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Effects of time of initiation of antiretroviral therapy in the treatment of patients with HIV/TB co-infection: A systemic review and meta-analysis.

ABSTRACT: This systemic review and meta-analysis aimed to investigate the burden of tuberculosis immune reconstitution syndrome (TB-IRIS) and associated mortality to highlight the importance of future direction in preventing and treatment of TB-IRIS. Randomized clinical trials (RCTs) that compared early antiretroviral therapy (ART) versus late ART were included. PubMed, EMBASE, Science Direct and Cochrane Central Register of Controlled Trials electronic databases were searched. This meta-analysis included 8 RCTs with a total of 4, 425 participants. The result of analysis showed that early initiation of ART was associated with increase in TB-IRIS (RR = 1.83; 95% CI: 1.24-2.70, p = 0.002; I2 = 74%, p = 0.0007) and TB-IRIS associated mortality (RR = 6.05; 95% CI: 1.06-34.59, p = 0.04; I2 = 0%, p = 0.78). Early ART was associated with overall mortality compared with late ART initiation. Grade 3 or 4 adverse events, achieving lower viral load and development of new AIDS-defining illness were not associated with the time of ART initiation. Early ART in HIV/TB co-infected patients resulted conclusive evidence of increased TB-IRIS incidence and TB-IRIS associated mortality. Hence, the finding calls for clinical judgment as to the benefits of initiating ART earlier against the risk of TB-IRIS and associated mortality.

SUBMITTER: Chelkeba L

PROVIDER: S-EPMC7251303 | biostudies-literature | 2020 Jul

REPOSITORIES: biostudies-literature

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Effects of time of initiation of antiretroviral therapy in the treatment of patients with HIV/TB co-infection: A systemic review and meta-analysis.

Chelkeba Legese L Fekadu Ginenus G Tesfaye Gurmu G Belayneh Firehiwot F Melaku Tsegaye T Mekonnen Zeleke Z

Annals of medicine and surgery (2012) 20200516

This systemic review and meta-analysis aimed to investigate the burden of tuberculosis immune reconstitution syndrome (TB-IRIS) and associated mortality to highlight the importance of future direction in preventing and treatment of TB-IRIS. Randomized clinical trials (RCTs) that compared early antiretroviral therapy (ART) versus late ART were included. PubMed, EMBASE, Science Direct and Cochrane Central Register of Controlled Trials electronic databases were searched. This meta-analysis included ...[more]

PMID: 32477514

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Project description:BACKGROUND:Data from randomized trials are lacking on the benefits and risks of initiating antiretroviral therapy in patients with asymptomatic human immunodeficiency virus (HIV) infection who have a CD4+ count of more than 350 cells per cubic millimeter. METHODS:We randomly assigned HIV-positive adults who had a CD4+ count of more than 500 cells per cubic millimeter to start antiretroviral therapy immediately (immediate-initiation group) or to defer it until the CD4+ count decreased to 350 cells per cubic millimeter or until the development of the acquired immunodeficiency syndrome (AIDS) or another condition that dictated the use of antiretroviral therapy (deferred-initiation group). The primary composite end point was any serious AIDS-related event, serious non-AIDS-related event, or death from any cause. RESULTS:A total of 4685 patients were followed for a mean of 3.0 years. At study entry, the median HIV viral load was 12,759 copies per milliliter, and the median CD4+ count was 651 cells per cubic millimeter. On May 15, 2015, on the basis of an interim analysis, the data and safety monitoring board determined that the study question had been answered and recommended that patients in the deferred-initiation group be offered antiretroviral therapy. The primary end point occurred in 42 patients in the immediate-initiation group (1.8%; 0.60 events per 100 person-years), as compared with 96 patients in the deferred-initiation group (4.1%; 1.38 events per 100 person-years), for a hazard ratio of 0.43 (95% confidence interval [CI], 0.30 to 0.62; P<0.001). Hazard ratios for serious AIDS-related and serious non-AIDS-related events were 0.28 (95% CI, 0.15 to 0.50; P<0.001) and 0.61 (95% CI, 0.38 to 0.97; P=0.04), respectively. More than two thirds of the primary end points (68%) occurred in patients with a CD4+ count of more than 500 cells per cubic millimeter. The risks of a grade 4 event were similar in the two groups, as were the risks of unscheduled hospital admissions. CONCLUSIONS:The initiation of antiretroviral therapy in HIV-positive adults with a CD4+ count of more than 500 cells per cubic millimeter provided net benefits over starting such therapy in patients after the CD4+ count had declined to 350 cells per cubic millimeter. (Funded by the National Institute of Allergy and Infectious Diseases and others; START ClinicalTrials.gov number, NCT00867048.).

