MinireviewSubstance use and HIV disease progression in the HAART era: Implications for the primary prevention of HIV
Introduction
Since the beginning of the HIV/AIDS pandemic, injection drug use (IDU) and non-injection drug use (NIDU) have been identified as important risk factors for HIV seroconversion (Colfax et al., 2010, Des Jarlais and Semaan, 2008, Hahn et al., 1989, Koblin et al., 2006, Stall, 1987). Consequently, ongoing recreational substance use and problematic patterns of substance use are common among HIV-positive persons. In a recent national, probability-based sample of adults receiving HIV care in the United States (US) more than one-third of participants reported using substances other than marijuana in the past year and 12.5% screened positive for a substance use disorder (Bing et al., 2001). Bearing in mind the elevated prevalence of substance use and substance use disorders among HIV-positive persons, an extensive literature has examined the plausible mechanisms whereby the use of various substances may lead to decrements in immune status and hastened HIV disease progression (Kapadia et al., 2005b). In vitro and animal studies have delineated numerous biological pathways whereby the use of different substances may impair immune status (Cabral, 2006, Donahoe and Vlahov, 1998, Liang et al., 2008, Pellegrino and Bayer, 1998). However, cohort studies conducted in the era prior to advent of highly active anti-retroviral therapy (HAART) provided equivocal evidence to support the hypothesis that substance use promotes more rapid HIV disease progression (Kapadia et al., 2005b). In the HAART era, it is well established that substance users are substantially less likely to initiate these potent regimens, take an adequate proportion of prescribed HAART medication doses, or suppress HIV replication to undetectable levels (Arnsten et al., 2002, Carrico et al., 2007, Celentano et al., 1998, Hinkin et al., 2007, Robison et al., 2008). These observed difficulties with HIV disease management among substance users provide a compelling rationale to examine whether substance use predicts more rapid HIV disease progression in the HAART era.
The overarching goal of the present review was to summarize findings from longitudinal cohorts that examined the effects of substance use on indices of HIV disease progression in the HAART era. Only cohort studies that collected follow-up data during the HAART era (i.e., after 1996) were eligible for inclusion. Although greater non-adherence to HAART is one plausible mechanism that explains the effect of substance use on more rapid HIV disease progression, burgeoning clinical research has highlighted that other biological and behavioral pathways may also partially explain these effects (Carrico et al., 2008, Carrico et al., 2007, Ellis et al., 2003). Thus, an important secondary goal of the present review was to examine the extent to which the effects of substance use on indices of HIV disease progression persist after controlling for HAART non-adherence. Drawing upon the review of this literature, I provide recommendations for further research that measures important confounding variables and examines the plausible bio-behavioral mechanisms for the effect of stimulant (cocaine, crack, and methamphetamine) use on HIV disease progression. Finally, the clinical implications of this literature are discussed with respect to recent efforts to implement universal voluntary counseling and testing for HIV followed by immediate initiation of HAART (i.e., “Test and Treat”) for the primary prevention of HIV infection (Das et al., 2010, Dieffenbach and Fauci, 2009, Montaner et al., 2010).
Section snippets
Substance use and HIV disease progression in the HAART era
Using PubMed, I searched for longitudinal cohort studies with the following key words: AIDS, cocaine, crack, disease progression, drug use, heroin, HIV, HIV viral load, injection drug use, methamphetamine, mortality, substance use, survival, and T-helper (CD4+) count. For studies published on or after 1996, the methods section was inspected to determine whether follow-up extended into the HAART era. Although 22 studies that met these criteria were identified, only 20 were determined to be
The effects of substance use on HIV progression may not be exclusively due to non-adherence
A primary focus of clinical research with HAART-treated substance users has been to examine the rates, patterns, and consequences of HAART non-adherence (Arnsten et al., 2002, Hinkin et al., 2007). The underlying assumption of these lines of research is that HAART adherence is the sole pathway whereby substance use relates to markers of more rapid HIV disease progression. On the contrary, several of the investigations that examined the effect of substance use on HIV disease markers and indices
Clinical implications of elevated HIV viral load for primary prevention
It is well established that elevated HIV viral load leads to the more effective transmission of HIV from mother to child or to uninfected sexual partners (Quinn et al., 2000, Tornatore et al., 2010). Informed by this basic understanding of the role of HIV viral load in the efficiency of transmission, recent mathematical modeling indicates that universal HIV voluntary counseling and testing followed by immediate initiation of HAART has the potential to substantially reduce HIV incidence (Granich
Conflict of interest statement
None.
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