Another NRTI-sparing regimen does well in treatment-naive patients

A nucleoside-sparing regimen based on raltegravir and ritonavir-boosted darunavir is as safe and effective as a traditional nucleoside-based HIV treatment combination, according to the results of a small US study presented to the Sixth International AIDS Society conference (IAS 2011) in Rome.

Patients taking the nucleoside-sparing regimen were just as likely as those taking tenofovir/FTC (Truvada) with ritonavir-boosted darunavir (Prezista) to have an undetectable viral load after six months of therapy. Increases in CD4 cell counts were comparable between the two regimens, which also had a similar impact on lipids.

“The NRTI [nucleoside reverse transcriptase inhibitor] sparing regimen of raltegravir and darunavir/ritonavir achieved similar safety and efficacy as tenofovir/FTC and darunavir/ritonavir and could provide an alternative approach in the treatment of antiretroviral-naive patients,” comment the investigators.

A second study showed that a two-drug nucleoside-sparing regimen consisting of once-daily maraviroc and ritonavir-boosted atazanavir also had good antiviral efficacy, but a small number of patients experienced a low level rebound in their viral load between weeks 24 and 48.

However a third study showed that maraviroc could be dosed once daily with the ritonavir-boosted protease inhibotor lopinavir, darunavir or atazanavir.

Antiretroviral therapy has dramatically improved the life expectancy of many HIV-positive patients. However, it can cause long-term side-effects, many of which appear to be caused by drugs in the NRTI class of anti-HIV medications.

Since 1996, triple-drug HIV therapy has been based on a backbone of two NRTI drugs.

Investigators from the US RADAR study wanted to see if the NRTIs could be replaced with the integrase inhibitor raltegravir (Isentress), a drug which has been shown to be a safe and effective therapy for both treatment-experienced and therapy-naive individuals.

They therefore designed a study involving 80 patients. All were starting HIV treatment for the first time and had a viral load above 5000 copies/ml.

The patients were randomised into two arms. Individuals in the first arm were treated with the nucleoside-sparing regimen of raltegravir and the protease inhibitor darunavir/ritonavir. Patients in the second arm received Truvada combined with darunavir/ritonavir.

The primary outcome of the study was the proportion of patients with an undetectable viral load after 24 weeks. Information was also gathered on CD4 cell changes and the impact of the alternative regimens on lipid levels.

Most of the patients (75%) were men, their average age was 42 years, and 38% were white. There were no significant differences between the two study arms, and at baseline the patients had a median CD4 cell count of 261 cells/mm³ and an average viral load of 4.72 log₁₀ copies/ml.

After 24 weeks of therapy, 86% of patients in the NRTI-sparing arm had achieved a viral load below 50 copies/ml, compared to 87% of individuals treated with Truvada.

CD4 cell changes at six months were also comparable between the two study arms, the median increase for the raltegravir-treated patients being 149 cells/mm³, compared to an increase of 125 cells/mm³ for patients taking the traditional NRTI-based therapy.

Both treatment regimens had a similar impact on lipid profiles and kidney function.

Three patients in the raltegravir arm stopped therapy compared to five individuals in the Truvada arm.

Serious adverse events occurred in three of the patients taking the nucleoside-sparing regimen as well as in one person treated with Truvada. There were two virological failures among the raltegravir-treated patients, but none in those taking an NRTI backbone. However, none of these differences was statistically significant.

The investigators were encouraged by these findings. The study will continue until week 48, but the researchers were aware that its findings are limited by the small sample size. They conclude, “a larger, appropriately powered study is warranted. Such a study (ANRS 143/NEAT 001; estimated enrolment 800 patients) is underway.”

A second study presented to the Rome conference also examined the safety and efficacy of NRTI-sparing regimens.

Investigators presented 48-week data comparing a combination of maraviroc (Celsentri) with ritonavir-boosted atazanavir (Reyataz) and Truvada which was also taken with atazanavir and a ritonavir booster.

Earlier 24-week results presented to last year’s International AIDS Conference were impressive, showing that the nucleoside-sparing regimen had similar potency to the Truvada-based combination, with 80% and 89% of patients respectively having a viral load below 50 copies/ml.

After a year of therapy, the proportion of patients in the NRTI-sparing arm with an undetectable viral load had fallen to 75% compared to 83% of individuals treated with an NRTI-based regimen.

However, all the patients in the nucleoside-sparing arm who experienced a rebound in their viral load between weeks 24 and 48 had only low-level viraemia: a viral load  below 200 copies/ml. Moreover, all the patients had re-suppressed their viral load to undetectable levels by week 48.

Bedimo R et al. RADAR study: raltegravir combined with boosted darunavir has similar safety and antiviral efficacy as tenofovir/emtricitabine combined with boosted ritonavir in antiretroviral-naïve patients. Sixth International AIDS Society Conference on HIV Pathogenesis, Treatment and Prevention, Rome, abstract MOPE214, 2011.

Mills A et al. 48-week results of a dual-therapy regimen of once-daily maraviroc (MVC) 150 mg in combination with ritonavir-boosted atazanavir (ATV/r) compared to emtricitabine/tenofovir (FTC/TDF) + ATV/r in treatment naive (TN) patients infected with CCR5-tropic HIV-1. Sixth International AIDS Society Conference on HIV Pathogenesis, Treatment and Prevention, Rome, abstract TUAB0103, 2011.

View abstract MOPE214 on the official conference website.

View abstract TUAB0103 on the official conference website.

View slides, with audio, for the presentation of abstract TUAB0103 on the official conference website.