The research team, led by Roberto Muga, MD, of the Hospital Universitari German Trias i Pujol in Barcelona, began with two major study objectives. The first was to evaluate changes in survival rates among IDUs in association with the use of combination antiretroviral therapy, along with other factors like improved prophylaxis against AIDS-related opportunistic infections and methadone treatment. The second was to determine whether combination HIV drug treatment improved survival outcomes among HIV-positive IDUs, compared to HIV-negative IDUs.

The researchers observed a total of 1181 HIV-positive and HIV-negative IDUs over three calendar periods. The first period involved 490 subjects followed between 1987 and 1992, the years of HIV monotherapy (the use of only one antiretroviral). The second period, involving 393 subjects, was between 1992 and 1996, the years of dual-drug regimens and the beginning of methadone therapy for opioid addiction in Spain. The third and final period, focusing on 298 subjects followed between 1997 and 2004, was the time in which combination antiretroviral therapy became widely available and methadone programs for IDUs were firmly established.

Most of the patients were injection heroin users referred from two outpatient clinics in cities adjacent to the research hospital in Barcelona, and were admitted for the first time into a substance abuse treatment program.

The patients in the study were 81 percent male, the average age was 28 years, and the average duration of injection drug use prior to enrollment was almost eight years. Approximately 59% of those enrolled were infected with HIV; 92% had hepatitis C virus (HCV) infection. Once enrolled, the subjects were followed for approximately 10 years.

Looking at all three groups as a whole, survival rates were worse among the HIV-infected IDUs compared to the HIV-negative IDUs. However, Dr. Muga's group estimate that survival rates among HIV-positive IDUs improved greatly between 1997 and 2004, whereas survival rates among HIV-negative IDUs remained the same during all three time periods. In fact, when focusing solely on the 1997-to-2004 period, the researchers estimate that survival rates among HIV-positive IDUs were similar to those estimated for HIV-negative IDUs in the study.

Dr. Muga and his colleagues note that the introduction of combination antiretroviral therapy was likely a significant factor in the improved survival outcomes. However, only one third of the HIV-infected IDUs in the study were receiving antiretroviral therapy, the authors write that "other factors are likely to have contributed to the improved survival among contemporary HIV-infected heroin users – namely, access to substitution therapy with methadone, prophylaxis for opportunistic infections, harm reduction interventions, and regular clinical care, as shown by previous studies."

The study did not produce any correlation between drug usage patterns (i.e., persistent, intermittent, or nonuse of drugs) and survival outcomes. Dr. Muga and his coauthors suggest that this is because "the pattern of [injection drug] use during and after drug treatment was subject to high variability." Other studies, however, have confirmed better survival rates among HIV-positive intermittent drug users, compared to persistent users.

Gregory D. Kirk, MD, PhD, of Johns Hopkins University Medical Center, and David Vlahov, PhD, of Johns Hopkins and the New York Academy of Medicine, note in an accompanying editorial that injection drug use carries high rates of mortality due to "violence, accidents and overdose." Yet the Barcelona study does not include data on the causes of mortality for any of the patient groups. The research team cites its "exhaustive linkage of the complete database of 1181 patients with the Catalonian mortality register" as a strong point of the study, but provide no further information on causes of death.

"Assessment of the reductions in AIDS-related deaths, compared with non-AIDS related causes of death, would be helpful for assessment of the effectiveness of both HAART on both outcomes," Drs. Kirk and Vlahov explain.

Researchers have debated the effectiveness of antiretroviral therapy for HIV-infected IDUs due to questions of adherence and other serious health complications that are associated with injection drug use. This study, however, supports other research demonstrating significant survival advantages among IDUs receiving necessary care and antiretroviral therapy.

The editorial declares that debates on whether drug therapies are effective for IDUs "divert attention from other important research questions and from daunting programmatic goals." Drs. Kirk and Vlahov call for more research on IDUs who "do not constitute one homogenous risk group" and that work should "provide more refined evaluations of injection and noninjection drug use."

Sources:

Muga R, Langohr K, Tor J, et al. Survival of HIV-infected injection drug users (IDUs) in the highly antiretroviral therapy era, relative to sex- and age-specific survival of HIV-uninfected IDUs. Clin Infect Dis 45:2007.

Kirk CD, and Vlahov D. Improving survival among HIV-infected injection drug users: how should we define success? Clin Infect Dis 45:2007.