Crack cocaine, disease progression, and mortality in a multicenter cohort of HIV-1 positive women

Autor: Judith A, Cook, Jane K, Burke-Miller, Mardge H, Cohen, Robert L, Cook, David, Vlahov, Tracey E, Wilson, Elizabeth T, Golub, Rebecca M, Schwartz, Andrea A, Howard, Claudia, Ponath, Michael W, Plankey, Alexandra M, Levine, Andrea, Levine, Dennis D, Grey
Rok vydání: 2008
Předmět:
Zdroj: AIDS. 22:1355-1363
ISSN: 0269-9370
DOI: 10.1097/qad.0b013e32830507f2
Popis: Recent research suggests that cocaine may directly affect the pathobiology of HIV by causing immune alterations in different lymphocytes such as helper T cells (CD4), suppressor/cytotoxic T cells (CD8), and natural killer (NK) cells.1 Studies show that cocaine interferes with the body’s ability to defend against infection by inhibiting the effector functions of neutrophils and macrophages, and by suppressing cytokine production, decreasing operation of important immune responses.2 Cocaine also enhances the replication of HIV in vitro.3 Cells from chronic cocaine users more readily support HIV replication and development of AIDS-defining opportunistic infections than cells from nonusers, suggesting a direct role for cocaine in the acquisition and progression of AIDS.2 Recently, cocaine has been shown to cause membrane permeability facilitating endothelial transmigration of infected dendritic cells across the blood brain barrier to the central nervous system.4 There is also evidence of cocaine-mediated alteration of immune responses and host resistance due to disturbances in the balance of Th1 pro-inflammatory versus Th2 anti-inflammatory cytokines and lipid bioeffectors.3 Epidemiologic research confirms that crack users are at high risk for HIV infection and progression.5-6 In a prospective study of HIV-seropositive drug users, crack use was significantly associated with progression to AIDS.7 A study of HIV-positive current and former drug users found that active cocaine use was the strongest predictor of failure to maintain viral suppression; 13% of active users maintained suppression vs. 46% of non-users.8 In a prospective cohort study, compared with nonusers and former users, active cocaine and heroin users experienced smaller median reductions in HIV-1 RNA and smaller median increases in CD4 from baseline, controlling for antiretroviral exposure, adherence, and socio-demographic factors.9 Compared to nonusers, the risk of AIDS-related opportunistic conditions was greater for persistent users and intermittent users during periods of active use, with no difference during periods of abstinence.10 Mixed results characterize studies of drug users in exclusively female U.S. cohorts. In a multi-center cohort of HIV-positive women, injection drug use was not associated with progression to AIDS.11 Another large multi-site cohort study found that hard drug use (i.e., cocaine, heroin, methadone, or injecting drugs) was significantly associated with AIDS-defining illnesses, but not with change in CD4, HIV-RNA, or mortality.12 In a third multi-site cohort of HIV+ women, non-injection drug use was associated with time to AIDS-defining event but not with AIDS-related mortality.13 While suggestive, these studies and others focusing on injection drug use do not uniformly demonstrate a link between illicit drug use and HIV-1 disease progression.14-17 Possible reasons include: diverse definitions of illness progression; failure to differentiate between active and nonactive users; and lack of distinction between mortality due to AIDS versus non-AIDS causes.17 Other reasons include lack of controls for highly active antiretroviral therapy (HAART) use and adherence, and inadequate follow-up periods. We addressed all of these issues by examining patterns of crack use and their association with four distinct measures of HIV/AIDS disease progression in a multi-center cohort over an eight-and-one-half-year period during the HAART era.
Databáze: OpenAIRE
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