Collateral benefits: how the practical application of Good Participatory Practice can strengthen HIV research in sub-Saharan Africa.

INTRODUCTION: The Good Participatory Practice (GPP): Guidelines for Biomedical HIV Prevention Trials, second edition (2011) were developed to provide clinical trial sponsors and implementers with a formal stakeholder engagement framework. As one of the largest African research institutes, Wits Reproductive Health and HIV Institute (Wits RHI) became an early adopter of GPP by implementing its principles within large-scale national and regional clinical trials. This article examines Wits RHI's lessons learned from implementing GPP, its ongoing efforts to institutionalize GPP, and the yet to be realized potential in creating fully sustainable structures for meaningful stakeholder engagement in HIV prevention research, implementation science and beyond. DISCUSSION: For the past seven years, Wits RHI has undertaken both centralized leadership roles in implementing GPP across multi-party regional research consortia as well as overseeing GPP for smaller investigator-driven trials. Through this iterative roll-out of GPP, key lessons have emerged. Obtaining upfront funding to support GPP activities throughout and between the research life cycle, and a trained multi-disciplinary team of GPP practitioners have helped facilitate an enabling environment for GPP implementation. We further recommend formally integrating stakeholder engagement into study documents, including monitoring and evaluation plans with indicators and performance metrics, to assist teams to track and refine their GPP strategies. Finally, institutionalizing resources and supporting organization-wide GPP along with ongoing support can help build efficiencies and maximize economies of scale toward a pragmatic and innovative application of the GPP Guidelines. CONCLUSIONS: Thanks to a growing global network of GPP practitioners and a burgeoning GPP Community of Practice, there has been substantive progress in making GPP an integral component of clinical HIV prevention research. The Wits RHI experience highlights the possibilities and the challenges to translating the GPP principles into concrete practices within specific clinical trials and across a research institute. Realizing the full potential of GPP, including direct and indirect - 'collateral benefits' will require the collective buy-in and support from sponsors, implementers and community stakeholders across the research field. As the HIV prevention research field expands, however, a more conscious and systematic implementation of GPP is timely.

Understanding treatment refusal among adults presenting for HIV-testing in Soweto, South Africa: a qualitative study.

HIV treatment initiatives have focused on increasing access to antiretroviral therapy (ART). There is growing evidence, however, that treatment availability alone is insufficient to stop the epidemic. In South Africa, only one third of individuals living with HIV are actually on treatment. Treatment refusal has been identified as a phenomenon among people who are asymptomatic, however, factors driving refusal remain poorly understood. We interviewed 50 purposively sampled participants who presented for voluntary counseling and testing in Soweto to elicit a broad range of detailed perspectives on ART refusal. We then integrated our core findings into an explanatory framework. Participants described feeling "too healthy" to start treatment, despite often having a diagnosis of AIDS. This subjective view of wellness was framed within the context of treatment being reserved for the sick. Taking ART could also lead to unintended disclosure and social isolation. These data provide a novel explanatory model of treatment refusal, recognizing perceived risks and social costs incurred when disclosing one's status through treatment initiation. Our findings suggest that improving engagement in care for people living with HIV in South Africa will require optimizing social integration and connectivity for those who test positive.

CD4 counts and viral loads of newly diagnosed HIV-infected individuals: implications for treatment as prevention.

OBJECTIVE: To report the viral load and CD4 count in HIV-infected, antiretroviral naïve, first -time HIV-testers, not immediately eligible for treatment initiation by current South Africa treatment guidelines. DESIGN: This was a cross-sectional study in a high-volume, free-of-charge HIV testing centre in Soweto, South Africa. METHODS: We enrolled first time HIV testers and collected demographic and risk-behaviour data and measured CD4 count and viral load. RESULTS: Between March and October 2011, a total of 4793 adults attended VCT and 1062 (22%) tested positive. Of the 1062, 799 (75%) were ART naïve and 348/799 (44%) were first-time HIV testers. Of this group of 348, 225 (65%) were female. Overall their median age, CD4 count and viral load was 34 years (IQR: 28-41), 364 (IQR: 238-542) cells/mm3 and 13,000 (IQR: 2050-98171) copies/ml, respectively. Female first time HIV testers had higher CD4 counts (419 IQR: 262-582 vs. 303 IQR: 199-418 cells/mm3) and lower viral loads (9,100 vs. 34,000 copies/ml) compared to males. Of 183 participants with CD4 count >350 cells/mm3, 62 (34%) had viral loads > 10,000 copies/ml. CONCLUSIONS: A large proportion of HIV infected adults not qualifying for immediate ART at the CD4 count threshold of 350 cells/mm3 have high viral loads. HIV-infected men at their first HIV diagnosis are more likely to have lower CD4 counts and higher viral loads than women.

