Study designs of evaluations included in the review
Clinical trials with at least 80% participant follow-up were eligible for inclusion. The trials included in the review had between 96 and 100% complete follow-up; follow-up was for 24 to 64 weeks.
Specific interventions included in the review
Studies that investigated once-a-day administration of at least three antiretroviral drugs were eligible for inclusion in the review. A low dose of ritonavir (RTV) to boost other protease inhibitors was not considered to be an additional drug to the regimen. The included studies used the following combinations in their once-a-day HAART regimen:
didanosine (ddI), emtricitabine (FTC) and efavirenz (EFV);
ddI, lamivudine (3TC) and EFV;
ddI, 3TC, EFV and adefovir dipivoxil;
ddI, nevirapine and EFV;
ddI, 3TC, indinavir and RTV; and
ddI, 3TC, saquinavir and RTV.
Details of the doses used in the studies were given. Directly observed therapy was used in one study.
Participants included in the review
Patients infected with HIV with detectable virus loads were eligible for inclusion. The majority of the participants in the studies were male. All participants were naive to antiretroviral therapy. The average baseline CD4 lymphocyte cell count of the participants was 164 to 471 cells/microL. The average baseline HIV-1 RNA load of the participants was 4.47 to 5.56 log10 copies/mL. Three studies reported that they included patients who were intravenous drug users.
Outcomes assessed in the review
Studies that reported undetectable HIV-1 RNA load at 24 and 48 weeks of follow-up were eligible for inclusion. The included studies reported the HIV-1 RNA load at 24 weeks (2 studies), 32 weeks (1 study), 48 weeks (4 studies), or 64 weeks (1 study). Seven studies had a lower limit of detection of 50 copies/mL, while the remaining study had a lower limit of detection of 400 copies/mL. The included studies also reported the average CD4 cell count increase. The adherence rate was measured in 5 studies: by pill count in one study and by self-report in the other 4 studies. Adverse events were also reported.
How were decisions on the relevance of primary studies made?
Two reviewers independently assessed the titles or abstracts of the identified studies to assess their relevance to the review. Both reviewers then independently assessed the full articles (or abstracts when full articles were not produced) for potential relevance. Any disagreements were resolved by consensus. The authors of 14 articles were asked to provide additional data to clarify ambiguities before including their data; 5 authors replied. For the other 9 studies, the decision on whether the study was eligible for inclusion in the review was based on the available information.
Weighted kappa statistics were used to measure the level of agreement between reviewers for the selection and inclusion of studies in the review. For duplicated or updated publications, only the most complete data set was included in the review.