Showing papers in "Journal of the International AIDS Society in 2019"

HIV pre-exposure prophylaxis for adolescent girls and young women in Africa: from efficacy trials to delivery.

Abstract: Introduction Adolescent girls and young women (AGYW) in Africa have high HIV incidence despite scale-up of HIV testing and HIV treatment. Placebo-controlled trials of tenofovir-based pre-exposure prophylaxi (PrEP) in diverse populations demonstrated that PrEP works with close to 100% effectiveness if taken with high, but not perfect, adherence. Divergent efficacy estimates among African AGYW led to demonstration and implementation projects to better understand motivations for HIV prevention, uptake, adherence and persistence to PrEP. To inform PrEP programmes, the design and initial findings from PrEP demonstration projects for AGYW are reviewed. Discussion Early lessons from PrEP implementation projects among young African women include: (1) awareness and demand creation with positive messaging about the benefits of PrEP are critical to motivate AGYW to consider this novel prevention technology and to foster awareness among peers, partners, parents and guardians to support AGYW's effective PrEP use; (2) PrEP initiation is high in projects that are integrating PrEP into youth-friendly clinics, family planning clinics and mobile clinics; (3) young African women at risk are initiating PrEP, based on behavioural characteristics, history of intimate partner violence, depression and 30% prevalence of chlamydia and/or gonorrhoea; (4) provision of youth-friendly PrEP delivery programmes that integrate reproductive health services, including contraception and the diagnosis and treatment of sexually transmitted infections, increase health impact; (5) messages that emphasize the necessity for high adherence while at potential risk of HIV exposure and support strategies that addresses AGYW's adherence challenges are essential; and, (6) a substantial proportion of AGYW do not persist with PrEP, and strategies are needed to help AGYW assess their ongoing need, motivation and challenges with persisting with PrEP. Conclusions PrEP is feasible to implement in integrated reproductive health service delivery models to reach African AGYW. While PrEP demonstration projects indicate that women with behavioural risks and high rates of sexually transmitted diseases are initiating PrEP; effective strategies to support AGYW's adherence and persistence with PrEP are needed. Lessons learned from oral PrEP delivery, a novel first generation HIV prevention product, are relevant to longer-acting and less adherence-dependent strategies which are currently in clinical trials.

HIV self-testing: breaking the barriers to uptake of testing among men and adolescents in sub-Saharan Africa, experiences from STAR demonstration projects in Malawi, Zambia and Zimbabwe.

Abstract: Introduction Social, structural and systems barriers inhibit uptake of HIV testing. HIV self-testing (HIVST) has shown promising uptake by otherwise underserved priority groups including men, young people and first-time testers. Here, we use characteristics of HIVST kit recipients to investigate delivery to these priority groups during HIVST scale-up in three African countries. Methods Kit distributors collected individual-level age, sex and testing history from all clients. These data were aggregated and analysed by country (Malawi, Zambia and Zimbabwe) for five distribution models: local community-based distributor (CBD: door-to-door, street and local venues), workplace distribution (WD), integration into HIV testing services (IHTS), or public health facilities (IPHF) and during demand creation for voluntary male medical circumcision (VMMC). Used kits were collected and re-read from CBD and IHTS recipients. Results Between May 2015 and July 2017, 628,705 HIVST kits were distributed in Malawi (172,830), Zambia (190,787) and Zimbabwe (265,091). Community-based models, the first to be established, accounted for 519,658 (82.7%) of kits distributed, with 275,419 (53.0%) used kits returned. Subsequent model diversification delivered 54,453 (8.7%) test-kits through IHTS, 23,561 (3.7%) through VMMC, 21,183 (3.4%) through IPHF and 9850 (1.7%) through WD. Men took 294,508 (48.2%) kits, and 263,073 (43.1%) went to young people (16 to 24 years). A higher proportion of male self-testers (65,577; 22.3%) were first-time testers than women (54,096; 17.1%) with this apparent in Zimbabwe (16.2% vs. 11.4%), Zambia (25.4% vs. 17.7%) and Malawi (27.9% vs. 25.9%). The highest proportions of first-time testers were in young (16 to 24 years) and older (>50 years) men (country-ranges: 18.7% to 35.9% and 13.8% to 26.8% respectively). Most IHTS clients opted for HIVST in preference to standard HTS in each of 12 delivery sites, with those selecting HIVST having lower HIV prevalence, potentially due to self-selection. Conclusions HIVST delivered at scale using several different models reached a high proportion of men, young people and first-time testers in Malawi, Zambia and Zimbabwe, some of whom may not have tested otherwise. As men and young people have limited uptake under standard facility-and community-based HIV testing, innovative male- and youth-sensitive approaches like HIVST may be essential to reaching UNAIDS fast-track targets for 2020.

Daily and event-driven pre-exposure prophylaxis for men who have sex with men in Belgium: results of a prospective cohort measuring adherence, sexual behaviour and STI incidence.

Abstract: INTRODUCTION Pre-Exposure Prophylaxis (PrEP) is highly effective in reducing the risk for HIV infection among men who have sex with men (MSM) and may have an important impact in slowing down the HIV epidemic. Concerns remain however about low adherence, increased risk behaviour and reduced condom use when using PrEP. The aim of this study was to assess these factors prospectively among MSM using daily and event-driven PrEP in Belgium. METHODS An open-label prospective cohort study was conducted from October 2017 to May 2018 at the Institute of Tropical Medicine, in Antwerp, Belgium. At enrolment, MSM at high risk for HIV chose between daily or event-driven PrEP. They were allowed to switch regimens or stop taking PrEP at each of their tri-monthly visits. Data were collected on an electronic case report form, web-based diary and self-administered questionnaire. Screening for HIV and other Sexually Transmitted Infections (STIs) was also performed. RESULTS Two hundred MSM were followed up for a total duration of 318 person-years. At month 18, 75.4% of the participants were on daily and 24.6% were on event-driven PrEP. The mean proportion of covered sex acts by PrEP for the complete follow-up period was 91.5% for all participants, 96.5% for daily and 67.0% for event-driven PrEP use. The number of casual and anonymous sex partners was significantly higher for daily users, as compared with event-driven users, but did not change over time. In contrast, the mean proportion of condomless receptive anal intercourse with casual and anonymous partners increased significantly during follow-up, for both daily and event-driven use (p < 0.0001 for all 4 trends). No new HIV infection was diagnosed during follow-up. The incidence of bacterial STIs was 75.4 per 100 person-years (95% CI 63.8 to 89.1). We did not detect a significant change in N. gonorrhoeae/C. trachomatis incidence over time. The incidence of hepatitis C was 2.9 per 100 person-years. CONCLUSIONS PrEP is an effective and well adopted HIV prevention tool for MSM in Belgium. Participants adapted daily and event-driven regimens to their own needs and were able to adapt their PrEP adherence to risk exposure.

Persistence on HIV preexposure prophylaxis medication over a 2-year period among a national sample of 7148 PrEP users, United States, 2015 to 2017.

