Abstract: Our search resulted in 1,148 records, of which two studies described trials that met our inclusion criteria. One trial was a small single-centre Australian trial of 70 antiretroviral-naive participants, while the other trial was a large, multicentre trial, conducted in 14 countries, of 1,216 antiretroviral-naive participants. In both trials over 60% of participants were male. As the therapeutic combinations compared in both trials were not identical, it was not possible to conduct a meta-analysis to increase the power of the results. The main findings, therefore, are from the much larger trial, which was of a high quality. This trial found that there was no statistically significant difference in the efficacy (measured by treatment failure) between nevirapine and efavirenz (EFZ), when used in combination with 3TC and d4T (RR = 1.16; 95%CI: 0.95, 1.41). There was no statistically significant difference between once daily or twice-daily dosing of NVP, when used in combination with 3TC and d4T (RR = 1.00; 95%CI: 0.83; 1.21). It also showed that, compared with NVP plus EFZ, 3TC and d4T, a once-daily dosing of NVP, in combination with 3TC and d4T, performs better in averting treatment failure (RR = 0.82; 95%CI: 0.67, 1.00) than does twice-daily dosing of NVP with 3TC and d4T (RR = 0.82; 95%CI: 0.69; 0.97). Frequency of toxicity was higher in participants receiving NVP, compared with EFZ. The combination of nevirapine, 3TC and d4T is as efficacious as a combination of efavirenz, 3TC and d4T. Once-daily NVP with twice-daily 3TC and d4T is as efficacious as twice-daily NVP, 3TC and d4T. However, toxicity may be increased in the once-daily NVP regime. Additional trials of sufficient duration are required to provide better evidence for the use of this combination as a first line therapy. Ideally, trials should use standardised assessment measures especially with respect to measuring viral load, so that results can be compared and combined in meta-analyses.

Plain-language summary: People infected with HIV/AIDS require an antiretroviral regimen that works well, has good activity against the virus, has few adverse effects (unintended negative effects of the drug) and that does not interact with other drugs. The regimen of nevirapine, stavudine and lamivudine is widely used as first-line therapy, and is recommended as such by the World Health Organization for so-called low-resource countries (in other words, for poor countries). This review identified two randomised controlled trials that assessed the efficacy of this drug combination. One trial was a small single-centre Australian trial of 70 participants, whereas the other trial was a large, multicentre trial, conducted in 14 countries, of 1,216 participants. In both trials over 60% of participants were male and none had been on previous antiretroviral treatment. As one trial was very small, we cannot be sure of its results. The main findings therefore come from the much larger trial. This trial compared the combination of nevirapine, stavudine and lamivudine with the combination of efavirenz, stavudine and lamivudine, and found that participants had similar treatment outcomes on either combination. It also found that taking nevirapine once a day with twice daily stavudine and lamivudine worked as well as taking nevirapine twice a day in combination with twice daily stavudine and lamivudine. Nevirapine did appear to cause more adverse effects compared with efavirenz, but additional assessment of this is necessary to be more certain. It is important that more trials which follow participants for a longer time be done to provide better evidence for the use of this combination as a first-line therapy. A trial assessing fixed-drug (providing drugs in a single tablet) is also required, as this reduces the number of pills people must take each day. These studies should include assessment of adverse effects, as well as tracking whether resistance to the drugs develop over time.