Background: Single-drug class regimens with nucleoside/nucleotide reverse transcriptase inhibitors (NRTIs) are generally not recommended as initial therapy because they are inferior compared with therapy with two NRTIs plus efavirenz. However, triple-NRTI combinations can be useful in specific circumstances such as in tuberculosis coinfection, pregnancy or dyslipidaemia. Here, we review the potential of such combinations to maintain viral suppression after induction of suppression by standard combination antiretroviral therapy (cART) and to evaluate the trade-off of NRTI-only regimens for metabolic control.
Methods: We conducted a systematic search of the literature in two databases from 1 January 1998 up to 1 March 2013: Medline, through the search engine PubMed, and Embase.
Results: A total of 11 randomized controlled trials (RCTs) with 2,105 patients and 3 observational studies with 2,639 patients were included. Studies including patients with mono- or dual-NRTI treatment before start of effective cART showed a tendency to higher failure rate because of resistance based on archived viral mutations. In studies with ART-naive subjects before start of cART, triple-NRTI combination showed virological activity comparable to two NRTIs plus a protease inhibitor or a non-nucleoside reverse transcriptase inhibitor in all RCTs, but not in one cohort study. Switching improved serum lipids significantly.
Conclusions: Of the studied triple-NRTI combinations only abacavir/lamivudine/zidovudine was sufficiently potent. Triple-NRTI maintenance after successful induction with two-class cART appeared successful in treatment-naive subjects and remains a useful option in specific circumstances, especially when other drugs are not available or drug interactions are an issue.