Perinatal HIV Research Unit

Johannesburg, South Africa

Perinatal HIV Research Unit

Johannesburg, South Africa
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Egger M.,University of Bern | Spycher B.D.,University of Bern | Sidle J.,Moi University | Weigel R.,Kamuzu Central Hospital | And 10 more authors.
PLoS Medicine | Year: 2011

Background: The World Health Organization estimates that in sub-Saharan Africa about 4 million HIV-infected patients had started antiretroviral therapy (ART) by the end of 2008. Loss of patients to follow-up and care is an important problem for treatment programmes in this region. As mortality is high in these patients compared to patients remaining in care, ART programmes with high rates of loss to follow-up may substantially underestimate mortality of all patients starting ART. Methods and Findings: We developed a nomogram to correct mortality estimates for loss to follow-up, based on the fact that mortality of all patients starting ART in a treatment programme is a weighted average of mortality among patients lost to follow-up and patients remaining in care. The nomogram gives a correction factor based on the percentage of patients lost to follow-up at a given point in time, and the estimated ratio of mortality between patients lost and not lost to follow-up. The mortality observed among patients retained in care is then multiplied by the correction factor to obtain an estimate of programme-level mortality that takes all deaths into account. A web calculator directly calculates the corrected, programme-level mortality with 95% confidence intervals (CIs). We applied the method to 11 ART programmes in sub-Saharan Africa. Patients retained in care had a mortality at 1 year of 1.4% to 12.0%; loss to follow-up ranged from 2.8% to 28.7%; and the correction factor from 1.2 to 8.0. The absolute difference between uncorrected and corrected mortality at 1 year ranged from 1.6% to 9.8%, and was above 5% in four programmes. The largest difference in mortality was in a programme with 28.7% of patients lost to follow-up at 1 year. Conclusions: The amount of bias in mortality estimates can be large in ART programmes with substantial loss to follow-up. Programmes should routinely report mortality among patients retained in care and the proportion of patients lost. A simple nomogram can then be used to estimate mortality among all patients who started ART, for a range of plausible mortality rates among patients lost to follow-up. © 2011 Egger et al.

Palumbo P.,Dartmouth College | Lindsey J.C.,Harvard University | Hughes M.D.,Harvard University | Cotton M.F.,Stellenbosch University | And 16 more authors.
New England Journal of Medicine | Year: 2010

Background: Single-dose nevirapine is the cornerstone of the regimen for prevention of mother-to-child transmission of human immunodeficiency virus (HIV) in resource-limited settings, but nevirapine frequently selects for resistant virus in mothers and children who become infected despite prophylaxis. The optimal antiretroviral treatment strategy for children who have had prior exposure to single-dose nevirapine is unknown. Methods: We conducted a randomized trial of initial therapy with zidovudine and lamivudine plus either nevirapine or ritonavir-boosted lopinavir in HIV-infected children 6 to 36 months of age, in six African countries, who qualified for treatment according to World Health Organization (WHO) criteria. Results are reported for the cohort that included children exposed to single-dose nevirapine prophylaxis. The primary end point was virologic failure or discontinuation of treatment by study week 24. Enrollment in this cohort was terminated early on the recommendation of the data and safety monitoring board. Results: A total of 164 children were enrolled. The median percentage of CD4+ lymphocytes was 19%; a total of 56% of the children had WHO stage 3 or 4 disease. More children in the nevirapine group than in the ritonavir-boosted lopinavir group reached a primary end point (39.6% vs. 21.7%; weighted difference, 18.6 percentage-points; 95% confidence interval, 3.7 to 33.6; nominal P = 0.02). Baseline resistance to nevirapine was detected in 18 of 148 children (12%) and was predictive of treatment failure. No significant between-group differences were seen in the rate of adverse events. Conclusions: Among children with prior exposure to single-dose nevirapine for perinatal prevention of HIV transmission, antiretroviral treatment consisting of zidovudine and lamivudine plus ritonavir-boosted lopinavir resulted in better outcomes than did treatment with zidovudine and lamivudine plus nevirapine. Since nevirapine is used for both treatment and perinatal prevention of HIV infection in resource-limited settings, alternative strategies for the prevention of HIV transmission from mother to child, as well as for the treatment of HIV infection, are urgently required. Copyright © 2010 Massachusetts Medical Society.

