Improving access to pre-exposure prophylaxis for adolescent girls and young women: recommendations from healthcare providers in eastern Zimbabwe.

BACKGROUND: In sub-Saharan Africa, adolescent girls and young women (AGYW) are at high risk of acquiring HIV. A growing number of sub-Saharan African countries are beginning to avail pre-exposure prophylaxis, or PrEP, but with limited success. Unpacking strategies to overcome barriers to the uptake of PrEP is critical to prevent HIV amongst AGYW. This article explores health professionals' views and recommendations on what is required to increase uptake of PrEP. METHODS: The study draws on interview data from 12 providers of HIV prevention services in eastern Zimbabwe. The healthcare providers were purposefully recruited from a mix of rural and urban health facilities offering PrEP. The interviews were transcribed and imported into NVivo 12 for thematic coding and network analysis. RESULTS: Our analysis revealed six broad strategies and 15 concrete recommendations which detail the range of elements healthcare providers consider central for facilitating engagement with PrEP. The healthcare providers called for: (1) PrEP marketing campaigns; (2) youth-friendly services or corners; (3) improved PrEP delivery mechanisms; (4) improvements in PrEP treatment; (5) greater engagement with key stakeholders, including with young people themselves; and (6) elimination of costs associated with PrEP use. These recommendations exemplify an awareness amongst healthcare providers that PrEP access is contingent on a range of factors both inside and outside of the clinical setting. CONCLUSIONS: Healthcare providers are at the frontline of the HIV epidemic response. Their community-embeddedness, coupled with their interactions and encounters with AGYW, make them well positioned to articulate context-specific measures for improving access to PrEP. Importantly, the breadth of their recommendations suggests recognition of PrEP use as a complex social practice that requires integration of a combination of interventions, spanning biomedical, structural, and behavioural domains.

Costs and cost-effectiveness of HIV counselling and testing modalities in Southern Mozambique.

OBJECTIVE: Despite the high HIV associated burden, Mozambique lacks data on HIV counselling and testing (HCT) costs. To help guide national HIV/AIDS programs, we estimated the cost per test for voluntary counselling and testing (VCT) from the patient's perspective and the costs per person tested and per HIV-positive individual linked to care to the healthcare provider for VCT, provider-initiated counselling and testing (PICT) and home-based testing (HBT). We also assessed the cost-effectiveness of these strategies for linking patients to care. METHODS: Data from a cohort study conducted in the Manhiça District were used to derive costs and linkage-to-care outcomes of the three HCT strategies. A decision tree was used to model HCT costs according to the likelihood of HCT linking individuals to care and to obtain the incremental cost-effectiveness ratios (ICERs) of PICT and HBT with VCT as the comparator. Sensitivity analyses were performed to assess robustness of base-case findings. FINDINGS: Based on costs and valuations in 2015, average and median VCT costs to the patient per individual tested were US$1.34 and US$1.08, respectively. Costs per individual tested were greatest for HBT (US$11.07), followed by VCT (US$7.79), and PICT (US$7.14). The costs per HIV-positive individual linked to care followed a similar trend. PICT was not cost-effective in comparison with VCT at a willingness-to-accept threshold of US$4.53, but only marginally given a corresponding base-case ICER of US$4.15, while HBT was dominated, with higher costs and lower impact than VCT. Base-case results for the comparison between PICT and VCT presented great uncertainty, whereas findings for HBT were robust. CONCLUSION: PICT and VCT are likely equally cost-effective in Manhiça. We recommend that VCT be offered as the predominant HCT strategy in Mozambique, but expansion of PICT could be considered in limited-resource areas. HBT without facilitated linkage or reduced costs is unlikely to be cost-effective.

How gender norms and 'good girl' notions prevent adolescent girls and young women from engaging with PrEP: qualitative insights from Zimbabwe.

