Investigating interventions to increase uptake of HIV testing and linkage to care or prevention for male partners of pregnant women in antenatal clinics in Blantyre, Malawi

Improved availability of HIV tests has led to increases in numbers testing and starting treatment in sub-Saharan Africa. Despite such remarkable progress, men continue to lag behind in HIV testing in the region including men in well-established heterosexual relationships, in which context HIV transmission is surprisingly high. We previously found HIV self-testing (HIVST) to be very effective at increasing the uptake of HIV testing in the general population in urban Blantyre, Malawi. This PhD investigated the effect of partner-delivered HIVST, providing HIVST kits to pregnant women in antenatal clinics (ANC) with or without additional interventions, including financial incentives, on uptake of testing and linkage to care or prevention. The PhD is made up of three main pieces of work: First, a systematic review was conducted to investigate the existing evidence regarding the effectiveness of demand-side (given to users) financial incentives on linkage to HIV treatment or voluntary medical male circumcision (VMMC) in low and middle income (LMIC) countries. Relevant electronic databases and conference proceedings were searched for randomised controlled trials. Seven trials were identified out of 1099 citations, with all showing significant improvement in linkage: four investigated VMMC and three investigated ART. Manuscript currently under review. Secondly, a formative study was carried out to identify additional potential interventions and to refine interventions identified as promising through the systematic review, before being tested in a subsequent trial. Undertaking this formative study ensured that interventions being considered for inclusion in the trial design were adapted to the local environment and prevailing social norms, by seeking input and feedback from would-be users of the service. Paper published in J Int AIDS Soc, 2017. Thirdly, a multi-arm two-stage cluster-randomised trial was conducted in Blantyre, Malawi. The paper describing the trial design is published in Trials, 2017; trial results manuscript is under review. Antenatal care clinic days were randomized to standard of care (SOC: personalised invitation to male friendly clinic for standard HIV testing and fast-track referral for HIV treatment or VMMC services) or one of five intervention arms: SOC plus two partner-delivered self-test kits with a) no addition, or financial incentives of b) US$3, c) US$10, d) lottery (10% chance of winning $30), or e) phone call. All incentives were conditional on attending the male friendly clinic. The primary outcome at 28 days, measured through attendance at the male friendly clinic, was: referral for antiretroviral therapy (ART) for HIV-positive men; or voluntary male medical circumcision (VMMC) scheduled if HIV-negative/uncircumcised; or counselling if HIV-negative/circumcised. At the end of stage 1, a planned interim analysis was performed and the HIVST-lottery arm was dropped for futility.Male partner HIV-testing was substantially increased in all HIVST arms (range 87.0% to 95.4% in the 5 arms, compared to 17.4% in the SOC arm), according to self-report by the woman at 28 days. Reaching the primary linkage outcome at 28 days was most likely for the partners of participants in clinic days randomised to the HIVST-$3 and the HIVST-$10 arms, with geometric means of 40.9% (adjusted risk ratio [aRR] 3.01, 95%CI:1.63-5.57) and 51.7% (aRR 3.72, 95%CI:1.85-7.48), respectively. Successful male linkage was also more likely in the HIVST-phone reminder (geometric mean 22.3%, aRR 1.58, 95%CI:1.07-2.33) and HIVST-alone (geometric mean 17.5%: aRR 1.45 (95%CI:0.99-2.13) compared to SOC (13.0%). Linkage in the HIVST-lottery arm (geometric mean 18.6%, aRR 1.43, 95%CI:0.96-2.13) was less pronounced than with the $3 or $10 fixed conditional-incentives, and clients disliked the uncertainty.Overall, 42/46 (91.3%) newly diagnosed HIV-positive men initiated ART and 135/222 (60.8%) HIV-negative and previously uncircumcised men had VMMC. No serious adverse events were reported. Cost per male partner attended clinic with confirmed HIV test result was $23.73 and $28.08 for $10 and $3 arms, respectively. Secondary distribution of HIVST kits from ANC clinics greatly increased partner-testing, and timely linkage within 28 days increased 3-fold with the combination of fixed financial incentives plus partner-delivered HIV self-test kits in this hard to reach group. This PhD project has demonstrated that novel trial designs such as adaptive MAMS can be applied to address pressing public health problems in Africa. The approach followed here, combining systematic review, qualitative pilot study, and multi-arm randomised trial is ideal for rapidly generating high quality evidence for interventions, such as financial incentives, where the effectiveness of different amounts may vary from one setting to the next.