News Article | February 15, 2017

[Seattle, USA, February 14, 2017] The non-profit research and development organization Drugs for Neglected Diseases initiative (DNDi) has released results of a study in South Africa that will make it easier for healthcare workers to treat children living with HIV who are co-infected with tuberculosis (TB). The study, presented as a late-breaker this week at the Conference on Retroviruses and Opportunistic Infections (CROI) in Seattle, provides essential evidence and data to counter the negative interactions between two critical HIV and TB treatments. "TB is extremely common in children with HIV but until now, when a child has both diseases, we simply did not know for certain if our approach to dosing was correct. This is crucial to ensure long-term control of the HIV virus and keep kids alive," said Dr Helena Rabie from Stellenbosch University and lead investigator of the DNDi study. "These kids are extremely neglected: HIV-positive children have fewer treatment options and in many cases cannot switch to different antiretrovirals when taking concomitant TB treatment." Protease inhibitors such as lopinavir (LPV) form a key component of HIV treatment, but must be "boosted" with ritonavir (RTV) to ensure they inhibit the virus. But when children are also treated for TB, the drug rifampicin, which forms the backbone of TB treatment, reduces the concentration of RTV and hence the effectiveness of LPV. To counteract this effect, the amount of ritonavir in the lopinavir/ritonavir (LPV/r) combination must be increased, a procedure known as "super-boosting". An earlier study had suggested that super-boosting LPV/r with ritonavir up to a 1:1 ratio during a child's simultaneous HIV and TB treatment, as opposed to the commonly used 4:1 ratio used during treatment for HIV alone, was effective. But the study included only 15 children. DNDi and partners aimed to consolidate the evidence around the safety and effectiveness of super-boosting through a larger study including 96 children - 30 of whom were under one year of age at enrollment - across five sites in South Africa. The final results presented this week at CROI show that this approach counteracts the negative interactions between LPV/r and rifampicin, easing the co-administration of HIV and TB treatment for this particularly vulnerable population. "This study brings the scientific proof needed so that health workers can give children the right dose and ensure that their HIV and TB treatment works," said Dr Marc Lallemant, Head of DNDi's HIV program. Interim results from the study were presented by DNDi to the World Health Organization (WHO) guidelines review committee, which recommended super-boosting of LPV/r in TB/HIV co-infected children in 2016. But further uptake by other countries of this therapeutic advance is hampered by the short shelf-life of pediatric RTV, as well as difficulties giving both LPV/r and stand-alone RTV to children, linked to their high alcohol content and extremely bitter taste. In Kenya and Uganda, DNDi and partners are piloting a more child-friendly formulation of LPV/r that comes in the form of pellets. In a separate study due to start in South Africa, DNDi and partners will pilot super-boosting in children co-infected with TB and HIV using a new solid RTV formulation. "DNDi's ultimate goal is to deliver a simple, first-line antiretroviral regimen that overcomes the many different barriers that stand in the way of giving treatment to infants and young children," said Dr Marc Lallemant. "With our industrial partners we're aiming to develop an easy-to-use '4-in-1' fixed-dose combination that is palatable, does not require refrigeration, and that thanks to super-boosting can address drug-drug interaction with medicines for TB." DNDi's HIV program is supported by UBS Optimus Foundation, Switzerland; UNITAID, Switzerland; Médecins Sans Frontières, International; the Agence française de Développement, France; and a number of private donors. DNDi wishes to acknowledge and thank its South African partners in the study: Stellenbosch University and Tygerberg Children's Hospital; Perinatal HIV Research Unit; Shandukani Research Centre; Empilweni Services and Research Unit, Rahima Moosa Mother and Child Hospital; Enhancing Care Foundation; Department of Health and Department of Science and Technology. DNDi also thanks its industrial partners AbbVie and Cipla Ltd for collaboration in the '4-in-1' project. A not-for-profit R&D organization, DNDi works to deliver new treatments for neglected diseases, in particular leishmaniasis, human African trypanosomiasis, Chagas disease, specific filarial infections, mycetoma, hepatitis C, and pediatric HIV. Since its inception in 2003, DNDi has with its partners developed two new antimalarial fixed-dose combinations, the only pediatric medication for Chagas disease, and a new combination treatment for sleeping sickness. Thanks to clinical trials led by DNDi, national or international guidelines have been changed for visceral leishmaniasis treatments in Africa and Asia, and for children co-infected with HIV and tuberculosis. Out of the Dark: Progress in Treating HIV/TB in Kids Part 1 - Children living with HIV and TB face a unique challenge: the drugs used to treat each disease can cancel each other out. This short video - filmed in July 2016 in Durban, South Africa - documents a promising study that was carried out by the Drugs for Neglected Diseases initiative (DNDi) to address this challenge. Out of the Dark: Progress in Treating HIV/TB in Kids Part 2 Part two of a short filmed in July 2016 in Durban, South Africa. Despite recent progress in treating children with HIV, kids like Mel are still neglected. Better treatments are needed.