BACKGROUND: Pre-exposure prophylaxis, or PrEP, has been hailed for its promise to provide women with user-control. However, gender-specific challenges undermining PrEP use are beginning to emerge. We explore the role of gender norms in shaping adolescent girls and young women's (AGYW) engagement with PrEP. METHODS: We draw on qualitative data from 12 individual interviews and three focus group discussions with AGYW from eastern Zimbabwe. Interviews were transcribed and thematically coded in NVivo 12. Emerging themes were further investigated using Connell's notion of 'emphasised femininity'. RESULTS: Participants alluded to the patriarchal society they are part of, with 'good girl' notions subjecting them to direct and indirect social control. These controls manifest themselves through the anticipation of intersecting sexuality- and PrEP-related stigmas, discouraging AGYW from engaging with PrEP. AGYW recounted the need for permission to engage with PrEP, forcing them to consider engaging with PrEP in secrecy. In addition, limited privacy at home, and fear of disclosure of their health clinic visits, further heightened their fear of engaging with PrEP. PrEP is not simply a user-controlled HIV prevention method, but deeply entrenched within public gender orders. CONCLUSION: AGYW face significant limitations in their autonomy to initiate and engage with PrEP. Those considering PrEP face the dilemma of Scylla and Charybdis: The social risks of stigmatisation or risks of HIV acquisition. Efforts to make PrEP available must form part of a combination of social and structural interventions that challenge harmful gender norms.

The short-term impact of a malaria elimination initiative in Southern Mozambique: Application of the synthetic control method to routine surveillance data.

In public health epidemiology, quasi-experimental methods are widely used to estimate the causal impacts of interventions. In this paper, we demonstrate the contribution the synthetic control method (SCM) can make in evaluating public health interventions, when routine surveillance data are available and the validity of other quasi-experimental approaches may be in question. In our application, we evaluate the short-term effects of a large-scale Mass Drug Administration (MDA) based malaria elimination initiative in Southern Mozambique. We apply the SCM to district level weekly malaria incidence data and compare the observed reduction in age group specific malaria incidence. Between August 2015 and April 2017, a total of 13,322 (78%) cases of malaria were averted relative to the synthetic control. During the peak malaria seasons, the elimination initiative resulted in an 87% reduction in Year 1 (December 2015-April 2016), and 79% reduction in Year 2 (December 2016-April 2017). Comparison with an interrupted time series approach shows the SCM accounts for pre-intervention trends in the data and post-intervention weather events influencing malaria cases. We conclude MDA brought about a drastic reduction in malaria burden and can be a useful addition to existing (or new) vector control strategies and tools in accelerating towards elimination.

Relationships between changes in HIV risk perception and condom use in East Zimbabwe 2003-2013: population-based longitudinal analyses.

BACKGROUND: Perceiving a personal risk for HIV infection is considered important for engaging in HIV prevention behaviour and often targeted in HIV prevention interventions. However, there is limited evidence for assumed causal relationships between risk perception and prevention behaviour and the degree to which change in behaviour is attributable to change in risk perception is poorly understood. This study examines longitudinal relationships between changes in HIV risk perception and in condom use and the public health importance of changing risk perception. METHODS: Data on sexually active, HIV-negative adults (15-54 years) were taken from four surveys of a general-population open-cohort study in Manicaland, Zimbabwe (2003-2013). Increasing condom use between surveys was modelled in generalised estimating equations dependent on change in risk perception between surveys. Accounting for changes in other socio-demographic and behavioural factors, regression models examined the bi-directional relationship between risk perception and condom use, testing whether increasing risk perception is associated with increasing condom use and whether increasing condom use is associated with decreasing risk perception. Population attributable fractions (PAFs) were estimated. RESULTS: One thousand, nine hundred eighty-eight males and 3715 females participated in ≥2 surveys, contributing 8426 surveys pairs. Increasing risk perception between two surveys was associated with higher odds of increasing condom use (males: adjusted odds ratio [aOR] = 1.39, 95% confidence interval [CI] = 0.85-2.28, PAF = 3.39%; females: aOR = 1.41 [1.06-1.88], PAF = 6.59%), adjusting for changes in other socio-demographic and behavioural factors. Those who decreased risk perception were also more likely to increase condom use (males: aOR = 1.76 [1.12-2.78]; females: aOR = 1.23 [0.93-1.62]) compared to those without change in risk perception. CONCLUSIONS: Results on associations between changing risk perception and increasing condom use support hypothesised effects of risk perception on condom use and effects of condom use on risk perception (down-adjusting risk perception after adopting condom use). However, low proportions of change in condom use were attributable to changing risk perception, underlining the range of factors influencing HIV prevention behaviour and the need for comprehensive approaches to HIV prevention.