Abstract: Introduction Persistence on preexposure prophylaxis for HIV prevention (PrEP) medication has rarely been reported for periods greater than one year, or in real-world settings. This study used pharmacy fill records for PrEP users from a national chain pharmacy to describe persistence on PrEP medication over a two-year period, and to explore correlates with PrEP medication persistence in a real-world setting. Methods We analysed de-identified pharmacy fill records of 7148 eligible individuals who initiated PrEP in 2015 at a national chain pharmacy. A standard algorithm was employed to identify TDF-FTC use for PrEP indication. We considered three time periods for persistence, defined as maintaining refills in PrEP care: year 1 (zero to twelve months), year 2 (thirteen to twenty-four months) and initiation to year 2 (zero to twenty-four months). Individuals with 16 or more days of TDF-FTC PrEP dispensed in a 1-month period for at least three-quarters of a given time period (e.g. nine of twelve months or eighteen of twenty-four months) were classified as persistent on PrEP medication for the period. Results Persistence was 56% in year 1, 63% in year 2 and 41% from initiation to year 2. Individuals aged 18 to 24 had the lowest persistence, with 29% from initiation to year 2. Men had higher persistence than women, with 42% compared to 20% persistent from initiation to year 2. Individuals with commercial insurance and individuals who utilized a community-based specialty pharmacy from the national chain also had higher persistence. Male gender, age >18 to 24 years, average monthly copay of $20 or less, commercial insurance, and utilization of a community-based specialty pharmacy were positively associated in adjusted models with persistence in year 1 and from initiation to year 2; the same correlates, with the exception of utilization of a community-based specialty pharmacy, were associated with higher persistence in year 2. Conclusions We found substantial non-persistence on PrEP medication in both year 1 and year 2. Across the entire 2-year period, only two out of every five users persisted on PrEP. Demographic, financial and pharmacy factors were associated with persistence. Further research is needed to explore how social, structural or individual factors may undermine or enhance persistence on PrEP, and to develop interventions to assist persistence on PrEP.

Diagnosing sexually transmitted infections in resource-constrained settings: challenges and ways forward.

Abstract: Introduction Sexually transmitted infections (STIs) remain prevalent and are increasing in several populations. Appropriate STI diagnosis is crucial to prevent the transmission and sequelae of untreated infection. We reviewed the diagnostic accuracy of syndromic case management and existing point-of-care tests (POCTs), including those in the pipeline, to diagnose STIs in resource-constrained settings. Methods We prioritized updating the systematic review and meta-analysis of the diagnostic accuracy of vaginal discharge from 2001 to 2015 to include studies until 2018. We calculated the absolute effects of different vaginal flowcharts and the diagnostic performance of POCTs on important outcomes. We searched the peer-reviewed literature for previously conducted systematic reviews and articles from 1990 to 2018 on the diagnostic accuracy of syndromic management of vaginal and urethral discharge, genital ulcer and anorectal infections. We conducted literature reviews from 2000 to 2018 on the existing POCTs and those in the pipeline. Results and discussions The diagnostic accuracy of urethral discharge and genital ulcer disease syndromes is relatively adequate. Asymptomatic Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG) infections limit the use of vaginal discharge and anorectal syndromes. The pooled diagnostic accuracy of vaginal syndromic case management for CT/NG is low, resulting in high numbers of overtreatment and missed treatment. The absolute effect of POCTs was reduced overtreatment and missed treatment. Findings of the reviews on syndromic case management underscored the need for low-cost and accurate POCTs for the identification, first, of CT/NG, and, second, of Mycoplasma genitalium (MG) and Trichomonas vaginalis (TV) and NG and MG resistance/susceptibility testing. Near-patient POCT molecular assays for CT/NG/TV are commercially available. The prices of these POCTs remain the barrier for uptake in resource-constrained settings. This is driving the development of lower cost solutions. Conclusions The WHO syndromic case management guidelines should be updated to raise the quality of STI management through the integration of laboratory tests. STI screening strategies are needed to address asymptomatic STIs. POCTs that are accurate, rapid, simple and affordable are urgently needed in resource-constrained settings to support the uptake of aetiological diagnosis and treatment.

Sexually transmitted infections and HIV in the era of antiretroviral treatment and prevention: the biologic basis for epidemiologic synergy

Abstract: Introduction HIV is a unique sexually transmitted infection (STI) that is greatly affected by other concomitant "classical" bacterial and viral STIs that cause genital ulcers and/or mucosal inflammation. STIs also serve as a marker for risky sexual behaviours. STIs increase infectiousness of people living with HIV by increasing the viral concentration in the genital tract, and by increasing the potential for HIV acquisition in people at risk for HIV. In addition, some STIs can increase blood HIV concentration and promote progression of disease. This review is designed to investigate the complex relationship between HIV and classical STIs. Discussion Treatment of STIs with appropriate antibiotics reduces HIV in blood, semen and female genital secretions. However, community-based trials could not reliably reduce the spread of HIV by mass treatment of STIs. Introduction of antiretroviral agents for the treatment and prevention of HIV has led to renewed interest in the complex relationship between STIs and HIV. Antiretroviral treatment (ART) reduces the infectiousness of HIV and virtually eliminates the transmission of HIV in spite of concomitant or acquired STIs. However, while ART interrupts HIV transmission, it does not stop intermittent shedding of HIV in genital secretions. Such shedding of HIV is increased by STIs, although the viral copies are not likely replication competent or infectious. Pre-exposure prophylaxis (PrEP) of HIV with the combination of tenofovir disoproxil fumarate and emtricitabine (TDF/FTC) prevents HIV acquisition in spite of concomitant STIs. Conclusions STIs remain pandemic, and the availability of ART may have led to an increase in STIs, as fear of HIV has diminished. Classical STIs present a huge worldwide health burden that cannot be separated from HIV, and they deserve far more attention than they currently receive.

Pre-exposure prophylaxis initiation and adherence among Black men who have sex with men (MSM) in three US cities: results from the HPTN 073 study.

Abstract: Author(s): Wheeler, Darrell P; Fields, Sheldon D; Beauchamp, Geetha; Chen, Ying Q; Emel, Lynda M; Hightow-Weidman, Lisa; Hucks-Ortiz, Christopher; Kuo, Irene; Lucas, Jonathan; Magnus, Manya; Mayer, Kenneth H; Nelson, LaRon E; Hendrix, Craig W; Piwowar-Manning, Estelle; Shoptaw, Steven; Watkins, Phaedrea; Watson, C Chauncey; Wilton, Leo | Abstract: IntroductionRandomized clinical trials have demonstrated the efficacy of antiretroviral pre-exposure prophylaxis (PrEP) in preventing HIV acquisition among men who have sex with men (MSM). However, limited research has examined initiation and adherence to PrEP among Black MSM (BMSM) in the United States (US) who are disproportionately represented among newly HIV infected and late to care individuals. This research reports on the HIV Prevention Trials Network 073 (HPTN 073) study aimed to examine PrEP initiation, utilization and adherence among Black MSM utilizing the theoretically principled, culturally informed and client-centered care coordination (C4) model.MethodsThe HPTN 073 study enrolled and followed 226 HIV-uninfected Black MSM in three US cities (Los Angeles, CA; Washington DC; and Chapel Hill, NC) from February 2013 through September 2015. Study participants were offered once daily oral emtricitabine/tenofovir (FTC/TDF) PrEP combined with C4 and followed up for 52nweeks. Participants received HIV testing, risk reduction education and clinical monitoring.ResultsOf the 226 men enrolled, 178 participants initiated PrEP (79%), and of these 64% demonstrated PrEP utilization at week 26 (mid-point of the study) based on pharmacokinetic testing. Condomless anal sex with an HIV-infected or unknown status casual male partner was statistically significantly associated with a greater likelihood of PrEP initiation (adjusted odds ratio (OR) 4.4, 95% confidence interval (CI) 1.7, 11.7). Greater age (≥25 vs. l25, OR 2.95, 95% CI 1.37 -6.37), perception of having enough money (OR 3.6, 95% CI 1.7 to 7.7) and knowledge of male partner taking PrEP before sex (OR 2.22, 95% CI 1.03 to 4.79) were statistically significantly associated with increased likelihood of PrEP adherence at week 26. Annualized HIV incidence was 2.9 (95% CI 1.2 to 7.9) among those who initiated PrEP, compared to 7.7 (95% CI 2.5 to 24.1) among those who did not initiate PrEP (pn=n0.18).ConclusionsResults suggest a high level of PrEP initiation among at-risk Black MSM, a group historically characterized as hard to reach. The data support the importance of addressing contextual factors that affect PrEP initiation and adherence, and of additional research on the ultimate benefit of PrEP in HIV prevention among Black MSM.

