Richard Mutemwa

PRO2000 vaginal gel for prevention of HIV-1 infection (Microbicides Development Programme 301): a phase 3, randomised, double-blind, parallel-group trial

Summary Background Innovative prevention strategies for HIV-1 transmission are urgently needed. PRO2000 vaginal gel was efficacious against HIV-1 transmission in studies in macaques; we aimed to assess efficacy and safety of 2% and 0·5% PRO2000 gels against vaginal HIV-1 transmission in women in sub-Saharan Africa. Methods Microbicides Development Programme 301 was a phase 3, randomised, double-blind, parallel-group trial, undertaken at 13 clinics in South Africa, Tanzania, Uganda, and Zambia. We randomly assigned sexually active women, aged 18 years or older (≥16 years in Tanzania and Uganda) without HIV-1 infection in a 1:1:1 ratio to 2% PRO2000, 0·5% PRO2000, or placebo gel groups for 52 weeks (up to 104 weeks in Uganda). Randomisation was done by computerised random number generator. Investigators and participants were masked to group assignment. The primary efficacy outcome was incidence of HIV-1 infection before week 52, which was censored for pregnancy and excluded participants without HIV-1 follow-up data or with HIV-1 infection at enrolment. HIV-1 status was established by rapid tests or ELISA at screening at 12 weeks, 24 weeks, 40 weeks, and 52 weeks, and confirmed in a central reference laboratory. The primary safety endpoint was an adverse event of grade 3 or worse. Use of 2% PRO2000 gel was discontinued on Feb 14, 2008, on the recommendation of the Independent Data Monitoring Committee because of low probability of benefit. This trial is registered at http://isrctn.org, number ISRCTN 64716212. Findings We enrolled 9385 of 15 818 women screened. 2591 (95%) of 2734 participants enrolled to the 2% PRO2000 group, 3156 (95%) of 3326 in the 0·5% PRO2000 group, and 3112 (94%) of 3325 in the placebo group were included in the primary efficacy analysis. Mean reported gel use at last sex act was 89% (95% CI 86–91). HIV-1 incidence was much the same between groups at study end (incidence per 100 woman-years was 4·5 [95% CI 3·8–5·4] for 0·5% PRO2000 vs 4·3 [3·6–5·2] for placebo, hazard ratio 1·05 [0·82–1·34], p=0·71), and at discontinuation (4·7 [3·8–5·8] for 2% PRO2000 gel, 3·9 [3·0–4·9] for 0·5% PRO2000 gel, and 3·9 [3·1–5·0] for placebo gel). Incidence of the primary safety endpoint at study end was 4·6 per 100 woman-years (95% CI 3·9–5·4) in the 0·5% PRO2000 group and 3·9 (3·2–4·6) in the placebo group; and was 4·5 (3·7–5·5) in the 2% PRO2000 group at discontinuation. Interpretation Although safe, 0·5% PRO2000 and 2% PRO2000 are not efficacious against vaginal HIV-1 transmission and are not indicated for this use. Funding UK Department for International Development, UK Medical Research Council, European and Developing Countries Clinical Trials Partnership, International Partnership for Microbicides, and Endo Pharmaceuticals Solutions.

Study protocol for the Integra Initiative to assess the benefits and costs of integrating sexual and reproductive health and HIV services in Kenya and Swaziland.

