A poor immunological response to HIV therapy six and twelve months after its initiation is associated with an increased risk of death, according to the results of a Zambian study published in the online edition of the Journal of Acquired Immune Deficiency Syndromes. The investigators undertook their study “so that long-term assessment of antiretroviral therapy can be made and the utilization of second-line therapy can be improved among patients in need”.
Monitoring of the effectiveness of HIV treatment in most resource-limited settings relies upon measuring CD4 cell counts. Viral load testing is rarely available. Investigators therefore wished to establish the relationship between immunological responses to antiretroviral therapy and the risk of death.
Their study population included two cohorts of individuals in Zambia who initiated antiretroviral therapy consisting of a non-nucleoside reverse transcriptase inhibitor (NNRTI) and two nucleoside reverse transcriptase inhibitors (NRTIs). The first cohort had CD4 cell counts available at baseline and six months after starting anti-HIV drugs. The second cohort consisted of people who had both baseline and twelve month CD4 cell counts.
A total of 24,366 individuals had six-month CD4 cell counts available and 17,920 had recorded CD4 cell counts at twelve months.
The six-month mortality rate was 2 per 100 person years, and the lost-to-follow-up rate was 10 per 100 person years. Few patients switched to second-line therapy, the rate being 1.4 per 100 patient years.
At twelve months, the mortality rate was 1.2 per 100 person years, the lost-to-follow-up rate was 9 per 100 person years, and the switch to second-line therapy rate was 2 per 100 person years.
Treatment failure at six months was defined as a decline in CD4 cell count from pre-treatment values, or an increase in CD4 cell count of 50 cells/mm3 or less. A total of 11% of patients fulfilled the first criterion and 23% the second.
Next the investigators analysed twelve-month responses to treatment. They found that 8% of patients had experienced a fall in their CD4 cell count since starting HIV treatment, that 4% had a CD4 cell count of less than 100 cells/mm3 and that, in 19%, their CD4 cell count had fallen by 30% or more from its peak on treatment. These individuals were also defined as having experienced immunological failure. The investigators also found that 8% of patients fulfilled two of the categories of twelve-month treatment failure and that 2% met all three categories.
After controlling for adherence, the risk of death six months after initiating HIV therapy was associated with a CD4 cell count below 100 cells/mm3 (adjusted hazard ratio [AHR] = 2.25, 95% CI: 1.91 to 2.64) and an increase in CD4 cell count of 10% of less from baseline (AHR = 2.60, 95% CI: 2.12 to 3.19).
The investigators’ analyses also showed that the twelve-month risk of death was predicted by a CD4 cell count of 200 cells/mm3 or less (AHR = 2.41, 95% CI: 1.83 to 3.17), and also an increase in CD4 cell count of less than 10% of baseline values (AHR = 3.41, 95% CI: 2.51 to 4.64).
“Our findings emphasize the importance of immunologic responses as measured by serial CD4 measurements in identifying patients at elevated risk of mortality,” comment the investigators.
They conclude, “to improve clinical outcomes, this marker should prompt a diagnostic workup for opportunistic infections, comprehensive assessment of adherence, and/or early diagnosis of treatment failure using virologic testing where available.” The authors continue, “given the poor correlation between CD4 cell counts and virologic failure, switching to second-line therapy without such evaluations may be premature and could limit future treatment options.”
Reference
C
hi BH et al. CD4+ response and subsequent risk of death among patients on antiretroviral therapy in Lusaka, Zambia. J Acquire Immune Defic Syndr (online edition), 2009.