Dataset Information

Impact of ART on TB case fatality stratified by CD4 count for HIV-positive TB patients in Cape Town, South Africa (2009-2011).

ABSTRACT: OBJECTIVE:To identify determinants of tuberculosis (TB) case fatality including the impact of antiretroviral therapy (ART) at different CD4 thresholds for HIV-positive adult and adolescent TB patients. METHODS:Through a retrospective analysis of the electronic TB database, we identified the HIV status of newly registered patients aged ?15 years. Multivariable Cox proportional hazard models were used to determine the risk factors for TB case fatality in these patients. RESULTS:In 2009, 2010, and 2011, 25,841, 26,104, and 25,554 newly registered adult TB patients were treated in primary health care clinics in Cape Town, of whom 49.7%, 50.4%, and 50.9% were HIV positive. ART uptake increased over 3 years from 43% to 64.9%, and case fatality of the HIV-positive patients decreased from 7.0% to 5.8% (P < 0.001). Female gender, increasing age, retreatment TB, low CD4 counts, and extrapulmonary TB were associated with increased case fatality, whereas patients on ART had a substantial decrease in case fatality. The difference in case fatality between patients on ART and not on ART was most pronounced at low CD4 counts with the positive influence of ART noted up to a CD4 count threshold of 350 cells per cubic millimeter (P < 0.001). Despite improvements in ART uptake, in 2011, 21% of the patients with CD4 counts <350 cells per cubic millimeter did not start ART during TB treatment. CONCLUSION:This study showed a relatively poor uptake of ART among severely immune-compromised TB patients. Patients with CD4 counts <350 cells per cubic millimeter were shown to clearly benefit from ART during TB treatment, and ART initiation should be prioritized for this category of patients.

SUBMITTER: Kaplan R

PROVIDER: S-EPMC4161924 | biostudies-literature | 2014 Aug

REPOSITORIES: biostudies-literature

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Impact of ART on TB case fatality stratified by CD4 count for HIV-positive TB patients in Cape Town, South Africa (2009-2011).

Kaplan Richard R Caldwell Judy J Middelkoop Keren K Bekker Linda-Gail LG Wood Robin R

Journal of acquired immune deficiency syndromes (1999) 20140801 5

<h4>Objective</h4>To identify determinants of tuberculosis (TB) case fatality including the impact of antiretroviral therapy (ART) at different CD4 thresholds for HIV-positive adult and adolescent TB patients.<h4>Methods</h4>Through a retrospective analysis of the electronic TB database, we identified the HIV status of newly registered patients aged ≥15 years. Multivariable Cox proportional hazard models were used to determine the risk factors for TB case fatality in these patients.<h4>Results</ ...[more]

PMID: 24820105

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Project description:In Cape Town, the roll-out of antiretroviral therapy (ART) has increased over the last decade with an estimated coverage of 63% of HIV- positive patients in 2013. The influence of ART on the characteristics of the population of HIV-positive patients presenting to the primary care TB programme is unknown. In this study, we examined trends in CD4 count distribution, ART usage and treatment outcomes among HIV-positive TB patients in Cape Town from 2009 to 2013.Data from the electronic TB register on all newly registered drug-sensitive TB patients ?18 years were analyzed retrospectively. Descriptive statistics were used to compare baseline characteristics, the CD4 count distribution and TB treatment outcomes both by year of treatment and ART status at the start of TB treatment. Survival analyses were used to assess the change in mortality risk during TB treatment over time, stratified by ART status at start of TB treatment.118,989 patients were treated over 5 years. HIV prevalence among TB patients decreased from 50.9% in 2009 to 49.0% in 2013. The absolute number of HIV-positive TB cases declined by 13.2% between 2010 and 2013. More patients entered the TB programme on ART in 2013 compared to 2009 (30.0% vs 9.9%). Among these, the CD4 count distribution showed a year by year shift to higher CD4 counts. In 2013, over 75% of ART-naïve TB patients still had a CD4 count <?350 cells/mm3. ART initiation among ART-naive patients increased from 37.0 to 77.7% and TB case fatality declined from 7.4 to 5.2% (p?<?0.001). In multivariate analysis a decrease in TB mortality was most strongly associated with CD4 count (Adjusted HR 0.82 per increase of 50 cells/mm3, 95% CI: 0.81-0.83, p?<?001) and the initiation of ART during TB treatment (Adjusted HR 0.39, 95% CI: 0.35-0.42, p?<?0.001).Comprehensive changes in the ART and TB treatment programmes resulted in incremental increases in ART coverage for HIV-positive TB patients and a subsequent decrease in TB case fatality due to increased ART uptake in HIV-positive ART-naïve patients. However TB still remained a major presenting opportunistic infection with the majority of cases occurring at low CD4 counts.

