Towards 90-90: Findings after two years of the HPTN 071 (PopART) cluster-randomized trial of a universal testing-and-treatment intervention in Zambia.

BACKGROUND: HPTN071(PopART) is a 3-arm community-randomised study in 21 peri-urban/urban communities in Zambia and the Western Cape of South Africa, with high HIV prevalence and high mobility especially among young adults. In Arm A communities, from November 2013 community HIV care providers (CHiPs) have delivered the "PopART" universal-test-and-treat (UTT) package in annual rounds, during which they visit all households and offer HIV testing. CHiPs refer HIV-positive (HIV+) individuals to routine HIV clinic services, where universal ART (irrespective of CD4 count) is offered, with re-visits to support linkage to care. The overall goal is to reduce population-level adult HIV incidence, through achieving high HIV testing and treatment coverage. METHODS AND FINDINGS: The second annual round was June 2015-October 2016. Included in analysis are all individuals aged ≥15 years who consented to participate, with extrapolation to the total population. Our three main outcomes are (1) knowledge of HIV+ status (2) ART coverage, by the end of Round 2 (R2) and compared with the start of R2, and (3) retention on ART on the day of consenting to participate in R2. We used "time-to-event" methods to estimate the median time to start ART after referral to care. CHiPs visited 45,631 households during R2, ~98% of the estimated total across the four communities, and for 94% (43,022/45,631) consent was given for all household members to be listed on the CHiPs' electronic register; 120,272 individuals aged ≥15 years were listed, among whom 64% of men (37,265/57,901) and 86% (53,516/62,371) of women consented to participate in R2. We estimated there were 6,521 HIV+ men and 10,690 HIV+ women in the total population of visited households; and that ~80% and ~90% of HIV+ men and women respectively knew their HIV+ status by the end of R2, fairly similar across age groups but lower among those who did not participate in Round 1 (R1). Among those who knew their HIV+ status, ~80% of both men and women were on ART by the end of R2, close to 90% among men aged ≥45 and women aged ≥35 years, but lower among younger adults, those who were resident in R1 but did not participate in R1, and those who were newly resident in the area of the community in which they were living in R2. Overall ART coverage was ~65% among HIV+ men and ~75% among HIV+ women, compared with the cumulative 90-90 target of 81%. Among those who reported ever taking ART, 93% of men and 95% of women self-reported they were on ART and missed 0 pills in the last 3 days. The median time to start ART after referral to care was ~6 months in R2, similar across the age range 25-54 years, compared with ~9.5 months in R1. The two main limitations to our findings were that a comparison with control-arm communities cannot be made until the end of the study; and that to extrapolate to the total population, assumptions were required about individuals who were resident, but did not participate, in R2. CONCLUSIONS: Overall coverage against the 90-90 targets was high after two years of intervention, but was lower among men, individuals aged 18-34 years, and those who did not participate in R1. Our findings reflect the relative difficulties for CHiPs to contact men at home, compared with women, and that it is challenging to reach high levels of testing and treatment coverage in communities with substantial mobility and in-migration. The shortened time to start ART after referral to care in R2, compared with R1, was likely attributable to multiple factors including an increased focus of the CHiPs on linkage to care; increasing community acceptance and understanding of the CHiPs, and of ART and UTT, with time; increased coordination with the clinics to facilitate linkage; and clinic improvements.

Socio-economic gradients in prevalent tuberculosis in Zambia and the Western Cape of South Africa.

OBJECTIVE: To describe the associations between socio-economic position and prevalent tuberculosis in the 2010 ZAMSTAR Tuberculosis Prevalence Survey, one of the first large tuberculosis prevalence surveys in Southern Africa in the HIV era. METHODS: The main analyses used data on 34 446 individuals in Zambia and 30 017 individuals in South Africa with evaluable tuberculosis culture results. Logistic regression was used to estimate adjusted odds ratios for prevalent TB by two measures of socio-economic position: household wealth, derived from data on assets using principal components analysis, and individual educational attainment. Mediation analysis was used to evaluate potential mechanisms for the observed social gradients. RESULTS: The quartile with highest household wealth index in Zambia and South Africa had, respectively, 0.55 (95% CI 0.33-0.92) times and 0.70 (95% CI 0.54-0.93) times the adjusted odds of prevalent TB of the bottom quartile. College or university-educated individuals in Zambia and South Africa had, respectively, 0.25 (95% CI 0.12-0.54) and 0.42 (95% CI 0.25-0.70) times the adjusted odds of prevalent TB of individuals who had received only primary education. We found little evidence that these associations were mediated via several key proximal risk factors for TB, including HIV status. CONCLUSION: These data suggest that social determinants of TB remain important even in the context of generalised HIV epidemics.

Cost analysis of two community-based HIV testing service modalities led by a Non-Governmental Organization in Cape Town, South Africa.