Van Rooyen H.,STIs and TB Unit | Van Rooyen H.,Human science Research Council | McGrath N.,London School of Hygiene and Tropical Medicine | McGrath N.,University of South Africa | And 7 more authors.
AIDS and Behavior | Year: 2013

Mounting evidence exists that mobile voluntary counselling and testing (VCT) is able to extend coverage to new localities and populations. We describe two feasibility and acceptability pilot studies conducted in rural and urban South Africa in preparation for the larger NIMH Project Accept HIV prevention trial. A total of 1,015 individuals participated in the pilot studies. Participants in rural Vulindlela were younger (median 22 years) compared to urban Soweto (p < 0.001). Young people were more likely to be first time testers in both sites (p = 0.01 in Vulindlela, p < 0.001 in Soweto), with significantly more men likely to be first time testers than women (p = 0.01 in Vulindlela, p < 0.001 in Soweto). User satisfaction with mobile VCT was extremely high in both sites. Our study shows that providing mobile, high-quality and easy to access services in a high prevalence context is a feasible way to engage youth, men and more rural populations in HIV counselling and testing. © 2012 Springer Science+Business Media New York.

Marrazzo J.M.,University of Washington | Ramjee G.,HIV Prevention Research Unit | Richardson B.A.,Fred Hutchinson Cancer Research Center | Gomez K.,FHI 360 | And 23 more authors.
New England Journal of Medicine | Year: 2015

BACKGROUND: Reproductive-age women need effective interventions to prevent the acquisition of human immunodeficiency virus type 1 (HIV-1) infection. METHODS: We conducted a randomized, placebo-controlled trial to assess daily treatment with oral tenofovir disoproxil fumarate (TDF), oral tenofovir-emtricitabine (TDF-FTC), or 1% tenofovir (TFV) vaginal gel as preexposure prophylaxis against HIV-1 infection in women in South Africa, Uganda, and Zimbabwe. HIV-1 testing was performed monthly, and plasma TFV levels were assessed quarterly. RESULTS: Of 12,320 women who were screened, 5029 were enrolled in the study. The rate of retention in the study was 91% during 5509 person-years of follow-up. A total of 312 HIV-1 infections occurred; the incidence of HIV-1 infection was 5.7 per 100 personyears. In the modified intention-to-treat analysis, the effectiveness was-49.0% with TDF (hazard ratio for infection, 1.49; 95% confidence interval [CI], 0.97 to 2.29),-4.4% with TDF-FTC (hazard ratio, 1.04; 95% CI, 0.73 to 1.49), and 14.5% with TFV gel (hazard ratio, 0.85; 95% CI, 0.61 to 1.21). In a random sample, TFV was detected in 30%, 29%, and 25% of available plasma samples from participants randomly assigned to receive TDF, TDF-FTC, and TFV gel, respectively. Independent predictors of TFV detection included being married, being older than 25 years of age, and being multiparous. Detection of TFV in plasma was negatively associated with characteristics predictive of HIV-1 acquisition. Elevations of serum creatinine levels were seen more frequently among participants randomly assigned to receive oral TDF-FTC than among those assigned to receive oral placebo (1.3% vs. 0.2%, P = 0.004). We observed no significant differences in the frequencies of other adverse events. CONCLUSIONS: None of the drug regimens we evaluated reduced the rates of HIV-1 acquisition in an intention-to-treat analysis. Adherence to study drugs was low. Copyright © 2015 Massachusetts Medical Society.