Access to HIV care in the context of universal test and treat : challenges within the ANRS 12249 TasP cluster-randomized trial in rural South Africa – Joseph Larmarange

Abstract: Authors Melanie Plazy, Kamal El Farouki, Collins Iwuji, Nonhlanhla Okesola, Joanna Orne-Gliemann, Joseph Larmarange, France Lert, Marie-Louise Newell, Francois Dabis, Rosemary DRAY-SPIRA, for the…

Patterns and clinical consequences of discontinuing HIV preexposure prophylaxis during primary care.

Abstract: Introduction Discontinuations of HIV preexposure prophylaxis (PrEP) by at-risk individuals could decrease the effectiveness of PrEP. Our objective was to characterize patterns of, reasons for, and clinical outcomes associated with PrEP discontinuations in primary care. Methods We conducted medical chart reviews for patients prescribed PrEP during 2011 to 2014 at a Boston community health centre specializing in healthcare for sexual and gender minorities. Patients were followed through 2015. We characterized patients' sociodemographics, relationship status, behavioural health conditions, patterns of and reasons for PrEP discontinuations, and HIV seroconversions. Cox proportional hazards models were used to assess patient factors associated with PrEP discontinuations. Results Of the 663 patients prescribed PrEP, the median age was 33 years, 96% were men who have sex with men (MSM) and 73% were non-Hispanic white; 40% were in committed relationships and 15% had HIV-infected partners. Patients either used PrEP continuously (60%), had 1 or more discontinuations (36%), or did not initiate PrEP (4%). Discontinuations were most often due to a decrease in HIV risk perception (33%), non-adherence to care plans (16%), or insurance barriers (12%). Of the 7 (1.1%) PrEP patients diagnosed with HIV, 1 was HIV-infected at baseline, 2 seroconverted while using PrEP, and 4 seroconverted after discontinuations. In a multivariable model adjusted for race/ethnicity, relationship status, substance use disorders, and insurance status, those who were less than 30 years old (aHR 2.0, 95% CI 1.4 to 2.9 for ages 18 to 24, aHR 2.2, 95% CI 1.6 to 3.1 for ages 25 to 29, vs. ages 30 to 39 years), who identified as transgender women (aHR 2.0, 95% CI 1.2 to 3.4, vs. cisgender men), and who had mental health disorders (aHR 1.2, 95% CI 1.1 to 1.4 for each additional disorder) were more likely to have discontinuations. Conclusions Discontinuations of PrEP use among this American sample of predominately MSM were common, particularly among patients who were younger, identified as transgender women, or had behavioural health issues. As HIV seroconversions occurred after discontinuations of PrEP, strategies to prevent inappropriate discontinuations are needed.

Drug-drug interactions between feminizing hormone therapy and pre-exposure prophylaxis among transgender women: the iFACT study.

Abstract: INTRODUCTION Concerns over potential drug-drug interactions (DDI) between feminizing hormone therapy (FHT) and pre-exposure prophylaxis (PrEP) have hampered uptake and adherence of PrEP among transgender women (TGW). To determine DDI between FHT and PrEP, we measured the pharmacokinetic (PK) parameters of blood plasma estradiol (E2) and tenofovir (TFV) in Thai TGW. METHODS Twenty TGW who never underwent orchiectomy and had not received injectable FHT within six months were enrolled between January and March 2018. FHT (E2 valerate and cyproterone acetate) were prescribed to participants at baseline until week 5, and then from week 8 until the end of study. Daily PrEP (tenofovir disoproxil fumarate/emtricitabine) was initiated at week 3 and continued without interruption. Intensive E2 PK parameters and testosterone concentration at 24 hours (C24 ) were measured at weeks 3 (without PrEP) and 5 (with PrEP), and intensive TFV PK parameters were measured at weeks 5 (with FHT) and 8 (without FHT). RESULTS Median (interquartile range) age, body mass index, and creatinine clearance were 21.5 (21-26) years, 20.6 (19.0-22.4) kg/m2 , and 116 (101-126.5) mL/min, respectively. The geometric mean (%CV) of area under curve from time zero to 24 hours (AUC0-24 ), maximum concentration (Cmax ), and C24 of E2 at weeks 3 and 5 were 775.13 (26.2) pg h/mL, 51.47 (26.9) pg/mL, and 15.15 (42.0) pg/mL; and 782.84 (39.6), 55.76 (32.9), and 14.32 (67.4), respectively. The geometric mean (%CV) of TFV AUC0-24 , Cmax , and C24 at weeks 5 and 8 were 2242.1 (26.5) ng h/mL, 353.9 (34.0) ng/mL, and 40.9 (31.4) ng/mL; and 2530.2 (31.3), 311.4 (30.0), and 49.8 (29.6), respectively. The geometric mean of TFV AUC0-24 and C24 at week 5 were significantly less than that at week 8 by 12% (p = 0.03) and 18% (p < 0.001), respectively. There were no significant changes in E2 PK parameters and median C24 of bioavailable testosterone between week 3 and week 5. CONCLUSIONS Our study demonstrated lower blood plasma TFV exposure in the presence of FHT, suggesting that FHT may potentially affect PrEP efficacy among TGW; but E2 exposure was not affected by PrEP. Further studies are warranted to determine whether these reductions in TFV are clinically significant. Clinical Trial Number: NCT03620734.

Effectiveness of dolutegravir-based regimens as either first-line or switch antiretroviral therapy: data from the Icona cohort

Abstract: Introduction Concerns about dolutegravir (DTG) tolerability in the real-life setting have recently arisen. We aimed to estimate the risk of treatment discontinuation and virological failure of DTG-based regimens from a large cohort of HIV-infected individuals. Methods We performed a multicentre, observational study including all antiretroviral therapy (ART)-naive and virologically suppressed treatment-experienced (TE) patients from the Icona (Italian Cohort Naive Antiretrovirals) cohort who started, for the first time, a DTG-based regimen from January 2015 to December 2017. We estimated the cumulative risk of DTG discontinuation regardless of the reason and for toxicity, and of virological failure using Kaplan-Meier curves. We used Cox regression model to investigate predictors of DTG discontinuation. Results About 1679 individuals (932 ART-naive, 747 TE) were included. The one- and two-year probabilities (95% CI) of DTG discontinuation were 6.7% (4.9 to 8.4) and 11.5% (8.7 to 14.3) for ART-naive and 6.6% (4.6 to 8.6) and 7.6% (5.4 to 9.8) for TE subjects. In both ART-naive and TE patients, discontinuations of DTG were mainly driven by toxicity with an estimated risk (95% CI) of 4.0% (2.6 to 5.4) and 2.5% (1.3 to 3.6) by one year and 5.6% (3.8 to 7.5) and 4.0% (2.4 to 5.6) by two years respectively. Neuropsychiatric events were the main reason for stopping DTG in both ART-naive (2.1%) and TE (1.7%) patients. In ART-naive, a concomitant AIDS diagnosis predicted the risk of discontinuing DTG for any reason (adjusted relative hazard (aRH) = 3.38, p = 0.001), whereas starting DTG in combination with abacavir (ABC) was associated with a higher risk of discontinuing because of toxicity (aRH = 3.30, p = 0.009). TE patients starting a DTG-based dual therapy compared to a triple therapy had a lower risk of discontinuation for any reason (adjusted hazard ratio (aHR) = 2.50, p = 0.037 for ABC-based triple-therapies, aHR = 3.56, p = 0.012 for tenofovir-based) and for toxicity (aHR = 5.26, p = 0.030 for ABC-based, aHR = 6.60, p = 0.024 for tenofovir-based). The one- and two-year probabilities (95% CI) of virological failure were 1.2% (0.3 to 2.0) and 4.6% (2.7 to 6.5) in the ART naive group and 2.2% (1.0 to 3.3) and 2.9% (1.5 to 4.3) in the TE group. Conclusions In this large cohort, DTG showed excellent efficacy and optimal tolerability both as first-line and switching ART. The low risk of treatment-limiting toxicities in ART-naive as well as in treated individuals reassures on the use of DTG in everyday clinical practice.

