Crack Cocaine Use Predicts HIV Disease Progression and Mortality in HIV Positive Women

By Ronald Baker, PhD

Recent research suggests that cocaine may directly affect the pathology of HIV disease by causing alterations in immune cells such as CD4 helper T cells, CD8 cytotoxic T cells, and natural killer (NK) cells [1]. Studies have also demonstrated that cocaine interferes with the body's ability to defend against infection by inhibiting the function of neutrophils and macrophages and by suppressing cytokine production, which in turn interferes with important immune responses [2].

Laboratory studies have shown that cocaine also enhances HIV replication [3]. Cells from chronic cocaine users more readily support viral replication and infection with AIDS-defining opportunistic pathogens compared with cells from non-users. This finding suggests that cocaine may play a direct role in the acquisition of HIV and progression of AIDS [2].

Recently, cocaine has been shown to cause changes in cell membrane permeability, facilitating endothelial transmigration of infected dendritic cells across the blood-brain barrier into the central nervous system [4]. Cocaine may also alter immune responses and host resistance due to disturbances in the balance of Th1 pro-inflammatory and Th2 anti-inflammatory cytokines [3].

Yet the associations between crack cocaine use and HIV disease progression in patients are poorly understood, especially among women. In an article published in the July 11, 2008 issue of AIDS, researchers explored the relationship between crack use and disease outcomes in a multicenter cohort of HIV-infected women.

The study included 1686 HIV positive women enrolled at 6 U.S. research centers participating in the Women's Interagency HIV Study. Approximately 80% were non-white and 29% used crack during the study period.

The investigators used Cox survival and random regression to analyze biannual observations made from April 1996 through September 2004. Outcome measures included death due to AIDS-related causes, CD4 cell count, HIV RNA level, and newly acquired AIDS-defining illnesses.

Results

• Persistent crack users were over 3 times more likely than non-users to die from AIDS-related causes, after controlling for age, race, use of HAART, self-reported 95% or better adherence, problem drinking, income, education, duration of illness, and baseline virological and immunological indicators.

• Persistent crack users and intermittent users in both active and abstinent phases had greater CD4 cell loss and higher HIV viral load after controlling for the same confounding factors.

• Persistent and intermittent crack users were more likely than non-users to develop new AIDS-defining illnesses after controlling for the same confounders.

• These results persisted when controlling for heroin use, any injection drug use, tobacco smoking, symptoms of depression symptoms, and hepatitis C virus coinfection.

In conclusion, the study authors wrote, "Use of crack cocaine independently predicts AIDS-related mortality, immunologic and virologic markers of HIV-1 disease progression, and development of AIDS-defining illnesses among women."

Discussion

According to the investigators, "Ours is the first study to show that use of crack cocaine in a large, national cohort of HIV-positive women is longitudinally associated with subsequent deterioration in immune status, failure of virologic suppression, development of AIDS-defining conditions, and mortality due to AIDS-related causes, even among those who reported adhering to HAART regimens 95% of the time or more."

However, the authors emphasized that "even in the face of this evidence, our analysis does not conclusively demonstrate that crack use causes AIDS-related morbidity and mortality."

The researchers were not able to rule out the possibility that other mechanisms might account for these associations. These might include greater sexual risk taking, poorer diet and nutrition, substandard living conditions, or other unknown confounders.

The challenges involved in treating crack addiction include high rates of treatment dropout, relapse, and repeat treatment. According to the authors, "This suggests the need for models that acknowledge crack users' diverse levels of readiness for change and recognize that work can be done, even with women who are not yet ready to alter their behavior or are just beginning to consider doing so."

"Helping individuals move from pre-contemplation to readiness for change," they continued "requires approaches that are assertive and 'strengths-based,' building on low-income minority women's intrinsic resources such as resilience and 'street smarts'."

Finally, the researchers concluded, "Culturally competent care is required in order to build the trust necessary for personal risk taking that accompanies willingness to change through addiction treatment and commitment to antiretroviral regimens."

Department of Psychiatry, University of Illinois at Chicago, Chicago, IL; Core Center and Stroger (formerly Cook County) Hospital, Chicago, IL; College of Public Health and Health Professions, University of Florida, Gainesville, FL; New York Academy of Medicine, New York, NY; Department of Preventive Medicine and Community Health, State University of New York Downstate Medical Center, Brooklyn, NY; Department of Epidemiology, Johns Hopkins School of Public Health, Baltimore, MD; International Center for AIDS Care and Treatment Programs, Mailman School of Public Health, Columbia University, New York, NY; Department of Clinical Pharmacy, University of California at San Francisco, San Francisco, CA; Department of Medicine, Georgetown University Medical Center, Washington, DC; City of Hope, Duarte, CA.

7/29/08

Reference
JA Cook, JK Burke-Miller, MH Cohen, and others. Crack cocaine, disease progression, and mortality in a multicenter cohort of HIV-1 positive women. AIDS 22(11): 1355-1363, July 11, 2008.

Other citations

1. W Xu, T Flick, J Mitchel, and others. Cocaine effects on immunocompetent cells: an observation of in vitro cocaine exposure. International Journal of Immunopharmacology 21:463-472. 1999.

2. GC Baldwin, MD Roth, DP Tashkin, and others. Acute and chronic effects of cocaine on the immune system and the possible link to AIDS. Journal of Neuroimmunology 83:133-138. 1998.

3. GA Cabral. Drugs of abuse, immune modulation, and AIDS. Journal of Neuroimmune Pharmacology 1:280-295. 2006.

4. MP Nair, SA Schwartz, SD Mahajan, and others. Drug abuse and neuropathogenesis of HIV infection: role of DC-SIGN and IDO. Journal of Neuroimmunology 157:56-60. 2004.