Search

Background Despite large-scale efforts to diagnose people living with HIV, 54% remain undiagnosed in sub-Saharan Africa. The gap in knowledge of HIV status and uptake of follow-on services remains wide with much lower rates of HIV testing among men compared to women. Here, we design a study to investigate the effect on uptake of HIV testing and linkage into care or prevention of partner-delivered HIV self-testing alone or with an additional intervention among male partners of pregnant women. Methods A phase II, adaptive, multi-arm, multi-stage cluster randomised trial, randomising antenatal clinic (ANC) days to six different trial arms. Pregnant women accessing ANC in urban Malawi for the first time will be recruited into either the standard of care (SOC) arm (invitation letter to the male partner offering HIV testing) or one of five intervention arms offering oral HIV self-test kits. Three of the five intervention arms will additionally offer the male partner a financial incentive (fixed or lottery amount) conditional on linkage after self-testing with one arm testing phone call reminders. Assuming that 25% of male partners link to care or prevention in the SOC arm, six clinic days, with a harmonic mean of 21 eligible participants, per arm will provide 80% power to detect a 0.15 absolute difference in the primary outcome. Cluster proportions will be analysed by a cluster summaries approach with adjustment for clustering and multiplicity. Discussion This trial applies adaptive methods which are novel and efficient designs. The methodology and lessons learned here will be important as proof of concept of how to design and conduct similar studies in the future. Although small, this trial will potentially present good evidence on the type of effective interventions for improving linkage into ART or prevention. The trial results will also have important policy implications on how to implement HIVST targeting male partners of pregnant women who are accessing ANC for the first time while paying particular attention to safety concerns. Contamination may occur if women in the intervention arms share their self-test kits with women in the SOC arm. Trial registration ISRCTN, ID: 18421340. Registered on 31 March 2016. Electronic supplementary material The online version of this article (doi:10.1186/s13063-017-2093-2) contains supplementary material, which is available to authorized users.

INTRODUCTION: New HIV testing strategies are needed to reach the United Nations' 90-90-90 target. HIV self-testing (HIVST) can increase uptake, but users' perspectives on optimal models of distribution and post-test services are uncertain. We used discrete choice experiments (DCEs) to explore the impact of service characteristics on uptake along the testing cascade. METHODS: DCEs are a quantitative survey method that present respondents with repeated choices between packages of service characteristics, and estimate relative strengths of preferences for service characteristics. From June to October 2016, we embedded DCEs within a population-based survey following door-to-door HIVST distribution by community volunteers in two rural Zimbabwean districts: one DCE addressed HIVST distribution preferences; and the other preferences for linkage to confirmatory testing (LCT) following self-testing. Using preference coefficients/utilities, we identified key drivers of uptake for each service and simulated the effect of changes of outreach and static/public clinics' characteristics on LCT. RESULTS: Distribution and LCT DCEs surveyed 296/329 (90.0%) and 496/594 (83.5%) participants; 81.8% and 84.9% had ever-tested, respectively. The strongest distribution preferences were for: (1) free kits - a $1 increase in the kit price was associated with a disutility (U) of -2.017; (2) door-to-door kit delivery (U = +1.029) relative to collection from public/outreach clinic; (3) telephone helpline for pretest support relative to in-person or no support (U = +0.415); (4) distributors from own/local village (U = +0.145) versus those from external communities. Participants who had never HIV tested valued phone helplines more than those previously tested. The strongest LCT preferences were: (1) immediate antiretroviral therapy (ART) availability: U = +0.614 and U = +1.052 for public and outreach clinics, respectively; (2) free services: a $1 user fee increase decreased utility at public (U = -0.381) and outreach clinics (U = -0.761); (3) proximity of clinic (U = -0.38 per hour walking). Participants reported willingness to link to either location; but never-testers were more averse to LCT. Simulations showed the importance of availability of ART: ART unavailability at public clinics would reduce LCT by 24%. CONCLUSIONS: Free HIVST distribution by local volunteers and immediately available ART were the strongest relative preferences identified. Accommodating LCT preferences, notably ensuring efficient provision of ART, could facilitate "resistant testers" to test while maximizing uptake of post-test services.

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.

