HIV-positive former IDUs have poorer immune response to HAART

Former injecting drug users are significantly less likely to experience a good immunological response to highly active antiretroviral therapy (HAART), even with sustained suppression of HIV, than other HIV risk groups, according to a Spanish study published in the November 5^th edition of AIDS. Although almost all the former injecting drug users were also coinfected with hepatitis C virus, the investigators believe that the suppressive effect of opiate and cocaine use on the immune system is the reason for the poor immune response to HAART rather than hepatitis coinfection.

Several studies have found that former or current injecting drug users have a poorer immunological recovery after starting HAART than other HIV risk groups. Two explanations for this have been offered: coinfection with hepatitis C virus, or the immunosuppressive effects of some drugs.

Investigators in Madrid conducted a retrospective analysis of 288 treatment-naive patients who started HAART after 1996 to establish if injecting drug users did indeed have a poorer immunological response to HAART and if they did, the possible causes.

A total of 176 patients (61%) were former injecting drug users. To be included in the study individuals were required to have maintained a viral load below 50 copies/ml for at least two years and to have baseline, pre-treatment CD4 cell count data available.

Immunological recovery was assessed in both the short-term and long-term by measuring CD4 cell count six months and 24 months after starting HAART. The main outcome of the study was the proportion of patients with a CD4 cell count increase of at least 50 cells/mm³ after 24 months of HAART.

At baseline, the former injecting drug users were significantly younger (34 vs. 38 years, p = 0. 003) than other HIV risk groups, and were more likely to be male (78 vs. 68%, p = 0.046). A total of 95% of former injecting drug users were coinfected with hepatitis C virus compared to 16% of patients in other HIV risk categories. Median CD4 cell count was lower at baseline amongst former injecting drug users (214 vs. 258 cells/mm³), but not significantly so (p = 0.4), and viral load was comparable (former injecting drug users, 80,000 copies/ml vs. 100,000 copies/ml for other HIV risk groups, p = 0.1).

After six, twelve and 18 months of HAART, former injecting drug users had significantly lower CD4 cell counts than other HIV risk groups. At six months the median CD4 cell count for former injecting drug users was only 346 cells/mm³ compared to 456 cells/mm³ for other HIV risk groups (p = 0.037).

After two years of HAART and complete viral suppression, the median CD4 cell count for former injecting drug users was 472 cells/mm³ compared to 588 cells/mm³ for all other HIV risk groups (p = 0.013).

Multivariate analysis showed that injecting drug users were significantly less likely than other HIV risk groups to achieve a CD4 cell gain of 50 cells/mm³ after two years of HAART (odds ratio 0.23).

A total of six patients died during the study, five of them former injecting drug users. However, the difference in death rate between groups was not statistically significant (p = 0.41).

“Intravenous drug use and not hepatitis C virus coinfection determined the amount and speed of the increase in CD4 cell count,” the investigators argue. However a limitation of this study is that virtually all former injecting drug users were also hepatitis C virus-positive (95%), making it difficult to determine the contribution of hepatitis C virus infection to a poorer immune response.

The investigators note that both opiates and cocaine can suppress immune function, therefore “blunting” CD4 cell count recovery after the initiation of HAART. The authors note that opiate use has been shown to cause long-term impairment of the capacity of T-lymphocytes to repair DNA damage, leading to a higher rate of cell apoptosis, and also reduces host defences against opportunistic infections.