BackgroundIn sub-Saharan Africa (SSA) there are strong arguments for the provision of integrated sexual and reproductive health (SRH) and HIV services. Most HIV transmissions are sexually transmitted or associated with pregnancy, childbirth, and breastfeeding. Many of the behaviours that prevent HIV transmission also prevent sexually transmitted infections and unintended pregnancies. There is potential for integration to increase the coverage of HIV services, as individuals who use SRH services can benefit from HIV services and vice-versa, as well as increase cost-savings. However, there is a dearth of empirical evidence on effective models for integrating HIV/SRH services. The need for robust evidence led a consortium of three organizations – International Planned Parenthood Federation, Population Council and the London School of Hygiene & Tropical Medicine – to design/implement the Integra Initiative. Integra seeks to generate rigorous evidence on the feasibility, effectiveness, cost and impact of different models for delivering integrated HIV/SRH services in high and medium HIV prevalence settings in SSA.Methods/designA quasi-experimental study will be conducted in government clinics in Kenya and Swaziland – assigned into intervention/comparison groups. Two models of service delivery are investigated: integrating HIV care/treatment into 1) family planning and 2) postnatal care. A full economic-costing will be used to assess the costs of different components of service provision, and the determinants of variations in unit costs across facilities/service models. Health facility assessments will be conducted at four time-periods to track changes in quality of care and utilization over time. A two-year cohort study of family planning/postnatal clients will assess the effect of integration on individual outcomes, including use of SRH services, HIV status (known/unknown) and pregnancy (planned/unintended). Household surveys within some of the study facilities’ catchment areas will be conducted to profile users/non-users of integrated services and demand/receipt of integrated services, before-and-after the intervention. Qualitative research will be conducted to complement the quantitative component at different time points. Integra takes an embedded ‘programme science’ approach to maximize the uptake of findings into policy/practice.DiscussionIntegra addresses existing evidence gaps in the integration evaluation literature, building on the limited evidence from SSA and the expertise of its research partners.Trial registrationCurrent Controlled Trials NCT01694862

Experiences of health care providers with integrated HIV and reproductive health services in Kenya: a qualitative study.

BackgroundThere is broad consensus on the value of integration of HIV services and reproductive health services in regions of the world with generalised HIV/AIDS epidemics and high reproductive morbidity. Integration is thought to increase access to and uptake of health services; and improves their efficiency and cost-effectiveness through better use of available resources. However, there is still very limited empirical literature on health service providers and how they experience and operationalize integration. This qualitative study was conducted among frontline health workers to explore provider experiences with integration in order to ascertain their significance to the performance of integrated health facilities.MethodsSemi-structured in-depth interviews were conducted with 32 frontline clinical officers, registered nurses, and enrolled nurses in Kitui district (Eastern province) and Thika and Nyeri districts (Central province) in Kenya. The study was conducted in health facilities providing integrated HIV and reproductive health services (post-natal care and family planning). All interviews were conducted in English, transcribed and analysed using Nvivo 8 qualitative data analysis software.ResultsProviders reported delivering services in provider-level and unit-level integration, as well as a combination of both. Provider experiences of actual integration were mixed. At personal level, providers valued skills enhancement, more variety and challenge in their work, better job satisfaction through increased client-satisfaction. However, they also felt that their salaries were poor, they faced increased occupational stress from: increased workload, treating very sick/poor clients, and less quality time with clients. At operational level, providers reported increased service uptake, increased willingness among clients to take an HIV test, and reduced loss of clients. But the majority also reported infrastructural and logistic deficiencies (insufficient physical room space, equipment, drugs and other medical supplies), as well as increased workload, waiting times, contact session times and low staffing levels.ConclusionsThe success of integration primarily depends on the performance of service providers which, in turn, depends on a whole range of facilitative organisational factors. The central Ministry of Health should create a coherent policy environment, spearhead strategic planning and ensure availability of resources for implementation at lower levels of the health system. Health facility staffing norms, technical support, cost-sharing policies, clinical reporting procedures, salary and incentive schemes, clinical supply chains, and resourcing of health facility physical space upgrades, all need attention. Yet, despite these system challenges, this study has shown that integration can have a positive motivating effect on staff and can lead to better sharing of workload - these are important opportunities that deserve to be built on.

Experiences of stigma among women living with HIV attending sexual and reproductive health services in Kenya: a qualitative study