Whoonga and the abuse and diversion of antiretrovirals in Soweto, South Africa.

Media reports have described recreational use of HIV antiretroviral medication in South Africa, but little has been written about this phenomenon in the scientific literature. We present original, qualitative data from eight semi-structured interviews that characterize recreational antiretroviral use in Soweto, South Africa. Participants reported that antiretrovirals, likely efavirenz, are crushed, mixed with illicit drugs (in a mixture known as whoonga), and smoked. They described medications being stolen from patients and expressed concern that antiretroviral abuse jeopardized the safety of both patients and users. Further studies are needed to understand the prevalence, patterns, and consequences of antiretroviral abuse and diversion.

Does routine prophylactic oral flucloxacillin reduce the incidence of post-circumcision infections?

BACKGROUND: Cost-effective and safe practices are required for the scale-up of medical male circumcision (MMC), a strategy recommended for biomedical HIV prevention. METHODS: A retrospective medical record review was conducted of post-circumcision wound infection incidence at a massive MMC program in Soweto, South Africa. We compared patients who received routine 250 mg prophylactic flucloxacillin 4 times daily orally for 5 days with those who did not receive prophylaxis. Patients with HIV infection and those with missing prophylaxis data were excluded from the analysis. Collated data included prophylaxis received, age, return for follow-up, and presence and grading of wound infection at follow-up. RESULTS: In total, 1,291 patients were eligible: 646 flucloxacillin recipients and 645 non-recipients. Median age of flucloxacillin recipients was 24 years (interquartile range 20-29 years) and for nonrecipients it was 23 years (interquartile range 16-28 years). Eighty-one percent of flucloxacillin recipients and 87% of nonrecipients (P = .0019) returned for follow-up. Wound infection was present in 0.7% (5 of 646) of flucloxacillin recipients and 1.2% (8 of 645) of non-recipients (P = .4). Use of routine prophylactic flucloxacillin did not significantly reduce incidence of post-MMC wound infection (odds ratio, 0.6; 95% confidence interval, 0-1.2). CONCLUSIONS: When compared with no prophylactic flucloxacillin, routine prophylactic flucloxacillin does not significantly reduce the risk of post-MMC wound infection in a massive circumcision program.

Antiretroviral therapy refusal among newly diagnosed HIV-infected adults.

OBJECTIVE: To determine rates and predictors of treatment refusal in newly identified HIV-infected individuals in Soweto, South Africa. DESIGN: It is designed as a cross-sectional study. METHODS: We analyzed data from adult clients (>18 years) presenting for voluntary counseling and testing (VCT) at the Zazi Testing Center, Perinatal HIV Research Unit to determine rates of antiretroviral therapy (ART) refusal among treatment-eligible, HIV-infected individuals (CD4(+) cell count < 200 cells/µl or WHO stage 4). Multiple logistic regression models were used to investigate factors associated with refusal. RESULTS: From December 2008 to December 2009, 7287 adult clients were HIV tested after counseling. Two thousand, five hundred and sixty-two (35%) were HIV-infected, of whom 743 (29%) were eligible for immediate ART. One hundred and forty-eight (20%) refused referral to initiate ART, most of whom (92%) continued to refuse after 2 months of counseling. The leading reason for ART refusal was given as 'feeling healthy' (37%), despite clients having a median CD4(+) cell count of 110 cells/µl and triple the rate of active tuberculosis as seen in nonrefusers. In adjusted models, single clients [adjusted odds ratio (AOR) 1.80, 95% confidence interval (CI) 1.06-3.06] and those with active tuberculosis (AOR 3.50, 95% CI 1.55-6.61) were more likely to refuse ART. CONCLUSION: Nearly one in five treatment-eligible HIV-infected individuals in Soweto refused to initiate ART after VCT, putting them at higher risk for early mortality. 'Feeling healthy' was given as the most common reason to refuse ART, despite a suppressed CD4(+) count and comorbidities such as tuberculosis. These findings highlight the urgent need for research to inform interventions targeting ART refusers.