I’m off to the airport now- and missing Bill Clinton’s closing speech . Thanks to those people who read these posts-It’s been a great conference, so huge, and so many varied presentations from around the globe. Best wishes, Phill 

Yesterday afternoon climaxed with some exciting late breaker oral presentations.

Headlines are:

CONSORT study- This study showed that isoniazid prophylaxis (vs placebo) reduced active Tuberculosis over a 4 year period. 1369 patients were given 12 months of INH. Participants were all HIV positive, and 50 on cART. Most benefit seemed to be in the first year, although an effect was seen over the full study course. The HR was 0.63 for active TB (95% CI 0.41-0.94) p=0.03.  They didn’t screen for latent T, unlike in Australia, because the Cape Town setting of this study meant that TB is exposure is the norm, indeed 40% had a history of prior TB. Interestingly 70% of the participants were already on cART, and 30% started cART at the commencement of the study. Resistance to INH in the 95 who did manifest TB remains to be determined. In such a high exposure environment, is this prophylaxis of latent TB or prophylaxis against new acquisition?

SPRING-2- Double blind double dummy RCT of 2 NRTIs plus dolutegravir or raltegravir in 800 treatment naives. VL 50 in 88% and 85% at 48 weeks respectively, proving non-inferiority. Both drugs were really well tolerated, andthere was little to choose between them. No treatment emergent II resistance was seen in the dolutegravir arm, and just one case in the raltegravir arm. There was no difference for VL 100,000 nor between truvada and kivexa as the backbone. Dolutegravir inhibits creatinine tubular secretion, so the eGFR appeared to drop by 15mls/min, but this was not a true reflection of renal function.. it muddies the waters a bit though when trying to interpret creatinines on people on tenofovir.

HPTN 052- this analysis of the treatment as prevention study analysed clinic events in those starting immediately, or waiting to CD4 of 250. A combined endpoint of nonAIDS and AIDS did not show a difference, but there was a statistically significant reduction in AIDS evets. Questions from the audience focussed on the fact that this was all driven by diagnoses of extrapulmonary TB from just one clinical site, and that the average CD4 at commencement in the delayed arm was about 220-230, so much lower than we would ever wait in Australia.

The best posters of the day were invited to give a 5 minute speech. I thought these two might interest you as much as they did me.

1)      Charpentier et al looked at outcomes of patients in France with a HIV VL 20 copies/ml (a level many labs are now using), to those with a VL 20-50copies/ml over a 12 months period. She found no statistical evidence of a greater likelihood of ultimately developing virological failure in the 20-50 copies/ml group. Although I did think the power was pretty limited to detect this... In fact 4% of the <20 groups developed virological failure, compared to 8% of the 20-50 group... So no p-value to speak of, but maybe something that merits repeating with bigger numbers.

2)      Finally Gale et al presented a study looking at whether we need to bother measuring CD4 counts after viral suppression. This was actually done by Chilton et al in the UK some years ago, but this study was from the US. In short, if the VL as undetectable, if the CD4 was >300 then less than 1% of patients had a CD4 drop to below 200 cells over 4 yrs of follow-up. Further CD4 did not lead to any clinical management changes that could not have been foreseen by measuring only VL. The exceptions of course are those starting IFN therapy, chemotherapy or other medical reasons to expect a possible CD4 drop that might require prophylaxis of OIs.

You’re probably aware that 3 studies were published in the last few months linking, particularly injectable contraception, to HIV transmission and susceptibility (Wand et al, Sullivan et al and Heffron et al). Renee Heffron was able to provide more data on her study (partners in prevention HIV/HSV transmission study). Despite cutting the data several ways, including new variables around potential sexual confounders, and performing various sensitivity analyses, the adjusted Hazard ratio for injectable contraception and HIV acquisition was still about 2.0.

The data though, is conflicting. Pollis presented a meta-analysis of the various studies in this field. Many of them were of too poor quality to provide firm data, and the studies were rarely purposefully designed with this endpoint in mind, but were often post-hoc analyses of other studies and unable to adequately control for all possible confounders.  Nonetheless, the WHO still recommend particular counselling to young women using injectable contraception that they really do need to use condoms thoroughly to reduce their HIV risk.