BackgroundResearchers have widely documented the pervasiveness of HIV stigma and discrimination, and its impact on people living with HIV. Only a few studies, however, have analysed the perceptions of women living with HIV accessing sexual and reproductive health (SRH) services. This study explores the experiences of stigma of HIV-positive clients attending family planning and post-natal services and implications for service use and antiretroviral therapy (ART) adherence. Our aim was to gain a better understanding of the impact of various dimensions of stigma on service use and ART adherence among HIV clients in order to inform the response of integrated SRH services.MethodsIn-depth interviews were conducted with 48 women living with HIV attending SRH services in two districts in Kenya. Data were coded using Nvivo 8 and analysed using a thematic analysis approach.ResultsFindings show that many women living with HIV report high levels of anticipated stigma, resulting in a desire to hide their status from family and friends for fear of being discriminated against. Many women feared desertion following disclosure of their positive status to partners. Consequently some women preferred to hide their status and adhere to HIV treatment in secret. However, the majority of study participants attending postnatal care (PNC) services also revealed that anticipated stigma does not adversely affect their HIV drug uptake and ART adherence, as their drive to live outweighs their fear of stigma. Our findings also seem to suggest a preference for specialist HIV services by some family planning (FP) clients because of better confidentiality and reduced opportunities for unwanted disclosure that could lead to stigma.ConclusionsThe findings highlight that anticipated stigma leading to low disclosure is widespread and sometimes reinforced by health providers’ actions and facility layout (contributing to enacted stigma). However, the motivation to stay healthy and look after the children appears in many cases to override fears of stigma related to ART adherence in our client-based sample.

Exploring experiences in peer mentoring as a strategy for capacity building in sexual reproductive health and HIV service integration in Kenya.

BackgroundThe Integra Initiative designed, tested, and adapted protocols for peer mentorship in order to improve service providers’ skills, knowledge, and capacity to provide quality integrated HIV and sexual and reproductive health (SRH) services. This paper describes providers’ experiences in mentoring as a method of capacity building. Service providers who were skilled in the provision of FP or PNC services were selected to undergo a mentorship training program and to subsequently build the capacity of their peers in SRH-HIV integration.MethodsA qualitative assessment was conducted to assess provider experiences and perceptions about peer mentoring. In-depth interviews were conducted with twelve mentors and twenty-three mentees who were trained in SRH and HIV integration. Interviews were recorded, transcribed, and imported to NVivo 9 for analysis. Thematic analysis methods were used to develop a coding framework from the research questions and other emerging themes.ResultsMentorship was perceived as a feasible and acceptable method of training among mentors and mentees. Both mentors and mentees agreed that the success of peer mentoring largely depended on cordial relationship and consensus to work together to achieve a specific set of skills. Mentees reported improved knowledge, skills, self-confidence, and team work in delivering integrated SRH and HIV services as benefits associated with mentoring. They also associated mentoring with an increase in the range of services available and the number of clients seeking those services. Successful mentorship was conditional upon facility management support, sufficient supplies and commodities, a positive work environment, and mentors selection.ConclusionMentoring was perceived by both mentors and mentees as a sustainable method for capacity building, which increased providers’ ability to offer a wide range of and improved access to integrated SRH and HIV services.

“One Teabag Is Better than Four”: Participants Response to the Discontinuation of 2% PRO2000/5 Microbicide Gel in KwaZulu-Natal, South Africa

Introduction The Microbicides Development Programme evaluated the safety and effectiveness of 0.5% and 2% PRO2000/5 microbicide gels in reducing the risk of vaginally acquired HIV. In February 2008 the Independent Data Monitoring Committee recommended that evaluation of 2% PRO2000/5 gel be discontinued due to futility. The Africa Centre site systematically collected participant responses to this discontinuation. Methods Clinic and field staff completed field reports using ethnographic participant observation techniques. In-depth-interviews and focus group discussions were conducted with participants discontinued from 2% gel. A total of 72 field reports, 12 in-depth-interviews and 3 focus groups with 250 women were completed for this analysis. Retention of discontinued participants was also analysed. Qualitative data was analysed using NVivo 2 and quantitative data using STATA 10.0. Results Participants responded initially with fear that discontinuation was due to harm, followed by acceptance after effective messaging, and finally with disappointment. Participants reported that their initial fear was exacerbated by being contacted and advised to visit the clinic for information about the closure. Operational changes were subsequently made to the contact procedures. By incorporating feedback from participants, messages were continuously revised to ensure that information was comprehensible and misconceptions were addressed quickly thereby enabling participants to accept the discontinuation. Participants were disappointed that 2% PRO2000/5 was being excluded as a HIV prevention option, but also that they would no longer have access to gel that improved their sexual relationships with their partners and assisted condom negotiations. In total 238 women were discontinued from gel and 185 (78%) went on to complete their scheduled follow-up period. Discussion The use of qualitative social science techniques allowed the site team to amend operational procedures and messaging throughout the discontinuation period. This proved instrumental in ensuring that the discontinuation was successfully completed in a manner that was both understandable and acceptable to participants. Trial registration Current Controlled Trials. ISRCTN64716212.