Onono M.,Kenya Medical Research Institute | Owuor K.,Maseno University | Turan J.,University of Alabama at Birmingham | Bukusi E.A.,Kenya Medical Research Institute | And 2 more authors.
AIDS Patient Care and STDs | Year: 2015

The aim of this study was to identify factors associated with prevention of mother-to-child transmission (PMTCT) in an area of Kenya with widely accessible free PMTCT services. A matched case-control study was conducted at 31 public facilities in western Kenya. HIV-infected mothers with infants aged 6 weeks to 6 months were interviewed and medical charts were reviewed. Cases were mothers of infants with a definitive diagnosis of HIV. Controls were mothers of infants testing HIV negative. Cases and controls were matched in a 1:3 ratio on socio-demographic factors. Fifty cases and 135 controls were enrolled. Conditional (matched) logistic regression analysis was conducted. Odds of being a case were higher for women who first learned their HIV status during pregnancy [OR:2.85, 95%CI:1.41-5.78], did not adhere to antiretroviral therapy (ART) [OR:3.35, 95%CI:1.48-7.58], or had a home delivery [OR:2.42, 95%CI:1.01-5.80]. Based on medical record review, cases had higher odds of their provider not following guidelines for prescription of ART for mothers [OR:8.61, 95%CI:2.83-26.15] and infants [OR:9.72, 95%CI:2.75-34.37]. Stigma from the community [OR:0.37, 95% CI:0.14-1.02] or facility [OR:0.38, 95%CI:0.04-3.41], did not increase the odds of MTCT. Poor adherence to PMTCT guidelines and recommendations by both infected women and health care providers hamper efforts to attain elimination of MTCT. © Copyright 2015, Mary Ann Liebert, Inc. 2015.

Madhi S.A.,Medical Research Council | Madhi S.A.,National Science Foundation | Madhi S.A.,University of Witwatersrand | Cutland C.L.,Medical Research Council | And 23 more authors.
New England Journal of Medicine | Year: 2014

Background: There are limited data on the efficacy of vaccination against confirmed influenza in pregnant women with and those without human immunodeficiency virus (HIV) infection and protection of their infants. p Methods: We conducted two double-blind, randomized, placebo-controlled trials of trivalent inactivated influenza vaccine (IIV3) in South Africa during 2011 in pregnant women infected with HIV and during 2011 and 2012 in pregnant women who were not infected. The immunogenicity, safety, and efficacy of IIV3 in pregnant women and their infants were evaluated until 24 weeks after birth. Immune responses were measured with a hemagglutination inhibition (HAI) assay, and influenza was diagnosed by means of reverse-transcriptase-polymerase-chain-reaction (RT-PCR) assays of respiratory samples. Results: The study cohorts included 2116 pregnant women who were not infected with HIV and 194 pregnant women who were infected with HIV. At 1 month after vaccination, seroconversion rates and the proportion of participants with HAI titers of 1:40 or more were higher among IIV3 recipients than among placebo recipients in both cohorts. Newborns of IIV3 recipients also had higher HAI titers than newborns of placebo recipiens. The attack rate for RT-PCR-confirmed influenza among both HIV-uninfected placebo recipients and their infants was 3.6%. The attack rates among HIV-uninfected IIV3 recipients and their infants were 1.8% and 1.9%, respectively, and the respective vaccine-efficacy rates were 50.4% (95% confidence interval [CI], 14.5 to 71.2) and 48.8% (95% CI, 11.6 to 70.4). Among HIV-infected women, the attack rate for placebo recipients was 17.0% and the rate for IIV3 recipients was 7.0%; the vaccine-efficacy rate for these IIV3 recipients was 57.7% (95% CI, 0.2 to 82.1). Conclusions: Influenza vaccine was immunogenic in HIV-uninfected and HIV-infected pregnant women and provided partial protection against confirmed influenza in both groups of women and in infants who were not exposed to HIV. Copyright © 2014 Massachusetts Medical Society.

