Women experience higher rates of adverse events during Hepatitis C virus therapy in HIV infection: A meta-analysis

Background: In HIV/HCV coinfection, adverse events (AE) during HCV therapy account for 12-39% of treatment discontinuations. It is unknown whether sex influences complications. Methods: Meta-analysis to study the effect of sex and other predictors of AEs in 3 randomized trials, ACTG 5071, APRICOT, and ANRSHCO2-RIBAVIC of Interferon (IFN) and Pegylated IFN (PEG), both with and without Ribavirin, in HIV/HCV coinfection. Primary endpoints were AEs requiring treatment discontinuation (AETD) or first dose modification (AEDM). Multi-covariate stratified logistic regression was used to study predictors and assess interactions with sex. Results: 21% of 1376 subjects were women; 61% had undetectable HIV RNA; 14% were antiretroviral therapy (ARV) naïve at entry; median CD4 was 485 cells/mm3. 17% had an AETD and 50% AEDM; women had more AETD than men, (24% vs. 16% p=0.003) and AEDM (61% vs. 48% p<0.0001). AETD and AEDM occurred earlier in women; but the types of AETD and AEDM were similar between sexes. 74% of AETDs and 49% of AEDMs involved constitutional AEs; 18% of AETDs depression; and 26% of AEDM neutropenia. We identified interactions with sex and BMI (p=0.04, continuous) and NNRTI (p=0.03); more AETDs were seen in men with lower BMI (p=0.01) and in women on NNRTIs (p=0.009). More AEDMs were seen with PEG (OR=2.07); older age (OR=1.48 per 10yrs); decreasing BMI (OR=1.04 per kg/m2); HCV genotype 1,4 (OR=1.31); Ishak 5,6 (OR=1.42); decreasing Hgb (OR=1.23 per g/dL); and decreasing ANC (1.04 per 500 cells/mm3). Interactions between sex and ARV-naïve status (p=0.001) and AZT (p=0.001) were identified: there were more AEDMs in ARV naïve women (p=0.06) and ARV experienced men (p=0.001); and higher AEDMs in women with AZT (p=0.0002). Conclusions: Although there was no difference in type of AE, AETD and AEDM were more frequent and occurred earlier in women. In women, ARV regimen may be an important predictor of AETDs during HCV therapy and should be explored as a predictor of AEs in HIV/HCV coinfection trials.

• Population(s)
  • Women
  • General HIV+ population
• Co-infections
  • Hepatitis B, C