Spillover HIV prevention effects of a cash transfer trial in East Zimbabwe: evidence from a cluster-randomised trial and general-population survey.

BACKGROUND: Benefits of cash transfers (CTs) for HIV prevention have been demonstrated largely in purposively designed trials, commonly focusing on young women. It is less clear if CT interventions not designed for HIV prevention can have HIV-specific effects, including adverse effects. The cluster-randomised Manicaland Cash Transfer Trial (2010-11) evaluated effects of CTs on children's (2-17 years) development in eastern Zimbabwe. We evaluated whether this CT intervention with no HIV-specific objectives had unintended HIV prevention spillover effects (externalities). METHODS: Data on 2909 individuals (15-54 years) living in trial households were taken from a general-population survey, conducted simultaneously in the same communities as the Manicaland Trial. Average treatment effects (ATEs) of CTs on sexual behaviour (any recent sex, condom use, multiple partners) and secondary outcomes (mental distress, school enrolment, and alcohol/cigarette/drug consumption) were estimated using mixed-effects logistic regressions (random effects for study site and intervention cluster), by sex and age group (15-29; 30-54 years). Outcomes were also evaluated with a larger synthetic comparison group created through propensity score matching. RESULTS: CTs did not affect sexual debut but reduced having any recent sex (past 30 days) among young males (ATE: - 11.7 percentage points [PP] [95% confidence interval: -26.0PP, 2.61PP]) and females (- 5.68PP [- 15.7PP, 4.34PP]), with similar but less uncertain estimates when compared against the synthetic comparison group (males: -9.68PP [- 13.1PP, - 6.30PP]; females: -8.77PP [- 16.3PP, - 1.23PP]). There were no effects among older individuals. Young (but not older) males receiving CTs reported increased multiple partnerships (8.49PP [- 5.40PP, 22.4PP]; synthetic comparison: 10.3PP (1.27PP, 19.2PP). No impact on alcohol, cigarette, or drug consumption was found. There are indications that CTs reduced psychological distress among young people, although impacts were small. CTs increased school enrolment in males (11.5PP [3.05PP, 19.9PP]). Analyses with the synthetic comparison group (but not the original control group) further indicated increased school enrolment among females (5.50PP [1.62PP, 9.37PP]) and condom use among younger and older women receiving CTs (9.38PP [5.90PP, 12.9PP]; 5.95PP [1.46PP, 10.4PP]). CONCLUSIONS: Non-HIV-prevention CT interventions can have HIV prevention outcomes, including reduced sexual activity among young people and increased multiple partnerships among young men. No effects on sexual debut or alcohol, cigarette, or drug consumption were observed. A broad approach is necessary to evaluate CT interventions to capture unintended outcomes, particularly in economic evaluations. TRIAL REGISTRATION: ClinicalTrials.gov , NCT00966849 . Registered August 27, 2009.

Accuracy of HIV Risk Perception in East Zimbabwe 2003-2013.

Risk perception for HIV infection is an important determinant for engaging in HIV prevention behaviour. We investigate the degree to which HIV risk perception is accurate, i.e. corresponds to actual HIV infection risks, in a general-population open-cohort study in Zimbabwe (2003-2013) including 7201 individuals over 31,326 person-years. Risk perception for future infection (no/yes) at the beginning of periods between two surveys was associated with increased risk of HIV infection (Cox regression hazard ratio = 1.38 [1.07-1.79], adjusting for socio-demographic characteristics, sexual behaviour, and partner behaviour). The association was stronger among older people (25+ years). This suggests that HIV risk perception can be accurate but the higher HIV incidence (1.27 per 100 person-years) illustrates that individuals may face barriers to HIV prevention behaviour even when they perceive their risks. Gaps in risk perception are underlined by the high incidence among those not perceiving a risk (0.96%), low risk perception even among those reporting potentially risky sexual behaviour, and, particularly, lack of accuracy of risk perception among young people. Innovative interventions are needed to improve accuracy of risk perception but barriers to HIV prevention behaviours need to be addressed too, which may relate to the partner, community, or structural factors.

Wealth differentials in the impact of conditional and unconditional cash transfers on education: findings from a community-randomised controlled trial in Zimbabwe.

