Study summaries from ICAAC 2012
Simon Collins, HIV i-Base
The following brief summaries on new drugs and treatment strategies include links to the ICAAC online abstracts and/or links to slidesets or articles posted at natap.org.
Dolutegravir results superior to efavirenz at week 48 in treatment-naive patients
The top-line results from the randomised, double-blinded, placebo-controlled, non-inferiority, Phase 3 SPRING study were released in July just prior to the IAS conference.
Dolutegravir (50 mg once-daily) was paired with abacavir/3TC and compared to efavirenz/tenofovir/FTC (Atripla) in 674 treatment-naive patients, generally in early stage infection.
At week 48, the dolutegravir arm showed superiority with 88% vs 81% of patients suppresed to <50 copies/mL (difference +7.4%; 95%CI: +2.5, +12.3; p=0.003).
This result was driven by fewer discontinuations due to toxicity in the dolutegravir arm (2% vs 10%). Virological failure occured in 4% of patients in each group.
Ref: Walmsley S et al. Dolutegravir (DTG; S/GSK1349572) + abacavir/lamivudine once daily statistically superior to tenofovir/emtricitabine/efavirenz: 48-week results – SINGLE (ING114467). 52nd ICAAC, 9-12 September 2012, San Francisco. Abstract H-556b.
Elvitegravir/cobicistat has no clinically significant interactions with methadone or buprenorphine
Results from two small PK studies in patients on stable opiate substitution therapy (n=12 methadone; n=18 buprenorphine) reported no indications of an interaction between elvitegravir/cobicistat and methadone and only modestly increased buprenorphine levels that did not require dose modification.
Ref: Bruce RD et al. Pharmacokinetics of cobicistat-boosted elvitegravir administered in combination with methadone or buprenorphine/naloxone. 52nd ICAAC, 9-12 September 2012, San Francisco. Abstract A-1250.
Albuvirtide: long-acting formulation T-20
The first in vivo virological data were presented for a new long-acting formulation of the fusion inhibitor T-20. This compound is in development with the Chinese company Chongquing Biotechnologies.
The limited information from the abstract reported results from a dose-finding study in Chinese HIV positive patients who received single IV injections daily for three days, followed by once-weekly injections for a further two weeks.
Mean maximum declines of 0.68 and 1.05 log copies/mL were reported with 160 mg and 320 mg doses respectively. In a single-dose study, viral reduction was maintained for 6-10 days, with albuvirtide showing a plasma half-life of 10-13 days.
Ref: Wu H et al. Albuvirtide, the first long-acting HIV fusion inhibitor, suppressed viral replication in HIV-infected adults. 52nd ICAAC, 9-12 September 2012, San Francisco. Abstract H554.
High rates of adherence and virological suppression with once-daily raltegravir and directly observed therapy (DOT) in IDU patients
Although results of once-daily raltegravir studies did not support a label change or further research into this dosing option, a Canadian study reported very high rates of success in a cohort of 121 HIV positive treatment experienced injecting drug users (n=103 male) that also included comprehensive adherence support. DOT ws used by 81% of patients.
Over a median follow-up of 12 (6-18) months, 80% of the cohort achieved or maintained virologic suppression to <50 copies/mL (appromiately half the group switched with undetectable viral load at baseline.
Importantly, CD4 counts increased by a median 80 cells/mm3 from a median of 425 cells/mm3 (range 20-1600) at baseline. Adherence exceeded 90%. Virologic rebound to >400 copies/mL occurred in 10% of patients but resuppression was achieved in all cases over the subsequent three months. There were no cases of emergent raltegravir resistance.
Ref: Stewart K et al. Safety and efficacy of once daily raltegravir to enhance adherence and efficacy of HAART in vulnerable HIV-infected patients. 52nd ICAAC, 9-12 September 2012, San Francisco. Abstract H-884.
Role of HIV DNA, recent cellular infection and poor immunological responses despite viral suppression
A group of French researchers looking at immunological non-responders despite viral suppression <50 copies/mL reported an association with HIV DNA as a marker of recent cellular infection and ongoing replication and overexpression of the activation marker CD38+, that was higher in patients with reduced CD4 responses on treatment. The natap report linked below report this study in detail.
Ref: Psomas KC et al. Poor CD4+ T-cell restoration linked to residual HIV-1 reverse transcription under antiretroviral therapy. 52nd ICAAC, 9-12 September 2012, San Francisco. Abstract H-1570a.