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Abacavir Looks as Safe and Effective as Tenofovir

A meta-analysis of 28 controlled trials did not find elevated heart attack risk with abacavir, and a Canadian study showed no greater risk of treatment failure among patients with high viral load, according to 2 recently published reports.

The association between use of abacavir (Ziagen, also in the Epzicom and Trizivir coformulations) and myocardial infarction (MI), or heart attack, remains controversial, as does the suggestion that abacavir may not work as well for people who start antiretroviral therapy (ART) with high HIV viral load.

While an analysis of the large observational D:A:D cohort showed an increased risk of MI among people taking abacavir, prior meta-analyses of clinical trials -- including one by the U.S. Food and Drug Administration (FDA) -- have not seen such a link.

Cardiovascular Risk

As described in the June 29, 2011, advance online issue of AIDS, Mario Cruciani and colleagues sought to combine all evidence from randomized controlled trials (RCTs) -- both published and unpublished -- to assess the effect of ART regimens containing abacavir on MI risk, major cardiovascular events overall, adverse events requiring treatment discontinuation, and overall mortality.

The investigators searched databases such as MEDLINE for relevant studies published in medical journals. They also looked at data presented at major HIV/AIDS conferences including the International AIDS Society Conference on HIV Pathogenesis, Treatment, and Prevention, the International AIDS Conference, the Conference on Retroviruses and Opportunistic Infections (CROI), the Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC), and European AIDS Clinical Society (EACS) meetings.

The meta-analysis included data from 28 RCTs including a total of 9233 participants (4376 taking abacavir-containing regimens and 4857 taking non-abacavir regimens).

Results

• MI data were available from 18 trials, yielding a total of 31 episodes among 7054 participants.
• Cardiovascular events data were available from 20 trials, showing 79 episodes among 7899 patients.
• Abacavir use was not significantly associated with greater likelihood of any adverse outcomes considered in this analysis, compared with non-abacavir regimens:

o      Occurrence of MIs: relative risk (RR) 0.73;

o      Major cardiovascular events: RR 0.95;

o      Adverse events requiring treatment discontinuation: RR 0.82;

o      Overall mortality: RR 1.20.

Based on these findings, the study authors concluded, "This meta-analysis of RCTs does not support the hypothesis that abacavir-containing [combination] ART regimens carry a greater risk of MI or major cardiovascular events relative to comparator [combination] ART."

Treatment Failure

In a related study described in the June 24, 2011, Journal of Acquired Immune Deficiency Syndromes, investigators with the Canoc (Canadian Observational Cohort) Collaboration compared the performance of regimens containing abacavir/lamivudine (the drugs in Epzicom) and those containing tenofovir/emtricitabine (the drugs in Truvada) for initial combination ART.

This retrospective observational cohort study looked at the relationship between time to regimen failure and choice of nucleoside/nucleotide reverse transcriptase inhibitors (NRTIs), defined as a composite of virological failure and switching or stopping NRTIs for any reason.

The analysis included 1764 HIV positive people who started combination ART for the first time using either abacavir/lamivudine or tenofovir/emtricitabine (588 and 1176 participants, respectively) in combination with efavirenz (Sustiva), nevirapine (Viramune), lopinavir/ritonavir (Kaletra), or boosted atazanavir (Reyataz). Injection drug users were not included.

Participants had least 6 months of follow-up after ART initiation, but median duration was much longer (34 months for abacavir/lamivudine recipients and 20 months for tenofovir/emtricitabine).

Results   

• Time to regimen failure was similar for abacavir/lamivudine and tenofovir/emtricitabine recipients, after adjusting for sex, province, baseline viral load, specific third agents, year of ART initiation, and availability of HLA-B*5701 abacavir hypersensitivity testing (adjusted hazard ratio [HR] 0.96).
• Patients taking abacavir/lamivudine were significantly more likely than those treated with tenofovir/emtricitabine to have baseline viral load > 100,000 copies/mL.
• There were no significant differences observed with regard to:

o      Time to virological failure: adjusted HR 0.84;

o      Switching or stopping NRTIs for reasons other than virological failure: adjusted HR 1.02;

o      Time to viral load suppression: adjusted HR 0.96.

• There were still no significant differences in outcomes when participants were stratified according to baseline viral load above or below 100,000 copies/mL.

"In our naive, non-injection drug user HIV-infected patients starting [combination] ART, there was no difference in time to regimen failure, virologic failure, switching/stopping nucleosides, or virologic suppression with [abacavir/lamivudine] versus [tenofovir/emtricitabine].

Taken together, these findings indicate that abacavir regimens work as well as the usual alternative in terms of both safety and efficacy. Results such as these may prompt the experts who determine U.S. federal treatment guidelines to restore abacavir as a preferred first-line agent.

Investigator affiliations:

Cruciani study: Centre of Community Medicine & HIV Outpatient Clinic, Verona, Italy; Department of Histology, Microbiology and Medical Biotechnology, University of Padua, Padua, Italy; Department of HIV and Genitourinary Medicine, Chelsea and Westminster Hospital, London, UK.

Tan study: University of Toronto, Toronto, Ontario; University Health Network, Toronto, Ontario; St. Michael's Hospital, Toronto, Ontario; British Columbia Centre for Excellence in HIV/AIDS, Vancouver, British Columbia; University of Ottawa, Ottawa, Ontario; Faculty of Medicine, University of British Columbia, Vancouver, British Columbia; Faculty of Health Sciences, Simon Fraser University, Vancouver, British Columbia; Montreal Chest Institute, Montreal, Quebec; McGill University, Montreal, Quebec; Clinique Medical L'Actuel, Montreal, Quebec; Ontario HIV Treatment Network, Toronto, Ontario; Women's College Hospital, Toronto, Ontario, Canada.

7/15/11

References

M Cruciani, V Zanichelli, G Serpelloni, et al. Abacavir use and cardiovascular disease events: a meta-analysis of published and unpublished data. AIDS (abstract). June 29, 2011 (Epub ahead of print).

DH Tan, K Chan, J Raboud (Canoc Collaboration). Comparison of abacavir/lamivudine and tenofovir/emtricitabine among treatment-naive HIV-infected patients initiating therapy. Journal of Acquired Immune Deficiency Syndromes (abstract). June 24, 2011 (Epub ahead of print).