We investigated (1) how household wealth affected the relationship between conditional cash transfers (CCT) and unconditional cash transfers (UCT) and school attendance, (2) whether CCT and UCT affected educational outcomes (repeating a year of school), (3) if baseline school attendance and transfer conditions affected how much of the transfers participants spent on education and (4) if CCT or UCT reduced child labour in recipient households. Data were analysed from a cluster-randomized controlled trial of CCT and UCT in 4043 households from 2009 to 2010. Recipient households received $18 dollars per month plus $4 per child. CCT were conditioned on above 80% school attendance, a full vaccination record and a birth certificate. In the poorest quintile, the odds ratio of above 80% school attendance at follow-up for those with below 80% school attendance at baseline was 1.06 (p = .67) for UCT vs. CCT. UCT recipients reported spending slightly more (46.1% (45.4-46.7)) of the transfer on school expenses than did CCT recipients (44.8% (44.1-45.5)). Amongst those with baseline school attendance of below 80%, there was no statistically significant difference between CCT and UCT participants in the proportion of the transfer spent on school expenses (p = .63). Amongst those with above 80% baseline school attendance, CCT participants spent 3.5% less (p = .001) on school expenses than UCT participants. UCT participants were no less likely than those in the control group to repeat a grade of school. CCT participants had .69 (.60-.79) lower odds vs. control of repeating the previous school grade. Children in CCT recipient households spent an average of .31 fewer hours in paid work than those in the control group (p < .001) and children in the UCT arm spent an average of .15 fewer hours in paid work each week than those in the control arm (p = .06).

Do risk, time and prosocial preferences predict risky sexual behaviour of youths in a low-income, high-risk setting?

Young people in sub-Saharan Africa are particularly at high risk of sexually transmitted infections. Little is known about their preferences and even less about their association with risky sexual behaviour. We conducted incentivized economic experiments to measure risk, time and prosocial preferences in Zimbabwe. Preferences measured at baseline predict biomarker and self-reported measures of risky sexual behaviour gathered 12 months later. We find robust evidence that individuals more altruistic at baseline are more likely to be Herpes Simplex Virus Type-2 (HSV-2) positive 12 months later. Analysis by sex shows this association is driven by our sample of women. Having more sexual partners is associated with greater risk tolerance amongst men and greater impatience amongst women. Results highlight heterogeneity in the association between preferences and risky sexual behaviour.

Associations between HIV stigma and health-related quality-of-life among people living with HIV: cross-sectional analysis of data from HPTN 071 (PopART).

People living with HIV (PLHIV) report lower health-related quality-of-life (HRQoL) than HIV-negative people. HIV stigma may contribute to this. We explored the association between HIV stigma and HRQoL among PLHIV. We used cross-sectional data from 3991 randomly selected PLHIV who were surveyed in 2017-2018 for HPTN 071 (PopART), a cluster randomised trial in Zambia and South Africa. Participants were 18-44 years, had laboratory-confirmed HIV infection, and knew their status. HRQoL was measured using the EuroQol-5-dimensions-5-levels (EQ-5D-5L) questionnaire. Stigma outcomes included: internalised stigma, stigma experienced in the community, and stigma experienced in healthcare settings. Associations were examined using logistic regression. Participants who had experienced community stigma (n = 693/3991) had higher odds of reporting problems in at least one HRQoL domain, compared to those who had not (adjusted odds ratio, aOR: 1.51, 95% confidence interval, 95% Cl: 1.16-1.98, p = 0.002). Having experienced internalised stigma was also associated with reporting problems in at least one HRQoL domain (n = 552/3991, aOR: 1.98, 95% CI: 1.54-2.54, p < 0.001). However, having experienced stigma in a healthcare setting was less common (n = 158/3991) and not associated with HRQoL (aOR: 1.04, 95% CI: 0.68-1.58, p = 0.850). A stronger focus on interventions for internalised stigma and stigma experienced in the community is required.

"It will not be easy to accept": Parents conflicting attitudes towards pre-exposure prophylaxis for HIV prevention amongst adolescent girls and young women.

