or harm occurred. CONCLUSION: Assisted partner notification improved partner testing and diagnosis of HIV-positive partners, with few reports of harm. WHO strongly recommends voluntary assisted HIV partner notification services to be offered as part of a comprehensive package of testing and care

Provider-Initiated HIV Testing and Counseling: Increased Uptake in Two Public Community Health Centers in South Africa and Implications for Scale-Up

BACKGROUND: International guidance recommends the scale up of routinely recommended, offered, and delivered health care provider-initiated HIV testing and counseling (PITC) to increase the proportion of persons who know their HIV status. We compared HIV test uptake under PITC to provider-referral to voluntary counseling and testing (VCT referral) in two primary health centers in South Africa. METHODS: Prior to introducing PITC, clinical providers were instructed to refer systematically selected study participants to VCT. After PITC and HIV rapid test training, providers were asked to recommend, offer and provide HIV testing to study participants during the clinical consultation. Participants were interviewed before and after their consultation to assess their HIV testing experiences. RESULTS: HIV test uptake increased under PITC (OR 2.85, 95% CI 1.71, 4.76), and more patients felt providers answered their questions on HIV (104/141 [74%] versus 73/118 [62%] for VCT referral; p 0.04). After three months, only 4/106 (3.8%) HIV-positive patients had registered for onsite HIV treatment. Providers found PITC useful, but tested very few patients (range 0-15). CONCLUSION: PITC increased the uptake of HIV testing compared with referral to onsite VCT, and patients reported a positive response to PITC. However, providing universal PITC will require strong leadership to train and motivate providers, and interventions to link HIV-positive persons to HIV treatment centers

Who are the missing men? Characterising men who never tested for HIV from population-based surveys in six sub-Saharan African countries.

INTRODUCTION: We sought to characterize men who had never tested for HIV, understand factors associated with not testing, and measure survey HIV test uptake among never testers. We analysed nationally representative Demographic and Health Surveys of six African countries from 2013 to 2016: Ethiopia, Malawi, Zimbabwe, Rwanda, Lesotho and Zambia. METHODS: Eligible men were household residents or overnight visitors aged 15 to 59 years. We analysed questionnaire responses on HIV testing, known behavioural risk factors, and corresponding HIV laboratory results. We used survey-weighted logistic regression to identify factors associated with never testing for HIV. RESULTS: Approximately double the proportion of men had never tested for HIV compared to women (Malawi: 30% vs. 17%, p < 0.0001; Zimbabwe: 35% vs. 19%, p < 0.0001; Lesotho: 34% vs. 15%, p < 0.0001; Zambia: 36% vs. 20%, p < 0.0001); although, less of a differential existed in Ethiopia (54% vs. 56%, p = 0.12) and Rwanda (19% vs. 14%, p < 0.0001). When offered a test during the survey, 85% to 99% of sexually active men who reported never previously testing, accepted testing. HIV positivity ranged from <0.05% to 14% for never tested men. After adjusting for age, factors associated with never having tested for HIV were never being married (aOR range: 1.46 to 10.39), not having children (aOR: 1.36 to 3.59) and lower education (less than primary education aOR: 2.77 to 5.59). CONCLUSIONS: Although higher proportions of men than women had never tested for HIV, 85% to 99% of men did accept a test when offered. Finding opportunities to offer HIV testing to single men without children, older men who have never tested, and those disadvantaged with less schooling and employment, alongside other facility and community-based services, will be important in identifying those living with undiagnosed HIV and improving men's health

Non-Communicable Diseases in Sub-Saharan Africa: The Case for Cohort Studies

Michelle Holmes and colleagues argue that there is an urgent need for longitudinal cohorts based in sub-Saharan Africa to address the growing burden of noncommunicable diseases in the region

Examining the effects of HIV self-testing compared to standard HIV testing services: a systematic review and meta-analysis.

INTRODUCTION: HIV self-testing (HIVST) is a discreet and convenient way to reach people with HIV who do not know their status, including many who may not otherwise test. To inform World Health Organization (WHO) guidance, we assessed the effect of HIVST on uptake and frequency of testing, as well as identification of HIV-positive persons, linkage to care, social harm, and risk behaviour. METHODS: We systematically searched for studies comparing HIVST to standard HIV testing until 1 June 2016. Meta-analyses of studies reporting comparable outcomes were conducted using a random-effects model for relative risks (RR) and 95% confidence intervals. The quality of evidence was evaluated using GRADE. RESULTS: After screening 638 citations, we identified five randomized controlled trials (RCTs) comparing HIVST to standard HIV testing services among 4,145 total participants from four countries. All offered free oral-fluid rapid tests for HIVST and were among men. Meta-analysis of three RCTs showed HIVST doubled uptake of testing among men (RR = 2.12; 95% CI: 1.51, 2.98). Meta-analysis of two RCTs among men who have sex with men showed frequency of testing nearly doubled (Rate ratio = 1.88; 95% CI: 1.17; 3.01), resulting in two more tests in a 12-15-month period (Mean difference = 2.13; 95% CI: 1.59, 2.66). Meta-analysis of two RCTs showed HIVST also doubled the likelihood of an HIV-positive diagnosis (RR = 2.02; 95% CI: 0.37, 10.76, 5.32). Across all RCTs, there was no indication of harm attributable to HIVST and potential increases in risk-taking behaviour appeared to be minimal. CONCLUSIONS: HIVST is associated with increased uptake and frequency of testing in RCTs. Such increases, particularly among those at risk who may not otherwise test, will likely identify more HIV-positive individuals as compared to standard testing services alone. However, further research on how to support linkage to confirmatory testing, prevention, treatment and care services is needed. WHO now recommends HIVST as an additional HIV testing approach

