Resistance

As with all other anti-HIV drugs, strains of HIV that are resistant to abacavir (Ziagen) may emerge after a period of treatment. The emergence of drug-resistant strains coincides with a fall in the effectiveness of the drug.

There is considerable cross-resistance amongst the nucleoside reverse transcriptase inhibitors (NRTIs). This means that once a patient has HIV that is resistant to one NRTI, other NRTIs will have less effect on HIV viral load. Abacavir may have an effect against HIV that has low-level resistance to some other NRTIs, but HIV that has multiple resistance mutations to NRTIs such as zidovudine (AZT, Retrovir), lamivudine (3TC, Epivir) and didanosine (ddI, Videx /VidexEC) is unlikely to be controlled by abacavir.1 Although people who have developed lamivudine resistance can still benefit from abacavir, if lamivudine resistance is combined with high-level zidovudine resistance, abacavir is unlikely to be effective.2 3

Resistance to abacavir tends to emerge slowly, since a number of mutations must develop for the drug’s efficacy to decrease. Low-level (two- to sixfold) reductions in effectiveness can occur following development of mutation M184V, which is usually associated with lamivudine resistance.4 Subsequent mutations K65R, L74V and Y115F confer high-level (tenfold or greater) resistance to abacavir.5 Similarly, the Q151M brings about low-level resistance to abacavir, but resistance is increased following additional mutations at positions 62, 75, 77 and 116.

Resistance seems to develop at similar rates in people taking abacavir once and twice a day.6

GlaxoSmithKline and ViroLogic investigated the degree of resistance that makes abacavir ineffective. The study reported that less than 4.5-fold resistance to abacavir does not substantially reduce the drug’s effects but that sevenfold or greater resistance renders abacavir largely ineffective.7

Cross-resistance to non-nucleoside reverse transcriptase inhibitors (NNRTIs) or protease inhibitors is very rare.

References

  1. Mellors J et al. Susceptibility of clinical HIV-1 isolates to 1592U89. Fifth Conference on Retroviruses and Opportunistic Infections, Chicago, abstract 687, 1998
  2. Katlama C et al. The role of abacavir (ABC, 1592) in antiretroviral therapy-experienced patients: results from a randomized, double-blind, trial. AIDS 14: 781-789, 2000
  3. Falloon J et al. HIV-1 genotype and phenotype correlate with virological response to abacavir, amprenavir and efavirenz in treatment-experienced patients. AIDS 16: 387-396, 2002
  4. Fenner TEO et al. Changes in codon 184 and phenotypic resistance of 65 different HIV-1 isolates to abacavir, 3TC and AZT. 40th Interscience Conference on Antimicrobial Agents and Chemotherapy, Toronto, abstract 1272, 2000
  5. Harrigan PR et al. Resistance profile of the human immunodeficiency virus type 1 reverse transcriptase inhibitor abacavir (1592U89) after monotherapy and combination therapy. J Infect Dis 181: 912-920, 2000
  6. Craig C et al. Analysis of virologic failure in a clinical trial of abacavir once-daily versus twice-daily with lamivudine and efavirenz. Eleventh Conference on Retroviruses and Opportunistic Infections, San Francisco, abstract 551, 2004
  7. Lanier RE et al. Determination of a clinically relevant phenotypic resistance 'cutoff' for abacavir using the phenosense assay. Eighth Conference on Retroviruses and Opportunistic Infections, Chicago, abstract 254, 2001
Community Consensus Statement on Access to HIV Treatment and its Use for Prevention

Together, we can make it happen

We can end HIV soon if people have equal access to HIV drugs as treatment and as PrEP, and have free choice over whether to take them.

Launched today, the Community Consensus Statement is a basic set of principles aimed at making sure that happens.

The Community Consensus Statement is a joint initiative of AVAC, EATG, MSMGF, GNP+, HIV i-Base, the International HIV/AIDS Alliance, ITPC and NAM/aidsmap
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NAM’s information is intended to support, rather than replace, consultation with a healthcare professional. Talk to your doctor or another member of your healthcare team for advice tailored to your situation.