Fichorova presented a complicated study trying to unravel the biological mechanism behind these findings. She looked at markers of inflammation or HIV susceptibility in the cervices of 800 women with and without and STI, and taking or not taking various forms of contraception. I got a bit stuck in the immunology and cytokine mire, but essentially she found that DMPA increased RANTES (some sort of marker of inflammation) in all women, and that DMPA also reduced protective mediators in the cervix. Not causal, but an initial attempt to provide biological plausibility to this theory.

The issue of breastfeeding for HIV positive mums was discussed in detail at a special session today. I tend to forget the legacy of previous advice to not breastfeed, combined with heavy marketing of formula feed. Would you have ever guessed that breastfeeding rates in some parts of South Africa are 6-8%! The WHO guidelines recommend exclusive breastfeeding for at least 6 months, since the mortality of HIV negative bottle-fed babies was increased 6 fold in resource poor settings. Plus the Mma Bana and Kisumu breastfeeding studies showed that cART could reduce the postnatal MTCT transmission rates.

How to tackle re-educate and change practice was discussed by Yogen Pillay from South Africa. They have taken both a top down (ministerial statements and the restriction of formula to prescription-only), and a bottom up approach (involvement of traditional healers and community peer workers), and are reaping slow but steady success. Ensuring time and space for women to breastfeed was key.  Prof Tyllaskar from Norway’s group also showed that a focus on the whole community was crucial to changing breastfeeding practice, not just targeting HIV positive women. He doubled breastfeeding rates over a year with a program of peer-counsellors as part of the larger PROMISE study in South Africa, Burkina Faso and Uganda. 

Not so relevant in the Australian context when safe, affordable, reliable and quality formulas are available if necessary for HIV positive mums, but a sobering insight into the impact the guidelines of the WHO and the advertising from formula companies can have on a vulnerable population who just want to protect their babies from HIV.

Drugs and therapeutic challenges were the themes of this morning’s session.

The plenary started with some excellent overview talks, especially one detailing the various attempts to induce activation of latently infected cells. Current strategies still in vogue are to use IL-7, (Eramune studies), or the HDACi inhibitor vorinostat. Studies using disulfiram or IFN-alpha have not been successful to date.

The next session was a series of important pharma-sponsored studies. First up Mills from Los Angeles presented 96 weeks data on maraviroc 150mg od with ritonavir boosted atazanavir, compared to truvada boosted atazanavir. It was a phase 2b study, so not many stats were presented. At 96 weeks 82% of the truvada arm were 50 copies/ml compared to 67.8% of the maraviroc arm. Most of the detectable VL in the maraviroc arm were in the 50-400 range, and the presenters focussed on this, and the lack of resistance and rather avoided discussing the primary outcome. I thought it was disappointing they appeared to gloss over this; surprisingly tese results have been taken as encouraging and a further study is planned, this time using ritonavir boosted darunavir and maraviroc.

Next up J Gallant presented the 48 weeks results of a ritonavir vs cobcistat booster comparison study. When used with truvada and atazanavir cobcicistat was non-inferior to ritonavir, in fact there was little to choose between them, except for the known rise in creatinine with cobicistat as it blocks creatinine active secretion in the tubules. Although non-significant, 5/6 who had renal dysfunction with cobicistat had proximal tubular disease, compared to 2/5 of renal dysfunction cases on ritonavir. Lipids were the same.

Pallela then presented the SPRIT study, which is a switch study from 2NRTIs plus a boosted PI to Eviplera. Patients were 50/ml prior to switching. Results showed switching did not compromise virological control, and lipids improved a bit. Thy did not stratify lipid changes by which PI was used. Interestingly, all 17 patients who were known to harbour the K103N mutation successfuly suppressed on a rilpivirine based regimen.

