"It's Not Like Taking Chocolates": Factors Influencing the Feasibility and Sustainability of Universal Test and Treat in Correctional Health Systems in Zambia and South Africa.

BACKGROUND: Sub-Saharan African correctional facilities concentrate large numbers of people who are living with HIV or at risk for HIV infection. Universal test and treat (UTT) is widely recognized as a promising approach to improve the health of individuals and a population health strategy to reduce new HIV infections. In this study, we explored the feasibility and sustainability of implementing UTT in correctional facilities in Zambia and South Africa. METHODS: Nested within a UTT implementation research study, our qualitative evaluation of feasibility and sustainability used a case-comparison design based on data from 1 Zambian and 3 South African correctional facilities. Primary data from in-depth interviews with incarcerated individuals, correctional managers, health care providers, and policy makers were supplemented by public policy documents, study documentation, and implementation memos in both countries. Thematic analysis was informed by an empirically established conceptual framework for health system analysis. RESULTS: Despite different institutional profiles, we were able to successfully introduce UTT in the South Africa and Zambian correctional facilities participating in the study. A supportive policy backdrop was important to UTT implementation and establishment in both countries. However, sustainability of UTT, defined as relevant government departments' capacity to independently plan, resource, and administer quality UTT, differed. South Africa's correctional facilities had existing systems to deliver and monitor chronic HIV care and treatment, forming a "scaffolding" for sustained UTT despite some human resources shortages and poorly integrated health information systems. Notwithstanding recent improvements, Zambia's correctional health system demonstrated insufficient material and technical capacity to independently deliver quality UTT. In the correctional facilities of both countries, inmate population dynamics and their impact on HIV-related stigma were important factors in UTT service uptake. CONCLUSION: Findings demonstrate the critical role of policy directives, health service delivery systems, adequate resourcing, and population dynamics on the feasibility and likely sustainability of UTT in corrections in Zambia and South Africa.

TB sequel: incidence, pathogenesis and risk factors of long-term medical and social sequelae of pulmonary TB - a study protocol

Background: Up to fifty percent of microbiologically cured tuberculosis (TB) patients may be left with permanent, moderate or severe pulmonary function impairment. Very few studies have systematically examined pulmonary outcomes in patients to understand the pathophysiologic basis and long-term socio-economic consequences of this injury. The planned multi-country, multi-centre observational TB cohort study, aims to advance the understanding of the clinical, microbiological, immunological and socio-economic risk factors affecting long-term outcome of pulmonary TB. It will also determine the occurrence of reversible and irreversible socio-economic consequences to patients, their households and the health sector related to pulmonary TB disease and its treatment

Do Incarcerated Populations Serve as a Reservoir for Tuberculosis in South Africa?

Tuberculosis (TB) prevalence among incarcerated populations is as much as 1,000 times higher than in the general population. This study evaluates whether correctional facilities serve as a reservoir through which TB is transmitted to surrounding communities. Tuberculosis test data were extracted from the South African National Health Laboratory Service database for patients tested for TB between 2005 and 2011. We conducted graphical analysis to assess the relationship of TB rates between incarcerated and non-incarcerated populations over time. We performed generalized linear modeling with a log link function to assess TB risk in communities surrounding correctional facilities, net of confounders. We assessed linkages between incarcerated and non-incarcerated populations over time using Granger causality analysis. Tuberculosis prevalence among incarcerated populations was four times higher than in the general population. Tuberculosis incidence rates in incarcerated and non-incarcerated populations followed similar trends over time. The presence of a correctional facility in a municipality was associated with 34.9% more detected TB cases (confidence interval: 11.6-63.2; P < 0.01), controlling for potential confounders. Detected TB in incarcerated populations did not have predictive power in explaining detected TB rates in the non-incarcerated population after controlling for serial correlation in the time series data. Despite high TB prevalence, trends in correctional facilities do not appear to be driving temporal trends in the general population. However, correctional facilities still act as a TB reservoir that raises the overall TB risk in the vicinity. Intensified TB control policies for correctional facilities, formerly incarcerated individuals, and surrounding communities will reduce TB prevalence overall.

High-dose rifampicin, moxifloxacin, and SQ109 for treating tuberculosis: a multi-arm, multi-stage randomised controlled trial.