Project description:IntroductionAlthough antiretroviral therapy (ART) reduces individual tuberculosis (TB) risk by two-thirds, the population-level impact remains uncertain. Cape Town reports high TB notification rates associated with endemic HIV. We examined population trends in TB notification rates during a 10-year period of expanding ART.MethodsAnnual Cape Town TB notifications were used as numerators and mid-year Cape Town populations as denominators. HIV-stratified population was calculated using overall HIV prevalence estimates from the Actuarial Society of South Africa AIDS and Demographic model. ART provision numbers from Western Cape government reports were used to calculate overall ART coverage. We calculated rates per 100,000 population over time, overall and stratified by HIV status. Rates per 100,000 total population were also calculated by ART use at treatment initiation. Absolute numbers of notifications were compared by age and sub-district. Changes over time were described related to ART provision in the city as a whole (ART coverage) and by sub-district (numbers on ART).ResultsFrom 2003 to 2013, Cape Town's population grew from 3.1 to 3.7 million inhabitants, and estimated HIV prevalence increased from 3.6 to 5.2%. ART coverage increased from 0 to 63% in 2013. TB notification rates declined by 16% (95% confidence interval (CI), 14-17%) from a 2008 peak (851/100,000) to a 2013 nadir (713/100,000). Decreases were higher among the HIV-positive (21% (95% CI, 19-23%)) than the HIV-negative (9% (95% CI, 7-11%)) population. The number of HIV-positive TB notifications decreased mainly among 0- to 4- and 20- to 34-year-olds. Total population rates on ART at TB treatment initiation increased over time but levelled off in 2013. Overall median CD4 counts increased from 146 cells/µl (interquartile range (IQR), 66, 264) to 178 cells/µl (IQR 75, 330; p<0.001). Sub-district antenatal HIV seroprevalence differed (10-33%) as did numbers on ART (9-29 thousand). Across sub-districts, infant HIV-positive TB decreased consistently whereas adult decreases varied.ConclusionsHIV-positive TB notification rates declined during a period of rapid scale-up of ART. Nevertheless, both HIV-positive and HIV-negative TB notification rates remained very high. Decreases among HIV positives were likely blunted by TB remaining a major entry to the ART programme and occurring after delayed ART initiation.

Project description:Traditional modes of investigating influenza nosocomial transmission have entailed a combination of confirmatory molecular diagnostic testing and epidemiological investigation. Common hospital-acquired infections like influenza require a discerning ability to distinguish between viral isolates to accurately identify patient transmission chains. We assessed whether influenza hemagglutinin sequence phylogenies can be used to enrich epidemiological data when investigating the extent of nosocomial transmission over a four-month period within a paediatric Hospital in Cape Town South Africa. Possible transmission chains/channels were initially determined through basic patient admission data combined with Maximum likelihood and time-scaled Bayesian phylogenetic analyses. These analyses suggested that most instances of potential hospital-acquired infections resulted from multiple introductions of Influenza A into the hospital, which included instances where virus hemagglutinin sequences were identical between different patients. Furthermore, a general inability to establish epidemiological transmission linkage of patients/viral isolates implied that identified isolates could have originated from asymptomatic hospital patients, visitors or hospital staff. In contrast, a traditional epidemiological investigation that used no viral phylogenetic analyses, based on patient co-admission into specific wards during a particular time-frame, suggested that multiple hospital acquired infection instances may have stemmed from a limited number of identifiable index viral isolates/patients. This traditional epidemiological analysis by itself could incorrectly suggest linkage between unrelated cases, underestimate the number of unique infections and may overlook the possible diffuse nature of hospital transmission, which was suggested by sequencing data to be caused by multiple unique introductions of influenza A isolates into individual hospital wards. We have demonstrated a functional role for viral sequence data in nosocomial transmission investigation through its ability to enrich traditional, non-molecular observational epidemiological investigation by teasing out possible transmission pathways and working toward more accurately enumerating the number of possible transmission events.

Project description:BackgroundWith an increasing number of countries implementing Option B+ guidelines of lifelong antiretroviral therapy (ART) for all pregnant and breastfeeding women, there is urgent need to identify effective approaches for retaining this growing and highly vulnerable population in ART care.MethodsNewly postpartum, breastfeeding women who initiated ART in pregnancy and met eligibility criteria were enrolled, and offered the choice of two options for postpartum ART care: (i) referral to existing network of community-based adherence clubs or (ii) referral to local primary health care clinic (PHC). Women were followed at study measurement visits conducted separately from either service. Primary outcome was a composite endpoint of retention in ART services and viral suppression [VS < 50 copies/mL based on viral load (VL) testing at measurement visits] at 12 months postpartum. Outcomes were compared across postpartum services using chi-square, Fisher's exact tests and Poisson regression models. The primary outcome was compared across services where women were receiving care at 12 months postpartum in exploratory analyses.ResultsBetween February and September 2015, 129 women (median age: 28.9 years; median time postpartum: 10 days) were enrolled with 65% opting to receive postpartum HIV care through an adherence club. Among 110 women retained at study measurement visits, 91 (83%) achieved the composite endpoint, with no difference between those who originally chose clubs versus those who chose PHC services. Movement from an adherence club to PHC services was common: 31% of women who originally chose clubs and were engaged in care at 12 months postpartum were attending a PHC service. Further, levels of VS differed significantly by where women were accessing ART care at 12 months postpartum, regardless of initial choice: 98% of women receiving care in an adherence club and 76% receiving care at PHC had VS < 50 copies/mL at 12 months postpartum (p = 0.001).ConclusionThis study found comparable outcomes related to retention and VS at 12 months postpartum between women choosing adherence clubs and those choosing PHC. However, movement between postpartum services among those who originally chose adherence clubs was common, with poorer VS outcomes among women leaving clubs and returning to PHC services.Trial registrationClinicalTrials.gov NCT02417675 , April 16, 2015 (retrospectively registered).

Dataset Information

Impact of ART on TB case fatality stratified by CD4 count for HIV-positive TB patients in Cape Town, South Africa (2009-2011).

Publications

Impact of ART on TB case fatality stratified by CD4 count for HIV-positive TB patients in Cape Town, South Africa (2009-2011).

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