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 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 AZT (zidovudine, Retrovir), 3TC (lamivudine, Epivir) and ddI (didanosine, Videx / VidexEC) is unlikely to be controlled by abacavir^[1]. Although people who have developed 3TC resistance can still benefit from abacavir, if 3TC resistance is combined with high-level AZT 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 resistance to 3TC 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 patients 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.