SUMMARY: Using a nucleoside/nucleotide reverse transcriptase inhibitor (NRTI) backbone containing abacavir (Ziagen, also in the Epzicom coformulation) was not associated with poorer response to interferon-based therapy for hepatitis C in HIV/HCV coinfected patients, researchers reported at the 17th Conference on Retroviruses and Opportunistic Infections (CROI 2010) last month in San Francisco. However, backbones containing zidovudine (AZT; Retrovir) and possibly didanosine (ddI; Videx) were associated with a lower likelihood of achieving a sustained response.

By Liz Highleyman

The effect of accompanying antiretroviral drugs on virological response to hepatitis C therapy using interferon plus ribavirin remains uncertain, given that prior studies have produced conflicting results. Like ribavirin, zidovudine can cause anemia, which may increase the risk of ribavirin dose reduction and premature discontinuation. Some studies have suggested that abacavir might be linked to poorer response, but data have not been consistent.

To further explore this issue, Juan Berenguer and colleagues evaluated the effect of antiretroviral drugs, particularly abacavir, on response to pegylated interferon plus ribavirin in HIV/HCV coinfected patients.

The investigators conducted a retrospective pooled analysis of 2 cohorts of HIV/HCV coinfected patients starting hepatitis C treatment: GESIDA 3603 (enrolled between January 2000 and July 2007 at 20 centers in Spain) and GESIDA 5006 (enrolled between January 2003 and June 2005 at 36 centers). In GESIDA 5006, the main objective was to evaluate the safety and efficacy of interferon-based therapy in coinfected patients taking ART that included tenofovir vs other NRTIs.

The analysis included a total of 1701 coinfected patients. Most (75%) were men and the median age was 41 years. A majority (63%) had hard-to-treat HCV genotypes 1 or 4, two-thirds had high HCV viral load, and 27% had advanced fibrosis or cirrhosis. Most (88%) were on ART, 74% had HIV viral load < 50 copies/mL, and the median baseline CD4 cell count was high, at 514 cells/mm3.

About 60% were treated with pegylated interferon alfa-2a (Pegasys) and 40% received pegylated interferon alfa-2b (PegIntron), both with ribavirin (typically weight-adjusted). The study outcome measure was sustained virological response (SVR), or undetectable HCV viral load 24 weeks after completion of treatment.

Results

	The overall SVR rate was 38%:
	25% for genotypes 1 and 4; 61% for genotypes 2 and 3.
	In a multiple logistic regression analysis, the following factors were independently associated with increased odds of sustained response:
	HCV genotype 2 or 3 (adjusted odd ratio [OR] 5.31); Absence of AIDS-defining conditions (adjusted OR 1.75); Baseline HVC RNA < 500,000 IU/mL (adjusted OR 1.73).
	44% of participants receiving any ART achieved SVR, compared with 37% of those not on any ART (not a significant difference).
	Looking at NRTI backbones yielded the following SVR rates:
	Tenofovir + lamivudine (3TC; Epivir) or emtricitabine (Emtriva): 42% (21% for genotypes 1 or 4 only); Lamivudine + stavudine (d4T; Zerit): 39% (19%); Abacavir + lamivudine (without zidovudine): 37% (26%); Zidovudine + lamivudine (all): 35% (19%); Zidovudine + lamivudine (without abacavir): 36% (18%); Zidovudine + lamivudine (with abacavir): 33% (19%); Didanosine + lamivudine or emtricitabine: 25% (17%); Didanosine + stavudine: 21% (10%).
	Regimens containing zidovudine (all and without abacavir) were significantly less effective than regimens containing tenofovir.
	Otherwise, the effect of other NRTI backbones had little effect on SVR.
	Response rates were lower with didanosine backbones, but few patients used such regimens and the differences did not reach statistical significance.
	No significant differences were found between the different backbones when repeating the analysis for patients receiving < 800 mg/kg ribavirin or less than the median or first quartile ribavirin doses.
	Likewise, no significant differences were found between the backbones when analyzing subgroup of patients with HCV genotype 1 or 4, or those with HCV RNA > 500,000 IU/mL.
	Also, no significant differences were found according to whether the NRTI backbone was accompanied by a NNRTI or a boosted or unboosted protease inhibitor.

Based on these findings, the investigators concluded, "Our results suggest that, with the exception of regimens including [zidovudine], accompanying antiretroviral drugs have little effect on virologic response to [pegylated interferon] plus ribavirin in HIV/HCV patients."

"We did not find abacavir to negatively impact the outcome of [pegylated interferon] plus ribavirin therapy even in difficult-to-treat patients such as those with genotypes 1 and 4 and high HCV RNA," they added.

Hosp Gen Univ Gregorio Marañón, Madrid, Spain; Hosp Donostia, Spain; Hosp Ramon y Cajal, Spain; Hosp Clin, Barcelona, Spain; Hosp Univ La Fe, Valencia, Spain; Hosp Univ La Paz, Madrid, Spain; Hosp Principe de Asturias, Spain.

3/2/10

Reference
J Berenguer, M von Wichmann, C Quereda, and others. Effect of Accompanying Antiretroviral Drugs on Virologic Response to PEG-IFN and Ribavirin in HIV/HCV-Co-infected Patients. 17th Conference on Retroviruses & Opportunistic Infections (CROI 2010). San Francisco. February 16-19, 2010. (Abstract 663).