April 7, 2011
Bronzed Aussie Surfer Dude: Howya going mate? Damn you really got chundered by that wave and rip. Hope ya don't mind my sayin' but that surfboard looked about as useful to you as an ashtray on a motorbike.
Dr. Bob: Cough, cough, cough, sputter, cough.
BASD: No worries mate; just keep breathing. She'll be apples.
Dr. Bob: Thanks, cough, cough, and what's that about "apples"?
BASD: That's "strine" (Aussie slang) for "everything will be all right."
Dr. Bob: I know that, you drongo! But how does "she'll be apples" translate into "everything will be all right?"
BASD: No clue, mate. Hey, since you're a bit of the celebrity 'round here. Any chance you'd answer a few medical questions? After you finish coughing up half the ocean, of course! That heaven-on-a-stick spunk of a lifesaver who just pulled you out of the drink suggested I keep you on dry land and away from your surfie mates for a bit. Fair dinkum. That rip looked like it could have tossed you halfway to Tassie (Tasmania).
Note to reader: Before proceeding, I should probably fill you in on what's going on here. I'm on Bondi Beach in Sydney, Australia with some friends (mates). I have just had a rather spectacular wipeout trying to surf. After being gobbled up by the wave and scraped helter-skelter across the ocean floor for a distance that seemed to me to be roughly the size of Manhattan Island, I was grabbed by a buffed smiling Aussie lifesaver (beach lifeguard). He then shouted, "Look out mate! There's a bluey over there. Let's get you outta here." As he cross-chest carried me across the rip, I saw something that looked like a giant blue condom with strings float by.
And now, back to our story ...
Dr. Bob: First, I have a question for you. What in bloody hell is a bluey?
BASD: A bluebottle.
Dr. Bob: A What?
BASD: You yanks call 'em Portuguese Man o' Wars or some such nonsense.
Dr. Bob: Aren't they deadly?
BASD: Well sure, can be, but usually they don't kill you.
Dr. Bob: Usually?
BASD: What are you reading?
Dr. Bob: I'm checking out bluebottles in this book, The Top 100 Most Venomous Creatures in Australia. Looks like the bluey didn't even make the top 100 list.
BASD: Now what are you doing?
Dr. Bob: Cross-checking another source downloaded onto my Kindle, Creatures and Things That Will Maim or Kill You Horribly While Visiting Australia, Volume 17. It says here a bluebottle may look like a jellyfish, but it isn't. Its stinging venom-filled tentacles can paralyze a fish or cause agony to humans. Serious stings cause fever, shock, breathing problems, heart problems and sometimes death. Damn, and it didn't even make it into the top 100 list???
BASD: Let's change the subject mate. Blueies are boring.
Dr. Bob: Boring? I hate to think what you'd find exciting.
BASD: So, here in Oz (Australia), it's been like a century since we've had a new HIV drug. What's up with that?
Dr. Bob: Well, in reality it's been three years since the last new antiretrovirals hit the market. But I agree three years is a bit of a dry spell. The good news is that a new NNRTI is on its way to pharmacy shelves very soon, and there are a few other promising new drugs in phase 2 and 3 development.
BASD: Cool. What's an NNRTI?
Dr. Bob: It's a non-nucleoside reverse transcriptase inhibitor or "non-nuke" for short. Non-nukes block the activity of reverse transcriptase, a critical enzyme in the HIV lifecycle, so that the virus can't convert itself from RNA to DNA. It's the reverse transcriptase-converted DNA that integrates into our DNA in CD4 cells and causes all sorts of havoc.
Non-nukes are often included in first-line combination antiretroviral regimens. Sustiva (efavirenz) has been the preferred non-nuke since it was introduced in 2002. It's one of the three antiretrovirals in Atripla. Viramune (nevirapine) is an alternative non-nuke, but has limitations. Intelence (etravirine) is the new kid on the block in the non-nuke family, but it's used only for HIVers who have resistance or intolerance to other non-nukes.
A new non-nuke, rilpivirine, appears to be on track for approval by the FDA in the States in May. From what I've heard, it will be approved for first-line use, like Sustiva. Ultimately the manufacturer would like to make a co-formulation single tablet of rilpivirine, tenofovir and emtricitabine, but this might take a while, as the FDA has recently asked for longer-term data on the co-formulated pill. The combination would become the second single-tablet, once-daily regimen. (Atripla was the first.) We've nicknamed the new combination "B-tripla!" (A real brand name has not yet been established.)
BASD: Atripla, B-tripla, that's funny mate. So is B-tripla B-better than Atripla?
Dr. Bob: Well, it depends on how you define better. The head-to-head comparisons of the two "tripla" triples (single-tablet, once-daily formulations of the three antiretrovirals) are still ongoing. The only difference between these two regimens is rilpivirine substitutes for Sustiva. Both are co-formulated in combination with tenofovir and emtricitabine.