BACKGROUND: Tuberculosis is the world's leading infectious disease killer. We aimed to identify shorter, safer drug regimens for the treatment of tuberculosis. METHODS: We did a randomised controlled, open-label trial with a multi-arm, multi-stage design. The trial was done in seven sites in South Africa and Tanzania, including hospitals, health centres, and clinical trial centres. Patients with newly diagnosed, rifampicin-sensitive, previously untreated pulmonary tuberculosis were randomly assigned in a 1:1:1:1:2 ratio to receive (all orally) either 35 mg/kg rifampicin per day with 15-20 mg/kg ethambutol, 20 mg/kg rifampicin per day with 400 mg moxifloxacin, 20 mg/kg rifampicin per day with 300 mg SQ109, 10 mg/kg rifampicin per day with 300 mg SQ109, or a daily standard control regimen (10 mg/kg rifampicin, 5 mg/kg isoniazid, 25 mg/kg pyrazinamide, and 15-20 mg/kg ethambutol). Experimental treatments were given with oral 5 mg/kg isoniazid and 25 mg/kg pyrazinamide per day for 12 weeks, followed by 14 weeks of 5 mg/kg isoniazid and 10 mg/kg rifampicin per day. Because of the orange discoloration of body fluids with higher doses of rifampicin it was not possible to mask patients and clinicians to treatment allocation. The primary endpoint was time to culture conversion in liquid media within 12 weeks. Patients without evidence of rifampicin resistance on phenotypic test who took at least one dose of study treatment and had one positive culture on liquid or solid media before or within the first 2 weeks of treatment were included in the primary analysis (modified intention to treat). Time-to-event data were analysed using a Cox proportional-hazards regression model and adjusted for minimisation variables. The proportional hazard assumption was tested using Schoelfeld residuals, with threshold p<0·05 for non-proportionality. The trial is registered with ClinicalTrials.gov (NCT01785186). FINDINGS: Between May 7, 2013, and March 25, 2014, we enrolled and randomly assigned 365 patients to different treatment arms (63 to rifampicin 35 mg/kg, isoniazid, pyrazinamide, and ethambutol; 59 to rifampicin 10 mg/kg, isoniazid, pyrazinamide, SQ109; 57 to rifampicin 20 mg/kg, isoniazid, pyrazinamide, and SQ109; 63 to rifampicin 10 mg/kg, isoniazid, pyrazinamide, and moxifloxacin; and 123 to the control arm). Recruitment was stopped early in the arms containing SQ109 since prespecified efficacy thresholds were not met at the planned interim analysis. Time to stable culture conversion in liquid media was faster in the 35 mg/kg rifampicin group than in the control group (median 48 days vs 62 days, adjusted hazard ratio 1·78; 95% CI 1·22-2·58, p=0·003), but not in other experimental arms. There was no difference in any of the groups in time to culture conversion on solid media. 11 patients had treatment failure or recurrent disease during post-treatment follow-up: one in the 35 mg/kg rifampicin arm and none in the moxifloxacin arm. 45 (12%) of 365 patients reported grade 3-5 adverse events, with similar proportions in each arm. INTERPRETATION: A dose of 35 mg/kg rifampicin was safe, reduced the time to culture conversion in liquid media, and could be a promising component of future, shorter regimens. Our adaptive trial design was successfully implemented in a multi-centre, high tuberculosis burden setting, and could speed regimen development at reduced cost. FUNDING: The study was funded by the European and Developing Countries Clinical Trials partnership (EDCTP), the German Ministry for Education and Research (BmBF), and the Medical Research Council UK (MRC).

High-dose rifapentine with moxifloxacin for pulmonary tuberculosis.

BACKGROUND: Tuberculosis regimens that are shorter and simpler than the current 6-month daily regimen are needed. METHODS: We randomly assigned patients with newly diagnosed, smear-positive, drug-sensitive tuberculosis to one of three regimens: a control regimen that included 2 months of ethambutol, isoniazid, rifampicin, and pyrazinamide administered daily followed by 4 months of daily isoniazid and rifampicin; a 4-month regimen in which the isoniazid in the control regimen was replaced by moxifloxacin administered daily for 2 months followed by moxifloxacin and 900 mg of rifapentine administered twice weekly for 2 months; or a 6-month regimen in which isoniazid was replaced by daily moxifloxacin for 2 months followed by one weekly dose of both moxifloxacin and 1200 mg of rifapentine for 4 months. Sputum specimens were examined on microscopy and after culture at regular intervals. The primary end point was a composite treatment failure and relapse, with noninferiority based on a margin of 6 percentage points and 90% confidence intervals. RESULTS: We enrolled a total of 827 patients from South Africa, Zimbabwe, Botswana, and Zambia; 28% of patients were coinfected with the human immunodefiency virus. In the per-protocol analysis, the proportion of patients with an unfavorable response was 4.9% in the control group, 3.2% in the 6-month group (adjusted difference from control, -1.8 percentage points; 90% confidence interval [CI], -6.1 to 2.4), and 18.2% in the 4-month group (adjusted difference from control, 13.6 percentage points; 90% CI, 8.1 to 19.1). In the modified intention-to-treat analysis these proportions were 14.4% in the control group, 13.7% in the 6-month group (adjusted difference from control, 0.4 percentage points; 90% CI, -4.7 to 5.6), and 26.9% in the 4-month group (adjusted difference from control, 13.1 percentage points; 90% CI, 6.8 to 19.4). CONCLUSIONS: The 6-month regimen that included weekly administration of high-dose rifapentine and moxifloxacin was as effective as the control regimen. The 4-month regimen was not noninferior to the control regimen. (Funded by the European and Developing Countries Clinical Trials Partnership and the Wellcome Trust; RIFAQUIN Current Controlled Trials number, ISRCTN44153044.).