Transgender women on oral HIV pre-exposure prophylaxis have significantly lower tenofovir and emtricitabine concentrations when also taking oestrogen when compared to cisgender men.

Abstract: Introduction Oral HIV Pre-Exposure Prophylaxis (PrEP) with tenofovir (TFV) disoproxil fumarate (TDF)/emtricitabine (FTC) is highly effective. Transgender women (TGW) have increased HIV risk, but have been underrepresented in trials. For TGW on oestrogens for gender-affirming hormone treatment (GAHT), TDF/FTC-oestrogen interactions may negatively affect HIV prevention or gender-affirming goals. Our aim was to evaluate any pharmacokinetic drug-drug interaction between GAHT and TDF/FTC. Methods We performed a pharmacokinetic study, in an urban outpatient setting in 2016 to 2018, of the effects of GAHT on TFV, FTC and the active forms TFV diphosphate (TFV-DP) and FTC triphosphate (FTC-TP) in eight TGW and eight cisgender men (CGM). At screening, participants were HIV negative. TGW were to maintain their GAHT regimens and have plasma oestradiol concentrations >100 pg/mL. Under direct observation, participants took oral TDF/FTC daily for seven days. At the last dose, blood was collected pre-dose, one, two, four, six, eight and twenty-four hours, and colon biopsies were collected at 24 hours to measure drug concentration. TGW versus CGM concentration comparisons used non-parametric tests. Blood and colon tissue were also obtained to assess kinase expression. Results Plasma TFV and FTC C24 (trough) concentrations in TGW were lower by 32% (p = 0.010) and 32% (p = 0.038) respectively, when compared to CGM. Plasma TFV and FTC 24-hr area under the concentration-time curve in TGW trended toward and was significantly lower by 27% (p = 0.065) and 24% (p = 0.028) respectively. Peak plasma TFV and FTC concentrations, as well as all other pharmacokinetic measures, were not statistically significant when comparing TGW to CGM. Oestradiol concentrations were not different comparing before and after TDF/FTC dosing. Plasma oestrogen concentration, renal function (estimated creatinine clearance and glomerular filtration rate), and TFV and FTC plasma concentrations (trough and area under the concentration-time curve) were all correlated. Conclusions GAHT modestly reduces both TFV and FTC plasma concentrations. In TGW taking GAHT, it is unknown if this reduction will impact the HIV protective efficacy of a daily PrEP regimen. However, the combination of an on demand (2 + 1 + 1) PrEP regimen and GAHT may result in concentrations too low for reliable prevention of HIV infection.

The impact and cost‐effectiveness of community‐based HIV self‐testing in sub‐Saharan Africa: a health economic and modelling analysis

Abstract: INTRODUCTION: The prevalence of undiagnosed HIV is declining in Africa, and various HIV testing approaches are finding lower positivity rates. In this context, the epidemiological impact and cost-effectiveness of community-based HIV self-testing (CB-HIVST) is unclear. We aimed to assess this in different sub-populations and across scenarios characterized by different adult HIV prevalence and antiretroviral treatment programmes in sub-Saharan Africa. METHODS: The synthesis model was used to address this aim. Three sub-populations were considered for CB-HIVST: (i) women having transactional sex (WTS); (ii) young people (15 to 24 years); and (iii) adult men (25 to 49 years). We assumed uptake of CB-HIVST similar to that reported in epidemiological studies (base case), or assumed people use CB-HIVST only if exposed to risk (condomless sex) since last HIV test. We also considered a five-year time-limited CB-HIVST programme. Cost-effectiveness was defined by an incremental cost-effectiveness ratio (ICER; cost-per-disability-adjusted life-year (DALY) averted) below US$500 over a time horizon of 50 years. The efficiency of targeted CB-HIVST was evaluated using the number of additional tests per infection or death averted. RESULTS: In the base case, targeting adult men with CB-HIVST offered the greatest impact, averting 1500 HIV infections and 520 deaths per year in the context of a simulated country with nine million adults, and impact could be enhanced by linkage to voluntary medical male circumcision (VMMC). However, the approach was only cost-effective if the programme was limited to five years or the undiagnosed prevalence was above 3%. CB-HIVST to WTS was the most cost-effective. The main drivers of cost-effectiveness were the cost of CB-HIVST and the prevalence of undiagnosed HIV. All other CB-HIVST scenarios had an ICER above US$500 per DALY averted. CONCLUSIONS: CB-HIVST showed an important epidemiological impact. To maximize population health within a fixed budget, CB-HIVST needs to be targeted on the basis of the prevalence of undiagnosed HIV, sub-population and the overall costs of delivering this testing modality. Linkage to VMMC enhances its cost-effectiveness.

Sexually transmitted hepatitis C virus infections: current trends, and recent advances in understanding the spread in men who have sex with men

Abstract: Introduction: Hepatitis C virus (HCV) is a major public health threat. Although the recent availability of highly effective directly acting antivirals created optimism towards HCV elimination, there is ongoing transmission of HCV in men who have sex with men (MSM). We here report current epidemiological trends and synthesise evidence on behavioural, network, cellular and molecular host factors associated with sexual transmission of HCV, in particular the role of HIV-1 co-infection. We discuss prevention opportunities focusing on the potential of HCV treatment. Methods: We searched MEDLINE, fact sheets from health professional bodies and conference abstracts using appropriate keywords to identify and select relevant reports. Results and discussion: Recent studies strongly suggest that HCV is transmitted via sexual contact in HIV-positive MSM and more recently in HIV-negative MSM eligible for or on pre-exposure prophylaxis. The reinfection risk following clearance is about 10 times the risk of primary infection. International connectedness of MSM transmission networks might contribute to ongoing reinfection. Some of these networks might overlap with networks of people who inject drugs. Although, the precise mechanisms facilitating sexual transmission remain unclear, damage to the mucosal barrier in the rectum could increase susceptibility. Mucosal dendritic cell subsets could increase HCV susceptibility by retaining HCV and transmitting the virus to other cells, allowing egress into blood and liver. Early identification of new HCV infections is important to prevent onward transmission, but early diagnosis of acute HCV infection and prompt treatment is hampered by the slow rate of HCV antibody seroconversion, which in rare cases may take more than a year. Novel tests such as testing for HCV core antigen might facilitate early diagnosis. Conclusions: High-risk sexual behaviour, network characteristics, co-infection with sexually transmitted infections like HIV-1 and other concomitant bacterial and viral sexually transmitted infections are important factors that lead to HCV spread. Targeted and combined prevention efforts including effective behavioural interventions and scale-up of HCV testing and treatment are required to halt HCV transmission in MSM.