BACKGROUND\ud Current diagnostics for HIV-associated tuberculosis are suboptimal, with missed diagnoses contributing to high hospital mortality and approximately 374 000 annual HIV-positive deaths globally. Urine-based assays have a good diagnostic yield; therefore, we aimed to assess whether urine-based screening in HIV-positive inpatients for tuberculosis improved outcomes.\ud \ud METHODS\ud We did a pragmatic, multicentre, double-blind, randomised controlled trial in two hospitals in Malawi and South Africa. We included HIV-positive medical inpatients aged 18 years or more who were not taking tuberculosis treatment. We randomly assigned patients (1:1), using a computer-generated list of random block size stratified by site, to either the standard-of-care or the intervention screening group, irrespective of symptoms or clinical presentation. Attending clinicians made decisions about care; and patients, clinicians, and the study team were masked to the group allocation. In both groups, sputum was tested using the Xpert MTB/RIF assay (Xpert; Cepheid, Sunnyvale, CA, USA). In the standard-of-care group, urine samples were not tested for tuberculosis. In the intervention group, urine was tested with the Alere Determine TB-LAM Ag (TB-LAM; Alere, Waltham, MA, USA), and Xpert assays. The primary outcome was all-cause 56-day mortality. Subgroup analyses for the primary outcome were prespecified based on baseline CD4 count, haemoglobin, clinical suspicion for tuberculosis; and by study site and calendar time. We used an intention-to-treat principle for our analyses. This trial is registered with the ISRCTN registry, number ISRCTN71603869.\ud \ud FINDINGS\ud Between Oct 26, 2015, and Sept 19, 2017, we screened 4788 HIV-positive adults, of which 2600 (54%) were randomly assigned to the study groups (n=1300 for each group). 13 patients were excluded after randomisation from analysis in each group, leaving 2574 in the final intention-to-treat analysis (n=1287 in each group). At admission, 1861 patients were taking antiretroviral therapy and median CD4 count was 227 cells per μL (IQR 79-436). Mortality at 56 days was reported for 272 (21%) of 1287 patients in the standard-of-care group and 235 (18%) of 1287 in the intervention group (adjusted risk reduction [aRD] -2·8%, 95% CI -5·8 to 0·3; p=0·074). In three of the 12 prespecified, but underpowered subgroups, mortality was lower in the intervention group than in the standard-of-care group for CD4 counts less than 100 cells per μL (aRD -7·1%, 95% CI -13·7 to -0·4; p=0.036), severe anaemia (-9·0%, -16·6 to -1·3; p=0·021), and patients with clinically suspected tuberculosis (-5·7%, -10·9 to -0·5; p=0·033); with no difference by site or calendar period. Adverse events were similar in both groups.\ud \ud INTERPRETATION\ud Urine-based tuberculosis screening did not reduce overall mortality in all HIV-positive inpatients, but might benefit some high-risk subgroups. Implementation could contribute towards global targets to reduce tuberculosis mortality.\ud \ud FUNDING\ud Joint Global Health Trials Scheme of the Medical Research Council, the UK Department for International Development, and the Wellcome Trust.

Globally, men have a higher epidemiologic burden of tuberculosis (incidence, prevalence, mortality) than women do, possibly due to differences in disease incidence, treatment initiation, self-cure, and/or untreated-tuberculosis mortality rates. Using a simple, sex-stratified compartmental model, we employed a Bayesian approach to explore which factors most likely explain men’s higher burden. We applied the model to smear-positive pulmonary tuberculosis in Vietnam (2006–2007) and Malawi (2013–2014). Posterior estimates were consistent with sex-specific prevalence and notifications in both countries. Results supported higher incidence in men and showed that both sexes faced longer durations of untreated disease than estimated by self-reports. Prior untreated disease durations were revised upward 8- to 24-fold, to 2.2 (95% credible interval: 1.7, 2.9) years for men in Vietnam and 2.8 (1.8, 4.1) years for men in Malawi, approximately a year longer than for women in each country. Results imply that substantial sex differences in tuberculosis burden are almost solely attributable to men’s disadvantages in disease incidence and untreated disease duration. The latter, for which self-reports provide a poor proxy, implies inadequate coverage of case-finding strategies. These results highlight an urgent need for better understanding of gender-related barriers faced by men and support the systematic targeting of men for screening.

