Patients who experience increases in their CD4 cell counts after initiating potent antiretroviral therapy can safely change therapy to a regimen based on the NNRTI nevirapine, according to an Indian study published in the August 15th edition of AIDS.
Initiating antiretroviral therapy with a nevirapine-containing regimen at higher CD4 cell counts can involve a risk of potentially serious liver toxicities. For this reason, it is recommended that men with a CD4 cell count above 400 cells/mm3 and women with a CD4 cell count above 250 cells/mm3 should not start anti-HIV therapy with a combination of drugs that contains nevirapine.
European data suggest that it is safe for patients who have experienced good increases in their CD4 cell count to subsequently switch to nevirapine.
However, there are limited data on the safety of switching to nevirapine for antiretroviral-experienced patients in resource-limited settings.
Investigators in India therefore conducted a prospective study including 36 individuals who had started anti-HIV treatment with an efavirenz-based regimen. All the patients started therapy with a CD4 cell count of 200 cells/mm3 or below, or between 201 – 350 cells/mm3 if they had developed an AIDS-defining illness.
At the time therapy with the efavirenz-based regimen was started, the patients had a median CD4 cell count of 162 cells/mm3. At the time efavirenz was replaced with nevirapine, CD4 cell count had increased to a median of 463 cells/mm3. At three-monthly intervals for the next year, the patients had blood tests to monitor their CD4 cell counts and liver function.
Median CD4 cell count increased to 562 cells/mm3 at the end of follow up. Liver function did not change significantly in the twelve months after switching to nevirapine. Indeed, the proportion of patients with elevated liver enzymes fell during follow up. At the time treatment was switched, five patients had grade 1 elevations in liver function, and one patient had grade 2 elevations. After a year of therapy with nevirapine, only one patient had grade 1 elevations with an additional patient having a grade 2 elevation.
“These data suggest that patients whose systems are immune reconstituted when switched to nevirapine-based HAART at elevated CD4 levels do not present with increased liver enzymes”, comment the investigators, adding, “this study suggests that nevirapine-based HAART at increased CD4 levels in those patients is effective, safe, and well-tolerated, while increasing CD4 T-lymphocyte counts.”
They believe that their findings could have important implications, writing “the number of HIV-infected patients newly placed on nevirapine therapy continues to increase globally. Greater understanding of the pathogenesis of nevirapine toxicity allows for improved clinical treatment guidelines.”
Furthermore, the investigators suggest that their findings could lead to significant financial savings. They note that efavirenz-based combinations are almost twice as expensive as those containing nevirapine.
Kumarasamy N et al. Safety of switching to nevirapine-based highly active antiretroviral therapy at elevated CD4 cell counts in a resource-constrained setting. J Acquir Immune Defic Syndr 45: 598 – 600, 2007.