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Validating WHO-Recommended Second-Line ART

July 15, 2013

Validating WHO-Recommended Second-Line ART

  1. Mauro Schechter, MD, PhD

A multinational, randomized trial documents similar efficacy with WHO-recommended second-line antiretroviral therapy and a raltegravir-based regimen.

  1. Mauro Schechter, MD, PhD

For HIV-infected patients in resource-limited settings, the WHO recommends using easily administered first-line antiretroviral therapy (ART): a non-nucleoside reverse transcriptase inhibitor (NNRTI) plus two nucleoside or nucleotide reverse transcriptase inhibitors (NRTIs). For patients who require second-line ART, the WHO recommends ritonavir-boosted lopinavir plus two or three NRTIs.

In an open-label trial spanning 37 sites on five continents, researchers randomized 541 HIV-infected adults with confirmed virologic failure after ≥24 weeks on first-line ART to receive either the WHO's recommended second-line regimen (control group) or boosted lopinavir plus raltegravir, an integrase inhibitor. Sites with access to resistance testing had to use it to guide NRTI choices; sites without such access used a simple algorithm to guide NRTI choices. In all, 479 of 492 patients (97%) who underwent resistance testing had at least one major resistance mutation to an NRTI.

In a modified intention-to-treat analysis, a viral load <200 copies/mL was achieved at 48 weeks by 81% of the control group and 83% of the raltegravir group, a nonsignificant difference. The finding persisted whether or not resistance testing was used to select the NRTI backbone, patients were stratified according to baseline viral load, or the viral-load outcome threshold was lowered to <50 copies/mL. Rates of death, overall adverse events, and serious adverse events were similar between the two treatment groups.

Comment

These findings document the efficacy of WHO-recommended second-line ART and show that resistance testing is not necessary to adequately manage patients with first-line ART failure, if appropriate algorithms are used. The main potential advantages of the raltegravir second-line regimen — simplicity, its NRTI-sparing nature, and the lack of need for resistance testing or algorithms — are offset by the potential limitations of third-line ART after second-line failure and by high cost. The former can be addressed in studies that compare the durability of the two second-line regimens; the latter is likely to depend on the approval of new integrase inhibitors, which should drive down prices.

Dr. Schechter is a Professor of Infectious Diseases at Universidade Federal do Rio de Janeiro, Head of the AIDS Research Laboratory at Hospital Universitario Clementino Fraga Filho, and Principal Investigator of Projeto Praça Onze at Hospital Escola São Francisco de Assis in Brazil. He reports no conflicts of interest.

Citation(s):

Reader Comments (1)

Woldegiorgis Asfawesen Physician, Internal Medicine, Ethiopia
Competing Interests: Nothing to disclose

we have been unconformtable when switching patient to second line ART without knowing the degree of resistance because decison to switch is done usually after registering definite immunologic and/or clinical failure which could lead to accumulation of multiple mutations. This may knock out all the NRTIs. I am realy relived to read the non-inferiority of the WHO recommended second line ART eventhough more studies could still be needed.

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