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Risk factors for early mortality on antiretroviral therapy in advanced HIV-infected adults.

ABSTRACT: BACKGROUND:Many HIV-infected individuals present with advanced HIV disease. These patients are at high risk of death after antiretroviral therapy (ART) initiation, but risk factors for death in these patients are unclear. METHODS:We used data from a multisite randomized trial comparing empiric vs. preventive tuberculosis therapy in HIV-infected adults initiating ART with CD4 T-cell counts less than 50 cells/?l to evaluate risk factors for death within 48 weeks after ART initiation. Cox proportional hazards models were fit to evaluate characteristics present at baseline and at 4 weeks after ART initiation, including the week 4 CD4 T-cell response and new opportunistic infections. RESULTS:Of 850 enrolled, the median pre-ART CD4 T-cell count was 18 cells/?l and 67 (7.9%) died. Baseline risk factors for death included lymphadenopathy, lower CD4 T-cell count, lower serum albumin, high white blood cell count, elevated neutrophil percentage, and lower hemoglobin. Among 746 participants with data at week 4, the median changes in CD4 T-cell count and viral load for those who died (n?=?43) vs. survived were 26 vs. 56 cells/?l and -2.7 vs. -2.7?log10 copies/ml, respectively. Each 20 cell/?l lower change in week 4 CD4 T-cell count was associated with a 20% increased risk of post week-4 mortality (adjusted hazard ratio 1.20, 1.01-1.42, P?=?.038). CONCLUSION:Evidence of active infection and suboptimal immunologic response during the first month of ART are associated with death in the first year after ART initiation in those with advanced HIV disease taking tuberculosis preventive therapy. Strategies to reduce early mortality in this population warrant further investigation.

SUBMITTER: Bisson GP

PROVIDER: S-EPMC5633516 | biostudies-literature | 2017 Oct

REPOSITORIES: biostudies-literature

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Risk factors for early mortality on antiretroviral therapy in advanced HIV-infected adults.

Bisson Gregory P GP Ramchandani Ritesh R Miyahara Sachiko S Mngqibisa Rosie R Matoga Mitch M Ngongondo McNeil M Samaneka Wadzanai W Koech Lucy L Naidoo Kogieleum K Rassool Mohammed M Kirui Fredrick F Banda Peter P Mave Vidya V Kadam Dileep D Leger Paul P Henestroza German G Manabe Yukari C YC Bao Jing J Kumwenda Johnstone J Gupta Amita A Hosseinipour Mina C MC

AIDS (London, England) 20171001 16

<h4>Background</h4>Many HIV-infected individuals present with advanced HIV disease. These patients are at high risk of death after antiretroviral therapy (ART) initiation, but risk factors for death in these patients are unclear.<h4>Methods</h4>We used data from a multisite randomized trial comparing empiric vs. preventive tuberculosis therapy in HIV-infected adults initiating ART with CD4 T-cell counts less than 50 cells/μl to evaluate risk factors for death within 48 weeks after ART initiation ...[more]

PMID: 28742529

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Project description:BackgroundA decline in mortality rates during the first 12 months of antiretroviral therapy (ART) has been mainly linked to increased ART initiation at higher CD4 counts and at less advanced World Health Organization (WHO) clinical stages of HIV infection; however, the role of improved patient care has not been well studied. We estimated improvements in early mortality due to improved patient care.MethodsWe conducted a retrospective cohort study of HIV-infected individuals ages 18 and older who initiated ART at the Mengo HIV Counseling and Home Care Clinic between 2006 and 2016. We conducted a mediation analysis using generalized structural equation models with inverse odds ratio weighting to estimate the natural direct and indirect effects of ART initiation time on early mortality.FindingsAmong 6,847 patients, most were female (69%), with a median age of 32 (interquartile range [IQR] = 28-38), versus a median age of 38 (IQR = 32-45) for males. The median CD4 count at ART initiation increased from 142 cells/ul (95% confidence interval [CI] = 135-150) in 2006-2010 to 302 cells/ul (95% CI = 283-323) in 2015-2016 (p < 0·001). The number of patients at WHO clinical stages I/II increased from 52% in 2006-2010 to 78% in 2015-2016 (p < 0·001). Annual early mortality decreased from 8·8 deaths/100 person years (PYS) in 2006 to 2.5 deaths/100 pys in 2016 (p < 0·001). Mediation by CD4 counts and WHO clinical stages accounted for 54% of the total effect of ART initiation timing on early mortality. In comparison, 46% remained as the direct effect, reflecting the contribution of improved patient care.InterpretationImproved patient care practices should be promoted as a strategy for reducing early mortality after ART initiation, above and beyond the effects from ART initiation at higher CD4 counts and less advanced WHO clinical stage alone.FundingThis research was supported by the President's Emergency Plan for AIDS Relief (PEPFAR), the National Institute of Allergy and Infectious Diseases Division of Intramural Research, and the National Cancer Institute.

