Strategies to Accelerate HIV Care and Antiretroviral Therapy Initiation After HIV Diagnosis: A Randomized Trial.

: Determine the effectiveness of strategies to increase linkage to care after testing HIV positive at mobile HIV testing in South Africa. : Unmasked randomized controlled trial. : Recruitment of adults testing HIV positive and not currently in HIV care occurred at 7 mobile HIV counseling and testing units in urban, periurban, and rural South Africa with those consenting randomized 1:1:1:1 into 1 of 4 arms. Three strategies were compared with standard of care (SOC): point-of-care CD4 count testing (POC CD4), POC CD4 plus longitudinal strengths-based counseling (care facilitation; CF), and POC CD4 plus transport reimbursement (transport). Participants were followed up telephonically and through clinic records and analyzed with an intention-to-treat analysis. : From March 2013 to October 2014, 2558 participants were enrolled, of whom 160 were excluded postrandomization. Compared with the SOC arm where 298 (50%) reported having entered care, linkage to care was 319 (52%) for POC CD4, hazard ratio (HR) 1.0 [95% confidence interval (CI): 0.89 to 1.2, P = 0.6]; 331 (55%) for CF, HR: 1.1 (95% CI: 0.84 to 1.3, P = 0.2); and 291 (49%) for transport, HR 0.97 (95% CI: 0.83 to 1.1, P = 0.7). Linkage to care verified with clinical records that occurred for 172 (29%) in the SOC arm; 187 (31%) in the POC CD4 arm, HR: 1.0 (95% CI: 0.86 to 1.3, P = 0.6); 225 (38%) in the CF arm, HR: 1.4 (95% CI: 1.1 to 1.7, P = 0.001); and 180 (31%) in the transport arm, HR: 1.1 (95% CI: 0.88 to 1.3, P = 0.5). : CF improved verified linkage to care from 29% to 38%.<br/

Tuberculosis Prevention in South Africa

Background South Africa has one of the highest per capita rates of tuberculosis (TB) incidence in the world. In 2012, the South African government produced a National Strategic Plan (NSP) to control the spread of TB with the ambitious aim of zero new TB infections and deaths by 2032, and a halving of the 2012 rates by 2016. Methods We used a transmission model to investigate whether the NSP targets could be reached if immediate scale up of control methods had happened in 2014. We explored the potential impact of four intervention portfolios; 1) “NSP” represents the NSP strategy, 2) “WHO” investigates increasing antiretroviral therapy eligibility, 3) “Novel Strategies” considers new isoniazid preventive therapy strategies and HIV “Universal Test and Treat” and 4) “Optimised” contains the most effective interventions. Findings We find that even with this scale-up, the NSP targets are unlikely to be achieved. The portfolio that achieved the greatest impact was “Optimised”, followed closely by “NSP”. The “WHO” and “Novel Strategies” had little impact on TB incidence by 2050. Of the individual interventions explored, the most effective were active case finding and reductions in pre-treatment loss to follow up which would have a large impact on TB burden. Conclusion Use of existing control strategies has the potential to have a large impact on TB disease burden in South Africa. However, our results suggest that the South African TB targets are unlikely to be reached without new technologies. Despite this, TB incidence could be dramatically reduced by finding and starting more TB cases on treatment

Attitudes to HIV voluntary counselling and testing among mineworkers in South Africa: will availability of antiretroviral therapy encourage testing?

We conducted a study to identify attitudes that influence uptake of HIV voluntary counselling and testing (VCT) amongst gold mine workers in South Africa; 105 healthy men were interviewed. The level of basic knowledge of HIV was high, but reported awareness of the extent of HIV infection in the workforce and perceived personal risk of HIV infection was low. Health issues were considered the most important indication for HIV testing and one-third had been tested. Fear of testing positive for HIV and the potential consequences, particularly stigmatization, disease and death, were the major identified barriers to VCT. Half of the participants felt workplace education programmes needed to be improved to promote VCT access. Twenty-six per cent became more favourably inclined towards HIV testing in response to information on improvements that have been made to the confidentiality and convenience of the company's VCT service. Only 14% then indicated that they would be more likely to access VCT if antiretroviral therapy became available. A vigorous community education programme is essential if the introduction of ART is to be effective in promoting uptake of VCT

Feasibility and acceptability of a specialist clinical service for HIV-infected mineworkers in South Africa.