BACKGROUND: Pre-exposure prophylaxis, or PrEP, is a pill that has been hailed as a 'game changer' for HIV prevention, based on the belief it provides adolescent girls and young women (AGYW) with a level of user-control. However, engagement with PrEP is often dependent on societal factors, such as social attitudes towards gender, sexuality, and PrEP. As parents' communication on sexual and reproductive health issues with AGYW are central to HIV prevention, it is critical to explore how parents talk and think about PrEP. OBJECTIVE: To examine parental attitudes towards PrEP for HIV prevention amongst adolescent girls and young women in eastern Zimbabwe. METHOD: A qualitative interview study with 14 parents from two districts in Manicaland, eastern Zimbabwe. Interviews were transcribed, translated, and subjected to thematic network analysis. The concept of 'attitudes' steered the analytical work. RESULTS: Parents' attitudes towards PrEP are conflictual, multi-layered, and contingent on the context in which they reflect and talk about PrEP. While parents aspired to be supportive of innovative HIV prevention methods and wanted to see girl-children protected from HIV, they struggled to reconcile this positive and accepting attitude towards PrEP with traditional 'good girl' notions, which stigmatize pre-marital sex. Although a few parents articulated an acceptance of PrEP use amongst their daughters, for many this was simply not possible. Many parents thus co-produce public gender orders that prevent adolescent girls and young women from engaging with PrEP. CONCLUSIONS: While parents' conflicting attitudes towards PrEP may provide spaces and opportunities for change, harmful gender norms and negative attitudes towards PrEP must be addressed at a community and cultural level. Only then can parents and their children have productive conversations about sexual health.

Strengthening the HIV prevention cascade to maximise epidemiological impact in eastern Zimbabwe: a modelling study.

BACKGROUND: HIV prevention cascades provide a systematic understanding of barriers to prevention. In this study we used mathematical modelling to understand the consequences of these barriers and how the cascade could be strengthened to maximise epidemiological impact, providing potentially important insights for programmes. METHODS: We used an individual-based model of HIV transmission (PopART-IBM), calibrated to data from the Manicaland cohort from eastern Zimbabwe. HIV prevention cascade estimates from this cohort were used as probabilities for indicators in the model representing an individual's motivation, access, and capacity to effectively use pre-exposure prophylaxis, voluntary male medical circumcision, and condoms. We examined how current barriers affect the number and distribution of HIV infections compared with a no-barrier scenario. Using assumptions about how interventions could strengthen the HIV prevention cascade, we estimated the reduction in HIV infections over a 10-year period through addressing different elements of the cascade. FINDINGS: 21 200 new potentially avertable HIV infections will occur over the next 10 years due to existing HIV prevention cascade barriers, 74·2% of the 28 500 new infections that would occur with existing barriers in a population of approximately 1·2 million adults. Removing these barriers would reduce HIV incidence below the benchmarks for epidemic elimination. Addressing all cascade steps in one priority population is substantially more effective than addressing one step across all populations. INTERPRETATION: Interventions exist in eastern Zimbabwe to reduce HIV towards elimination, but barriers of motivation, access, and effective use prevent their full effect being realised. Interventions need to be multilayered and address all steps along the HIV prevention cascade. Models incorporating the HIV prevention cascade can help to identify the main barriers to greater effectiveness. FUNDING: National Institutes of Mental Health, Bill & Melinda Gates Foundation, and Medical Research Council Centre for Global Infectious Disease Analysis funding from the UK Medical Research Council and UK Foreign, Commonwealth & Development Office (FCDO).

The effect of universal testing and treatment for HIV on health-related quality of life - An analysis of data from the HPTN 071 (PopART) cluster randomised trial.

