Association of ongoing drug and alcohol use with non-adherence to antiretroviral therapy and higher risk of AIDS and death: results from ACTG 362

Drug and alcohol use have been associated with a worse prognosis in short-term and cross-sectional analyses of HIV-infected populations, but longitudinal effects on adherence to antiretroviral therapy (ART) and clinical outcomes in advanced AIDS are less well characterized. We assessed self-reported drug and alcohol use in AIDS patients, and examined their association with non-adherence and death or disease progression in a multicenter observational study. We defined non-adherence as reporting missed ART doses in the 48 hours before study visits. The association between drug use and ART non-adherence was evaluated using repeated measures generalized estimating equation (GEE) models. The association between drug and alcohol use and time to new AIDS diagnosis or death was evaluated via Cox regression models, controlling for covariates including ART adherence. Of 643 participants enrolled between 1997 and 1999 and followed through 2007, at entry 39% reported ever using cocaine, 24% amphetamines, and 10% heroin. Ongoing drug use during study follow-up was reported by 9% using cocaine, 4% amphetamines, and 1% heroin. Hard drug (cocaine, amphetamines, or heroin) users had 2.1 times higher odds (p=0.001) of ART non-adherence in GEE models and 2.5 times higher risk (p=0.04) of AIDS progression or death in Cox models. Use of hard drugs was attenuated as a risk factor for AIDS progression or death after controlling for non-adherence during follow-up (HR = 2.11, p=0.08), but was still suggestive of a possible adherence-independent mechanism of harm. This study highlights the need to continuously screen and treat patients for drug use as a part of ongoing HIV care.     

Information on Center Characteristics as Costs' Determinants in Multicenter Clinical Trials: Is Modeling Center Effect Worth the Effort?

Objectives:  Several methodological problems arise when health outcomes and resource utilization are collected at different sites. To avoid misleading conclusions in multi-center economic evaluations the center effect needs to be taken into adequate consideration. The aim of this article is to compare several models, which make use of a different amount of information about the enrolling center.
Methods:  To model the association of total medical costs with the levels of two sets of covariates, one at patient and one at center level, we considered four statistical models, based on the Gamma model in the class of the Generalized Linear Models with a log link, which use different amount of information on the enrolling centers. Models were applied to Cost of Strategies after Myocardial Infarction data, an international randomized trial on costs of uncomplicated acute myocardial infarction (AMI).
Results:  The simple center effect adjustment based on a single random effect results in a more conservative estimation of the parameters as compared with approaches which make use of deeper information on the centers characteristics.
Conclusions:  This study shows, with reference to a real multicenter trial, that center information cannot be neglected and should be collected and inserted in the analysis, better in combination with one or more random effect, taking into account in this way also the heterogeneity among centers because of unobserved centers characteristics.     

Use of and adherence to antiretroviral therapy is associated with decreased sexual risk behavior in HIV clinic patients

Previous research suggested that the availability of highly active antiretroviral therapy (ART) was associated with increased risky sexual behavior. This study examined the relationship between unprotected anal or vaginal sex (UAV) and ART use and adherence in a cross-sectional survey conducted in 874 randomly selected, sexually active patients at 6 public HIV clinics in California. Patients completed a standardized interview in 1998-1999 regarding HIV history, sexual behavior, illicit drug use, and ART use and adherence. Thirty-four percent reported UAV, defined as anal or vaginal sex without a condom within the past 3 months. Of 79% on ART, 26% reported <95% adherence. Decreased odds for UAV were found for both ART use, odds ratio (OR) 0.5 (95% CI 0.4-0.7, P < 0.001) and adherence to ART of > or = 95%, OR 0.6 (95% CI 0.4-0.8, P < 0.001). These relationships persisted in most stratified analysis for both ART use and adherence but in multivariate analysis only for ART use. An undetectable HIV RNA was associated with decreased odds of UAV, OR 0.6 (95% CI 0.5-0.8, P < 0.001). Contrary to expectations, use of and adherence to ART and their consequent suppression of HIV were associated with a decreased prevalence of self-reported risky sexual behavior.     

Distinguishing molecular forms of HIV-1 in Asia with a high-throughput, fluorescent genotyping assay, MHAbce v.2

High-resolution HIV-1 genotyping of large sample sets is crucial to define the evolving and dynamic epidemics in Asia. Here we present MHAbce v.2, a multi-region hybridization assay that individually discriminates subtypes B, C, CRF01_AE, and virtually all of their described recombinants, based on real-time PCR using subtype-specific TaqMan probes in 8 regions throughout the viral genome. In a validation panel (n=70), the assay performed with a sensitivity of 95.7% and specificity of 99.8%. The assay was field-tested on samples from a retrospective MTCT cohort (n=180; Lampang Province, Northern Thailand; 1996-1998). 177/180 of the samples were typeable, and 94.4% were typed as CRF01_AE. The remaining strains represented even proportions of subtype B and B/CRF01_AE recombinants and were confirmed by sequencing, revealing early links between the heterosexual and IDU HIV-1 epidemics in Thailand. MHAbce v.2, with an area of application including China, India, Southeast Asia, and the Pacific Rim, can be used to develop a comprehensive and detailed picture of this important component of the HIV/AIDS pandemic.