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Analysis of the Impact of Antiretroviral Drug Changes on Survival of Patients with Advanced-Stage AIDS with Multidrug-Resistant HIV Infection.

ABSTRACT: OBJECTIVES:This article aims to elucidate the relationship between antiretroviral (ARV) medication changes and all-cause mortality using a total of 368 patients recruited from the United States (78%), United Kingdom (11%), and Canada (11%). METHODS:Data sources included demographic characteristics, ARV treatment history and modifications, and clinical biomarker data from the completed OPTions In Management with Antiretrovirals clinical trial. Descriptive analysis and graphical trajectory representation of ARV drug modifications and biomarker changes were undertaken. Three hypotheses aimed at assessing the impact of ARV modification parameters on clinical outcomes were tested. Kaplan-Meier survival techniques as well as Cox proportional hazard regression models were employed. RESULTS:Results from the analyses suggest that (1) switching therapy strategy from an intensified ARV regimen to a less intense one or vice versa, (2) having a moderate number (up to 2) of ARV drug changes per 6 months, and (3) changes based on clinical/HIV-related reasons or nonclinical reasons compared to ARV drug regimen changes due to clinical non-HIV reasons improved survival. CONCLUSION:Modifications in the ARV regimens of HIV-infected patients with multidrug resistance are associated with improved survival.

SUBMITTER: Ma R

PROVIDER: S-EPMC6748500 | biostudies-literature | 2019 Jan-Dec

REPOSITORIES: biostudies-literature

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Analysis of the Impact of Antiretroviral Drug Changes on Survival of Patients with Advanced-Stage AIDS with Multidrug-Resistant HIV Infection.

Ma Rui R Jung Tae Hyun TH Peduzzi Peter N PN Brown Sheldon T ST Kyriakides Tassos C TC

Journal of the International Association of Providers of AIDS Care 20190101

<h4>Objectives</h4>This article aims to elucidate the relationship between antiretroviral (ARV) medication changes and all-cause mortality using a total of 368 patients recruited from the United States (78%), United Kingdom (11%), and Canada (11%).<h4>Methods</h4>Data sources included demographic characteristics, ARV treatment history and modifications, and clinical biomarker data from the completed OPTions In Management with Antiretrovirals clinical trial. Descriptive analysis and graphical tra ...[more]

PMID: 31272313

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Project description:BackgroundHIV-infection is associated with increased mortality during multidrug-resistant tuberculosis treatment, but the extent to which the use of antiretroviral therapy (ART) and anti-tuberculosis medications modify this risk are unclear. Our objective was to evaluate how use of these treatments altered mortality risk in HIV-positive adults with multidrug-resistant tuberculosis.MethodsWe did an individual patient data meta-analysis of adults 18 years or older with confirmed or presumed multidrug-resistant tuberculosis initiating tuberculosis treatment between 1993 and 2016. Data included ART use and anti-tuberculosis medications grouped according to WHO effectiveness categories. The primary analysis compared HIV-positive with HIV-negative patients in terms of death during multidrug-resistant tuberculosis treatment, excluding those lost to follow up, and was stratified by ART use. Analyses used logistic regression after exact matching on country World Bank income classification and drug resistance and propensity-score matching on age, sex, geographic site, year of multidrug-resistant tuberculosis treatment initiation, previous tuberculosis treatment, directly observed therapy, and acid-fast-bacilli smear-positivity to obtain adjusted odds ratios (aORs) and 95% CIs. Secondary analyses were conducted among those with HIV-infection.FindingsWe included 11 920 multidrug-resistant tuberculosis patients. 2997 (25%) were HIV-positive and on ART, 886 (7%) were HIV-positive and not on ART, and 1749 (15%) had extensively drug-resistant tuberculosis. By use of HIV-negative patients as reference, the aOR of death was 2·4 (95% CI 2·0-2·9) for all patients with HIV-infection, 1·8 (1·5-2·2) for HIV-positive patients on ART, and 4·2 (3·0-5·9) for HIV-positive patients with no or unknown ART. Among patients with HIV, use of at least one WHO Group A drug and specific use of moxifloxacin, levofloxacin, bedaquiline, or linezolid were associated with significantly decreased odds of death.InterpretationUse of ART and more effective anti-tuberculosis drugs is associated with lower odds of death among HIV-positive patients with multidrug-resistant tuberculosis. Access to these therapies should be urgently pursued.FundingAmerican Thoracic Society, Canadian Institutes of Health Research, US Centers for Disease Control and Prevention, European Respiratory Society, Infectious Diseases Society of America.

Project description:BACKGROUND: Multidrug-resistant (MDR) and extensively drug-resistant (XDR) tuberculosis (TB) have emerged in high-HIV-prevalence settings, which generally lack laboratory infrastructure for diagnosing TB drug resistance. Even where available, inherent delays with current drug-susceptibility testing (DST) methods result in clinical deterioration and ongoing transmission of MDR and XDR-TB. Identifying clinical predictors of drug resistance may aid in risk stratification for earlier treatment and infection control. METHODS: We performed a retrospective case-control study of patients with MDR (cases), XDR (cases) and drug-susceptible (controls) TB in a high-HIV-prevalence setting in South Africa to identify clinical and demographic risk factors for drug-resistant TB. Controls were selected in a 1:1:1 ratio and were not matched. We calculated odds ratios (OR) and performed multivariate logistic regression to identify independent predictors. RESULTS: We enrolled 116, 123 and 139 patients with drug-susceptible, MDR, and XDR-TB. More than 85% in all three patient groups were HIV-infected. In multivariate analysis, MDR and XDR-TB were each strongly associated with history of TB treatment failure (adjusted OR 51.7 [CI 6.6-403.7] and 51.5 [CI 6.4-414.0], respectively) and hospitalization more than 14 days (aOR 3.8 [CI 1.1-13.3] and 6.1 [CI 1.8-21.0], respectively). Prior default from TB treatment was not a risk factor for MDR or XDR-TB. HIV was a risk factor for XDR (aOR 8.2, CI 1.3-52.6), but not MDR-TB. Comparing XDR with MDR-TB patients, the only significant risk factor for XDR-TB was HIV infection (aOR 5.3, CI 1.0-27.6). DISCUSSION: In this high-HIV-prevalence and drug-resistant TB setting, a history of prolonged hospitalization and previous TB treatment failure were strong risk factors for both MDR and XDR-TB. Given high mortality observed among patients with HIV and drug-resistant TB co-infection, previously treated and hospitalized patients should be considered for empiric second-line TB therapy while awaiting confirmatory DST results in settings with a high-burden of MDR/XDR-TB.

Dataset Information

Analysis of the Impact of Antiretroviral Drug Changes on Survival of Patients with Advanced-Stage AIDS with Multidrug-Resistant HIV Infection.

Publications

Analysis of the Impact of Antiretroviral Drug Changes on Survival of Patients with Advanced-Stage AIDS with Multidrug-Resistant HIV Infection.

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