Background: HIV treatment has clear Health-Related Quality-of-Life (HRQoL) benefits. However, little is known about how Universal Testing and Treatment (UTT) for HIV affects HRQoL. This study aimed to examine the effect of a combination prevention intervention, including UTT, on HRQoL among People Living with HIV (PLHIV). Methods: Data were from HPTN 071 (PopART), a three-arm cluster randomised controlled trial in 21 communities in Zambia and South Africa (2013-2018). Arm A received the full UTT intervention of door-to-door HIV testing plus access to antiretroviral therapy (ART) regardless of CD4 count, Arm B received the intervention but followed national treatment guidelines (universal ART from 2016), and Arm C received standard care. The intervention effect was measured in a cohort of randomly selected adults, over 36 months. HRQoL scores, and the prevalence of problems in five HRQoL dimensions (mobility, self-care, performing daily activities, pain/discomfort, anxiety/depression) were assessed among all participants using the EuroQol-5-dimensions-5-levels questionnaire (EQ-5D-5L). We compared HRQoL among PLHIV with laboratory confirmed HIV status between arms, using adjusted two-stage cluster-level analyses. Results: At baseline, 7,856 PLHIV provided HRQoL data. At 36 months, the mean HRQoL score was 0.892 (95% confidence interval: 0.887-0.898) in Arm A, 0.886 (0.877-0.894) in Arm B and 0.888 (0.884-0.892) in Arm C. There was no evidence of a difference in HRQoL scores between arms (A vs C, adjusted mean difference: 0.003, -0.001-0.006; B vs C: -0.004, -0.014-0.005). The prevalence of problems with pain/discomfort was lower in Arm A than C (adjusted prevalence ratio: 0.37, 0.14-0.97). There was no evidence of differences for other HRQoL dimensions. Conclusions: The intervention did not change overall HRQoL, suggesting that raising HRQoL among PLHIV might require more than improved testing and treatment. However, PLHIV had fewer problems with pain/discomfort under the full intervention; this benefit of UTT should be maximised during roll-out.

Conditional cash transfers to improve education and health: an ex ante evaluation of Red de Protección Social, Nicaragua.

Using baseline data from a randomized experiment, this article extends and tests in the context of health, the feasibility of a recently proposed reduced form approach to ex ante evaluations of social programs with an application to a conditional cash transfer program in Nicaragua. It uses a behavioural model to estimate the impact on preventive care utilization outcomes for children younger than 3 years. It validates the model with the results of the experiment and then simulates two alternate policy scenarios. The model performs well in predicting the health related outcomes and shows different results for the two sets of policy scenarios. In addition, simulations are also carried out for the school component of the cash transfer program.

Cost and cost-effectiveness of a universal HIV testing and treatment intervention in Zambia and South Africa: evidence and projections from the HPTN 071 (PopART) trial.

BACKGROUND: The HPTN 071 (PopART) trial showed that a combination HIV prevention package including universal HIV testing and treatment (UTT) reduced population-level incidence of HIV compared with standard care. However, evidence is scarce on the costs and cost-effectiveness of such an intervention. METHODS: Using an individual-based model, we simulated the PopART intervention and standard care with antiretroviral therapy (ART) provided according to national guidelines for the 21 trial communities in Zambia and South Africa (for all individuals aged >14 years), with model parameters and primary cost data collected during the PopART trial and from published sources. Two intervention scenarios were modelled: annual rounds of PopART from 2014 to 2030 (PopART 2014-30; as the UNAIDS Fast-Track target year) and three rounds of PopART throughout the trial intervention period (PopART 2014-17). For each country, we calculated incremental cost-effectiveness ratios (ICERs) as the cost per disability-adjusted life-year (DALY) and cost per HIV infection averted. Cost-effectiveness acceptability curves were used to indicate the probability of PopART being cost-effective compared with standard care at different thresholds of cost per DALY averted. We also assessed budget impact by projecting undiscounted costs of the intervention compared with standard care up to 2030. FINDINGS: During 2014-17, the mean cost per person per year of delivering home-based HIV counselling and testing, linkage to care, promotion of ART adherence, and voluntary medical male circumcision via community HIV care providers for the simulated population was US$6·53 (SD 0·29) in Zambia and US$7·93 (0·16) in South Africa. In the PopART 2014-30 scenario, median ICERs for PopART delivered annually until 2030 were $2111 (95% credible interval [CrI] 1827-2462) per HIV infection averted in Zambia and $3248 (2472-3963) per HIV infection averted in South Africa; and $593 (95% CrI 526-674) per DALY averted in Zambia and $645 (538-757) per DALY averted in South Africa. In the PopART 2014-17 scenario, PopART averted one infection at a cost of $1318 (1098-1591) in Zambia and $2236 (1601-2916) in South Africa, and averted one DALY at $258 (225-298) in Zambia and $326 (266-391) in South Africa, when outcomes were projected until 2030. The intervention had almost 100% probability of being cost-effective at thresholds greater than $700 per DALY averted in Zambia, and greater than $800 per DALY averted in South Africa, in the PopART 2014-30 scenario. Incremental programme costs for annual rounds until 2030 were $46·12 million (for a mean of 341 323 people) in Zambia and $30·24 million (for a mean of 165 852 people) in South Africa. INTERPRETATION: Combination prevention with universal home-based testing can be delivered at low annual cost per person but accumulates to a considerable amount when scaled for a growing population. Combination prevention including UTT is cost-effective at thresholds greater than $800 per DALY averted and can be an efficient strategy to reduce HIV incidence in high-prevalence settings. FUNDING: US National Institutes of Health, President's Emergency Plan for AIDS Relief, International Initiative for Impact Evaluation, Bill & Melinda Gates Foundation.