Contrasting predictors of poor antiretroviral therapy outcomes in two South African HIV programmes: a cohort study.

BACKGROUND: Many national antiretroviral therapy (ART) programmes encourage providers to identify and address baseline factors associated with poor treatment outcomes, including modifiable adherence-related behaviours, before initiating ART. However, evidence on such predictors is scarce, and providers judgement may often be inaccurate. To help address this evidence gap, this observational cohort study examined baseline factors potentially predictive of poor treatment outcomes in two ART programmes in South Africa, with a particular focus on determinants of adherence. METHODS: Treatment-naïve patients starting ART were enrolled from a community and a workplace ART programme. Potential baseline predictors associated with poor treatment outcomes (defined as viral load > 400 copies/ml or having discontinued treatment by six months) were assessed using logistic regression. Exposure variables were organised for regression analysis using a hierarchical framework. RESULTS: 38/227 (17%) of participants in the community had poor treatment outcomes compared to 47/117 (40%) in the workplace. In the community, predictors of worse outcomes included: drinking more than 20 units of alcohol per week, having no prior experience of chronic medications, and consulting a traditional healer in the past year (adjusted odds ratio [aOR] 15.36, 95% CI 3.22-73.27; aOR 2.30, 95%CI 1.00-5.30; aOR 2.27, 95% CI 1.00-5.19 respectively). Being male and knowing someone on ART were associated with better outcomes (aOR 0.25, 95%CI 0.09-0.74; aOR 0.44, 95%CI 0.19-1.01 respectively). In the workplace, predictors of poor treatment outcomes included being uncertain about the health effects of ART and a traditional healer's ability to treat HIV (aOR 7.53, 95%CI 2.02-27.98; aOR 4.40, 95%CI 1.41-13.75 respectively). Longer pre-ART waiting time (2-12 weeks compared to <2 weeks) predicted better treatment outcomes (aOR 0.13, 95% CI 0.03-0.56). CONCLUSION: Baseline predictors of poor treatment outcomes were largely unique to each programme, likely reflecting different populations and pathways to HIV care. In the workplace, active promotion of HIV testing may have extended ART to individuals who, without provider initiation, would not have spontaneously sought care. As provider-initiated testing makes ART available to individuals less motivated to seek care, patients may need additional adherence support, especially addressing uncertainty about the health benefits of ART.

Use of traditional medicine by HIV-infected individuals in South Africa in the era of antiretroviral therapy.

As antiretroviral therapy (ART) becomes more available in African countries, the potential for interaction with traditional medicines becomes more important. We carried out a cross-sectional survey among individuals with moderate or advanced HIV disease attending a workplace clinic providing ART in South Africa to determine prevalence of traditional medicine use, source, recommended products and costs. Among 44 clinic attendees (100% male, median age 42 years, 30 taking ART), 37 (84%) reported ever using traditional medicines, 25 obtained from a healer or herbalist, eight from their own fields and four from a pharmacy. Fourteen of the 44 (32%) were currently using traditional medicines, most frequently African potato (9/14) and Aloe vera (3/14). Seven out of 30 persons taking ART (23%) reported currently using traditional medicines. Participants spent 4 - 27 pounds per month on traditional medicines. Traditional medicine use is common among individuals with moderate and advanced HIV disease. Concomitant use with ART has the potential for drug interactions and should be discussed routinely in ART counselling. Further work is warranted to investigate whether commonly used traditional medicines interact with ART in vivo.