WHO HIV treatment guidelines now recommend initiating ART when the CD4 count declines to <350 cells/μL instead of <200 cells/μL [23]. Initiation of antiretrovirals at this higher CD4 cell count threshold
is associated with a reduced risk of progression to AIDS or death [37], an improved chance of immune restoration [38], and a lower risk of developing antiretroviral-related toxicities [39] and antiretroviral resistance [40] compared with initiation of antiretrovirals at a CD4 count <200 cells/μL. In resource-limited selleckchem settings where nevirapine is widely used, there has been concern that these benefits may be offset by increased nevirapine-associated hepatotoxicity, especially among women with CD4 counts between 250 and 350 cells/μL. Access to alternative antiretrovirals such as efavirenz or protease inhibitors may be limited because of their potential teratogenicity risks and high cost. Our data support the expansion of nevirapine-based ART to women with a CD4 count <350 cells/μL. Although serious nevirapine-associated hepatotoxicity occurred among women in these resource-limited
settings, the rate of nevirapine-associated hepatotoxicity was low (3–5%). Further, the risk was not uniquely greater for women with higher baseline CD4 counts; women with the lowest CD4 counts (<50 cells/μL) PI3K inhibitor were at similar risk for rash-associated hepatotoxicity to women with high CD4 counts (≥200 cells/μL). Our data also suggest that early transaminase monitoring (baseline and weeks 2 and 4) identifies the majority of women experiencing nevirapine-associated hepatotoxicity. Initiating HIV-infected women with CD4 counts ≥250 cells/μL on an efavirenz-based regimen for at least 6 months and then changing to nevirapine does not appear to lead to a spike in hepatotoxicity or rash when patients are changed to nevirapine, despite CD4 counts that exceed 250 cells/μL Mannose-binding protein-associated serine protease [41–43]. This strategy is an alternative method to minimize the risk of both
hepatotoxicity and teratogenicity. Hepatotoxicity may not occur under these circumstances because nevirapine is introduced after the initial rapid immune recovery on ART has occurred. There were several limitations to our study. First, all of the participants in this study were women and therefore the findings cannot necessarily be extrapolated to men in these settings. However, the issue of nevirapine use and hepatotoxicity might be more relevant to women in resource-limited settings than men. Women who are pregnant or may become pregnant cannot use nevirapine’s alternative, efavirenz, because of that agent’s teratogenic potential. Secondly, rash may have been more difficult to diagnose in participants with dark skin.