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Antiretroviral therapy in primary HIV infection Evaluation of: SPARTAC Trial Investigators, Fidler S, Porter K et al. Shortcourse antiretroviral therapy in primary HIV infection. N. Engl. J. Med. 368, 207–217 (2013). The timing of antiretroviral therapy (ART) in patients who present with primary HIV infection is uncertain. This paper compared three strategies: ART for 48 weeks; ART for 12 weeks; or no therapy in 366 patients with primary HIV infection. They showed that 48 weeks of ART significantly reduced the risk of needing definitive therapy (after a median follow-up of 4.2 years). However, the median delay in needing to start definitive therapy (61 weeks) is not significantly greater than the amount of treatment given (48 weeks) to achieve this result, suggesting that the clinical benefit of immediate ART in primary HIV infection is not yet clear.
William G Powderly Division of Infectious Diseases, Washington University School of Medicine, 660 South Euclid Avenue, St Louis, MO 63110, USA Tel.: +1 314 454 8215 [email protected]
KEYWORDS: antiretroviral therapy n direct comparison n HIV disease progression n primary HIV infection n randomized clinical trial
Although antiretroviral therapy (ART) has dramatically altered the natural history of HIV infection and has led to almost normal life expectancy for many infected individuals [1], questions remain regarding its optimal use. One issue that has been controversial since the advent of effective ART has been the timing of therapy. In one particular situation, acute or primary HIV infection, it has been unclear whether starting ART immediately changes the natural history by delaying disease progression [2]. In simple terms, the clinical research question has been whether aggressive initial therapy with effective ART would delay the need to start definitive therapy by slowing the immune decline seen with untreated infection. Methods & results
In the current paper, a collaborative group of international investigators performed an open-label randomized trial of three strategies in patients with primary HIV infection. Primary HIV infection was defined as infection occurring in the 6 months prior to randomization and subjects were identified on the basis of a series of welldefined virologic, immunologic or clinical criteria. Eligible subjects were then randomized to receive, on a 1:1:1 ratio, ART for 48 weeks, ART for 12 weeks or no therapy. It should be noted that by currently prevailing guidelines no treatment was regarded as standard of care. The precise ART to be used was not prescribed by the study, although a standard regimen of two nucleoside reverse transcriptase inhibitors plus a ritonavir-boosted protease inhibitor was the study-recommended regimen to minimize the risk of undertreating resistant HIV infection. The primary end point of the trial was a delay in disease progression as defined as a composite of a CD4+ T-cell count of
Antiretroviral therapy in primary HIV infection Evaluation of: SPARTAC Trial Investigators, Fidler S, Porter K et al. Shortcourse antiretroviral therapy in primary HIV infection. N. Engl. J. Med. 368, 207–217 (2013). The timing of antiretroviral therapy (ART) in patients who present with primary HIV infection is uncertain. This paper compared three strategies: ART for 48 weeks; ART for 12 weeks; or no therapy in 366 patients with primary HIV infection. They showed that 48 weeks of ART significantly reduced the risk of needing definitive therapy (after a median follow-up of 4.2 years). However, the median delay in needing to start definitive therapy (61 weeks) is not significantly greater than the amount of treatment given (48 weeks) to achieve this result, suggesting that the clinical benefit of immediate ART in primary HIV infection is not yet clear.
William G Powderly Division of Infectious Diseases, Washington University School of Medicine, 660 South Euclid Avenue, St Louis, MO 63110, USA Tel.: +1 314 454 8215 [email protected]
KEYWORDS: antiretroviral therapy n direct comparison n HIV disease progression n primary HIV infection n randomized clinical trial
Although antiretroviral therapy (ART) has dramatically altered the natural history of HIV infection and has led to almost normal life expectancy for many infected individuals [1], questions remain regarding its optimal use. One issue that has been controversial since the advent of effective ART has been the timing of therapy. In one particular situation, acute or primary HIV infection, it has been unclear whether starting ART immediately changes the natural history by delaying disease progression [2]. In simple terms, the clinical research question has been whether aggressive initial therapy with effective ART would delay the need to start definitive therapy by slowing the immune decline seen with untreated infection. Methods & results
In the current paper, a collaborative group of international investigators performed an open-label randomized trial of three strategies in patients with primary HIV infection. Primary HIV infection was defined as infection occurring in the 6 months prior to randomization and subjects were identified on the basis of a series of welldefined virologic, immunologic or clinical criteria. Eligible subjects were then randomized to receive, on a 1:1:1 ratio, ART for 48 weeks, ART for 12 weeks or no therapy. It should be noted that by currently prevailing guidelines no treatment was regarded as standard of care. The precise ART to be used was not prescribed by the study, although a standard regimen of two nucleoside reverse transcriptase inhibitors plus a ritonavir-boosted protease inhibitor was the study-recommended regimen to minimize the risk of undertreating resistant HIV infection. The primary end point of the trial was a delay in disease progression as defined as a composite of a CD4+ T-cell count of