Project description:BACKGROUND:Studies have shown that early ART initiation in TB/HIV co-infected patients lowers mortality. One way to implement earlier ART commencement could be through integration of TB and HIV services, a more efficient model of care than separate, vertical programs. We present a model of full TB/HIV integration and estimate its effect on time to initiation of ART. METHODOLOGY/PRINCIPAL FINDINGS:We retrospectively reviewed TB registers and clinical notes of 209 TB/HIV co-infected adults with a CD4 count <250 cells/µl and registered for TB treatment at one primary care clinic in a South African township between June 2008 and May 2009. Using Kaplan-Meier and Cox proportional hazard analysis, we compared time between initiation of TB treatment and ART for the periods before and after full, "one-stop shop" integration of TB and HIV services (in December 2009). Potential confounders were determined a priori through directed acyclic graphs. Robustness of assumptions was investigated by sensitivity analyses. The analysis included 188 patients (100 pre- and 88 post-integration), yielding 56 person-years of observation. Baseline characteristics of the two groups were similar. Median time to ART initiation decreased from 147 days (95% confidence interval [CI] 85-188) before integration of services to 75 days (95% CI 52-119) post-integration. In adjusted analyses, patients attending the clinic post-integration were 1.60 times (95% CI 1.11-2.29) more likely to have started ART relative to the pre-integration period. Sensitivity analyses supported these findings. CONCLUSIONS/SIGNIFICANCE:Full TB/HIV care integration is feasible and led to a 60% increased chance of co-infected patients starting ART, while reducing time to ART initiation by an average of 72 days. Although these estimates should be confirmed through larger studies, they suggest that scale-up of full TB/HIV service integration in high TB/HIV prevalence settings may shorten time to ART initiation, which might reduce excess mortality and morbidity.

Project description:BackgroundFor people with HIV and CD4+ counts >500 cells/mm3, early initiation of antiretroviral therapy (ART) reduces serious AIDS and serious non-AIDS (SNA) risk compared with deferral of treatment until CD4+ counts are <350 cells/mm3. Whether excess risk of AIDS and SNA persists once ART is initiated for those who defer treatment is uncertain.MethodsThe Strategic Timing of AntiRetroviral Treatment (START) trial, as previously reported, randomly assigned 4684 ART-naive HIV-positive adults with CD4+ counts .500 cells/mm3 to immediate treatment initiation after random assignment (n = 2325) or deferred treatment (n= 2359). In 2015, a 57% lower risk of the primary end point (AIDS, SNA, or death) for the immediate group was reported, and the deferred group was offered ART. This article reports the follow-up that continued to December 31, 2021. Cox proportional-hazards models were used to compare hazard ratios for the primary end point from randomization through December 31, 2015, versus January 1, 2016, through December 31, 2021.ResultsThrough December 31, 2015, approximately 7 months after the cutoff date from the previous report, the median CD4+ count was 648 and 460 cells/mm3 in the immediate and deferred groups, respectively, at treatment initiation. The percentage of follow-up time spent taking ART was 95% and 36% for the immediate and deferred groups, respectively, and the time-averaged CD4+ difference was 199 cells/mm3. After January 1, 2016, the percentage of follow-up time on treatment was 97.2% and 94.1% for the immediate and deferred groups, respectively, and the CD4+ count difference was 155 cells/mm3. After January 1, 2016, a total of 89 immediate and 113 deferred group participants experienced a primary end point (hazard ratio of 0.79 [95% confidence interval, 0.60 to 1.04] versus hazard ratio of 0.47 [95% confidence interval, 0.34 to 0.65; P<0.001]) before 2016 (P=0.02 for hazard ratio difference).ConclusionsAmong adults with CD4+ counts >500 cells/mm3, excess risk of AIDS and SNA associated with delaying treatment initiation was diminished after ART initiation, but persistent excess risk remained. (Funded by the National Institute of Allergy and Infectious Diseases and others.).

Project description:BackgroundSwaziland has the highest adult HIV prevalence and second highest rate of TB/HIV coinfection globally. Recently, the Ministry of Health and partners have increased integration and co-location of TB/HIV services, but the timing of antiretroviral therapy (ART) relative to TB treatment-a marker of program quality and predictor of outcomes-is unknown.MethodsWe conducted a retrospective analysis of programmatic data from 11 purposefully-sampled facilities to evaluate timely ART provision for HIV-positive TB patients enrolled on TB treatment between July-November 2014. Timely ART was defined as within two weeks of TB treatment initiation for patients with CD4<50/μL or missing, and within eight weeks otherwise. Descriptive statistics were estimated and logistic regression used to assess factors independently associated with timely ART.ResultsOf 466 HIV-positive TB patients, 51.5% were male, median age was 35 (interquartile range [IQR]: 29-42), and median CD4 was 137/μL (IQR: 58-268). 189 (40.6%) were on ART prior to, and five (1.8%) did not receive ART within six months of TB treatment initiation. Median time to ART after TB treatment initiation was 15 days (IQR: 14-28). Almost 90% started ART within eight weeks, and 45.5% of those with CD4<50/μL started within two weeks. Using thresholds for "timely ART" according to baseline CD4 count, 73.3% of patients overall received timely ART after TB treatment initiation. Patients with CD4 50-200/μL or ≥200/μL had significantly higher odds of timely ART than patients with CD4<50/μL, with adjusted odds ratios of 11.5 (95% confidence interval [CI]: 5.0-26.6) and 9.6 (95% CI: 4.6-19.9), respectively. TB cure or treatment completion was achieved by 71.1% of patients at six months, but this was not associated with timely ART.ConclusionsThis study demonstrates the relative success of integrated and co-located TB/HIV services in Swaziland, and shows that timely ART uptake for HIV-positive TB patients can be achieved in resource-limited, but integrated settings. Gaps remain in getting patients with CD4<50/μL to receive ART within the recommended two weeks post TB treatment initiation.

Dataset Information

Effects of time of initiation of antiretroviral therapy in the treatment of patients with HIV/TB co-infection: A systemic review and meta-analysis.

Publications

Effects of time of initiation of antiretroviral therapy in the treatment of patients with HIV/TB co-infection: A systemic review and meta-analysis.

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