Give PrEP a chance: moving on from the “risk compensation” concept

Abstract: Introduction While bio-behavioural interventions (BIs) for sexually transmitted infections (STIs) and HIV prevention have shown their effectiveness (e.g. treatment for syphilis, HPV vaccination or pre-exposure prophylaxis [PrEP]), they have also aroused major concerns regarding behavioural changes that could counteract their benefit. Risk compensation (RC) fears concerning BIs in the HIV/STIs prevention field are intimately linked to representations, judgements and social control on sexual behaviour. With an increasing number of PrEP studies describing a rise in STIs due to RC, this paper argues for a shift away from the focus on RC and proposes a more constructive approach to respond to the needs of people living with HIV and populations most at risk. Discussion The concept of RC, stemming from road safety and derived from economic theory, relies on rational theoretical models of human behaviour. Although widely applied in several contexts its use has been reasonably questioned. Major methodological issues regarding RC have been raised within HIV/AIDS literature. Although behavioural changes (e.g. condomless sex and number of sexual partners) are often erroneously assimilated with RC, there is no evidence that behavioural changes have undermined the effectiveness of previous and current BIs. Still, PrEP has not escaped RC concerns. Increases in condomless sex within the context of growing uptake of PrEP signals a continued need for integrated and innovative HIV and STI prevention strategies and a comprehensive sexual health approach. Routine HIV/STI testing, peer-led counselling, and identification of sexual health needs within the PrEP model of care could become a gold standard in the sexual health field for all populations. Conclusions RC remains a frequent argument against the availability and provision of prevention methods for vulnerable populations. Individuals should be able to benefit from the full panel of BIs options available, to find and adapt methods according to their needs. Current, past and future PrEP users, with other stakeholders, may provide valuable insight into innovative solutions and programmes to control HIV and other STIs.

Randomized controlled trial of a positive affect intervention to reduce HIV viral load among sexual minority men who use methamphetamine

Abstract: IntroductionIn the era of HIV treatment as prevention (TasP), evidence‐based interventions that optimize viral suppression among people who use stimulants such as methamphetamine are needed to improve health outcomes and reduce onward transmission risk. We tested the efficacy of positive affect intervention delivered during community‐based contingency management (CM) for reducing viral load in sexual minority men living with HIV who use methamphetamine.MethodsConducted in San Francisco, this Phase II randomized controlled trial tested the efficacy of a positive affect intervention for boosting and extending the effectiveness of community‐based CM for stimulant abstinence to achieve more durable reductions in HIV viral load. From 2013 to 2017, 110 sexual minority men living with HIV who had biologically confirmed, recent methamphetamine use were randomized to receive a positive affect intervention (n = 55) or attention‐control condition (n = 55). All individual positive affect intervention and attention‐control sessions were delivered during three months of community‐based CM where participants received financial incentives for stimulant abstinence. The 5‐session positive affect intervention was designed to provide skills for managing stimulant withdrawal symptoms as well as sensitize individuals to natural sources of reward. The attention‐control condition consisted of neutral writing exercises and self‐report measures.ResultsMen randomized to the positive affect intervention displayed significantly lower log10 HIV viral load at six, twelve and fifteen months compared to those in the attention‐control condition. Men in the positive affect intervention also had significantly lower risk of at least one unsuppressed HIV RNA (≥200 copies/mL) over the 15‐month follow‐up. There were concurrent, statistically significant intervention‐related increases in positive affect as well as decreases in the self‐reported frequency of stimulant use at six and twelve months.ConclusionsDelivering a positive affect intervention during community‐based CM with sexual minority men who use methamphetamine achieved durable and clinically meaningful reductions in HIV viral load that were paralleled by increases in positive affect and decreases in stimulant use. Further clinical research is needed to determine the effectiveness of integrative, behavioural interventions for optimizing the clinical and public health benefits of TasP in sexual minority men who use stimulants such as methamphetamine.

Exploring social harms during distribution of HIV self-testing kits using mixed-methods approaches in Malawi.

Abstract: Introduction: HIV self-testing (HIVST) provides couples and individuals with a discreet, convenient and empowering testing option. As with all HIV testing, potential harms must be anticipated and mitigated to optimize individual and public health benefits. Here, we describe social harms (SHs) reported during HIVST implementation in Malawi, and propose a framework for grading and responding to harms, according to their severity. Methods: We report findings from six HIVST implementation studies in Malawi (2011 to 2017) that included substudies investigating SH reports. Qualitative methods included focus group discussions, in-depth interviews and critical incident interviews. Earlier studies used intensive quantitative methods (post-test questionnaires for intimate partner violence, household surveys, investigation of all deaths in HIVST communities). Later studies used post-marketing reporting with/without community engagement. Pharmacovigilance methodology (whereby potentially life-threatening/changing events are defined as “serious”) was used to grade SH severity, assuming more complete passive reporting for serious events. Results: During distribution of 175,683 HIVST kits, predominantly under passive SH reporting, 25 serious SHs were reported from 19 (0.011%) self-testers, including 15 partners in eight couples with newly identified HIV discordancy, and one perinatally infected adolescent. There were no deaths or suicides. Marriage break-up was the most commonly reported serious SH (sixteen individuals; eight couples), particularly among serodiscordant couples. Among new concordant HIV-positive couples, blame and frustration was common but rarely (one episode) led to serious SHs. Among concordant HIV-negative couples, increased trust and stronger relationships were reported. Coercion to test or disclose was generally considered “well-intentioned” within established couples. Women felt empowered and were assertive when offering HIVST test kits to their partners. Some women who persuaded their partner to test, however, did report SHs, including verbal or physical abuse and economic hardship. Conclusions: After more than six years of large-scale HIVST implementation and in-depth investigation of SHs in Malawi, we identified approximately one serious reported SH per 10,000 HIVST kits distributed, predominantly break-up of married serodiscordant couples. Both “active” and “passive” reporting systems identified serious SH events, although with more complete capture by “active” systems. As HIVST is scaled-up, efforts to support and further optimize community-led SH monitoring should be prioritized alongside HIVST distribution. Keywords: HIV/AIDS; HIV self-test; HIV testing; social harms; Malawi

Challenges of HIV diagnosis and management in the context of pre‐exposure prophylaxis (PrEP), post‐exposure prophylaxis (PEP), test and start and acute HIV infection: a scoping review

Abstract: Introduction Knowledge of HIV status relies on accurate HIV testing, and is the first step towards access to HIV treatment and prevention programmes. Globally, HIV-status unawareness represents a significant challenge for achieving zero new HIV infections and deaths. In order to enhance knowledge of HIV status, the World Health Organisation (WHO) recommends a testing strategy that includes the use of HIV-specific antibody point-of-care tests (POCT). These POCTs do not detect acute HIV infection, the stage of disease when viral load is highest but HIV antibodies are undetectable. Complicating things further, in the presence of antiretroviral therapy (ART) for pre-exposure prophylaxis (PrEP) or post-exposure prophylaxis (PEP), other currently available testing technologies, such as viral load detection for diagnosis of acute HIV infection, may yield false-negative results. In this scoping review, we evaluate the evidence and discuss alternative HIV testing algorithms that may mitigate diagnostic dilemmas in the setting of increased utilization of ART for immediate treatment and prevention of HIV infection. Discussion Missed acute HIV infection prevents people living with HIV (PLHIV) from accessing early treatment, increases likelihood of onward transmission, and allows for inappropriate initiation or continuation of PrEP, which may result in HIV drug resistance. While immediate ART is recommended for all PLHIV, studies have shown that starting ART in the setting of acute HIV infection may result in a delayed or complete absence of development of HIV-specific antibodies, posing a diagnostic challenge that is particularly pertinent to resource-limited, high HIV burden settings where HIV-antibody POCTs are standard of care. Similarly, ART used as PrEP or PEP may supress HIV RNA viral load, complicating current HIV testing algorithms in resource-wealthy settings where viral detection is included. As rollout of PrEP continues, HIV testing algorithms may need to be modified. Conclusions With increasing use of PrEP and ART in acute infection we anticipate diagnostic challenges using currently available HIV testing strategies. Research and surveillance are needed to determine the most appropriate assays and optimal testing algorithms that are accurate, affordable and sustainable.

