Women experience higher rates of adverse events during hepatitis C virus therapy in HIV infection: a meta-analysis.

University of California, Los Angeles, CA, USA.
JAIDS Journal of Acquired Immune Deficiency Syndromes (Impact Factor: 4.39). 10/2010; 55(2):170-5. DOI: 10.1097/QAI.0b013e3181e36420
Source: PubMed

ABSTRACT 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.
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.
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/m); 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/mm). 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).
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.

  • [Show abstract] [Hide abstract]
    ABSTRACT: The intensity and prevalence of viral infections are typically higher in males than in females. In contrast, disease outcome can be worse for females. Males and females also differ in their responses to prophylaxis and therapeutic treatments for viral diseases. In response to vaccines against herpes viruses, hepatitis viruses, influenza viruses, and others, females consistently mount higher humoral immune responses and experience more frequent and severe adverse reactions than males. Males and females also differ in the absorption, metabolism, and clearance of antiviral drugs. The pharmacological effects, including toxicity and adverse reactions, of antiviral drugs are typically greater in females than males. The efficacy of antiviral drugs at reducing viral load also differs between the sexes, with antiviral treatments being better at clearing HIV and hepatitis C virus in females, but showing greater reduction of herpes simplex virus and influenza A virus loads in males. Biological variables, including hormone and genes, as well as gender-specific factors related to access and compliance to drug regimens must be considered when evaluating male-female differences in responses to treatments for viral diseases. Clinicians, epidemiologists, and basic biomedical scientists should design experiments that include both males and females, develop a priori hypotheses that the sexes will differ in their responses to and the outcome of vaccines and antiviral treatments, and statistically analyze outcome data by sex. Knowledge that the sexes differ in response to prophylaxis and therapeutic treatments for viral diseases should influence the recommended course of treatment differently for males and females.
    Handbook of experimental pharmacology 01/2012; DOI:10.1007/978-3-642-30726-3_22
  • [Show abstract] [Hide abstract]
    ABSTRACT: Hepatitis C virus (HCV) and HIV are common coinfections that convey a shortened lifespan, mostly related to liver disease. Treatment against HCV in the coinfected patient is notoriously more complex and challenging. There are no optimal treatment algorithms for HIV/HCV coinfected patients as efficacy of approved anti-HCV therapies is low with relevant side effects. The use of direct-acting antivirals for anti-HCV therapy has the potential to improve therapeutic efficacy, but also increase side effects and drug-drug interactions. In spite of all of this, the most important and significant fact is that chronic hepatitis C is potentially curable, and the eradication of the HCV infection is a crucial outcome in this population. The establishment of a productive collaboration among the regulatory agencies, the medical community and the pharmaceutical industry could lead to faster access to more effective HCV therapies for the coinfected patient and eventually stop the progression of liver disease in these patients.
    Expert Review of Anticancer Therapy 10/2012; 10(10):1117-28. DOI:10.1586/eri.12.107 · 3.06 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: In HIV-infected individuals, coinfection with HBV and/or HCV is common because of shared modes of transmission. It is known that HIV accelerates progression of liver disease and results in increased morbidity and mortality associated with viral hepatitis, but it is less clear if viral hepatitis has a direct effect on HIV. Treatment of viral hepatitis improves outcomes and should be considered in all HIV-infected patients. Treatment of HBV without concurrent treatment of HIV is risky because resistance can occur in both viruses if regimens are not carefully chosen.
    Infectious Disease Clinics of North America 09/2014; 28(3):477-499. DOI:10.1016/j.idc.2014.05.005 · 2.31 Impact Factor


Available from