News Article | November 27, 2016

The first HIV vaccine efficacy study to launch anywhere in seven years is now testing whether an experimental vaccine regimen safely prevents HIV infection among South African adults. The study, called HVTN 702, involves a new version of the only HIV vaccine candidate ever shown to provide some protection against the virus. HVTN 702 aims to enroll 5,400 men and women, making it the largest and most advanced HIV vaccine clinical trial to take place in South Africa, where more than 1,000 people become infected with HIV every day. "If deployed alongside our current armory of proven HIV prevention tools, a safe and effective vaccine could be the final nail in the coffin for HIV," said Anthony S. Fauci, M.D., director of the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health and a co-funder of the trial. "Even a moderately effective vaccine would significantly decrease the burden of HIV disease over time in countries and populations with high rates of HIV infection, such as South Africa." The experimental vaccine regimen being tested in HVTN 702 is based on the one investigated in the RV144 clinical trial in Thailand led by the U.S. Military HIV Research Program and the Thai Ministry of Health. The Thai trial delivered landmark results in 2009 when it found for the first time that a vaccine could prevent HIV infection, albeit modestly. The new regimen aims to provide greater and more sustained protection than the RV144 regimen and has been adapted to the HIV subtype that predominates in southern Africa, a region that includes the country of South Africa. "The people of South Africa are making history by conducting and participating in the first HIV vaccine efficacy study to build on the results of the Thai trial," said HVTN 702 Protocol Chair Glenda Gray, M.B.B.C.H., F.C.Paed. (SA). "HIV has taken a devastating toll in South Africa, but now we begin a scientific exploration that could hold great promise for our country. If an HIV vaccine were found to work in South Africa, it could dramatically alter the course of the pandemic." Dr. Gray is president and chief executive officer of the South African Medical Research Council; research professor of pediatrics at the University of the Witwatersrand, Johannesburg; and a founding director of the Perinatal HIV Research Unit at Chris Hani Baragwanath Hospital in Soweto, South Africa. Co-chairing the protocol with Dr. Gray are Linda-Gail Bekker, M.D., Ph.D.; Fatima Laher, M.D.; and Mookho Malahleha, M.B.Ch.B., M.P.H. Dr. Bekker is deputy director of the Desmond Tutu HIV Centre at the University of Cape Town and chief operating officer of the Desmond Tutu HIV Foundation in Cape Town, South Africa. Dr. Laher is a director of the Perinatal HIV Research Unit at Chris Hani Baragwanath Hospital. Dr. Malahleha is deputy director of Setshaba Research Centre in Soshanguve, South Africa. The experimental vaccine regimen tested in the Thai trial was found to be 31.2 percent effective at preventing HIV infection over the 3.5-year follow-up after vaccination. In the HVTN 702 study, the design, schedule and components of the RV144 vaccine regimen have been modified in an attempt to increase the magnitude and duration of vaccine-elicited protective immune responses. As the regulatory sponsor of HVTN 702, NIAID is responsible for all operational aspects of this pivotal Phase 2b/3 trial, which is enrolling HIV-uninfected, sexually active men and women aged 18 to 35 years. The NIAID-funded HIV Vaccine Trials Network (HVTN) is conducting the trial at 15 sites across South Africa. Results are expected in late 2020. HVTN 702 begins just months after interim results were reported for HVTN 100, its predecessor clinical trial, which found that the new vaccine regimen was safe for the 252 study participants and induced comparable immune responses to those reported in RV144. HVTN 100 and HVTN 702 are part of a larger HIV vaccine research endeavor led by the Pox-Protein Public-Private Partnership, or P5--a diverse group of public and private organizations committed to building on the success of the RV144 trial. The P5 aims to produce an HIV vaccine that could have a significant public health benefit in southern Africa and to advance scientists' understanding of the immune responses associated with preventing HIV infection. P5 members include NIAID, the Bill & Melinda Gates Foundation, the South African Medical Research Council, HVTN, Sanofi Pasteur, GSK and the U.S. Military HIV Research Program. The HVTN 702 vaccine regimen consists of two experimental vaccines: a canarypox vector-based vaccine called ALVAC-HIV and a two-component gp120 protein subunit vaccine with an adjuvant to enhance the body's immune response to the vaccine. The vaccines do not contain HIV and therefore do not pose any danger of HIV infection to study participants. Both ALVAC-HIV (supplied by Sanofi Pasteur) and the protein vaccine (supplied by GSK) have been modified from the versions used in RV144 to be specific to HIV subtype C, the predominant HIV subtype in southern Africa. Additionally, the protein subunit vaccine in HVTN 702 is combined with MF59 (also supplied by GSK), a different adjuvant than the one used in RV144, in the hope of generating a more robust immune response. Finally, the HVTN 702 vaccine regimen includes booster shots at the one-year mark in an effort to prolong the early protective effect observed in RV144. The study volunteers are being randomly assigned to receive either the investigational vaccine regimen or a placebo. All study participants will receive a total of five injections over one year. The safety of HVTN 702 study participants will be closely monitored throughout the trial, and participants will be offered the standard of care for preventing HIV infection. Study participants who become infected with HIV in the community will be referred to local medical providers for care and treatment and will be counseled on how to reduce their risk of transmitting the virus. HVTN 702 is one of many NIAID-supported HIV prevention trials in progress in southern Africa. These include the AMP Studies, which are testing infusions of the VRC01 antibody; the open-label HOPE study, which is examining a dapivirine vaginal ring; and HPTN 076 and 077, which are studying long-acting injectable rilpivirine and cabotegravir, respectively. NIAID conducts and supports research--at NIH, throughout the United States, and worldwide--to study the causes of infectious and immune-mediated diseases, and to develop better means of preventing, diagnosing and treating these illnesses. News releases, fact sheets and other NIAID-related materials are available on the NIAID website. About the National Institutes of Health (NIH): NIH, the nation's medical research agency, includes 27 Institutes and Centers and is a component of the U.S. Department of Health and Human Services. NIH is the primary federal agency conducting and supporting basic, clinical, and translational medical research, and is investigating the causes, treatments, and cures for both common and rare diseases. For more information about NIH and its programs, visit http://www. .

