September 29, 2006
For a variety of reasons, many HIV-infected patients begin antiretroviral treatment when their CD4+ cell counts are extremely low. Although many patients with low CD4+ cell counts who have good adherence to their regimen can achieve an undetectable HIV viral load, their CD4+ cell counts may not increase significantly above a count of 200/mm3. It is known that patients with CD4+ cell counts below 200/mm3 who are not on antiretroviral treatment are at significant risk of developing AIDS-defining illnesses, such as opportunistic infections or certain cancers. It is less clear whether patients with advanced HIV disease who start antiretroviral treatment who are able to achieve viral suppression but whose CD4+ cell count remains below 200/mm3 are still at risk for developing opportunistic infections.
Mona Loutfy and colleagues attempt to answer this question by studying the British Columbia HIV-infected cohort.1 Patients with a baseline CD4+ cell count of less than 200 and a detectable HIV-1 viral load who were antiretroviral na?ve and started antiretroviral treatment between August 1996 and September 2003 were included in the study.
Patients also had to achieve an undetectable viral load within the first year of antiretroviral treatment. The primary endpoint was non-accidental death or an AIDS event and whether the CD4+ cell count was below or above 200 after one year of antiretroviral treatment. A univariate Cox proportional hazard regression model was used in the analysis.
Two hundred and ninety nine patients were identified that met the inclusion criteria, of which, 202 did and 97 did not achieve a CD4+ cell count more than 200/mm3 after one year of antiretroviral treatment. Overall, the mean age was 42 years, 86% male, 15% were injection drug users and 50% used an NNRTI in their first antiretroviral regimen.
There were no significant demographic differences between the two groups. The only significant baseline difference in the two groups was the CD4+ cell count. The median CD4+ cell count for the entire group was 80/mm3, but it was 40/mm3 in those who did not achieve a CD4+ cell count of more than 200/mm3 and it was 120/mm3 at baseline for those who did.
There were 27 endpoints overall, 21 AIDS defining illnesses and six deaths. 10/97 (10.3%) and 17/202 (8.4%) patients had clinical endpoints. 4/97 (4.1%) and 5/202 (2.5%) had clinical events after one year of follow-up. Significant variables associated with a decreased likelihood of an event were an adherence rate of more than 95%, higher baseline CD4+ cell count, and time-dependent CD4+ cell count. Failure to achieve a CD4+ cell count of more than 200/mm3 was associated with a hazard ratio (HR) of 3.08 for developing a clinical event and a HR of 3.94 after one year, both of which just bordered on statistical significance.
The study indicates that patients who do not achieve a CD4+ cell count of more than 200/mm3 are at somewhat greater risk of developing AIDS clinical events than those who do. The total number of events was small in each group but the trend did favor increased events in those whose CD4+ cell counts remained below 200/mm3. This group also had significantly less CD4+ cells prior to starting antiretroviral treatment and was thus at greater risk from the outset.
Interestingly, clinical events happened at a median of 2.2 months after starting antiretroviral treatment, most likely when their CD4 count was still significantly depressed. We were not told whether all or some of these patients were taking opportunistic infection prophylaxis medications, which could have affected whether they developed a clinical endpoint or not. It was apparent though that adherence to antiretroviral meds was very important in helping prevent clinical events.
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