Improving risk perception and uptake of voluntary medical male circumcision with peer-education sessions and incentives, in Manicaland, East Zimbabwe: study protocol for a pilot randomised trial.

BACKGROUND: Voluntary medical male circumcision (VMMC) is a key component of combination HIV-prevention programmes. Several high-HIV-prevalence countries in sub-Saharan Africa, including Zimbabwe, are looking to scale up VMMC activities. There is limited evidence on how a combination of social learning from peer education by a role model with different behavioural incentives influences demand for VMMC in such settings. METHODS/DESIGN: This matched-cluster randomised controlled trial with 1740 participants will compare two behavioural incentives against a control with no intervention. In the intervention clusters, participants will participate in an education session delivered by a circumcised young male ("role model") on the risks of HIV infection and the benefits from medical male circumcision. All participants will receive contributions towards transport costs to access medical male circumcision at participating clinics. Via blocked randomisation, in the intervention clusters participants will be randomly assigned to receive one of two types of incentives - fixed cash payment or lottery payment - both conditional on undergoing surgical VMMC. In two sites, a community-led intervention will also be implemented to address social obstacles and to increase support from peers, families and social structures. Baseline measures of endpoints will be gathered in surveys. Follow-up assessment at 6 months will include self-reported uptake of VMMC triangulated with clinic data. DISCUSSION: This is the first trial to pilot-test social learning to improve risk perception and self-efficacy and to address the fear of pain associated with VMMC and possible present-biased preferences with front-loaded compensations as well as fixed or lottery-based cash payments. This study will generate important knowledge to inform HIV-prevention policies about the effectiveness of behavioural interventions and incentives, which could be easily scaled-up. TRIAL REGISTRATION: This trial has been registered on ClinicalTrials.gov (identifier: NCT03565588). Registered on 21 June 2018.

Application of the HIV prevention cascade to identify, develop and evaluate interventions to improve use of prevention methods: examples from a study in east Zimbabwe.

INTRODUCTION: The HIV prevention cascade could be used in developing interventions to strengthen implementation of efficacious HIV prevention methods, but its practical utility needs to be demonstrated. We propose a standardized approach to using the cascade to guide identification and evaluation of interventions and demonstrate its feasibility for this purpose through a project to develop interventions to improve HIV prevention methods use by adolescent girls and young women (AGYW) and potential male partners in east Zimbabwe. DISCUSSION: We propose a six-step approach to using a published generic HIV prevention cascade formulation to develop interventions to increase motivation to use, access to and effective use of an HIV prevention method. These steps are as follows: (1) measure the HIV prevention cascade for the chosen population and method; (2) identify gaps in the cascade; (3) identify explanatory factors (barriers) contributing to observed gaps; (4) review literature to identify relevant theoretical frameworks and interventions; (5) tailor interventions to the local context; and (6) implement and evaluate the interventions using the cascade steps and explanatory factors as outcome indicators in the evaluation design. In the Zimbabwe example, steps 1-5 aided development of four interventions to overcome barriers to effective use of pre-exposure prophylaxis (PrEP) in AGYW (15-24 years) and voluntary medical male circumcision in male partners (15-29). For young men, prevention cascade analyses identified gaps in motivation and access as barriers to voluntary medical male circumcision uptake, so an intervention was designed including financial incentives and an education session. For AGYW, gaps in motivation (particularly lack of risk perception) and access were identified as barriers to PrEP uptake: an interactive counselling game was developed addressing these barriers. A text messaging intervention was developed to improve PrEP adherence among AGYW, addressing reasons underlying lack of effective PrEP use through improving the capacity ("skills") to take PrEP effectively. A community-led intervention (community conversations) was developed addressing community-level factors underlying gaps in motivation, access and effective use. These interventions are being evaluated currently using outcomes from the HIV prevention cascade (step 6). CONCLUSIONS: The prevention cascade can guide development and evaluation of interventions to strengthen implementation of HIV prevention methods by following the proposed process.