Global implementation of PrEP for HIV prevention: setting expectations for impact.

Abstract: Introduction Questions remain whether HIV pre-exposure prophylaxis (PrEP) can be translated into a successful public health intervention, leading to a decrease in population-level HIV incidence. We use examples from HIV treatment and contraceptives to discuss expectations for PrEP uptake, adherence, and persistence and their combined impact on the epidemic. Discussion Targets for PrEP uptake must be based on the local HIV epidemic and will depend on appropriate estimates of the key populations at risk for HIV. However, there is evidence that targets, once established, can successfully be met and that uptake may increase with awareness. Messaging around adherence should include that daily adherence is the goal (except for those MSM for whom event-driven dosing is a good fit), but perfect adherence should not be a barrier. Ideally, clients persist on PrEP for as long as they are at risk for HIV. While PrEP will be most effective when coverage is focused on high-risk populations, normalizing rather than stigmatizing PrEP will be highly beneficial. Conclusions While many challenges to PrEP implementation exist, we focused on the three key steps of uptake, adherence and persistence as measurable processes that can lead to improved coverage and decreased HIV incidence.

ART adherence and viral suppression are high among most non-pregnant individuals with early-stage, asymptomatic HIV infection: an observational study from Uganda and South Africa.

Abstract: INTRODUCTION The success of universal antiretroviral therapy (ART) access and aspirations for an AIDS-free generation depend on high adherence in individuals initiating ART during early-stage HIV infection; however, adherence may be difficult in the absence of illness and associated support. METHODS From March 2015 to October 2017, we prospectively observed three groups initiating ART in routine care in Uganda and South Africa: men and non-pregnant women with early-stage HIV infection (CD4 > 350 cells/μL), pregnant women with early-stage HIV infection and men and non-pregnant women with late-stage HIV infection (CD4 0.72). In South Africa, median adherence was higher in early/non-pregnant versus early/pregnant or late/non-pregnant participants (76%, 37%, 52%; p < 0.001), with similar trends in viral suppression (86%, 51%, 79%; p < 0.001). Among early/non-pregnant individuals in Uganda, adherence was higher with increasing age and lower with structural barriers; whereas in South Africa, adherence was higher with regular income, higher perceived stigma and use of other medications, but lower with maladaptive coping and cigarette smoking. DISCUSSION ART adherence among non-pregnant individuals with early-stage infection is as high or higher than with late-stage initiation, supporting universal access to ART. Challenges remain for some pregnant women and individuals with late-stage infection in South Africa and highlight the need for differentiated care delivery.

High risk and low uptake of pre-exposure prophylaxis to prevent HIV acquisition in a national online sample of transgender men who have sex with men in the United States.

Abstract: Introduction Trans masculine people who have sex with cisgender ("cis") men ("trans MSM") may be at-risk for HIV infection when they have cis MSM partners or share needles for hormone or recreational drug injection. Limited data are available characterizing indications and uptake of pre-exposure prophylaxis (PrEP) in trans MSM. The aim of this study was to assess PrEP indication and uptake as a means of primary HIV prevention for adult trans MSM in the U.S. Methods Between November and December 2017, a national convenience sample of trans MSM in the U.S. (n = 857) was recruited using participatory methodologies and completed an online survey of demographics, HIV risk, PrEP, behavioural and psychosocial factors. Self-reported receptive anal sex or frontal/vaginal sex (with or without a condom) with a cis male sex partner in past six months was an eligibility criterion. A multivariable logistic regression procedure was used to model PrEP indications (yes/no) per an interpretation of U.S. Centers of Disease Control and Prevention recommendations among those without HIV (n = 843). Results The diverse sample was 4.9% Black; 22.1% Latinx ethnicity; 28.4% non-binary gender identity; 32.6% gay-identified; 82.7% on testosterone. Overall, 84.1% had heard of PrEP. Of these, 33.3% reported lifetime PrEP use (21.8% current and 11.5% past). Based on HIV behavioural risk profiles in the last six months, 55.2% of respondents had indications for PrEP. In a multivariable model, factors associated with PrEP indication included where met sex partners, not having sex exclusively with cismen, higher perceived HIV risk, greater number of partners and high cis male partner stigma (all p Discussion The majority of trans MSM in this sample had a PrEP indication. Stigma was associated with risk for HIV acquisition and represents a critical target for HIV biobehavioural prevention interventions for trans MSM, who appear to be underutilizing PrEP. Conclusions Results from this study support the full inclusion of trans MSM in HIV biobehavioural prevention efforts. Public health interventions and programmes are needed to reach trans MSM that attend to general MSM risk factors as well as to vulnerabilities specific to trans MSM, including the context of stigma from cis male sexual partners.

PrEP interest and HIV-1 incidence among MSM and transgender women in coastal Kenya.

Abstract: Introduction There is emerging data on HIV-1 incidence among MSM in sub-Saharan Africa (SSA), but no known estimate of HIV-1 incidence among transgender women (TGW) in the region has yet been reported. We assessed HIV-1 incidence and pre-exposure prophylaxis (PrEP) interest in men who have sex with men exclusively (MSME), men who have sex with men and women (MSMW) and TGW in coastal Kenya. Methods HIV-1-seronegative individuals who had participated in an HIV testing study in 2016 were traced and retested in 2017 according to Kenyan guidelines. All participants were assigned male sex at birth and had male sex partners; additional data on gender identity and sexual orientation were obtained. We assessed the factors associated with HIV-1 acquisition using Poisson regression and calculated HIV-1 incidence in MSME, MSMW and TGW. PrEP interest was assessed through focus group discussions to characterize subcategories' perceived PrEP needs. Results Of the 168 cohort participants, 42 were classified as MSME, 112 as MSMW and 14 as TGW. Overall, HIV-1 incidence was 5.1 (95% confidence interval (CI): 2.6 to 9.8) per 100 person-years (PY): 4.5 (95% CI: 1.1 to 17.8] per 100 PY among MSME, 3.4 (95% CI: 1.3 to 9.1) per 100 PY among MSMW and 20.6 (95% CI: 6.6 to 63.8] per 100 PY among TGW. HIV-1 acquisition was associated with exclusive receptive anal intercourse (aIRR 13.0, 95% CI 1.9 to 88.6), history of an STI in preceding six months (aIRR 10.3, 95% CI 2.2 to 49.4) and separated/divorced marital status (aIRR 8.2 (95%: 1.1 to 62.2). Almost all (98.8%) participants were interested in initiating PrEP. MSME and TGW felt that PrEP would lead to increases in condomless anal or group sex. Conclusions TGW had a very high HIV-1 incidence compared with MSME and MSMW. Subcategories of MSM anticipated different PrEP needs and post-PrEP risk behaviour. Further studies should assess if TGW may have been wrongly categorized as MSM in other HIV-1 incidence studies in the region.

PrEP uptake preferences among men who have sex with men in China: results from a National Internet Survey.