BACKGROUND: In South Africa, the financing and sustainability of HIV services is a priority. Community-based HIV testing services (CB-HTS) play a vital role in diagnosis and linkage to HIV care for those least likely to utilise government health services. With insufficient estimates of the costs associated with CB-HTS provided by NGOs in South Africa, this cost analysis explored the cost to implement and provide services at two NGO-led CB-HTS modalities and calculated the costs associated with realizing key HIV outputs for each CB-HTS modality. METHODS: The study took place in a peri-urban area where CB-HTS were provided from a stand-alone centre and mobile service. Using a service provider (NGO) perspective, all inputs were allocated by HTS modality with shared costs apportioned according to client volume or personnel time. We calculated the total cost of each HTS modality and the cost categories (personnel, capital and recurring goods/services) across each HTS modality. Costs were divided into seven pre-determined project components, used to examine cost drivers. HIV outputs were analysed for each HTS modality and the mean cost for each HIV output was calculated per HTS modality. RESULTS: The annual cost of the stand-alone and mobile modalities was $96,616 and $77,764 respectively, with personnel costs accounting for 54% of the total costs at the stand-alone. For project components, overheads and service provision made up the majority of the costs. The mean cost per person tested at stand-alone ($51) was higher than at the mobile ($25). Linkage to care cost at the stand-alone ($1039) was lower than the mobile ($2102). CONCLUSIONS: This study provides insight into the cost of an NGO led CB-HTS project providing HIV testing and linkage to care through two CB-HIV testing modalities. The study highlights; (1) the importance of including all applicable costs (including overheads) to ensure an accurate cost estimate that is representative of the full service implementation cost, (2) the direct link between test uptake and mean cost per person tested, and (3) the need for effective linkage to care strategies to increase linkage and thereby reduce the mean cost per person linked to HIV care.

Diabetes mellitus in Zambia and the Western Cape province of South Africa: Prevalence, risk factors, diagnosis and management.

AIMS: To determine the prevalence of and risk factors for diabetes mellitus and examine its diagnosis and management in the study communities. METHODS: This is a population-based cross-sectional study among adults in 24 communities from Zambia and the Western Cape (WC) province of South Africa. Diabetes is defined as a random blood glucose concentration (RBG)⩾11.1mmol/L, or RBG<11.1mmol/L but with a self-reported prior diabetes diagnosis. For individuals with a prior diagnosis of diabetes, RBG<7.8mmol/L was considered to be an acceptable level of glycaemia. RESULTS: Among 45,767 Zambian and 12,496 WC participants the age-standardised prevalence of diabetes was 3.5% and 7.2% respectively. The highest risk groups identified were those of older age and those with obesity. Of those identified to have diabetes, 34.5% in Zambia and 12.7% in WC were previously unaware of their diagnosis. Among Zambian participants with diabetes, this proportion was lower among individuals with better education or with higher household socio-economic position. Of all those with previously diagnosed diabetes, 66.0% in Zambia and 59.4% in WC were not on any diabetes treatment, and 34.4% in Zambia and 32.7% in WC had a RBG concentration beyond the recommended level, ⩾7.8mmol/L. CONCLUSIONS: The diabetes risk factor profile for our study communities is similar to that seen in high-income populations. A high proportion of individuals with diabetes are not on diabetes treatment and of those on treatment a high proportion have high glycaemic concentrations. Such data may assist in healthcare planning to ensure timely diagnosis and management of diabetes.

HPTN 071 (PopART): rationale and design of a cluster-randomised trial of the population impact of an HIV combination prevention intervention including universal testing and treatment - a study protocol for a cluster randomised trial.

BACKGROUND: Effective interventions to reduce HIV incidence in sub-Saharan Africa are urgently needed. Mathematical modelling and the HIV Prevention Trials Network (HPTN) 052 trial results suggest that universal HIV testing combined with immediate antiretroviral treatment (ART) should substantially reduce incidence and may eliminate HIV as a public health problem. We describe the rationale and design of a trial to evaluate this hypothesis. METHODS/DESIGN: A rigorously-designed trial of universal testing and treatment (UTT) interventions is needed because: i) it is unknown whether these interventions can be delivered to scale with adequate uptake; ii) there are many uncertainties in the models such that the population-level impact of these interventions is unknown; and ii) there are potential adverse effects including sexual risk disinhibition, HIV-related stigma, over-burdening of health systems, poor adherence, toxicity, and drug resistance.In the HPTN 071 (PopART) trial, 21 communities in Zambia and South Africa (total population 1.2 m) will be randomly allocated to three arms. Arm A will receive the full PopART combination HIV prevention package including annual home-based HIV testing, promotion of medical male circumcision for HIV-negative men, and offer of immediate ART for those testing HIV-positive; Arm B will receive the full package except that ART initiation will follow current national guidelines; Arm C will receive standard of care. A Population Cohort of 2,500 adults will be randomly selected in each community and followed for 3 years to measure the primary outcome of HIV incidence. Based on model projections, the trial will be well-powered to detect predicted effects on HIV incidence and secondary outcomes. DISCUSSION: Trial results, combined with modelling and cost data, will provide short-term and long-term estimates of cost-effectiveness of UTT interventions. Importantly, the three-arm design will enable assessment of how much could be achieved by optimal delivery of current policies and the costs and benefits of extending this to UTT. TRIAL REGISTRATION: ClinicalTrials.gov NCT01900977.

