Increasing the number of drugs in antiretroviral therapy may improve survival in people with HIV infection

Rutherford, George W. MD

AIDS Research Institute; Department of Epidemiology and Biostatistics; University of California, San Francisco, USA

Abstracted from:Jordan R, Gold L, Cummins C, Hyde C. Systematic review and meta-analysis of evidence for increasing numbers of drugs in antiretroviral combination therapy. Br Med J 2002; 324: 1-10 .

Evidence-based Healthcare 6(4):p 163-164, December 2002.

BACKGROUND

Since the introduction of zidovudine in 1987, many antiretroviral agents have become available for people with HIV infection. Treatment with two or three different drugs is accepted practice. Evidence for increasing the number of drugs used in antiretroviral therapy is of limited quality.

OBJECTIVE

To assess whether increasing the number of drugs in antiretroviral therapy improves disease progression and survival rates for people with HIV infection.

METHOD

Systematic review with meta-analysis.

SEARCH STRATEGY

MEDLINE, EMBASE, Cinahl, PsychLit, HealthSTAR, the Cochrane Library, internet sites and reference lists were searched to February 2001. Pharmaceutical companies were contacted for additional studies.

INCLUSION/EXCLUSION CRITERIA

Trials were eligible if they compared a licensed antiretroviral drug or combination with no treatment, placebo or other antiretroviral treatment for people with any stage of HIV infection. There was no language restriction. Studies lasting less than 12 weeks were excluded. Fifty-four randomised controlled trials with 20,404 participants were included. Participants were aged over 12 years with less than 6 months previous antiretroviral therapy. Trials lasted between 12 weeks and 4.8 years.

ANALYSIS

Two independent reviewers assessed studies using a standard checklist. Meta-analysis and meta-regression were performed using extracted data.

OUTCOMES

Disease progression; death; CD4 count; plasma viral load.

MAIN RESULTS

Combining two or three antiretroviral drugs improved clinical and surrogate outcomes (Table 1). There is little evidence about the effect of combining four or more antiretroviral drugs.

Table 1 Disease progression or death among people with HIV infection following antiretroviral therapy with one or more drugs
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AUTHORS' CONCLUSIONS

Findings support the use of triple therapy for people with HIV infection. There is inadequate evidence for combinations of four drugs or more.

NOTE

There was heterogeneity in effect sizes due to the use of different drugs and variable study quality.