Introduction: Although HIV infection and its associated co-morbidities remain the commonest reason for hospitalisation in Africa, their impact on economic costs and health-related quality of life (HRQoL) are not well understood. This information is essential for decision-makers to make informed choices about how to best scale-up anti-retroviral treatment (ART) programmes. This study aimed to quantify the impact of HIV infection and ART on economic outcomes in a prospective cohort of hospitalised patients with high HIV prevalence.\ud \ud Methods: Sequential medical admissions to Queen Elizabeth Central Hospital, Malawi, between June-December 2014 were followed until discharge, with standardised classification of medical diagnosis and estimation of healthcare resources used. Primary costing studies estimated total health provider cost by medical diagnosis. Participants were interviewed to establish direct non-medical and indirect costs. Costs were adjusted to 2014 US$ and INT$. HRQoL was measured using the EuroQol EQ-5D. Multivariable analyses estimated predictors of economic outcomes.\ud \ud Results: Of 892 eligible participants, 80.4% (647/892) were recruited and medical notes found. In total, 447/647 (69.1%) participants were HIV-positive, 339/447 (75.8%) were on ART prior to admission, and 134/647 (20.7%) died in hospital. Mean duration of admission for HIV-positive participants not on ART and HIV-positive participants on ART was 15.0 days (95%CI: 12.0-18.0) and 12.2 days (95%CI: 10.8-13.7) respectively, compared to 10.8 days (95%CI: 8.8-12.8) for HIV-negative participants. Mean total provider cost per hospital admission was US$74.78 (bootstrap 95%CI: US$25.41-US$124.15) higher for HIV-positive than HIV-negative participants. Amongst HIV-positive participants, the mean total provider cost was US$106.87 (bootstrap 95%CI: US$25.09-US$106.87) lower for those on ART than for those not on ART. The mean total direct non-medical and indirect cost per hospital admission was US$87.84. EQ-5D utility scores were lower amongst HIV-positive participants, but not significantly different between those on and not on ART. \ud \ud Conclusions: HIV-related hospital care poses substantial financial burdens on health systems and patients; however, per-admission costs are substantially lower for those already initiated onto ART prior to admission. These potential cost savings could offset some of the additional resources needed to provide universal access to ART.

Introduction\ud \ud Although HIV infection and its associated co-morbidities remain the commonest reason for hospitalisation in Africa, their impact on economic costs and health-related quality of life (HRQoL) are not well understood. This information is essential for decision-makers to make informed choices about how to best scale-up anti-retroviral treatment (ART) programmes. This study aimed to quantify the impact of HIV infection and ART on economic outcomes in a prospective cohort of hospitalised patients with high HIV prevalence.\ud \ud Methods\ud \ud Sequential medical admissions to Queen Elizabeth Central Hospital, Malawi, between June-December 2014 were followed until discharge, with standardised classification of medical diagnosis and estimation of healthcare resources used. Primary costing studies estimated total health provider cost by medical diagnosis. Participants were interviewed to establish direct non-medical and indirect costs. Costs were adjusted to 2014 US$ and INT$. HRQoL was measured using the EuroQol EQ-5D. Multivariable analyses estimated predictors of economic outcomes.\ud \ud Results\ud \ud Of 892 eligible participants, 80.4% (647/892) were recruited and medical notes found. In total, 447/647 (69.1%) participants were HIV-positive, 339/447 (75.8%) were on ART prior to admission, and 134/647 (20.7%) died in hospital. Mean duration of admission for HIV-positive participants not on ART and HIV-positive participants on ART was 15.0 days (95%CI: 12.0–18.0) and 12.2 days (95%CI: 10.8–13.7) respectively, compared to 10.8 days (95%CI: 8.8–12.8) for HIV-negative participants. Mean total provider cost per hospital admission was US$74.78 (bootstrap 95%CI: US$25.41-US$124.15) higher for HIV-positive than HIV-negative participants. Amongst HIV-positive participants, the mean total provider cost was US$106.87 (bootstrap 95%CI: US$25.09-US$106.87) lower for those on ART than for those not on ART. The mean total direct non-medical and indirect cost per hospital admission was US$87.84. EQ-5D utility scores were lower amongst HIV-positive participants, but not significantly different between those on and not on ART.\ud \ud Conclusions\ud \ud HIV-related hospital care poses substantial financial burdens on health systems and patients; however, per-admission costs are substantially lower for those already initiated onto ART prior to admission. These potential cost savings could offset some of the additional resources needed to provide universal access to ART.