It’s HIV treatment, but not as we know it!

Tuesday 22nd July 

In a program mixed with sessions on searching for a cure or simply arguing for the right for marginalised groups in developing countries to receive treatment, the oral abstract session titled ‘Antiretroviral therapy: not all strategies are created equal’ presented several studies of novel antiretroviral treatment.

The first presentation was presented by Eric Le Fevre who discussed the results of the MODERN trial, which was a phase 3, randomised, double-blind trial that compared triple therapy (TDF/FTC+DRV800/RTV100mg) versus nucleoside/nucleotide sparring, dual therapy (Maraviroc 150mg QD+DRV800/RTV100mg) in HIV positive patients naive to antiretroviral therapy.

Sadly at week 48 the study was terminated early due to inferiority of the Maraviroc containing regimen with only 77.3% subjects reaching the primary endpoint of HIV viral load < 20 copies/ml versus 86.8% of subjects on triple therapy.

Response was actually worse in subjects with a viral load > 100,000 copies and also in subjects with lower CD4 counts at baseline (200-350 cells) but pleasingly there was no emergence of resistance to study drug. Therefore, it still seems that a 3 drug regimen is still the gold standard for HIV therapy with possibly a greater benefit of including N(t)RTIs in the combination when treating subjects with a lower CD4 count.

Marina Klein from Canada then presented data on switching from a first antiretroviral regimen while virologically suppressed showing that it can be associated with increased risk of virological failure.

In Canada’s largest HIV treatment cohort (CANOC), 36% subjects switched from their original HIV treatment regimen, although the reasons for switch were not clearly identified – presumed to be for toxicity, simplification, tolerability or drug-drug interactions. Switching actually seemed to occur on average quite early at 0.8 years and was more common in women and people who inject drugs (PWID).

Klein reported that switching was more likely to be related to treatment failure, as identified as HIV VL > 1000 copies/ml, although did not present what proportion of subjects actually failed treatment. This does highlight some concerns about switching treatment and more specific switch studies should be considered before initiating switches in our patients.

And finally, Mark Boyd from the Kirby Institute in Australia presented interesting data from the Second-line resistance substudy, which aimed to examine the contribution of baseline N(t)RTI-resistance as well as other potential predictive variables to virological failure (VF).

Interestingly, they found that virological failure was associated with self-reported non-adherence, a higher baseline global genotypic sensitivity score (which should actually have indicated a better result), a baseline viral load of greater than 100,000 copies/mL, and race. He concluded that investment in effective adherence interventions and support are still needed.

The afternoon oral abstract session on pre-exposure prophylaxis (PrEP) was extremely well attended, showing a great interest in this area. There were two thought-provoking presentations from an open label ‘extension study’ of the well-known iPrEX study with the catchy title of ‘OLE’.

The first presentation by Kimberly Koester was based on 60 in-depth interviews of OLE participants. Interestingly and pleasingly, subjects stated that PrEP did not, in most cases, actually lead to increased condomless sex and condom use actually increased in younger participants. A major feature of being on PrEP was a decrease in stress, fear and guilt associated with sex. It would therefore seem that PrEP is being used as a supplement to existing HIV prevention strategies.

Jean-Michel Molina from France then presented interesting data from the Ipergay study that looked at high risk MSM who were enrolled in an ongoing, randomised, double-blind, placebo-controlled trial of ‘on demand’ PrEP with oral TDF/FTC.

Subjects were instructed to take 2 pills of TDF/FTC or placebo before sex (2 to 24 hours before), and 2 pills after sex (1 pill every 24 hours). Between February 2012 to May 2013, 153 patients were randomised with a median age of 35 years and median number of 2 episodes of sexual intercourses/week. During their last sexual intercourse (n=543), according to computer-assisted self report, 53% subjects used PrEP as scheduled, 28% used PrEP but did not follow the treatment schedule, and 19% did not use PrEP.

In order to look for drug concentration they collected blood and hair samples but only 59 hair samples from 38 patients were available for analysis – apparently not enough subjects had hair! TFV and FTC were detected in 51% and 49% of subjects in the TDF/FTC arm, and 14% and 0% in the placebo arm, respectively. 548 plasma samples from the first 113 randomized subjects were analysed. TFV and FTC were detected in 86% and 82% (75-100%) of patients in the TDF/FTC arm, and 4% (0-6%) and 3% (0-6%) in the placebo arm, respectively.

So despite variable adherence rates, there were acceptable levels of drug in plasma.

More interestingly, Robert Grant presented more data from the OLE study, especially looking at Tenofovir diphosphate levels in dried blood spots of subjects continuing in the iPrEX extension study. Those subjects with higher drug concentration levels and who reported ≥ 4 days of medication showed a 100% risk reduction in HIV incidence compared with a risk reduction of 84% with 2-3 tablets per week. Results of this study were published online today (July 22) in Lancet Infectious Diseases.