Treatment with peg-IFN and ribavirin is relatively well-tolerated in HIV/HCV-co-infected patients, although new side-effects, including pancreatitis and severe weight loss, may result from the interaction of ribavirin with antiretroviral drugs. Overall, therapy provides cure to one third of patients, a rate significantly lower than that seen in HCV-monoinfected individuals. Given that relapses are common, extended periods of therapy should be investigated.

We examined 516G>T polymorphisms at the gene encoding the cytochrome P450 in 100 human immunodeficiency virus-positive subjects who were receiving efavirenz (EFV). Elevated plasma EFV concentrations were found in 40% of subjects with the polymorphic homozygous genotype and 19% of subjects with the heterozygous genotype. Conversely, 20% of subjects with the wild-type genotype had subtherapeutic concentrations of EFV. CYP2B6-516 genotyping may help to identify subjects who have plasma EFV concentrations that are outside of the therapeutic range.

Polymorphisms at MDR1-3435 significantly influence ATV plasma concentrations, as does being Caucasian patients with CT/TT genotypes, having lower ATV levels, even using ritonavir boosting. On the other hand, although ATV plasma concentrations directly correlate with bilirubin levels, the risk of severe hyperbilirubinemia is further increased in the presence of the UGT1A1-TA7 allele.

Nevirapine plasma levels were measured in 70 HIV-infected patients, 33 of whom developed transaminase elevations. Higher nevirapine levels and hepatitis C virus infection were found to be independent predictors of liver toxicity. Moreover, in individuals with chronic hepatitis C, nevirapine concentrations greater than 6 microg/ml were associated with a 92% risk of liver toxicity. Therefore, monitoring nevirapine levels, especially in individuals with chronic hepatitis C, may be warranted.

Ribavirin (RBV) in combination with pegylated interferon alpha (pegIFN) is currently the standard treatment of hepatitis C virus (HCV) infection. The development of anemia requires a reduction in RBV doses in a substantial proportion of patients, limiting their chances of treatment response. The primary goal of this study was to assess if early monitoring of RBV plasma levels could help to predict anemia as well as early HCV RNA response in HIV/HCV-coinfected individuals. The secondary goal was to evaluate if antiretroviral drugs might influence RBV plasma levels. Plasma RBV concentrations were measured at weeks 4 and 12 in 98 HIV/HCV-coinfected individuals who initiated therapy with pegIFN-2a (180 microg/wk) plus RBV (800-1200 mg/d). RBV plasma levels correlated with RBV dose per kilogram of body weight (P = 0.02). Larger drops in hemoglobin levels were independently associated with higher RBV plasma levels and zidovudine (ZDV) use (P < 0.001). Likewise, higher RBV levels (P = 0.007) and HCV genotype 3 (P < 0.001) were found to be independent predictors of virologic response at week 4. Similar findings were obtained at week 12. Patients receiving ZDV concomitantly showed significantly higher RBV plasma concentrations compared with those who did not (3.28 mug/mL vs. 2.51 mug/mL; P = 0.002). RBV levels were not significantly altered by the coadministration of other nucleoside/nucleotide analogues. In summary, RBV plasma levels correlate with the development of anemia and with the achievement of an early virologic response. Therefore, early therapeutic drug monitoring might help to tailor RBV dosages, improving the efficacy and safety of anti-HCV treatment.