ASHM Report Back

Clinical posts from members and guests of the Australasian Society for HIV, Viral Hepatitis and Sexual Health Medicine (ASHM) from various international medical and scientific conferences on HIV, AIDS, viral hepatitis, and sexual health.

Jeffrey Post

Jeffrey Post

Jeff is an infectious diseases specialist at Prince of Wales Hospital, Sydney and chairs the Australian Antiretroviral Guidelines Panel.

One thread at the conference was the outcomes of, and associations with, renal dysfunction.

In the D:A:D Study (abstract 865) 2.1% of the cohort developed an eGFR of less than 70 after a median follow-up of 4.5 years. The investigators identified that TDF, LPV/r and ATV (boosted in 75% of cases) were all associated with an incidence rate ratio (IRR) of approximately 1.1 per year of exposure for the development of an eGFR less than 70.  Switching off TDF was more common at eGFR levels between 60 and 70. Predictors of eGFR less than 70 were age, prior AIDS, current CD4 count, HCV or HBV coinfection and diabetes.

More data from the SMART study (abstract 866) were presented. This time eGFR and cystatin C levels were associated with mortality and other events in a sample of over 4000 subjects. They comment that cystatin C (a potential marker of GFR) may be affected by other issues in HIV infection and may not be an ideal marker of GFR in this population.

Others identified an independent association between renal impairment and cardiovascular events (abstract 868, from the ICONA cohort in Italy) and microalbuminuria in cART naive individuals and death (abstract 869).

In all, there is accumulating evidence that markers of renal dysfunction in the HIV infected population are likely to have similar prognostic significance as in the general population. This is worth discussing if people are considering whether to commence therapy above a CD4 count of 350 where a survival benefit has been convincingly demonstrated. The results from the START study are even more keenly awaited in light of these new data.

Tagged in: CROI2012

The renal effects of tenofovir were associated with blood levels (abstract 603) at the conference. Another presentation (abstract 103) examined a prodrug of tenofovir, GS-7340, in a 10 day monotherapy study. This produg was associated with 88% lower plasma levels of tenofovir than when the currently prescribed prodrug TDF (tenofovir disproxil fumarate) was administered. It was highly potent and is likely to be studied further as an alternative to TDF.

Tagged in: CROI2012 GS-7340

The new "booster" drug, COBISTAT, is part of the "QUAD" single pill (see QUAD post) and a number of studies are in planning and in progress looking at the use of this agent. It may allow new regimens such as a once daily combination pill with a protease inhibitor for the first time.

Tagged in: CROI2012

The once daily dosed integrase inhibitor DOLUTEGRAVIR was the subject of a handful of presentations at the conference. Week 96 results from the SPRING-1 study were reported. This was a phase 2 study of 205 people comparing different doses of Dolutegravir (10, 24 and 50mg) with efavirenz, both in combination with a TDF/FTC or ABC/3TC backbone. At week 96 the proportion with a HIV viral load less than 50 copies per ml was 88% in the 50mg dolutegravr arm and 72% in the efavrenz arm (a non signficant difference). The treatment appeared well tolerated, although there was a mild elevation in serum creatinine, thought to be due to effects on renal secretion of creatinine and not real impairment of GFR. Phase 3 studies of this agent, which could provide a once daily integrase inhibitor regimen, are underway.

Tagged in: CROI2012

Two important HIV HCV coinfection phase 2 studies of HCV protease inhibitor therapy in combination with PEG-IFN and ribavirin for HCV genotype 1 were presented today with SVR12 data (sustained virological response 12 weeks after treatment cessation) available. Both studies found approximately 30% higher response rates (a marked advance in this patient group), but there were some caveats.

Abstract 46 (presented by Doug Dieterich) reported that Telaprevir with PEG-IFN-alpha-2a and ribavirin had higher SVR12 rates than with PEG-IFN-alpha-2a and ribavirin alone (74 vs 45%).

Abstract 47 (presented by Mark Sulkowski) examined Boceprevir with PEG-IFN-alpha-2b and ribavirin (n=64) which was compared with PEG-IFN-alpha-2b and ribavirin in people with genotype 1 HCV infection with significant differences in SVR12 (61 vs 27%).

The sample sizes were small (less than 100) and both studies reveal expected toxicity profiles with the addition of the HCV protease inhibitor.

Other data presented at the conference revealed the very significant drug-drug interactions (including with many HIV drugs) with these compounds that will mean that their use will need careful thought. Jurgen Rockstroh summarised the state of play with these agents in abstract 72 and suggested management strategies based on the current evidence.

The therapeutic outlook for people with HIV and HCV coinfection looks much more promising with these early data and phase 3 studies in progress or planned and a number of new HCV agents in the pipeline. Watch this space.

Tagged in: CROI2012
New data on the role of HCV protease inhibitors in HIV coinfection will be presented at this year's CROI
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