Abstract: Introduction HIV incidence among men who have sex with men (MSM) is high in China. Pre-exposure prophylaxis (PrEP) is a promising mean to prevent HIV transmission but it is not widely available in China. We conducted a large Internet-based online survey to assess the willingness of Chinese MSM to take PrEP and associated factors to their uptake preferences. Methods Between 19 January and 6 February, 2017, 4581 MSM aged over 15 years were recruited via a social networking app to take an online PrEP survey. HIV status at the time of the survey being conducted was not one of recruitment criteria. Participants were asked if they had heard of PrEP, if they had concerns about PrEP, and if they would be ready to uptake PrEP should it be provided. When asked if participants were willing to take PrEP, they were asked to select from the following responses: "definitely not," "probably not," "not sure," "probably yes," and "definitely yes." In the final analysis, we grouped these five-level Likert scale responses into three-level responses as "definitely yes," "probably yes," and "no (definitely not/probably not/not sure)." Descriptive analysis and multinomial logistic regressions were conducted to assess the associations of PrEP adoption readiness and uptake concerns with HIV risk behaviours and demographic characteristics. Results MSM from 33 geographical regions of China participated in the survey. The majority were younger than 25 (65.2%) and had attended college (68.6%). HIV prevalence was high (6.8%) and 43.3% reported a history of unprotected anal sex. Only 22.4% of participants had heard of PrEP. When asked if they would uptake PrEP, 26.0% said "definitely yes," 49.6% were "probably yes," and 24.4% said "no." PrEP adoption readiness was associated with having previously heard of PrEP and expressing concerns about accessibility and cost. Worries about side effects, low perceived HIV risk, preference for condoms, and never having received HIV testing were negatively associated with PrEP uptake willingness. Conclusion Young and well-educated Chinese MSM reported a low willingness to uptake PrEP despite being high-risk for HIV. Effective education, especially through online mediums, will be critical to optimize this group's PrEP uptake.

Why interventions to prevent intimate partner violence and HIV have failed young women in southern Africa

Abstract: INTRODUCTION Adolescent girls and young women aged 15 to 24 years have some of the highest HIV incidence rates globally, with girls two to four times more likely to be living with HIV than their male peers. High levels of intimate partner violence (IPV) experienced by this age group is a significant risk factor for HIV acquisition. While behavioural interventions to prevent IPV and HIV in southern Africa have seen some success in reducing self-reported experiences of IPV, these interventions have largely failed to achieve similar outcomes for young women. DISCUSSION We identify three main reasons for the failure of IPV/HIV interventions for many young women in southern Africa. First, interventions are usually developed without the meaningful involvement of both young women and young men. Youth input into research design is largely focused on user testing or consultation of targeted groups, involving relatively low levels of participation. Second, interventions are focused on addressing individual risk factors rather than broader social and structural contexts of being a young woman. "Risk factor" interventions, rather than supporting women's agency, can pose a major barrier for supporting changes in behaviour among young women because they often fail to dislodge well-entrenched gender and age-related inequalities. Third, current intervention models have not adequately accounted for changes in gender norms and relationships across southern Africa. Individuals are getting married later in life (or not at all), new technologies are transforming romantic interactions and opening new opportunities for violence, and discussions about women's rights are both challenging gender inequalities and reinforcing them. CONCLUSIONS In order to move beyond the status quo of current approaches, and to support real innovation, IPV/HIV prevention interventions need to be co-developed with youth as part of a meaningful participatory process of research, intervention design, youth involvement in development and implementation. This process of co-development needs to be radical and break with the current focus on adapting existing interventions to meet the needs of young people, which are not well understood and often do not directly reflect their priorities. Broader social contexts and compound lenses are needed to avoid narrow approaches and to accommodate evolving norms.

Sustained high HIV case-finding through index testing and partner notification services: experiences from three provinces in Zimbabwe.

Abstract: INTRODUCTION Several countries in southern Africa have made significant progress towards reaching the Joint United Nations Programme on HIV/AIDS goal of ensuring that 90% of people living with HIV are aware of their status. In Zimbabwe, progress towards this "first 90" was estimated at 73% in 2016. To reach the remaining people living with HIV who have undiagnosed infection, the Zimbabwe Ministry of Health and Child Care has been promoting index testing and partner notification services (PNS). We describe the implementation of index testing and PNS under the Zimbabwe HIV Care and Treatment (ZHCT) project and the resulting uptake, HIV positivity rate and links to HIV treatment. METHODS The ZHCT project has been implemented since March 2016, covering a total of 12 districts in three provinces. To assess the project's performance on index testing, we extracted data on HIV testing from the district health information system (DHIS 2) from March 2016 to May 2018, validated it using service registers and calculated monthly HIV positivity rates using Microsoft Excel. Data were disaggregated by district, province, sex and service delivery point. We used SPSS to assess for statistical differences in paired monthly HIV positivity rates by sex, testing site, and province. RESULTS The average HIV positivity rate rose from 10% during the first six months of implementation to more than 30% by August 2016 and was sustained above 30% through May 2018. The overall facility HIV positivity rate was 4.1% during the same period. The high HIV positivity rate was achieved for both males and females (mean monthly HIV positivity rate of 31.3% for males and 33.7% for females), with females showing significantly higher positivity compared to males (p < 0.001). The ZHCT mean monthly HIV positivity rate from index testing (32.6%) was significantly higher than that achieved through provider-initiated testing and counselling and other facility HIV testing modalities (4.1%, p < 0.001). CONCLUSIONS The ZHCT project has demonstrated successes in implementing index testing and PNS by attaining a high HIV positivity rate sustained over the study period. As the country moves towards HIV epidemic control, index testing and PNS are critical strategies for targeted HIV case identification.

The Self-Testing AfRica (STAR) Initiative: accelerating global access and scale-up of HIV self-testing.

Abstract: Introduction HIV self-testing (HIVST) was first proposed as an additional option to standard HIV testing services in the 1980s. By 2015, two years after the first HIVST kit was approved for the American market and the year in which Unitaid invested in the "HIV Self-Testing AfRica (STAR) Initiative," HIVST remained unexplored with negligible access in low- and middle-income countries (LMIC). However, rapid progress had been made. This commentary outlines the interlinked market, regulatory and policy barriers that had inhibited product development and kept HIVST out of LMIC policy. We detail the components of STAR that enabled rapid HIVST scale-up, including critical investments in implementation, research, market forecasting, and engagement with manufacturers and regulators. Discussion The STAR Initiative has generated crucial information about how to distribute HIVST products effectively, ethically and efficiently. Service delivery models range from clinic-based distribution to workplace and partner-delivered approaches to reach first-time male testers, to community outreach to sex workers and general population "hotspots." These data directly informed supportive policy, notably the 2016 WHO guidelines strongly recommending HIVST as an additional testing approach, and regulatory change through support for WHO prequalification of the first HIVST kit in 2017. In July 2015, only two countries had national HIVST policies and were implementing HIVST. Three years later, 59 countries have policies, actively implemented in 28, with an additional 53 countries reporting policies under development. By end-November 2018 several quality-assured HIVST products had been registered, including two WHO prequalified tests. STAR Initiative countries have drafted regulations governing in vitro diagnostics, including HIVST products. With enabling policies, pre-qualification and regulations in place, donor procurement of kits has increased rapidly, to a forecasted estimate of 16 million HIVST kits procured by 2020. Conclusions The STAR Initiative provided a strong foundation to introduce HIVST in LMICs and allow for rapid scale-up based on the wealth of multi-country evidence gathered. Together with sustained coordination and acceleration of market development work, HIVST can help address the testing gap and provide a focused and cost-effective means to expand access to treatment and prevention services.