Occupational settings offer an ideal opportunity to provide preventive health services for HIV-infected workers. A specialized clinic was established in a mining hospital in the Free State, South Africa, with the primary aim of delivering preventive therapy such as isoniazid to those at high risk of tuberculosis (individuals with HIV infection or silicosis), and cotrimoxazole to those at highest risk for opportunistic infections. The clinic design has taken regard of the importance of minimizing stigma, protecting confidentiality, monitoring potential side effects, supporting adherence and identification of prophylaxis failure. The clinic opened in April 1999 and, by August 2001, 1773 patients had attended at least once; 1762 are HIV-infected and 11 have silicosis. Of those with HIV infection, most were asymptomatic at their first visit. The clinic has achieved high acceptability: 99% of persons who were actively recruited to the service agreed to attend. The number still attending after a median of 13 months from recruitment was 1,270 (72%) and only 48 (2.7%) have declined continued attendance. Most losses were due to termination of employment unrelated to a medical condition. The clinic has already been successfully replicated in two other regions of the mining health service in South Africa and provides a model for workplace HIV clinical services that could be used for implementation of further interventions such as antiretroviral therapy

TB Fast Track: a study to evaluate the effect of a point-of-care TB test-and-treat algorithm on early mortality in people with HIV accessing ART, a trial with randomisation at clinic level

Background Early mortality for HIV-positive people starting antiretroviral therapy (ART) remains high in resource-limited settings, with tuberculosis the most important cause. Existing rapid diagnostic tests for tuberculosis lack sensitivity among HIV-positive people, and consequently, tuberculosis treatment is either delayed or started empirically (without bacteriological confirmation). We developed a management algorithm for ambulatory HIV-positive people, based on body mass index and point-of-care tests for haemoglobin and urine lipoarabinomannan (LAM), to identify those at high risk of tuberculosis and mortality. We designed a clinical trial to test whether implementation of this algorithm reduces six-month mortality among HIV-positive people with advanced immunosuppression. Methods/design The TB Fast Track study is an open, pragmatic, cluster randomised superiority trial, with 24 primary health clinics randomised to implement the intervention or standard of care. Adults (aged ≥18 years) with a CD4 count of 150 cells/μL or less, who have not received any tuberculosis treatment in the last three months, or ART in the last six months, are eligible. In intervention clinics, the study algorithm is used to classify individuals as at high, medium or low probability of tuberculosis. Those classified as high probability start tuberculosis treatment immediately, followed by ART after two weeks. Medium-probability patients follow the South African guidelines for test-negative tuberculosis and are reviewed within a week, to be re-categorised as low or high probability. Low-probability patients start ART as soon as possible. The primary outcome is all-cause mortality at six months. Secondary outcomes include severe morbidity, time to ART start and cost-effectiveness. Discussion This trial will test whether a primary care-friendly management algorithm will enable nurses to identify HIV-positive patients at the highest risk of tuberculosis, to facilitate prompt treatment and reduce early mortality. There remains an urgent need for better diagnostic tests for tuberculosis, especially for people with advanced HIV disease, which may render empirical treatment unnecessary. Trial registration This trial was registered with Current Controlled Trials (identifier: ISRCTN35344604) on 12 September 2012

Rationing tests for drug-resistant tuberculosis - who are we prepared to miss?

BACKGROUND: Early identification of patients with drug-resistant tuberculosis (DR-TB) increases the likelihood of treatment success and interrupts transmission. Resource-constrained settings use risk profiling to ration the use of drug susceptibility testing (DST). Nevertheless, no studies have yet quantified how many patients with DR-TB this strategy will miss. METHODS: A total of 1,545 subjects, who presented to Lima health centres with possible TB symptoms, completed a clinic-epidemiological questionnaire and provided sputum samples for TB culture and DST. The proportion of drug resistance in this population was calculated and the data was analysed to demonstrate the effect of rationing tests to patients with multidrug-resistant TB (MDR-TB) risk factors on the number of tests needed and corresponding proportion of missed patients with DR-TB. RESULTS: Overall, 147/1,545 (9.5%) subjects had culture-positive TB, of which 32 (21.8%) had DR-TB (MDR, 13.6%; isoniazid mono-resistant, 7.5%; rifampicin mono-resistant, 0.7%). A total of 553 subjects (35.8%) reported one or more MDR-TB risk factors; of these, 506 (91.5%; 95% CI, 88.9-93.7%) did not have TB, 32/553 (5.8%; 95% CI, 3.4-8.1%) had drug-susceptible TB, and only 15/553 (2.7%; 95% CI, 1.5-4.4%) had DR-TB. Rationing DST to those with an MDR-TB risk factor would have missed more than half of the DR-TB population (17/32, 53.2%; 95% CI, 34.7-70.9). CONCLUSIONS: Rationing DST based on known MDR-TB risk factors misses an unacceptable proportion of patients with drug-resistance in settings with ongoing DR-TB transmission. Investment in diagnostic services to allow universal DST for people with presumptive TB should be a high priority

Adherence to Tuberculosis Therapy among Patients Receiving Home-Based Directly Observed Treatment: Evidence from the United Republic of Tanzania.

