Three- or four- versus two-drug antiretroviral maintenance regimens for HIV infection (Cochrane Review)

A substantive amendment to this systematic review was last made on 22 February 2000. Cochrane reviews are regularly checked and updated if necessary.

Background: Combination antiretroviral therapy administered to HIV-infected individuals has been shown to improve immunologic function and delay the progression of HIV infection. However, because patient adherence to complicated combination-therapy antiretroviral regimens is difficult and because of concerns regarding cumulative toxicity of antiretroviral drugs, regimens that utilize fewer antiretroviral agents are desirable.

Objectives: To compare the use three- or four- versus two-drug antiretroviral maintenance regimens following successful induction therapy for HIV infection.

Search strategy: The following electronic databases were searched for relevant randomized trials or reviews:1. MEDLINE for the years 1982-1999 using the search terms human immunodeficiency virus, antiretroviral therapy, maintenance therapy, zidovudine, lamivudine, indinavir, stavudine, saquinivir, nelfinavir, didanosine, zalcitabine, ritonovir, AIDS, anti-HIV agents, HIV infection and HIV seropositivity2. AIDSLINE for the years 1982-1999 using the search terms antiretroviral therapy, maintenance therapy, zidovudine, lamidvudine, indinavir, stavudine, saquinivir, nelfinavir, didanosine, zalcitabine, ritonovir, anti-HIV agents3. The Cochrane Database of Systematic Reviews, Database of Abstracts of Reviews of Effectiveness and the Cochrane Clinical Trials Register in the Cochrane Library, Issue 2, 1999.4. The specialist register of trials maintained by the Cochrane Collaborative Review Group on HIV Infection and AIDS5. AIDSTRIALS, a specialist registry of current and completed trials maintained by the U.S. National Library of MedicineThe abstracts of relevant conferences, including the International Conferences on AIDS, the Conference on Retroviruses and Opportunistic Infections, the Infectious Disease Society of America annual meeting and the Interscience Conference on Antimicrobial Agents and Chemotherapy, as indexed by AIDSLINE, were also reviewed. All reference lists of all review articles and primary articles identified were searched.

Selection criteria: Randomized controlled trials in which HIV-infected adults who had successfully completed three- or four-drug antiretroviral induction therapy were randomized to maintenance therapy with three or four drugs or maintenance therapy with two drugs. Successful induction therapy was defined by a plasma viral load of less than 500 copies/ml.

Data collection and analysis: Two reviewers assessed eligibility and trial quality. Attempts were made to contact the authors of the included abstract. Data on the number of patients experiencing loss of viral suppression were abstracted by two reviewers. The data were pooled, where appropriate, to yield odds ratios, using random effects models.

Main results: Four trials were identified including three published studies and one abstract. Compared to three- or four-drug maintenance therapy, maintenance therapies including fewer drugs were associated with a higher risk of virologic failure (loss of HIV suppression to non-detectable levels). Combining the results of all four studies yielded an odds ratio of 5.55 (95% confidence interval, 3.14 - 9.80). Similar results were obtained when the one abstract was excluded (odds ratio, 5.48; 95% confidence interval, 2.82 - 10.65).Performing subgroup analyses of studies using the same induction and maintenance regimens gave similar results. Maintenance regimens of zidovudine and lamivudine compared to maintenance regimens with zidovuine, lamivudine and indinavir, were associated with significantly higher rates of virologic failure (odds ratio, 4.57; 95% confidence interval, 1.80 - 11.58). Similarly, maintenace regimens that discontinued one or more protease inhibitor after including them in induction therapy were also associated with a significantly higher risk of virologic failure (odds ratio, 6.15; 95% confidence interval, 3.40 -11.10).

Reviewers' conclusions: Although it is desirable to reduce the number of antiretroviral drugs given in combination therapy for reasons of compliance and toxicity, maintenance regimens with fewer drugs are associated with significantly increased risk of loss of viral suppression. Successful induction therapy, as evidenced by suppresion of viral load, should not be modified in the maintenance phase unless clinically necessary.

Citation: Rutherford GW, Feldman KA, Kennedy, GE. Three- or four- versus two-drug antiretroviral maintenance regimens for HIV infection (Cochrane Review). In: The Cochrane Library, Issue 3, 2003. Oxford: Update Software.

---

This is an abstract of a regularly updated, systematic review prepared and maintained by the Cochrane Collaboration. The full text of the review is available in The Cochrane Library (ISSN 1464-780X).

The Cochrane Library is designed and produced by Update Software Ltd.

Update Software Ltd, Summertown Pavilion, Middle Way, Oxford OX2 7LG, UK
(Tel:+44 1865 513902; Fax:+44 1865 516918)

File Reference: AB002037.htm