Does service integration improve technical quality of care in low-resource settings? An evaluation of a model integrating HIV care into family planning services in Kenya

Abstract The aim of this study was to investigate association between HIV and family planning integration and technical quality of care. The study focused on technical quality of client‐provider consultation sessions. The cross‐sectional study observed 366 client‐provider consultation sessions and interviewed 37 health care providers in 12 public health facilities in Kenya. Multilevel random intercept and linear regression models were fitted to the matched data to investigate relationships between service integration and technical quality of care as well as associations between facility‐level structural and provider factors and technical quality of care. A sensitivity analysis was performed to test for hidden bias. After adjusting for facility‐level structural factors, HIV/family planning integration was found to have significant positive effect on technical quality of the consultation session, with average treatment effect 0.44 (95% CI: 0.63‐0.82). Three of the 12 structural factors were significantly positively associated with technical quality of consultation session including: availability of family planning commodities (9.64; 95% CI: 5.07‐14.21), adequate infrastructure (5.29; 95% CI: 2.89‐7.69) and reagents (1.48; 95% CI: 1.02‐1.93). Three of the nine provider factors were significantly positively associated with technical quality of consultation session: appropriate provider clinical knowledge (3.14; 95% CI: 1.92‐4.36), job satisfaction (2.02; 95% CI: 1.21‐2.83) and supervision (1.01; 95% CI: 0.35‐1.68), while workload (−0.88; 95% CI: −1.75 to − 0.01) was negatively associated. Technical quality of the client‐provider consultation session was also determined by duration of the consultation and type of clinic visit and appeared to depend on whether the clinic visit occurred early or later in the week. Integration of HIV care into family planning services can improve the technical quality of client‐provider consultation sessions as measured by both health facility structural and provider factors.

Numbers, systems, people: how interactions influence integration. Insights from case studies of HIV and reproductive health services delivery in Kenya

Abstract Drawing on rich data from the Integra evaluation of integrated HIV and reproductive‐health services, we explored the interaction of systems hardware and software factors to explain why some facilities were able to implement and sustain integrated service delivery while others were not. This article draws on detailed mixed‐methods data for four case‐study facilities offering reproductive‐health and HIV services between 2009 and 2013 in Kenya: (i) time‐series client flow, tracking service uptake for 8841 clients; (ii) structured questionnaires with 24 providers; (iii) in‐depth interviews with 17 providers; (iv) workload and facility data using a periodic activity review and cost‐instruments; and (v) contextual data on external activities related to integration in study sites. Overall, our findings suggested that although structural factors like stock‐outs, distribution of staffing and workload, rotation of staff can affect how integrated care is provided, all these factors can be influenced by staff themselves: both frontline and management. Facilities where staff displayed agency of decision making, worked as a team to share workload and had management that supported this, showed better integration delivery and staff were able to overcome some structural deficiencies to enable integrated care. Poor‐performing facilities had good structural integration, but staff were unable to utilize this because they were poorly organized, unsupported or teams were dysfunctional. Conscientious objection and moralistic attitudes were also barriers. Integra has demonstrated that structural integration is not sufficient for integrated service delivery. Rather, our case studies show that in some cases excellent leadership and peer‐teamwork enabled facilities to perform well despite resource shortages. The ability to provide support for staff to work flexibly to deliver integrated services and build resilient health systems to meet changing needs is particularly relevant as health systems face challenges of changing burdens of disease, climate change, epidemic outbreaks and more.

Putting the human into health systems: achieving functional integration of service delivery in Kenya and Swaziland

Background The Integra Initiative has evaluated different models of integrating FP/PNC and HIV testing and treatment services in Kenya and Swaziland. Human and physical resource integration (“structural” integration) is the usual outcome measure of “successful” service integration. Integra research has shown that in fact functional integration (clients actually receiving integrated care) does not necessarily follow. Much depends on the actions of individual providers and their managers in combination with systems and other factors. This paper provides a meta-analysis from a range of Integra data to investigate the human factors influencing successful “functional” service integration.