\ud \ud Non-adherence to tuberculosis (TB) treatment is the leading contributor to the selection of drug-resistant strains of Mycobacterium tuberculosis and subsequent treatment failure. Tanzania introduced a TB Patient Centred Treatment (PCT) approach which gives new TB patients the choice between home-based treatment supervised by a treatment supporter of their own choice, and health facility-based treatment observed by a medical professional. The aim of this study was to assess the extent and determinants of adherence to anti-TB therapy in patients opting for home-based treatment under the novel PCT approach. In this cross-sectional study, the primary outcome was the percentage of patients adherent to TB therapy as detected by the presence of isoniazid in urine (IsoScreen assay). The primary analysis followed a non-inferiority approach in which adherence could not be lower than 75%. Logistic regression was used to examine the influence of potentially predictive factors. A total of 651 new TB patients were included. Of these, 645 (99.1%) provided urine for testing and 617 patients (95.7%; 90%CI 94.3-96.9) showed a positive result. This result was statistically non-inferior to the postulated adherence level of 75% (p<0.001). Adherence to TB therapy under home-based Directly Observed Treatment can be ensured in programmatic settings. A reliable supply of medication and the careful selection of treatment supporters, who preferably live very close to the patient, are crucial success factors. Finally, we recommend a cohort study to assess the rate of adherence throughout the full course of TB treatment

What causes symptoms suggestive of tuberculosis in HIV-positive people with negative initial investigations?

OBJECTIVE: To identify the causes of symptoms suggestive of tuberculosis (TB) among people living with the human immunodeficiency virus (PLHIV) in South Africa. METHODS: A consecutive sample of HIV clinic attendees with symptoms suggestive of TB (1 of cough, weight loss, fever or night sweats) at enrolment and at 3 months, and negative initial TB investigations, were systematically evaluated with standard protocols and diagnoses assigned using standard criteria. TB was 'confirmed' if Mycobacterium tuberculosis was identified within 6 months of enrolment, and 'clinical' if treatment started without microbiological confirmation. RESULTS: Among 103 participants, 50/103 were pre-antiretroviral therapy (ART) and 53/103 were on ART; respectively 68% vs. 79% were female; the median age was 35 vs. 45 years; the median CD4 count was 311 vs. 508 cells/mm³. Seventy-two (70%) had 5% measured weight loss and 50 (49%) had cough. The most common final diagnoses were weight loss due to severe food insecurity (n = 20, 19%), TB (n = 14, 14%: confirmed n = 7; clinical n = 7), other respiratory tract infection (n = 14, 14%) and post-TB lung disease (n = 9, 9%). The basis for TB diagnosis was imaging (n = 7), bacteriological confirmation from sputum (n = 4), histology, lumbar puncture and other (n = 1 each). CONCLUSION: PLHIV with persistent TB symptoms require further evaluation for TB using all available modalities, and for food insecurity in those with weight loss

The Effect of Tuberculosis on Mortality in HIV Positive People: A Meta-Analysis

Tuberculosis is a leading cause of death in people living with HIV (PLWH). We conducted a meta analysis to assess the effect of tuberculosis on mortality in people living with HIV. Meta-analysis of cohort studies assessing the effect of tuberculosis on mortality in PLWH. To identify eligible studies we systematically searched electronic databases (until December 2008), performed manual searches of citations from relevant articles, and reviewed conference proceedings. Multivariate hazard ratios (HR) of mortality in PLWH with and without tuberculosis, estimated in individual cohort studies, were pooled using random effect weighting according to "Der Simonian Laird method" if the p-value of the heterogeneity test was <0.05. Fifteen cohort studies were systematically retrieved. Pooled overall analysis of these 15 studies estimating the effect of tuberculosis on mortality in PLWH showed a Hazard Ratio (HR) of 1.8 (95% confidence interval (CI): 1.4-2.3). Subanalysis of 8 studies in which the cohort was not exposed to highly active antiretroviral therapy (HAART) showed an HR of 2.6 (95% CI: 1.8-3.6). Subanalysis of 6 studies showed that tuberculosis did not show an effect on mortality in PLWH exposed to HAART: HR 1.1 (95% CI: 0.9-1.3). These results provide an indication of the magnitude of benefit to an individual that could have been expected if tuberculosis had been prevented. It emphasizes the need for additional studies assessing the effect of preventing tuberculosis or early diagnosis and treatment of tuberculosis in PLWH on reducing mortality. Furthermore, the results of the subgroup analyses in cohorts largely exposed to HAART provide additional support to WHO's revised guidelines, which include promoting the initiation of HAART for PLWH co-infected with tuberculosis. The causal effect of tuberculosis on mortality in PLWH exposed to HAART needs to be further evaluated once the results of more cohort studies become availabl