HIV-HCV Coinfected Women May Experience More Pegylated Interferon and Ribavirin Side Effects than Men

By Liz Highleyman

Treatment of chronic hepatitis C with pegylated interferon plus ribavirin can cause side effects that may lead to dose reduction or discontinuation of therapy.

As reported at the 16th Conference on Retroviruses and Opportunistic Infections (CROI 2009) last week in Montreal, Debika Bhattacharya and colleagues performed a meta-analysis to examine the effect of sex and other predictors of adverse events in 3 pivotal trials of pegylated interferon, with or without ribavirin, in HIV/HCV coinfected patients: APRICOT, ACTG A5071, and ANRS HC02-RIBAVIC.

Out of 1376 total participants, 21% were women. Participants had relatively well-preserved immune function (median CD4 count 485 cells/mm3), were antiretroviral-naive at study entry, and 61% achieved undetectable HIV viral load.

Results

Overall, 50% of patients experienced adverse events (AEs) requiring a first dose modification.

17% required premature treatment discontinuation due to side effects.

Women were more significantly likely than men to experience AEs leading to dose modification (61% vs 48%; P < 0.0001) or treatment discontinuation (24% vs. 16%; P = 0.003).

AEs occurred earlier in women on average.

Types of AEs leading to treatment changes were similar in women and men.

The most common reasons for dose reduction were constitutional symptoms such as fatigue and headache (49%), followed by neutropenia (26%).

The most common reasons for treatment discontinuation were constitutional symptoms (74%), followed by depression (18%).

Older patients experienced more side effects overall (odds ratio [OR] 1.70 per 10 years)

More AEs leading to treatment discontinuation were seen among men with lower body mass and women taking non-nucleoside reverse transcriptase inhibitors (NNRTIs).

More AEs requiring dose reduction were seen with pegylated versus conventional interferon (OR 2.07), older age (OR 1.48 per 10 years), decreasing body mass index (OR 1.04 per kg/m2), HCV genotype 1 or 4 (OR 1.31), severe liver fibrosis or cirrhosis (Ishak 5-6; OR 1.42), and decreasing hemoglobin level (OR 1.23 per g/dL).

More AEs leading to dose reduction were observed in antiretroviral-naive women and in men with prior treatment.

There was a high rate of adverse events requiring treatment discontinuation in women taking zidovudine (AZT, Retrovir), which can cause anemia.

"Although there was no difference in type of adverse event, women are more likely to have [AEs requiring treatment discontinuation or dose reduction], and for them to occur more rapidly than in men," the researchers concluded.

In women, they added, "antiretroviral regimen may be an important predictor of [AEs requiring treatment discontinuation] during HCV therapy and should be explored as a predictor of adverse events in future HIV-HCV coinfection trials.

Univ of California, Los Angeles, CA; Harvard School of Public Health, Boston, MA; Groupe Hosp Univ Est, Univ Paris 6, INSERM U707, France; Massachusetts General Hospital, Boston, MA; Univ of California, San Francisco, CA; Univ of California, San Diego, CA.

2/20/09

Reference
D Bhattacharya, T Umbleja, F Carrat, and others. Women Experience Higher Rates of Adverse Events during HCV Therapy in HIV Infection. 16th Conference on Retroviruses and Opportunistic Infections (CROI 2009). Montreal, Canada. February 8-11, 2009. Abstract 845.