Evaluation of the Capilia TB assay for culture confirmation of Mycobacterium tuberculosis infections in Zambia and South Africa.

The performance and cost of the Capilia TB assay were evaluated for use in a resource-limited setting. The sensitivity and specificity were 99.6% and 99.5%, respectively. The incremental costs of the Capilia test were estimated to be $1.46 and $1.84 when the test was added to liquid and solid culture processes, respectively. These findings suggest that the Capilia TB assay represents a rapid, simple, and inexpensive Mycobacterium tuberculosis identification test that can be used in resource-limited settings.

Use of light-emitting diode fluorescence microscopy to detect acid-fast bacilli in sputum.

BACKGROUND: Fluorescence microscopy offers well-described benefits, compared with conventional light microscopy, for the evaluation of sputum smear samples for tuberculosis. However, its use in resource-limited settings has been limited by the high cost of the excitatory light source. We evaluated the diagnostic performance of fluorescence microscopy, using novel light-emitting diode (LED) technology as an alternative to the conventional mercury vapor lamp (MVP). METHODS: Routinely collected sputum specimens from persons suspected to have tuberculosis who attended community clinics were stained with auramine O and were evaluated using 2 different excitatory light sources (MVP and LED); these specimens were then Ziehl-Neelsen stained and reexamined using light microscopy. Two microscopists independently evaluated all smears. Bacterial culture provided the gold standard. RESULTS: Of the 221 sputum specimens evaluated, 36 (16.3%) were positive for Mycobacterium tuberculosis by culture. Sensitivity and specificity documented for the different modalities were 84.7% and 98.9%, respectively, for the LED assessment; 73.6% and 99.8%, respectively, for the MVP assessment; and 61.1% and 98.9%, respectively, for light microscopy. kappa values for interreader variation were 0.87 for the LED assessment, 0.79 for the MVP assessment, and 0.77 for light microscopy. The mean time to read a negative smear was 1.4 min with fluorescence microscopy and 3.6 min with light microscopy, reflecting a time savings of 61% with fluorescence microscopy. CONCLUSION: LED fluorescence microscopy provides a reliable alternative to conventional methods and has many favorable attributes that facilitate improved, decentralized, diagnostic services.

Radiographic signs and symptoms in children treated for tuberculosis: possible implications for symptom-based screening in resource-limited settings.

BACKGROUND: The World Health Organization advises active tracing of children younger than 5 years old in household contact with a sputum smear-positive tuberculosis index case. This study compared radiographic disease manifestations in 2 groups of children treated for tuberculosis in an endemic setting: those who presented with suspicious symptoms; and those actively traced as household contacts of an adult index case. METHODS: We conducted a prospective descriptive study from February 2003 through October 2004 at 5 primary health care clinics in Cape Town South Africa, including all children (younger than 5 years old) treated for tuberculosis (TB). RESULTS: A total of 326 children (younger than 5 years old) received antituberculosis treatment; 190 (58.3%) presented with suspicious symptoms, and 136 (41.7%) were actively traced contacts. Children were categorized as; "not TB" 71 (22%), intrathoracic tuberculosis 230 (70%) and extrathoracic tuberculosis 25 (8%). Significantly more actively traced contacts were categorized as "not TB" (odds ratio, 7.4; 95% confidence interval, 3.8-14.3), or demonstrated elements of the primary complex only on the chest radiograph (odds ratio, 26.2; 95% confidence interval, 8.6-89.2), compared with children who presented with suspicious symptoms. Of all children diagnosed with intrathoracic tuberculosis, 20 of 230 (9%) reported no symptoms, all of whom demonstrated elements of the primary complex only. CONCLUSIONS: The majority of actively traced contacts had minimal disease. Symptom-based screening would have identified all but 9% of children diagnosed with intrathoracic tuberculosis, all of whom demonstrated elements of the primary complex only. Further investigation is required to establish whether symptom-based screening can be justified to improve access to preventive chemotherapy in resource-limited endemic settings.

TB: a partnership for the benefit of research and community.

A public-private partnership (PPP) involving Stellenbosch University in South Africa and GlaxoSmithKline (GSK) has benefited both research and a local community where tuberculosis (TB) is endemic. The venture, part of GSK's Action TB programme, enabled the University's Desmond Tutu TB Centre to establish an epidemiological field site in two suburbs of Cape Town where the annual risk of TB infection is 3.5%. Collaboration between the centre and GSK focused on the development of a surrogate marker model able to predict patient outcome with relative accuracy. Such models may be useful tools for diagnosis/prognosis and for shortening clinical trials of novel TB agents. Other research findings stemming from the Action TB partnership suggest that exogenous reinfection is responsible for the majority of relapse cases and that adults often have infection with multiple strains. The local community has been empowered by the implementation of the Directly Observed Treatment, Short-course (DOTS) programme and benefited from improved education about health in general and TB in particular. The centre has also provided employment for many local people in field work and other roles. Meanwhile, national and international publicity about the centre's work has aided in generating the essential political will to allocate resources and shape healthcare priorities, benefiting this impoverished community.