Repositioning Implementation Science in the HIV Response: Looking Ahead From AIDS 2018.

BACKGROUND: Implementation science (IS) occupies a critical place in HIV/AIDS research, reflected by a scientific track ("Track E") at the biannual International AIDS Conference. IS seeks to identify health delivery strategies that cost-effectively translate the efficacy of evidence-based interventions for HIV prevention, testing, and treatment into impact on HIV incidence, quality of life, and mortality. METHOD: We reviewed the content of Track E, and other presentations relevant to IS, at the 22nd International AIDS Conference held in Amsterdam in 2018. We identified key findings and themes and made recommendations for areas where the field can be strengthened by the 2020 meeting. RESULTS: Trials of "treat all" strategies in Africa showed mixed evidence of effect. Innovations in HIV testing included expanding self-testing and index testing, which are reaching groups, such as men, where previously testing rates have been low. Adherence clubs and other innovations are being trialed to improve retention in care, with mixed findings. The implementation of pre-exposure prophylaxis for HIV prevention continues but with many challenges remaining in identifying implementation strategies that strengthen demand and support continuation. DISCUSSION: IS for HIV/AIDS treatment and prevention continues to expand. IS for primary HIV prevention must be prioritized with a dearth of rigorous, intersectoral studies in this area. The weakness of routine data must be addressed. Costing and financing studies should form a stronger component of the conference agenda. Implementation scientists must continue to grapple with the methodological challenges posed by the real-world context for their research

Estimating HIV pre-exposure prophylaxis need and impact in Malawi, Mozambique and Zambia: A geospatial and risk-based analysis.

BACKGROUND: Pre-exposure prophylaxis (PrEP), a WHO-recommended HIV prevention method for people at high risk for acquiring HIV, is being increasingly implemented in many countries. Setting programmatic targets, particularly in generalised epidemics, could incorporate estimates of the size of the population likely to be eligible for PrEP using incidence-based thresholds. We estimated the proportion of men and women who would be eligible for PrEP and the number of HIV infections that could be averted in Malawi, Mozambique, and Zambia using prioritisation based on age, sex, geography, and markers of risk. METHODS AND FINDINGS: We analysed the latest nationally representative Demographic and Health Surveys (DHS) of Malawi, Mozambique, and Zambia to determine the proportion of adults who report behavioural markers of risk for HIV infection. We used prevalence ratios (PRs) to quantify the association of these factors with HIV status. Using a multiplier method, we combined these proportions with the number of new HIV infections by district, derived from district-level modelled HIV estimates. Based on these numbers, different scenarios were analysed for the minimum number of person-years on PrEP needed to prevent 1 HIV infection (NNP). An estimated total of 38,000, 108,000, and 46,000 new infections occurred in Malawi, Mozambique, and Zambia in 2016, corresponding with incidence rates of 0.43, 0.63, and 0.57 per 100 person-years. In these countries, 9%-20% of new infections occurred among people with a sexually transmitted infection (STI) in the past 12 months and 40%-42% among people with either an STI or a non-regular sexual partner (NP) in the past 12 months (STINP). The models estimate that around 50% of new infections occurred in districts with incidence rates ≥1.0% in Mozambique and Zambia and ≥0.5% in Malawi. In Malawi, Mozambique, and Zambia, 35.1%, 21.9%, and 12.5% of the population live in these high-incidence districts. In the most parsimonious scenario, if women aged 15-34 years and men 20-34 years with an STI in the past 12 months living in high-incidence districts were to take PrEP, it would take a minimum of 65.8 person-years on PrEP to avert 1 HIV infection per year in Malawi, 35.2 in Mozambique, and 16.4 in Zambia. Our findings suggest that 3,300, 5,200, and 1,700 new infections could be averted per year in the 3 countries, respectively. Limitations of our study are that these values are based on modelled estimates of HIV incidence and self-reported behavioural risk factors from national surveys. CONCLUSIONS: A large proportion of new HIV infections in these 3 African countries were estimated to occur among people who had either an STI or an NP in the past year, providing a straightforward means to set PrEP targets. Greater prioritisation of PrEP by district, sex, age, and behavioural risk factors resulted in lower NNPs thereby increasing PrEP cost-effectiveness, but also diminished the overall impact on reducing new infections