Women Experience Higher Rates of Adverse Events during Hepatitis C Virus Therapy in HIV Infection: A Meta-analysis

Debika Bhattacharya, MD; T. Umbleja, MS; F. Carrat, MD, PhD; R. T. Chung, MD; M. G. Peters, MD; F. Torriani, MD; J. Andersen, PhD; J. S. Currier, MD, MSc


J Acquir Immune Defic Syndr. 2010;55(2):170-175. 

In This Article

Abstract and Introduction


Background: In HIV/ hepatitis C virus (HCV) coinfection, adverse events (AEs) 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: Twenty-one percent of 1376 subjects were women; 61% had undetectable HIV RNA; 14% were antiretroviral (ARV) therapy naive at entry; median CD4 was 485 cells per cubicmillimeter. Seventeen percent 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. Seventy-four percent of AETDs and 49% of AEDMs involved constitutional AEs; 18% of AETD depression; and 26% of AEDM neutropenia. We identified interactions with sex and body mass index (BMI) (P = 0.04, continuous) and nonnucleoside reverse transcriptase inhibitor (P = 0.03); more AETDs were seen in men with lower BMI (P = 0.01) and in women on nonnucleoside reverse transcriptase inhibitors (P = 0.009). More AEDMs were seen with PEG [odds ratio (OR) = 2.07]; older age (OR = 1.48 per 10 years); 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 absolute neutrophil count (1.04 per 500 cells/mm3). Interactions between sex and ARV-naive status (P = 0.001) and zidovudine (P = 0.001) were identified: There were more AEDMs in ARV-naive women (P = 0.06) and ARV-experienced men (P = 0.001) and higher AEDMs in women with zidovudine (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.


HIV and hepatitis C virus (HCV) coinfection is common, with reported prevalences of 16%-33% in HIV-infected individuals in the United States.[1,2] Liver-related mortality is the leading cause of death among HIV-infected persons in the United States in the highly active antiretroviral therapy era.[3] When compared with HCV monoinfection, hepatitis C therapy is less effective in HIV- and HCV-coinfected individuals due, in part, to high rates of treatment discontinuation.[4–6] In HCV infection without HIV, the percentage of discontinuations secondary to adverse events (AEs) or laboratory abnormalities ranged from 7% to 21%,[7–9] whereas in HIV coinfection, treatment discontinuations occurred in 12%-39%.[4–6] Understanding the role of factors such as sex and its relationship with the development of adverse drug reactions will be critical to improving treatment outcomes in HIV and HCV coinfection.

In HCV monoinfection, women are more likely to experience anemia with interferon and ribavirin therapy[10] and may be more likely to develop depression.[11–13] In HIV infection, studies with nucleoside analogue therapy suggested that women were more likely to require dose modifications, to develop severe symptoms, and to experience AEs related to didanosine.[14,15] There is little known, however, about the sex differences in AEs during HCV therapy in HIV/HCV coinfection. Additionally, the relationship between female sex, AEs during therapy, and other factors potentially related to AEs such as body mass index (BMI) and antiretroviral (ARV) regimen have not been well described in HIV and HCV coinfection.

The aim of our study was to investigate whether female sex was associated with an increased incidence and/or more rapid onset of AEs requiring treatment modification or discontinuation. In addition, we examined whether factors such as ARV regimen and BMI were important in predicting AEs in women and men.


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