The incidence, predictors and management of anaemia and its association with virological response in HCV / HIV coinfected persons treated with long-term pegylated interferon alfa 2a and ribavirin

Abstract

Background: The association of anaemia with outcomes in the HCV/HIV coinfected persons undergoing HCV treatment remains unclear.

Aims: To study the incidence, predictors and management of anaemia, and its association with outcomes among persons treated with pegylated interferon and weight-based ribavirin.

Methods: Retrospective analysis of a prospective controlled treatment trial of HCV/HIV coinfection.

Results: Among 329 subjects enrolled, 40% developed anaemia during the first 12-18 weeks of treatment (median haemoglobin decrease at week 4: 2.2 g/dL). Among 169 subjects who achieved early virological response and received therapy for 72 weeks, 55% eventually developed anaemia. However, median haemoglobin levels stayed stable after 12-18 weeks of initial therapy. Among these 169 subjects, 45% were prescribed an erythropoiesis stimulating agent (ESA), with 17% receiving it prior to a drop in haemoglobin meeting protocol definition of anaemia. Only 27% completed the study without any ribavirin dose modification. Age >40 years, lower BMI, zidovudine use and lower entry haemoglobin were significant predictors of anaemia in the multi-covariate model. Among all 329, sustained virological response (SVR) rate was similar in those with or without anaemia (23% vs. 30%; P=0.17) with no evidence of association between anaemia or ESA use and treatment response.

Conclusions: Anaemia is common in HCV/HIV coinfected persons undergoing HCV treatment, and only a minority of them are able to maintain ribavirin dose. Persons with age >40 years, lower baseline haemoglobin and lower baseline BMI should be monitored carefully. Prescription of erythropoiesis stimulating agent is common, but anaemia or erythropoiesis stimulating agent use is not associated with SVR.

Figure 1

The schema for A5178 study.

Figure 2

(a) Time to anaemia (Step 1). (b) Time to anaemia (Steps 1 + 3). Follow-up was censored at the initiation of an erythropoeisis stimulating agent, ribavirin dose reduction or discontinuation. Step 1 refers to all subjects who entered the trial (N = 329); Step 3 refers to subjects who completed at least 12 weeks of therapy, demonstrated an early virological response defined as a drop in HCV RNA of at least 2 log₁₀ at week 12, and were assigned to continue treatment with pegylated interferon and weight-based ribavirin for a total of 72 weeks.

Figure 3

Change in haemoglobin from study entry. * Medians with interquartile range are plotted at each time point. Step 1 refers to all subjects who entered the trial (N = 329); Step 3 refers to subjects who completed at least 12 weeks of therapy, demonstrated an early virological response defined as a drop in HCV RNA of at least 2 log₁₀ at week 12, and were assigned to continue treatment with pegylated interferon and weight-based ribavirin for a total of 72 weeks.

Figure 4

Change in haemoglobin among subjects who entered Step 3, by gender. * Medians with interquartile range are plotted at each time point. ** FUP0, FUP12, FUP24 are follow-up visits at 0, 12 and 24 weeks after treatment discontinuation respectively.

Figure 5

Anaemia on Step 1 and response to treatment. * EVR = early virological response defined as at least a 2 log10 drop from HCV RNA from entry or undetectable (<600 IU/mL) HCV RNA at week 12; cEVR = complete early virological response defined as undetectable HCV RNA at week 12; SVR = sustained virological response defined as undetectable (<60 IU/mL) HCV RNA at 24 weeks after treatment discontinuation.