HIV-positive injecting drug users need to commence HAART when their CD4 cell count is above 350 cells/mm3, a level substantially higher than that recommended by current treatment guidelines, to gain a survival benefit equal to that of HIV-negative drug users, according to a United States study published in the September 15th edition of The Journal of Infectious Diseases.
Investigators from the AIDS Linked to Intravenous Experience (ALIVE) study in Baltimore gathered data from 920 HIV-negative drug users and 583 HIV-positive injecting drug users between 1997 and 2001. The HIV-positive individuals were stratified into one of seven categories according to whether they used, started, or changed HAART and their CD4 cell count.
Mortality rates were calculated and a model developed to evaluate the survival benefit which HAART conferred.
Median follow-up for patients receiving HAART was 2.4 years, two years for HIV-positive patients not taking HAART, and four years for HIV-negative individuals. Almost three-quarters of all the entire study were male, a little under 93% were African American, 74% were unemployed and the median age was 41.5 years.
The all cause mortality rate was lowest amongst the HIV-negative individuals at 19.9 per 1000 patient years. Amongst HIV-positive patients with a CD4 cell count above 350 cells/mm3 who were treated with HAART the all cause mortality rate was 24.1 per 1000 patient years. However, this was not a statistically significant increased rate of mortality compared to the HIV-negative injecting drug users (p = 0.76).
Mortality increased to 50.5 per 1000 patient years for HAART-treated patients with a CD4 cell count between 200-350 cells/mm3 (p = 0.006 compared to HIV-negative) and 86.7 per 1000 patient years for HAART-treated individuals with a CD4 cell count below 200 cells/mm3 (p < 0.001 compared to HIV-negative).
In a separate analysis restricted to HIV-positive patients, the investigators found that using HAART did not confer an additional significant survival benefit for patients with CD4 cell counts above 350 cells/mm3 (p = 0.27), or between 200 and 350 cells/mm3 (p = 0.32), but did for individuals with a CD4 cell count below 200 cells/mm3 (p = 0.01).
The investigators then adjusted their data comparing all cause mortality between HIV-positive and HIV-negative patients for potential confounding factors including demographics, alcohol and drug use, health insurance, sexual activities, treatment for substance abuse, and past hospitalisation. They found that all cause mortality was still comparable between HIV-negative individuals and HIV-positive patients who started HAART with a CD4 cell count above 350 cells/mm3. However, all cause mortality remained significantly higher amongst HIV-positive patients with CD4 cell counts between 200 and 350 cells/mm3 and those with a CD4 cell count below 200 cells/mm3 (p = 0.001).
In further analysis the investigators looked at AIDS-related mortality and non-AIDS related mortality comparing the incidence in individuals who received HAART and those who did not. They found that AIDS-related mortality was similar between HAART-treated and non-treated patients at all CD4 cell count strata except for patients with a CD4 cell count below 200 cells/mm3, where the HAART-treated patients experienced a significant survival benefit (p = 0.01).
Viral load was also examined by the investigators. They found that for patients with a CD4 cell count above 350 cells/mm3 who took HAART viral load was not a significant factor in survival. However, individuals with a CD4 cell count between 200 and 350 cells/mm3 and a viral load below 55,000 copies/ml had a survival rate similar to HIV-negative individuals (p = 0.68), whereas those with a viral load above 55,000 copies had significantly worse survival rates than HIV-negative injecting drug users (p < 0.001).
The investigators write, “our results suggest that HAART should be initiated or switched to at higher CD4 cell levels than currently recommended” in HIV-positive injecting drug users. They conclude, “our study demonstrates that, among IDUs, HAART initiated at CD4 cell counts above 350 cells/mm3 was associated with a survival rate comparable to that of HIV-seronegative IUDs, even after accounting for factors associated with access to care. This result suggests that, to optimise survival in HIV-seropositive IDUs, initiation of HAART at CD4 cell levels higher than the current treatment guidelines indicate might be considered.”