Background:  With a HIV prevalence of ~4.4%, Nigeria has the fifth largest number of HIV-infected patients globally. Through PEPFAR funding and in collaboration with Harvard University, ART programs have been scaled up at 10 major treatment sites throughout the country of Nigeria. As part of the program, patients are provided with ART and wrap-around care services. Through monitoring of evaluation of laboratory data using defined panic values, we can identify patients with signs of hepatotoxicity. Our goal is to evaluate patients with signs of toxicity and identify potential predictors of poor ART response.

Methods:  Monitoring of clinical responses is provided through the PEPFAR funding. Patient samples are drawn and tested at baseline, months 3, 6, and 12 post-initiation, and then every 6 months thereafter. Our goal in the present project was to determine the level of ART-related toxicities experienced by program enrollees and to evaluate predictors of these toxicities. For our treatment population, toxicity-related laboratory panic values are defined as alanine aminotransferase (ALT) ≥120 IU/mL, hemoglobin (Hg) ≤8 g/dL or creatinine (Cr) ≥260 mM/L.

Results:  As of September 2007, a total of 28,875 adult patients have been placed on ART through the Harvard PEPFAR program. Of the patients on ART, 3151 (11%) have had at least one ALT, Hg, or Cr that hit a panic value post-initiation. The most common panic value was Hg ≤8 (57%). Most patients experiencing toxicity were on first-line, nevirapine-containing regimens (82%). A majority of patients with toxicity were women (61%; p = 0.28) and had no previous experience with antiretrovirals (ARV) prior to PEPFAR entry (73%; p = 0.021). The median age for those with signs of toxicity was 35 years. Of those patients that had panic values, medians were 159 IU/mL for ALT, 424 mM/L for Cr and 7.2 g/dL for Hg. Median CD4 count at baseline for patients experiencing toxicities was 129 cells/mm³ as compared to 162 for those patients that did not have signs of toxicity.

Conclusions:  A majority of the patients that exhibited signs of hepatotoxicity were on first-line drugs, had no previous ARV experience prior to their enrollment in the PEPFAR program, and had lower CD4 counts at baseline. Co-infection with hepatitis may play a role in the hepatotoxicities seen in the group. By understanding these predictors of ARV-related toxicity, we can better target efforts and develop specific monitoring plans to improve overall drug tolerance.