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Tuberculosis incidence rates during 8 years of follow-up of an antiretroviral treatment cohort in South Africa: comparison with rates in the community.

ABSTRACT: BACKGROUND:Although antiretroviral therapy (ART) is known to be associated with time-dependent reductions in tuberculosis (TB) incidence, the long-term impact of ART on incidence remains imprecisely defined due to limited duration of follow-up and incomplete CD4 cell count recovery in existing studies. We determined TB incidence in a South African ART cohort with up to 8 years of follow-up and stratified rates according to CD4 cell count recovery. We compared these rates with those of HIV-uninfected individuals living in the same community. METHODOLOGY/PRINCIPAL FINDINGS:Prospectively collected clinical data on patients receiving ART in a community-based cohort in Cape Town were analysed. 1544 patients with a median follow-up of 5.0 years (IQR 2.4-5.8) were included in the analysis. 484 episodes of incident TB (73.6% culture-confirmed) were diagnosed in 424 patients during 6506 person-years (PYs) of follow-up. The TB incidence rate during the first year of ART was 12.4 (95% CI 10.8-14.4) cases/100PYs and decreased to 4.92 (95% CI 3.64-8.62) cases/100PYs between 5 and 8 years of ART. During person-time accrued within CD4 cell strata 0-100, 101-200, 201-300, 301-400, 401-500, 501-700 and ?700 cells/µL, TB incidence rates (95% CI) were 25.5 (21.6-30.3), 11.2 (9.4-13.5), 7.9 (6.4-9.7), 5.0 (3.9-6.6), 5.1 (3.8-6.8), 4.1 (3.1-5.4) and 2.7 (1.7-4.5) cases/100PYs, respectively. Overall, 75% (95% CI 70.9-78.8) of TB episodes were recurrent cases. Updated CD4 cell count and viral load measurements were independently associated with long-term TB risk. TB rates during person-time accrued in the highest CD4 cell count stratum (>700 cells/µL) were 4.4-fold higher that the rate in HIV uninfected individuals living in the same community (2.7 versus 0.62 cases/100PYs; 95%CI 0.58-0.65). CONCLUSIONS/SIGNIFICANCE:TB rates during long-term ART remained substantially greater than rates in the local HIV uninfected populations regardless of duration of ART or attainment of CD4 cell counts exceeding 700 cells/µL.

SUBMITTER: Gupta A

PROVIDER: S-EPMC3316623 | biostudies-literature | 2012

REPOSITORIES: biostudies-literature

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Tuberculosis incidence rates during 8 years of follow-up of an antiretroviral treatment cohort in South Africa: comparison with rates in the community.

Gupta Ankur A Wood Robin R Kaplan Richard R Bekker Linda-Gail LG Lawn Stephen D SD

PloS one 20120330 3

<h4>Background</h4>Although antiretroviral therapy (ART) is known to be associated with time-dependent reductions in tuberculosis (TB) incidence, the long-term impact of ART on incidence remains imprecisely defined due to limited duration of follow-up and incomplete CD4 cell count recovery in existing studies. We determined TB incidence in a South African ART cohort with up to 8 years of follow-up and stratified rates according to CD4 cell count recovery. We compared these rates with those of HI ...[more]

PMID: 22479548

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Project description:Background:Hypertension, with a prevalence of 25.6% is a serious public health concern in Iran. Objective:To investigate the population-based incidence of hypertension and its potential risk factors in Tehranian adults during a median follow-up of 13.1 years. Methods:A total of 6,533 non-hypertensive participants (women = 3,639), aged ?20 years participated in the study. Crude and age-standardized incidence rates per 1000 person-years were calculated for each sex, separately. Multivariable Cox proportional hazard models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CI) for all potential risk factors. Results:The crude and age-standardized incidence rates (95% CI) of hypertension per 1000 person-years were 29.7 (27.8-31.6) and 34.9 (32.5-37.4) among men and 25.8 (24.3-27.3) and 38.7 (35.5-42.0) among women, respectively. The incidence rate of hypertension in younger age groups was higher among men. However, after the 4th decade, the incidence rate was higher among women. Significant interactions of sex with age groups, body mass index categories, marital status, hypertriglyceridemia and glycemic categories were found in multivariable analyses (all p-values < 0.05). In the multivariable model, the risk in both sexes was found to be significantly associated with older age, obesity, and normal or high normal blood pressure (BP). Moreover, factors such as being overweight [HR: 1.20 (1.00-1.44)], former smoking [2.15 (1.52-3.04)], hypertriglyceridemia [1.23 (1.06-1.43)] and pre-diabetes status [1.19 (1.02-1.39)] were significant predictors of incident hypertension among women. Central obesity was found to be a significant predictor among men [1.26 (1.03-1.54)]. The optimism-corrected Harrell's C index (95% CI) in the categorical adjusted model was 0.75 (0.74-0.79) among men and 0.75 (0.74-0.76) among women. Conclusion:In the Tehranian population, nearly 2.7% of total participants (3% of men and 2.6% of women) develop hypertension each year. Obesity and high BP levels are the main modifiable risk factors in both sexes. Hypertriglyceridemia, prediabetes and former smoking are risk factors for hypertension among women.

Project description:BackgroundRising resistance of HIV-1 to non-nucleoside reverse transcriptase inhibitors (NNRTIs) threatens the success of the global scale-up of antiretroviral therapy (ART). The switch to WHO-recommended dolutegravir (DTG)-based regimens could reduce this threat due to DTG's high genetic barrier to resistance. We used mathematical modeling to predict the impact of the scale-up of DTG-based ART on NNRTI pretreatment drug resistance (PDR) in South Africa, 2020 to 2040.Methods and findingsWe adapted the Modeling Antiretroviral drug Resistance In South Africa (MARISA) model, an epidemiological model of the transmission of NNRTI resistance in South Africa. We modeled the introduction of DTG in 2020 under 2 scenarios: DTG as first-line regimen for ART initiators, or DTG for all patients, including patients on suppressive NNRTI-based ART. Given the safety concerns related to DTG during pregnancy, we assessed the impact of prescribing DTG to all men and in addition to (1) women beyond reproductive age; (2) women beyond reproductive age or using contraception; and (3) all women. The model projections show that, compared to the continuation of NNRTI-based ART, introducing DTG would lead to a reduction in NNRTI PDR in all scenarios if ART initiators are started on a DTG-based regimen, and those on NNRTI-based regimens are rapidly switched to DTG. NNRTI PDR would continue to increase if DTG-based ART was restricted to men. When given to all men and women, DTG-based ART could reduce the level of NNRTI PDR from 52.4% (without DTG) to 10.4% (with universal DTG) in 2040. If only men and women beyond reproductive age or on contraception are started on or switched to DTG-based ART, NNRTI PDR would reach 25.9% in 2040. Limitations include substantial uncertainty due to the long-term predictions and the current scarcity of knowledge about DTG efficacy in South Africa.ConclusionsOur model shows the potential benefit of scaling up DTG-based regimens for halting the rise of NNRTI resistance. Starting or switching all men and women to DTG would lead to a sustained decline in resistance levels, whereas using DTG-based ART in all men, or in men and women beyond childbearing age, would only slow down the increase in levels of NNRTI PDR.

Dataset Information

Tuberculosis incidence rates during 8 years of follow-up of an antiretroviral treatment cohort in South Africa: comparison with rates in the community.

Publications

Tuberculosis incidence rates during 8 years of follow-up of an antiretroviral treatment cohort in South Africa: comparison with rates in the community.

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