Katz I.T.,Brigham and Women's Hospital | Katz I.T.,Harvard University | Essien T.,Perinatal HIV Research Unit | Marinda E.T.,University of Witwatersrand | And 8 more authors.
AIDS | Year: 2011

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. © 2011 Wolters Kluwer Health Lippincott Williams & Wilkins.

Hoffmann C.J.,Johns Hopkins University | Chaisson R.E.,Johns Hopkins University | Martinson N.A.,Johns Hopkins University | Martinson N.A.,Perinatal HIV Research Unit
PLoS ONE | Year: 2014

Objectives: Many randomized and cohort studies have reported a survival benefit with cotrimoxazole prophylaxis without detecting a difference in tuberculosis (TB) incidence by cotrimoxazole status. However, several in vitro studies have reported that cotrimoxazole possesses anti-TB activity. We sought to compare TB incidence and TB diagnostic yield by cotrimoxazole use among participants in a well characterized cohort of HIV-infected adults living in a high TB prevalence region. Methods: We analyzed prospective data from a long-term longitudinal cohort of adults receiving HIV care and TB investigations in Soweto, South Africa. Using longitudinal analysis, we compared total and laboratory confirmed TB incidence by cotrimoxazole status as well as all-cause mortality. In addition, we compared TB culture results by cotrimoxazole status. Results: In a multivariable analysis, adjusted for sex, body mass index, WHO clinical stage, time-updated CD4 count, and antiretroviral therapy status, we observed an association between cotrimoxazole and an increase in TB incidence (hazard ratio 1.7, 95% CI: 1.2, 2.2). However, when restricted to laboratory-confirmed TB, there was no association between cotrimoxazole and TB incidence (hazard ratio: 0.97, 95% CI: 0.39, 2.4). In TB cases, we found no difference in the proportion of positive sputum cultures or days to culture positivity by cotrimoxazole status. Cotrimoxazole was associated with a reduction in mortality. Conclusions: In this cohort with a mortality benefit from cotrimoxazole, we found an increased risk of all TB among individuals using cotrimoxazole, likely a result of residual confounding, but no association between use of cotrimoxazole and laboratory-confirmed TB. Cotrimoxazole did not compromise TB diagnosis. © 2014 Hoffmann et al.

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