An ongoing dialogue on HIV/AIDS, infectious diseases,
July 27th, 2014
Really Rapid Review — AIDS 2014, Melbourne
For the second time — the first time was in Sydney, 2007 — the annual “summer” international AIDS conference took place in Australia, this time in Melbourne way down in the southern part of the country. I’ll note again how the crash of Malaysia Airlines flight MH-17 cast a sad note over the opening sessions, and throughout the conference many people gave moving tributes to friend and colleague Joep Lange.
This being the larger of the two international meetings, there was plenty of non-medical, non-scientific content, all of which I’ll completely pass over in this Really Rapid Review©.
(Except to say that Bill Clinton and security entourage walked right past me — he waved hello, though clearly not to me personally.)
With the usual up-front apologies for inadvertently omitting something important, off we go.
- When given with darunavir/ritonavir, maraviroc was inferior to TDF/FTC for initial therapy. We knew this already from the press release last year, but this was the first time we’ve seen the data. Failure rates particularly high with lower CD4 cell counts. Interesting conference dynamic when the presenting author was asked about whether the dose of maraviroc (150 mg mg daily) was too low — he responded rapid-fire with around 5 studies justifying the dose, quite a performance.
- As maintenance therapy, atazanavir/ritonavir plus lamivudine (two drugs) was non-inferior to atazanavir/ritonavir plus 2 NRTIs (three drugs). As with the GARDEL study of LPV/r + 3TC, these results are still more evidence of the magic of 3TC/FTC. Study is called “SALT” — can you guess what this stands for?
- As maintenance therapy, lopinavir/ritonavir plus lamivudine (two drugs) was non-inferior to lopinavir/ritonavir plus 2 NRTIs (three drugs). Again … magic of 3TC/FTC! And this one was called “OLE” — another clever title, please guess the origin.
- Given the results of the above three studies, perhaps we shouldn’t be surprised that for virologically suppressed patients, raltegravir plus ATV/r was clearly worse than ATV/r plus 2 NRTIs — the study was stopped by the DSMB for more virologic failures in the experimental arm. What’s causing the underperformance of these two drug regimens that don’t have 3TC/FTC? To quote my friend Joel Gallant, “the only good nuke-sparing regimens contain a nuke.” (When you steal a line that good, you must give credit.)
- The SECOND LINE study found after failing 2NRTIs/NNRTI, second-line treatment with lopinavir/r with either raltegravir (two new drugs) or NRTIs (one new drug plus recycled but still partially active drugs) were non-inferior. In this resistance analysis of the study, having more resistance at study entry lead to a higher likelihood of treatment success. A paradox? Not really, this has been seen before — patients with the worst adherence have the least resistance, hence they do poorly on their next regimens too.
- The SAILING study showed that dolutegravir was superior to raltegravir in treatment experienced patients, and this detailed resistance analysis found that the difference was quite pronounced in those treated only with NRTIs. 0/32 receiving DTG plus NRTIs failed treatment, vs 7/32 for RAL plus NRTIs; for M184V +/- thymidine-associated mutations, there 0/13 DTG vs 4/12 RAL failures.
- In this large analysis of a Spanish treatment cohort, HIV RNA between 20-50 cop/mL did not increase the risk of treatment failure compared to those with HIV RNA < 20 cop/mL. Reassuring, because we don’t know how to manage those patients anyway!
- In an observational Canadian cohort study, patients who switched therapy while virologically suppressed had significantly greater risk of failure than those who didn’t switch. Not surprisingly, the switchers vs non-switchers differed substantially — enough so that this study was this meeting’s winner of the “Unmeasured Confounding Influenced Outcome” award, a limitation the presenter acknowledged.
- How often should we be measuring viral loads in our stable suppressed patients? In this HIV Outpatient Study (HOPS) analysis, virologic suppression rates were similar between those who did and did not have HIV RNA measured more than twice a year. Could save a boatload of money if the frequency of these tests could be reduced in selected stable patients.
- What are some of the predictors of prescribing guidelines-concordant HIV treatment in the USA? Glad to see that being an ID specialist was one of them! (Love the title of the abstract too…)
- Tons on PrEP at the meeting, but the study that got the most attention was an interim analysis of a French study of intermittent PrEP, called “IPERGAY”, which stands for … something. Adherence excellent so far in this “event driven” strategy, no outcomes data yet. Note that the comparator arm to the intermittent PrEP is placebo, as PrEP is not approved or strongly endorsed in France.
- More indirect evidence that intermittent PrEP could be the way to go from this iPrEx analysis, which found 100% protection in those participants whose blood levels suggested 4X/week adherence to daily TDF/FTC.
- Don’t share cuticle scissors with someone who is viremic. Enough said.
