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Chu R.,McMaster University | Chu R.,Biostatistics Unit | Mills E.J.,McMaster University | Mills E.J.,University of Ottawa | And 9 more authors.
AIDS Research and Therapy | Year: 2013

Background: Tuberculosis (TB) disease affects survival among HIV co-infected patients on antiretroviral therapy (ART). Yet, the magnitude of TB disease on mortality is poorly understood.Methods: Using a prospective cohort of 22,477 adult patients who initiated ART between August 2000 and June 2009 in Uganda, we assessed the effect of active pulmonary TB disease at the initiation of ART on all-cause mortality using a Cox proportional hazards model. Propensity score (PS) matching was used to control for potential confounding. Stratification and covariate adjustment for PS and not PS-based multivariable Cox models were also performed.Results: A total of 1,609 (7.52%) patients had active pulmonary TB at the start of ART. TB patients had higher proportions of being male, suffering from AIDS-defining illnesses, having World Health Organization (WHO) disease stage III or IV, and having lower CD4 cell counts at baseline (p < 0.001). The percentages of death during follow-up were 10.47% and 6.38% for patients with and without TB, respectively. The hazard ratio (HR) for mortality comparing TB to non-TB patients using 1,686 PS-matched pairs was 1.37 (95% confidence interval [CI]: 1.08 - 1.75), less marked than the crude estimate (HR = 1.74, 95% CI: 1.49 - 2.04). The other PS-based methods and not PS-based multivariable Cox model produced similar results.Conclusions: After controlling for important confounding variables, HIV patients who had TB at the initiation of ART in Uganda had an approximate 37% increased hazard of overall mortality relative to non-TB patients. © 2013 Chu et al.; licensee BioMed Central Ltd.

Mugo N.R.,University of Washington | Mugo N.R.,Kenya Medical Research Institute | Hong T.,University of Washington | Celum C.,University of Washington | And 12 more authors.
JAMA - Journal of the American Medical Association | Year: 2014

IMPORTANCE: Antiretroviral preexposure prophylaxis (PrEP), using tenofovir disoproxil fumarate (TDF) and combination emtricitabine/tenofovir disoproxil fumarate (FTC+TDF), is efficacious for prevention of human immunodeficiency virus (HIV) acquisition. PrEP could reduce periconception HIV risk, but the effect on pregnancy outcomes is not well defined. OBJECTIVE: To assess pregnancy incidence and outcomes among women using PrEP during the periconception period. DESIGN, SETTING, AND PARTICIPANTS: Randomized trial among 1785 HIV-serodiscordant heterosexual couples (the Partners PrEP Study) in which the female partner was HIV uninfected that demonstrated that PrEP was efficacious for HIV prevention, conducted between July 2008 and June 2013 at 9 sites in Kenya and Uganda. INTERVENTIONS: Daily oral TDF (n = 598), combination FTC+TDF (n = 566), or placebo (n = 621) through July 2011, when PrEP demonstrated efficacy for HIV prevention. Thereafter, participants continued receiving active PrEP without placebo. Pregnancy testing occurred monthly and study medication was discontinued when pregnancy was detected. MAIN OUTCOMES AND MEASURES: Pregnancy incidence, birth outcomes (live births, pregnancy loss, preterm birth, congenital anomalies), and infant growth. RESULTS: A total of 431 pregnancies occurred. Pregnancy incidencewas 10.0 per 100 person-years amongwomen assigned placebo, 11.9 among those assigned TDF (incidence difference, 1.9; 95%CI, -1.1 to 4.9 [P = .22 vs placebo]), and 8.8 among those assigned FTC+TDF (incidence difference, -1.3; 95%CI, -4.1 to 1.5 [P = .39 vs placebo]). Before discontinuation of the placebo treatment group in July 2011, the occurrence of pregnancy loss (96 of 288 pregnancies)was 42.5%for women receiving FTC+TDF compared with 32.3%for those receiving placebo (difference for FTC+TDF vs placebo, 10.2%; 95%CI, -5.3%to 25.7%; P = .16) andwas 27.7%for those receiving TDF alone (difference vs placebo, -4.6%; 95%CI, -18.1% to 8.9%; P = .46). After July 2011, the frequency of pregnancy loss (52 of 143 pregnancies)was 37.5%for FTC+TDF and 36.7%for TDF alone (difference, 0.8%; 95%CI, -16.8%to 18.5%; P = .92). Occurrence of preterm birth, congenital anomalies, and growth throughout the first year of life did not differ significantly for infants born to women who received PrEP vs placebo. CONCLUSIONS AND RELEVANCE: Among HIV-serodiscordant heterosexual African couples, differences in pregnancy incidence, birth outcomes, and infant growth were not statistically different for women receiving PrEP with TDF alone or combination FTC+TDF compared with placebo at conception. Given that PrEP was discontinued when pregnancy was detected and that CIs for the birth outcomes were wide, definitive statements about the safety of PrEP in the periconception period cannot be made. These results should be discussed with HIV-uninfected women receiving PrEP who are considering becoming pregnant. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00557245.