There have been two phase 3 studies (ECHO and THRIVE) comparing Sustiva (efavirenz) and rilpivirine. The data show rilpivirine is non-inferior (that's science-babble that means the study drug is no worse nor better than the drug it's being tested against). The good news is that rilpivirine was better tolerated than Sustiva. It also didn't raise cholesterol and triglycerides like Sustiva can. The not-so-good news is that Atripla performed better in folks with high viral loads (over 100,000) and that there was more virologic failure and resistance in the rilpivirine group. Another potentially worrisome finding was that rilpivirine resistance caused cross-resistance to Intelence, which hasn't been seen with Atripla.
BASD: Sustiva totally mind-warped me. It was like there were a few 'roos loose in my upper paddock. Really mate, I felt a few sausages short of a BBQ.
Dr. Bob: Actually I think a fair number of you Aussies already have a wicked case of the crazies, even without the Sustiva. How else can you explain the tendency of many Australian men of a certain age to wear knee-high socks with Bermuda shorts? And what about swimming in waters infested with sharks and stinging blue condoms?
BASD: You yanks are so hung up on sharks. Bloody oath mate, no one's been killed by a shark around here in ages ... I'd say it's been a couple of months at least.
Dr. Bob: "Couple of months?" Wow, and I'm supposed to find that news comforting?
BASD: But really mate, I couldn't take Sustiva. I was warned about vivid dreams, but didn't expect it would turn me into a resident of Zombieland.
Dr. Bob: I took Sustiva for a few weeks a number of years ago. I loved the vivid dreams. I remember waking Steve up just to tell him what I was dreaming about. The inhabitants of my Sustiva-induced dreamworld all seemed to be attired to appear in a Lady Gaga video, and I remember a particularly vivid three-way with Madonna and George Clooney. Although I can understand those who didn't live through the '70s (or at least sat through the current Broadway production of Priscilla Queen of the Desert) might be a bit put off by the sheer zaniness of the dream visions. For most folks on Sustiva the vivid dreams (or screaming nightmares) and other annoying side effects (difficulty concentrating, dizziness, mood changes, depression, etc.) tend to diminish after the first month or so. But there are other potential problems with Sustiva as well, including a load of drug-drug interactions, increases in cholesterol and triglycerides and the possibility of birth defects if taken by pregnant women.
BASD: So. the convenient once-daily dosing of Sustiva (or Atripla when it's combined with tenofovir and emtricitabine) is really counterbalanced by all the side effects and thingos?
Dr. Bob: Thingos?
BASD: Yeah, you know, wadjamacalits.
Dr. Bob: There you go again. Moving on. I should point out that since its approval in 2002, Sustiva (and Atripla) remains the preferred drug in all the published treatment guidelines. Its potency has never been bested in a clinical trial. Overall, compared to other antiretrovirals, it has an excellent long-term safety profile. Plus, it has a really, really long half-life.
BASD: You mean like Cher's?
Dr. Bob: Well, um, sorta, I guess.
BASD: So if Sustiva's so good, why even bother with rilpivirine?
Dr. Bob: Rilpivirine appears to have clear advantages over Sustiva in terms of side effects and should prove to be an attractive option for HIVers with low viral loads who are just starting treatment or for folks who can't tolerate Sustiva.
BASD: You ready to get wet again? How about you take my boogie-board and stay closer to shore. I'll try your surfboard on the bigger waves with the rest of the waxheads (surfers).
Dr. Bob: What about the blueies?
BASD: No worries mate. The water is fine. Just have a look at all the ankle biters (Aussie children) out there. Besides, blueies are nothing compared to box jellyfish, but they are more common up north.
Dr. Bob: I read about them in my travel books! They are the most poisonous creatures on the planet, aren't they?
BASD: Yeah, but if you stay out on dry land, you'll probably just get bitten by one of our giant poisonous spiders or venomous snakes.
Dr. Bob: I just read in my Truly Terrible Ways to Die While on Vacation Down Under book that out of the 10 most venomous and deadly snakes known to man, 11 of them reside here in Oz. And that they kill so fast that when bitten by one of these unspeakable slithering horrors, the victim's last words are "say, isn't that a sna ..."
I put the book down with trepidation and head for the water roller-coaster and the big blue floating potentially deadly condoms, which now seem as tame as baby kangaroos. But I ask you, dear reader, how much can a koala bear?
Want to get in touch with Dr. Bob? You can reach him through his "Ask the Experts" forum, by sending a message to the Robert James Frascino AIDS Foundation, or by leaving a comment for him below. (If it's a private message, or if it includes personal info such as your e-mail address or phone number, we won't post the comment, but we will send it along to him.)