- There’s no doubt that HIV positive MSM have more anal dysplasia and anal cancer than their HIV negative counterparts, and high grade squamous intraepithelial lesions (HSIL) are thought to be a strong precursor to cancer. But this well done Australian study found that more than half of HSIL lesions regressed spontaneously, making the optimal treatment uncertain. Great name for the study, by the way — Study of the Prevention of Anal Cancer (SPANC).
- In HIV/HCV coinfection (genotypes 1-4), sofosbuvir plus ribavirin cured over 80% of patients, with perhaps the only weakness the genotype 1a patients with cirrhosis. This combination remains the treatment of choice for genotype 2; for genotype 1, sofosbuvir/ledipasvir is imminent.
- Speaking of imminent approvals for genotype 1 HCV, the “3D” regimen of ABT-450/r/ombitasvir (three drugs coformulated) plus dasabuvir plus RBV cured over 95% of coinfected patients. Interestingly, some of them received atazanavir-based regimens, using the “r” (ritonavir) in the HCV regimen to provide the boost.
- A small study of this same combination found that it was safe and effective (again, cure > 95%) in patients on methadone or buprenorphine, with no adjustments required of the narcotic replacement therapy.
- Cure research has taken a beating recently, especially with the virologic relapses of the two Boston stem cell transplant patients and the Mississippi baby. But the research goes on, and here a study demonstrated clearly measurable increases in HIV RNA after infusions of the potent HDAC inhibitor romidepsin — suggesting a reversal of HIV latency! The current thought is that this sort of treatment plus other measures (vaccine? immune augmentation otherwise?) may decrease the latent reservoir.
A few brief impressions of Melbourne, top of the World’s Most Livable City rankings by The Economist since 2011.
- The people were uniformly nice, polite, energetic, and helpful. All of them! There must be some ornery and disagreeable Melbourne natives someplace, but they are either extremely small in number or they are carefully hidden away, far from where tourists roam.
- As a tennis-crazy person, even though I knew it was illogical, I kind of expected Melbourne to be hot — think of the Australian Open in January, matches held in blistering 40 degree celsius heat with blinding sun, players taken into the locker room for IV hydration, etc. Of course this city’s location in the way south of Australia means it’s not “summer” here at all (see the first line up there), it’s just flat-out winter — cool, cloudy, kind of like Seattle in October/November — but nothing (and I mean nothing) like a Boston winter. Wear a sweater and/or a light coat and you’re fine.
- The city has the largest street tram service in the world, and somehow it all works: the streetcars don’t seem to interfere with the traffic or pedestrians, and the stops have incredibly clear and helpful signs telling you not only how long you need to wait for the next car, but the next 3 cars after that. Imagine that on the Boston T on Commonwealth Avenue!
- Food is outstanding, with strong Asian influences everywhere, and many of the restaurants are charmingly located on narrow alleyways, with indoor/outdoor dining overlapping to make the alleys seem like outdoor rooms. Tipping is barely required — kind of viewed as sort of a strange American custom. I asked about tipping in one restaurant, as I didn’t have the right currency for both the bill and a tip, and the waitress said (in all sincerity), “That’s very kind of you, but we’re just fine, thank you.”
- This is a city of true coffee fanatics, proven by the fact that there are only two Starbucks in all of Melbourne — but don’t go to them! From humble little snack bars to high-end bean emporia, the quality of the coffee here is off the charts sensational. Maybe that’s why everyone is so nice? Helpful for jet lag adjustment too.
- Given all of the above wonderfulness, perhaps it’s no surprise that Melbourne is no bargain. (#6 most expensive city in the world, according to this list.) Not eager to see my next credit card statement, yikes.
Next year’s meeting is in Vancouver, which no doubt will celebrate the incredible 1996 Vancouver meeting that introduced effective HIV therapy to the world. Or, to quote Kevin DeCock:
The International AIDS Conference in Vancouver is synonymous with the introduction of highly active antiretroviral therapy (HAART), now just referred to as ART.
He said it, not me!
One more time, thanks, Dr. Sax. Your RRR is already an essential ítem in the modern HIV history. Eppur, a classic! In my opinión, in the very next future it will be a SRR (Sustained Rapid Review).
Greetings from Spain.
Thanks for this excellent summary, Dr. Sax. I was one of the few folks from CDC approved for the conference, so I’ve been trying to share some useful summaries with all my colleagues who could not attend.
Excellent Rapid Review! Congratulations!
Thank you for this rapid review, Dr. Sax. They are always, always appreciated.
I have to admit, I’m having a hard time understanding the SECOND-LINE paradox. Is the assumption that a patient with poor adherence to the first regimen will carry this behavior over to the second regimen? Additionally, if the patients with the worst adherence have the least resistance, then who has the most resistance?
John, yes to the first question. As for the second question, we learned in the 1990s that the patients with the worst resistance tend to be those who do not achieve virologic suppression despite excellent adherence, then are maintained on the failing regimen for a prolonged period. This was more common with the toxic and less potent regimens we used back then.
Excellent overview. Many thanks. So helpful for HIV physicians trying to keep up.