When starting antiretroviral (ARV) therapy—especially for those starting treatment after the immune system has become suppressed—it is essential to maintain a CD4 count above 200 cells, even if viral load is undetectable. This is the conclusion of a study reported by Mona Loutfy, MD, of the University of Toronto and her colleagues at the Fifth International AIDS Society (IAS) Conference on HIV Pathogenesis, Treatment and Prevention in Cape Town on Monday, July 20.

Growing evidence suggests that a discordant response to ARV therapy—notably an undetectable viral load without a notable improvement in the CD4 cell count—does not adequately protect against disease progression. This seems to be particularly true for HIV-positive people who do not begin treatment until their CD4 cell count is already below 200.

To explore the implications of discordant responses to ARV therapy, Loutfy’s group reviewed the medical records of 4,576 HIV-positive individuals initiating triple-drug HIV treatment, beginning in 2000, at clinics in British Columbia, Ontario and Quebec. About 1,700 of those individuals had been followed for at least two years, with continuous viral load and CD4 count measurements, and were thus included in the analysis.

Sixteen percent were female and averaged 41 years old when treatment was started. The average CD4 count upon starting treatment was 171 cells; the average viral load was 100,000 copies/mL. After two years, the average CD4 count was 410 cells. Despite maintaining undetectable viral loads, 176 patients were unable to get or keep their CD4 count above 200 cells after two years of treatment.

There were 43 clinical events—defined as a new AIDS-related disease diagnosis or death—after two years of follow-up. Thirty-six of the clinical events reported were death.

Intravenous drug use and a CD4 count below 200 after two years of treatment were significantly associated with a greater risk of a clinical event. Interestingly, individuals receiving ARV therapy in Ontario had a reduced risk for a new AIDS-related complication or death.

Men, individuals with a history of intravenous drug use, those entering with very low CD4 counts and people initiating treatment with a Kaletra (lopinavir/ritonavir)–based regimen were less likely to see their two-year CD4 count increase above 200.  

Loutfy and her colleagues say these data confirm the significance of an immunologic discordant response to treatment, underscoring the need to closely monitor both viral load and CD4 cell responses to treatment. The authors point out, however, that the actual number of clinical events was quite low and recommend additional analyses involving even larger cohorts to yield firm conclusions.