Project description:BackgroundIn countries with a high seroprevalence of human immunodeficiency virus type 1 (HIV-1), HIV infection contributes significantly to infant mortality. We investigated antiretroviral-treatment strategies in the Children with HIV Early Antiretroviral Therapy (CHER) trial.MethodsHIV-infected infants 6 to 12 weeks of age with a CD4 lymphocyte percentage (the CD4 percentage) of 25% or more were randomly assigned to receive antiretroviral therapy (lopinavir-ritonavir, zidovudine, and lamivudine) when the CD4 percentage decreased to less than 20% (or 25% if the child was younger than 1 year) or clinical criteria were met (the deferred antiretroviral-therapy group) or to immediate initiation of limited antiretroviral therapy until 1 year of age or 2 years of age (the early antiretroviral-therapy groups). We report the early outcomes for infants who received deferred antiretroviral therapy as compared with early antiretroviral therapy.ResultsAt a median age of 7.4 weeks (interquartile range, 6.6 to 8.9) and a CD4 percentage of 35.2% (interquartile range, 29.1 to 41.2), 125 infants were randomly assigned to receive deferred therapy, and 252 infants were randomly assigned to receive early therapy. After a median follow-up of 40 weeks (interquartile range, 24 to 58), antiretroviral therapy was initiated in 66% of infants in the deferred-therapy group. Twenty infants in the deferred-therapy group (16%) died versus 10 infants in the early-therapy groups (4%) (hazard ratio for death, 0.24; 95% confidence interval [CI], 0.11 to 0.51; P<0.001). In 32 infants in the deferred-therapy group (26%) versus 16 infants in the early-therapy groups (6%), disease progressed to Centers for Disease Control and Prevention stage C or severe stage B (hazard ratio for disease progression, 0.25; 95% CI, 0.15 to 0.41; P<0.001). Stavudine was substituted for zidovudine in four infants in the early-therapy groups because of neutropenia in three infants and anemia in one infant; no drugs were permanently discontinued. After a review by the data and safety monitoring board, the deferred-therapy group was modified, and infants in this group were all reassessed for initiation of antiretroviral therapy.ConclusionsEarly HIV diagnosis and early antiretroviral therapy reduced early infant mortality by 76% and HIV progression by 75%. (ClinicalTrials.gov number, NCT00102960.)

Project description:For adults with human immunodeficiency virus (HIV) infection who have CD4+ T-cell counts that are greater than 200 and less than 350 per cubic millimeter and who live in areas with limited resources, the optimal time to initiate antiretroviral therapy remains uncertain.We conducted a randomized, open-label trial of early initiation of antiretroviral therapy, as compared with the standard timing for initiation of therapy, among HIV-infected adults in Haiti who had a confirmed CD4+ T-cell count that was greater than 200 and less than 350 per cubic millimeter at baseline and no history of an acquired immunodeficiency syndrome (AIDS) illness. The primary study end point was survival. The early-treatment group began taking zidovudine, lamivudine, and efavirenz therapy within 2 weeks after enrollment. The standard-treatment group started the same regimen of antiretroviral therapy when their CD4+ T-cell count fell to 200 per cubic millimeter or less or when clinical AIDS developed. Participants in both groups underwent monthly follow-up assessments and received isoniazid and trimethoprim-sulfamethoxazole prophylaxis with nutritional support.Between 2005 and 2008, a total of 816 participants--408 per group--were enrolled and were followed for a median of 21 months. The CD4+ T-cell count at enrollment was approximately 280 per cubic millimeter in both groups. There were 23 deaths in the standard-treatment group, as compared with 6 in the early-treatment group (hazard ratio with standard treatment, 4.0; 95% confidence interval [CI], 1.6 to 9.8; P=0.001). There were 36 incident cases of tuberculosis in the standard-treatment group, as compared with 18 in the early-treatment group (hazard ratio, 2.0; 95% CI, 1.2 to 3.6; P=0.01).Early initiation of antiretroviral therapy decreased the rates of death and incident tuberculosis. Access to antiretroviral therapy should be expanded to include all HIV-infected adults who have CD4+ T-cell counts of less than 350 per cubic millimeter, including those who live in areas with limited resources. (ClinicalTrials.gov number, NCT00120510.)

Project description:BACKGROUND:Identifying characteristics of HIV-infected adults likely to have poor treatment outcomes can be useful for targeting interventions efficiently. Research in economics and psychology suggests that individuals' intertemporal time preferences, which indicate the extent to which they trade-off immediate vs. future cost and benefits, can influence various health behaviors. While there is empirical support for the association between time preferences and various non-HIV health behaviors and outcomes, the extent to which time preferences predict outcomes of those receiving antiretroviral therapy (ART) has not been examined previously. METHODS:HIV-infected adults initiating ART were enrolled at a health facility in Kenya. Participants' time preferences were measured at enrollment and used to classify them as having either a low or high discount rate for future benefits. At 48 weeks, we assessed mortality and ART adherence, as measured by Medication Event Monitoring System (MEMS). Logistic regression models adjusting for socio-economic characteristics and risk factors were used to determine the association between time preferences and mortality as well as MEMS adherence ?90%. RESULTS:Overall, 44% (96/220) of participants were classified as having high discount rates. Participants with high discount rates had significantly higher 48-week mortality than participants with low discount rates (9.3% vs. 3.1%; adjusted odds ratio 3.84; 95% CI 1.03, 14.50). MEMS adherence ?90% was similar for participants with high vs. low discount rates (42.3% vs. 49.6%, AOR 0.70; 95% CI 0.40, 1.25). CONCLUSION:High discount rates were associated with significantly higher risk of mortality among HIV-infected patients initiating ART. Greater use of time preference measures may improve identification of patients at risk of poor clinical outcomes. More research is needed to further identify mechanisms of action and also to build upon and test the generalizability of this finding.

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Risk factors for early mortality on antiretroviral therapy in advanced HIV-infected adults.

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Risk factors for early mortality on antiretroviral therapy in advanced HIV-infected adults.

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