Point-of-care viral load monitoring: outcomes from a decentralized HIV programme in Malawi.

Abstract: INTRODUCTION Routinely monitoring the HIV viral load (VL) of people living with HIV (PLHIV) on anti-retroviral therapy (ART) facilitates intensive adherence counselling and faster ART regimen switch when treatment failure is indicated. Yet standard VL-testing in centralized laboratories can be time-intensive and logistically difficult in low-resource settings. This paper evaluates the outcomes of the first four years of routine VL-monitoring using Point-of-Care technology, implemented by Medecins Sans Frontieres (MSF) in rural clinics in Malawi. METHODS We conducted a retrospective cohort analysis of patients eligible for routine VL- testing between 2013 and 2017 in four decentralized ART-clinics and the district hospital in Chiradzulu, Malawi. We assessed VL-testing coverage and the treatment failure cascade (from suspected failure (first VL>1000 copies/mL) to VL suppression post regimen switch). We used descriptive statistics and multivariate logistic regression to assess factors associated with suspected failure. RESULTS AND DISCUSSION Among 21,400 eligible patients, VL-testing coverage was 85% and VL suppression was found in 89% of those tested. In the decentralized clinics, 88% of test results were reviewed on the same day as blood collection, whereas in the district hospital the median turnaround-time for results was 85 days. Among first-line ART patients with suspected failure (N = 1544), 30% suppressed (VL<1000 copies/mL), 35% were treatment failures (confirmed by subsequent VL-testing) and 35% had incomplete VL follow-up. Among treatment failures, 80% (N = 540) were switched to a second-line regimen, with a higher switching rate in the decentralized clinics than in the district hospital (86% vs. 67%, p < 0.01) and a shorter median time-to-switch (6.8 months vs. 9.7 months, p < 0.01). Similarly, the post-switch VL-testing rate was markedly higher in the decentralized clinics (61% vs. 26%, p < 0.01). Overall, 79% of patients with a post-switch VL-test were suppressed. CONCLUSIONS Viral load testing at the point-of-care in Chiradzulu, Malawi achieved high coverage and good drug regimen switch rates among those identified as treatment failures. In decentralized clinics, same-day test results and shorter time-to-switch illustrated the game-changing potential of POC-based VL-testing. Nevertheless, gaps were identified along all steps of the failure cascade. Regular staff training, continuous monitoring and creating demand are essential to the success of routine VL-testing.

Economic cost analysis of door-to-door community-based distribution of HIV self-test kits in Malawi, Zambia and Zimbabwe

Abstract: INTRODUCTION: HIV self-testing (HIVST) is recommended by the World Health Organization in addition to other testing modalities to increase uptake of HIV testing, particularly among harder-to-reach populations. This study provides the first empirical evidence of the costs of door-to-door community-based HIVST distribution in Malawi, Zambia and Zimbabwe. METHODS: HIVST kits were distributed door-to-door in 71 sites across Malawi, Zambia and Zimbabwe from June 2016 to May 2017. Programme expenditures, supplemented by on-site observation and monitoring and evaluation data were used to estimate total economic and unit costs of HIVST distribution, by input and site. Inputs were categorized into start-up, capital and recurrent costs. Sensitivity and scenario analyses were performed to assess the impact of key parameters on unit costs. RESULTS: In total, 152,671, 103,589 and 93,459 HIVST kits were distributed in Malawi, Zambia and Zimbabwe over 12, 11 and 10 months respectively. Across these countries, 43% to 51% of HIVST kits were distributed to men. The average cost per HIVST kit distributed was US$8.15, US$16.42 and US$13.84 in Malawi, Zambia and Zimbabwe, respectively, with pronounced intersite variation within countries driven largely by site-level fixed costs. Site-level recurrent costs were 70% to 92% of full costs and 20% to 62% higher than routine HIV testing services (HTS) costs. Personnel costs contributed from 26% to 52% of total costs across countries reflecting differences in remuneration approaches and country GDP. CONCLUSIONS: These early door-to-door community HIVST distribution programmes show large potential, both for reaching untested populations and for substantial economies of scale as HIVST programmes scale-up and mature. From a societal perspective, the costs of HIVST appear similar to conventional HTS, with the higher providers' costs substantially offsetting user costs. Future approaches to minimizing cost and/or maximize testing coverage could include unpaid door-to-door community-led distribution to reach end-users and integrating HIVST into routine clinical services via direct or secondary distribution strategies with lower fixed costs.

Community-led HIV testing services including HIV self-testing and assisted partner notification services in Vietnam: lessons from a pilot study in a concentrated epidemic setting.

Abstract: Introduction The HIV epidemic in Vietnam is concentrated in key populations and their partners - people who inject drugs, men who have sex with men, sex workers and partners of people living with HIV. These groups have poor access to and uptake of conventional HIV testing services (HTS). To address this gap, lay provider- and self-testing and assisted partner notification (aPN) were introduced and delivered by the community. We explored the feasibility and effectiveness of implementing aPN as part of community testing services for key populations. Methods Lay provider testing and self-testing was started in January 2017, and targeted key populations and their partners. Since July 2017, aPN was introduced. HTS was offered at drop-in houses or coffee shops in Thai Nguyen and Can Tho provinces. All self-testing was assisted and observed by peer educators. Both in-person and social network methods were used to mobilize key populations to test for HIV and offer HTS to partners of people living with HIV. Client-level data, including demographic information and self-reported risk behaviour, were collected on site by peer educators. Results Between January 2017 and May 2018, 3978 persons from key populations were tested through community-led HTS; 66.7% were first-time testers. Of the 3978 clients, 3086 received HTS from a lay provider and 892 self-tested in the presence of a lay provider. Overall, 245 (6.2% of tested clients) had reactive results, 231 (94.3%) were confirmed to be HIV positive; 215/231 (93.1%) initiated antiretroviral therapy (ART). Of 231 adult HIV-positive clients, 186 (80.5%) were provided voluntary aPN, and 105 of their partners were contacted and received HTS. The ratio of partners who tested for HIV per index client was 0.56. Forty-four (41.9%) partners of index clients receiving HTS were diagnosed with HIV, 97.7% initiated ART during the study period. No social harm was identified or reported. Conclusions Including aPN as part of community-led HTS for key populations and their partners is feasible and effective, particularly for reaching first-time testers and undiagnosed HIV clients. Scale-up of aPN within community-led HTS for key populations is essential for achieving the United Nations 90-90-90 targets in Vietnam.

The role of saliva in gonorrhoea and chlamydia transmission to extragenital sites among men who have sex with men: new insights into transmission.

Abstract: Introduction Gonorrhoea and chlamydia cases have been rising among gay, bisexual and other men who have sex with men (MSM) over the last decade. The majority of cases are extragenital and occur at the oropharynx and anorectum. The aim of this narrative review was to review the risk factors and mode of transmission for gonorrhoea and chlamydia at the oropharynx and anorectum among MSM. Results and discussion New evidence suggests that oropharyngeal gonorrhoea can be transmitted by kissing in addition to through the established route of condomless oral sex; and anorectal gonorrhoea can be acquired when saliva is used as a lubricant for anal sex and rimming in addition to the established route of condomless penile-anal sex in MSM. In contrast, condomless penile-anal sex remains the major route for chlamydia transmission. Conclusions Substantial transmission of gonorrhoea may occur with practices other than the established routes of condomless oral and/or anal sex and hence condoms may not be effective in preventing gonorrhoea transmission to extragenital sites. In contrast, condoms are effective for chlamydia control because it is mainly transmitted through condomless penile-anal sex. Novel interventions for gonorrhoea that reduce the risk of transmission at extragenital site are required.