HTB

Similar viral load reductions at week 4 when dolutegravir is used with 2- or 3-drug initial ART

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Simon Collins, HIV i-Base

Given the number of independent groups reporting data from studies using dolutegravir monotherapy at the EACS conference in October 2015 [1], it was strange to see no further updates from these groups at CROI 2016.

One related study that managed to slip into CROI as poster was an analysis from the PADDLE study that at EACS reported rapid viral suppression sustained to 24 weeks from using initial therapy with dolutegravir plus lamivudine (DTG+3TC) dual therapy. [2]

In order to look at early viral dynamics from this strategy Omar Sued from the Fundación Huésped, Buenos Aires and colleagues compared viral load results in PADDLE to historical data from the SPRING and SINGLE studies where dolutegravir was started with two NRTIs.

Although PADDLE included more intensive monitoring, data was only calculated in this analysis for time-points that were shared by all three studies, ie at weeks 2, 4, 8, 12 and 24.

Viral load changes were similar after a dual therapy regimen DTG/3TC compared to two DTG-based triple therapy regimens. Two-way ANOVA revealed significant effects for treatment (F2,1605=30.3 p<0.001) and time (F4,1605=22.8 p<0.001), without significant interactions. (See Table 1).

Table 1: Viral load reductions with dolutegravir in 2 vs 3 drug combinations
PADDLE SINGLE SPRING-1
BL pVL

(mean+SD)

4.43

(0.50)

4.30

(0.45)

4.31

(0.52)

Av. effects

(mean ±SD)

-2.75

(±0.45)

-2.53 (

±0.49)

-2.61

(±0.48)

Comment

These results, albeit encouraging, should be interpreted with caution, as the analysis is based on a cross-study comparison of mean values and PADDLE is a small pilot study.

Comparitive viral dynamics really require looking at very early time points over the first few hours and days. Of interest, the PADDLE study did collect this early data.

References:

  1. Collins S. Why dolutegravir might get us closer to ending AIDS: next step, further research, Reports for EACS conference. HIV Treatment Bulletin, November/December 2015.
    https://i-base.info/htb/29326
    Sued OG et al. Comparable viral decay in dual and triple dolutegravir-based antiretroviral therapy. Poster abstract 947.
    http://www.croiconference.org/sessions/comparable-viral-decay-dual-and-triple-dolutegravir-based-antiretroviral-therapy (Abstract)
    http://www.croiconference.org/sites/default/files/posters-2016/947.pdf  (PDF poster)

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