Improving risk perception and uptake of pre-exposure prophylaxis (PrEP) through interactive feedback-based counselling with and without community engagement in young women in Manicaland, East Zimbabwe: study protocol for a pilot randomized trial.

BACKGROUND: HIV incidence in adolescent girls and young women remains high in sub-Saharan Africa. Progress towards uptake of HIV prevention methods remains low. Studies of oral pre-exposure prophylaxis (PrEP) have shown that uptake and adherence may be low due to low-risk perception and ambivalence around using antiretrovirals for prevention. No evidence exists on whether an interactive intervention aimed at adjusting risk perception and addressing the uncertainty around PrEP will improve uptake. This pilot research trial aims to provide an initial evaluation of the impact of an interactive digital tablet-based counselling session, correcting risk perception, and addressing ambiguity around availability, usability, and effectiveness of PrEP. METHODS/DESIGN: This is a matched-cluster randomized controlled trial which will compare an interactive tablet-based education intervention against a control with no intervention. The study will be implemented in eight sites. In each site, two matched clusters of villages will be created. One cluster will be randomly allocated to intervention. In two sites, a community engagement intervention will also be implemented to address social obstacles and to increase support from peers, families, and social structures. A total of 1200 HIV-negative young women aged 18-24 years, not on PrEP at baseline, will be eligible. Baseline measures of endpoints will be gathered in surveys. Follow-up assessment at six months will include biomarkers of PrEP uptake and surveys. DISCUSSION: This will be the first randomized controlled trial to determine whether interactive feedback counselling leads to uptake of HIV prevention methods such as PrEP and reduces risky sexual behavior. If successful, policymakers could consider such an intervention in school-based education campaigns or as post-HIV-testing counselling for young people. TRIAL REGISTRATION: Clinicaltrials.gov, NCT03565575. Registered on 21 June 2018.

Work and home productivity of people living with HIV in Zambia and South Africa.

OBJECTIVE: To compare number of days lost to illness or accessing healthcare for HIV-positive and HIV-negative individuals working in the informal and formal sectors in South Africa and Zambia. DESIGN: As part of the HPTN 071 (PopART) study, data on adults aged 18-44 years were gathered from cross-sectional surveys of random general population samples in 21 communities in Zambia and South Africa. Data on the number of productive days lost in the last 3 months, laboratory-confirmed HIV status, labour force status, age, ethnicity, education, and recreational drug use was collected. METHODS: Differences in productive days lost between HIV-negative and HIV-positive individuals ('excess productive days lost') were estimated with negative binomial models, and results disaggregated for HIV-positive individuals after various durations on antiretroviral treatment (ART). RESULTS: From samples of 19 330 respondents in Zambia and 18 004 respondents in South Africa, HIV-positive individuals lost more productive days to illness than HIV-negative individuals in both countries. HIV-positive individuals in Zambia lost 0.74 excess productive days [95% confidence interval (CI) 0.48-1.01; P < 0.001] to illness over a 3-month period. HIV-positive in South Africa lost 0.13 excess days (95% CI 0.04-0.23; P = 0.007). In Zambia, those on ART for less than 1 year lost most days, and those not on ART lost fewest days. In South Africa, results disaggregated by treatment duration were not statistically significant. CONCLUSION: There is a loss of work and home productivity associated with HIV, but it is lower than existing estimates for HIV-positive formal sector workers. The findings support policy makers in building an accurate investment case for HIV interventions.

Allocation rules for global donors.

In recent years, donors such as the Bill and Melinda Gates Foundation have made an enormous contribution to the reduction of the global burden of disease. It has been argued that such donors should prioritise interventions based on their cost-effectiveness, that is to say, the ratio of costs to benefits. Against this, we argue that the donor should fund not the most cost-effective interventions, but rather interventions which are just cost-ineffective for the country, thus encouraging the country to contribute its own domestic resources to the fight against disease. We demonstrate that our proposed algorithm can be justified within the context of a model of the problem as a leader-follower game, in which a donor chooses to subsidise interventions which are implemented by a country. We argue that the decision rule we propose provides a basis for the allocation of aid money which is efficient, fair and sustainable.