Finally Elion et al presented the 96 weeks data on study 145, a raltegravir versus elvitegravir double blind double dummy study in treatment experienced patients. I think all patients had a boosted PI in their regimen already, which makes interpreting differential lipid and GI toxicity difficult. Results were pretty equal between the arms with around 55-60% 50copies/ml, a CD4 rise of 200 cells,  and about 40% discontinuations. Each arm developed resistance mutations to integrase inhibitors in 7% of cases. The resistance pattern was different however, with less N155H mutations in the elvitegravir arm, and a broader range of mutations seen. How this will impact on sequencing IIs and the role of dolutegravir aftr either raltegravir or elvitegravir failure was unfortunately not discussed.

Earlier today I went to an oral abstract presentation (MOAC03) on Access to and retention of antiretroviral treatment.

Despite improved mortality, a study from the UK (M Kall et al) found that PWLHA were still at 2 fold risk of non-AIDS mortality compared to the general population, at all age ranges. This contrasts with data from the AHOD study which demonstrated that Standard mortality ratios, particularly for those undetectable for a few years, and of older age, were not particularly increased.  A difference between these findings might be that the UK  study was not able to take into account last CD4 count before death, a possible important factor.

Another interesting study, performed in part by a Melbourne study group  (McMahon et al) looked at methods to improve retention in care; an important aspect if treatment is to be rolled out further. Specifically they performed a meta-analysis of physical patient tracing studies, in other words studies where patients were actively followed up in person (rather than by telephone call or not followed up), if they became lost to follow up. They found that of about 50 studies addressing this issue, on average lost to follow up rates were lower (7% vs 15%) if physical tracing occurred, and retention on cART was slightly better.  The cost effectiveness of this approach is yet to be tested, and apparently a randomised controlled trial is planned to address this. Many Australian clinics have SMS based reminders or follow-up processes, but unfortunately this study could not include analysis of these techniques.

On a lighter note, I was served an entire half duck in a restaurant last night, and breakfast is so large I don’t need to eat any lunch all day! Might have to go for a quick jog to burn it all off.

Just got back from a debate on “treatment as prevention”, although the speakers only really disagreed on how easy such a policy would be to achieve, rather than whether it is the right strategy. Julio Montaner from British Columbia pointed out the reductions in HIV diagnoses in his setting, which he attributes to increased use of HAART and Kenneth Mayer from the US discussed not losing focus on testing since 54% of infections are from the 21% of those living with HIV but untested.

It was left to the co-chair Sean Stub from the USA to question the ethics, coercion and autonomy issues that need to considered, and also the potential legal ramifications for those who do not accept treatment as prevention… are they now at risk of prosecution for transmission?

Hello- and welcome to this conference report.

The conference formally opened last night, with speeches from, amongst others, Jim Kim, (the head of the world bank), Ban Ki-Moon, (the UN secretary general) and the mayor of Washington. However, despite rampant speculation, there was no sign of Barack Obama or George W Bush, who were both billed to speak, or at least if they were there I couldn’t see them for the swathes of people.

The theme of the speeches was one of optimism. It seemed they were saying that now we know how to stop HIV spreading through treating it, we must now aim for the eradication of transmission. The focus was certainly on treatment-as-prevention, although poverty, stigma and access to condoms were also given some attention. A website: www.2endAIDS.org has been launched to promote the Washington Declaration.

However, many of these scripted speeches repeated the same stuff, and more interesting were the smaller, more human stories presented.  We got to hear from Florence, a women living with HIV in Nigeria, and her 13 year old HIV negative daughter, and how they wished that every mother and child had access to the prevention measures that had secured her daughter’s health. There were also some powerful and moving videos of community-based prevention programs from across the globe.

My favourite was the award (The Elizabeth Taylor award) given to two Iranian doctors recently released from prison, the Ayerai brothers, who had been jailed for several years for setting up an HIV, sexual health and drug use clinic in their country; apparently this amounted to treason. Whilst in prison they set about improving the health and wellbeing of other prisoners through needle education and smoking cessation. Remarkable guys. They were presented their award by the actor Sharon Stone, minus ice-pick. The venerable doctors seemed very excited about this. Perhaps they were thinking of the same scene in Basic Instinct that I was.

The conference proper starts this morning, so I’m off to breakfast to flick through the 430 page conference program book and the 100 page program supplement to decide what to attend.