Maximal suppression achieved with three drugs: no additional virological impact of raltegravir intensification

HIV Treat Bull - 2009 Sep/Oct;10(9/10): 05

Simon Collins, HIV i-Base

A late-breaker presentation by Rajesh Gandhi and colleagues from ACTG 5244 provided addtional data that are important for understanding the impact of HAART on the pathogenesis of HIV.^[1]

Several small studies have already shown similar results (including Maldarelli et al at last years Resistance Workshop).^[2]

This new study benefited from larger patient numbers and intensification with an integrase inhibitor.

The study randomised 53 patients to either add raltegravir or placebo to their combination for 12 weeks. At week 12, patients crossed over to the alternative arm for a further 12 weeks. The primary endpoint was averaged plasma viral load between weeks 10 and 12. Patients needed to be on HAART for at least one year, with viral suppression <50 copies/mL (but have viral load >0.02 copies/mL at baseline using a more sensitive test).

Median baseline CD4 count and viral load were 589 cells/mm³ and 1.7 copies/mL (a similar low level has been reported in other studies). The median viral load at week 10/12 did not differ between the raltegravir (n=25) and placebo (n=24) groups (1.1 vs. 1.7 c/mL, p=0.80), nor did the median change in viral load from baseline to week 10/12 (-0.3 and -0.1 c/mL, p=0.52). There was also no significant change from weeks 10/12 to weeks 22/24 during the cross-over study.

Interestingly, there was a trend towards greater CD4 cell count increases from baseline to week 12 in the raltegravir group (+42 vs. -44 cells/mm³, p=0.08), which reversed after the cross-over.

Comment:

This study supports the hypothesis that effective HAART (that maintains viral suppression to <50 copies/mL) stops onging viral evolution, and that residual HIV originates from recent activation of latently infected cells.

This demonstrates a ceiling of antiretrovial activity that many patients achieve with current three-drug combinations – though treatment- experienced patients may benefit from using additional drugs to overcome drug resistance.

References:

1. Gandhi R et al. Raltegravir (RAL) intensification does not reduce low-level residual viremia in HIV-1-infected patients on antiretroviral therapy (ART): results from ACTG A5244. IAS Conf HIV Pathog Treat 2009 Jul 19-22;5th:. Late breaker oral abstract WELBB104.

2. Collins, S. Lack of virological impact of treatment intensification in suppressed patients supports latent viral reservoir as source of residual viraemia. Reports from XVII Intl HIV Drug Resistance Workshop (IHDRW) 2008, Sitges. HIV Treat Bull 2008 Jul/Aug; 9(7/8):9.

2009-09-10
IB2009-09-05

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