Mills E.J.,University of Ottawa | Bakanda C.,AIDS Support Organization TASO | Birungi J.,AIDS Support Organization TASO | Mwesigwa R.,AIDS Support Organization TASO | And 4 more authors.
AIDS | Year: 2011

OBJECTIVE: Evaluations of CD4 cell count and other prognostic factors on the survival of HIV patients in sub-Saharan Africa are extremely limited. Funders have been reticent to recommend earlier initiation of treatment. We aimed to examine the effect of baseline CD4 cell count on mortality using data from HIV patients receiving combination antiretroviral therapy (cART) in Uganda. DESIGN: Observational study of patients aged at least 14 years enrolled in 10 clinics across Uganda for which The AIDS Support Organization (TASO) has data. METHODS: CD4 cell count was stratified into categories (<50, 50-99, 100-149, 150-199, 200-249, 250-299, >300 cells/μl) and Cox proportional hazards regression was used to model the associations between CD4 cell count and mortality. RESULTS: A total of 22 315 patients were included. 1498 patients died during follow-up (6.7%) and 1433 (6.4%) of patients were lost to follow-up. Crude mortality rates (CMRs) ranged from 53.8 per 1000 patient-years [95% confidence interval (CI) 48.8-58.8] among those with CD4 cell counts of less than 50, to 15.7, (95% CI 12.1-19.3) among those with at least 300 cells/μl. Relative to a baseline CD4 cell count of less than 50 cells/μl, the risk of mortality was 0.75 (95% CI 0.65-0.88), 0.60 (95% CI 0.51-0.70), 0.43 (0.37-0.50), and 0.41 (0.33-0.51) for those with baseline CD4 cell counts of 50-99, 100-149, 150-249, and ≥250 cells/μl, respectively. CONCLUSION: Earlier initiation of cART is associated with increased survival benefits over deferred treatment. © 2011 Lippincott Williams & Wilkins, Inc.

Mills E.J.,University of Ottawa | Mills E.J.,British Columbia Center for Excellence in | Bakanda C.,AIDS Support Organization TASO | Birungi J.,AIDS Support Organization TASO | And 5 more authors.
Journal of the International AIDS Society | Year: 2011

Background: Because men in Africa are less likely to access HIV/AIDS care than women, we aimed to determine if men have differing outcomes from women across a nationally representative sample of adult patients receiving combination antiretroviral therapy in Uganda. Methods. We estimated survival distributions for adult male and female patients using Kaplan-Meier, and constructed multivariable regressions to model associations of baseline variables with mortality. We assessed person-years of life lost up to age 55 by sex. To minimize the impact of patient attrition, we assumed a weighted 30% mortality rate among those lost to follow up. Results: We included data from 22,315 adults receiving antiretroviral therapy. At baseline, men tended to be older, had lower CD4 baseline values, more advanced disease, had pulmonary tuberculosis and had received less treatment follow up (all at p < 0.001). Loss to follow up differed between men and women (7.5 versus 5.9%, p < 0.001). Over the period of study, men had a significantly increased risk of death compared with female patients (adjusted hazard ratio 1.43, 95% CI 1.31-1.57, p < 0.001). The crude mortality rate for males differed importantly from females (43.9, 95% CI 40.7-47.0/1000 person-years versus 26.9, 95% CI 25.4-28.5/1000 person years, p < 0.001). The probability of survival was 91.2% among males and 94.1% among females at 12 months. Person-years of life lost was lower for females than males (689.7 versus 995.9 per 1000 person-years, respectively). Conclusions: In order to maximize the benefits of antiretroviral therapy, treatment programmes need to be gender sensitive to the specific needs of both women and men. Particular efforts are needed to enroll men earlier into care. © 2011 Mills et al; licensee BioMed Central Ltd.

Druyts E.,University of Ottawa | Dybul M.,Georgetown University | Kanters S.,Simon Fraser University | Nachega J.,Stellenbosch University | And 7 more authors.
AIDS | Year: 2013

BACKGROUND: HIV/AIDS has historically had a sex and gender-focused approach to prevention and care. Some evidence suggests that HIV-positive men have worse treatment outcomes than their women counterparts in Africa. METHODS: We conducted a systematic review and meta-analysis of the effect of sex on the risk of death among participants enrolled in antiretroviral therapy (ART) programs in Africa since the rapid scale-up of ART. We included all cohort studies evaluating the effect of sex (male, female) on the risk of death among participants enrolled in regional and national ART programs in Africa. We identified these studies by searching MedLine, EMBASE, and Cochrane CENTRAL. We used a DerSimonian-Laird random-effects method to pool the proportions of men receiving ART and the hazard ratios for death by sex. RESULTS: Twenty-three cohort studies, including 216008 participants (79892 men) contributed to our analysis. The pooled proportion of men receiving ART was 35% [95% confidence interval (CI): 33-38%]. The pooled hazard ratio estimate indicated a significant increase in the risk of death for men when compared to women [hazard ratio: 1.37 (95% CI: 1.28-1.47)]. This was consistent across sensitivity analyses. INTERPRETATION: The proportion of men enrolled in ART programs in Africa is lower than women. Additionally, there is an increased risk of death for men enrolled in ART programs. Solutions that aid in reducing these sex inequities are needed. © 2013 Wolters Kluwer Health | Lippincott Williams & Wilkins.

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