Specialties & Topics
- Arthritis/Rheumatic Disease
- Breast Cancer
- GERD/Peptic Ulcers
An ongoing dialogue on HIV/AIDS, infectious diseases,
February 19th, 2017
The Conference on Retroviruses and Opportunistic Infections (CROI) returned to Seattle this past week for its 24th meeting. It’s the 4th time CROI has been held in Seattle, an excellent city for a meeting of this size, which includes “only” 4200 people. The convention center is pleasant and user-friendly — big but not cavernous, actually encourages interactions with colleagues — and there are numerous hotels and restaurants within walking distance, plus more Starbucks per square foot than any place on the planet.
From a content perspective, the big change for CROI 2017 was the return of numerous studies on antiretroviral therapy, studies involving both approved and investigational agents. The last several years, by contrast, had relative dominance of pre-exposure prophylaxis and hepatitis C studies. With PrEP, one had the sense at the meeting that we’re now waiting for the next strategies (long-acting injectables, for example).
As for hepatitis C, well that’s been all but solved (except for the implementation part). How do you improve on 97%-plus cured. Hooray!
On to the summary, a Really Rapid Review™ of the most interesting studies at the conference (at least from one perspective, ahem). Links are to the conference website (as usual excellent), abstract #’s are in brackets, and be sure to check out some of the oral presentations here. The list is roughly organized into epidemiology/prevention, treatment, cure, and opportunistic infections. Please tell me what I missed in the comments section.
And, because I was involved in a few of the studies listed below, for full disclosure I’ve inserted a special Puppy text emoticon to draw attention to that fact. ੯ੁૂ‧̀͡u (Make sure you click on them. Woof.)
- New HIV infections in the USA continue to decline . From 2008–2014, the annual number of HIV infections dropped 3.6% per year, and the percentage of persons with undiagnosed infection declined at around the same rate. That’s the good news. The bad news is that new infections continue to increase in young black and Hispanic men who have sex with men. For the record, we’re down to 37,600 cases/year in the USA, and I expect this will continue to drop since PrEP use didn’t really start until 2014.
- Among participants in the HIV Outpatient Study, the proportion of time spent with HIV RNA > 1500 has dropped dramatically since 2000 . This higher proportion of diagnosed, treated, and suppressed patients must be the primary reason why HIV incidence has declined in the USA.
- Doxycyline administered as post-exposure prophylaxis reduced the incidence of chlamydia and syphilis among participants in the IPERGAY PrEP study [91LB]. No effect on gonorrhea. Significantly more GI adverse events in doxycycline recipients. Interesting results — but definitely not enough evidence yet to make this a policy recommendation, a fact stressed by the lead author, Jean-Michel Molina.
- A case of PrEP failure occurred despite good adherence and no transmitted resistance . The case illustrates the likely importance of “inoculum” in PrEP failure — the person had a very high number of potential exposures. It’s worth looking at the full poster presentation, as the clinical and laboratory manifestations of acute HIV infection were unusual, possibly influenced by being on TDF/FTC.
- In treatment-naive patients, the investigational NNRTI doravirine was non-inferior to boosted darunavir [45LB]. 84% vs 80% < 50/copies at week 48, with a trend toward doravirine being better with very high (>500,000) baseline HIV RNA. Favorable aspects of this treatment included once-daily dosing, few CNS side effects, and a better metabolic profile that darunavir. Only 1 of 364 doravirine-treated patients developed resistance, a low number for NNRTI strategy; none did in the darunavir arm. And note the abbreviations — “DOR” vs “DRV”! A coforumulated DOR/TDF/3TC tablet is in development. ੯ੁૂ‧̀͡u
- In virologically suppressed patients with no history of resistance, dolutegravir plus rilpivirine maintained virologic suppression as well as continuing current therapy . 95% < 50 in each study arm at week 48. Only one of 513 patients in the DTG + RPV arm failed with resistance (she clearly stopped therapy). There was a slightly higher rate of discontinuations due to adverse events in switchers (3% vs <1%), likely at least in part due to the open label design. Note that this is a rare success for an NRTI-free treatment strategy, a fact emphasized by Jose Arribas in his outstanding oral presentation on treatment simplification. A coformulated DTG/RPV tablet is in development, to be used in follow-up studies.
- In a phase 2 double-blind clinical trial, bictegravir + TAF/FTC was comparable to dolutegravir + TAF/FTC . Responses 97% and 91% at week 48, respectively; more details in the published paper. Bictegravir is an investigational once-daily, unboosted integrase inhibitor with activity against wild-type and most resistant viruses and few predicted drug interactions. A coformulated BIC/TAF/FTC tablet is in development — and being used in the phase 3 program, which is fully enrolled. ੯ੁૂ‧̀͡u
- In a single-arm study, dolutegravir plus lamivudine maintained virologic suppression . Study included 110 patients with no history of failure and who tolerated an 8-week “lead in” of DTG + 2NRTIs first. One virologic failure (no resistance), one almost failure with low-level viremia. Comparative clinical studies ongoing. Study is called “LAMIDOL”, which sounds like a skin cream.
- Dolutegravir monotherapy increases risk of virologic failure and resistance [451LB]. So we now have several studies that show this strategy to be a bad idea. To quote the abstract: “The genetic barrier of DTG monotherapy is insufficient to allow for maintenance monotherapy.” Here are more details on the resistance pathways in several other studies. Let’s stop doing this, ok? Thoughtful editorial to this effect by Joel Gallant says the same thing, though much more eloquently.
- Transmitted drug resistance did not reduce antiviral efficacy in this large treatment study . This is a surprising finding, as several prior studies have shown that transmitted NNRTI resistance does reduce the activity of these regimens. One possible explanation is the greater potency of TDF/FTC vs AZT/3TC.
- Case report of DTG resistance in a treatment-naive patient [500LB]. Baseline HIV RNA 1,970,000 and CD4 78. The fact that CROI accepted a single case of this event shows how incredibly rare this is.
- Darunavir but not atazanavir associated with an increased risk of cardiovascular events [128LB]. It’s a DAD analysis, and the effect (a 53% increase) was comparable to lopinavir and indinavir. Is this a class effect, ameliorated by atazanavir’s bilirubin-raising properties?
- More discontinuations due to neuropsychiatric side effects on DTG than RAL or EVG/c . Concomitant ABC/3TC with DTG appears to be a strong contributor. Note that rates of d/c due to adverse events overall did not differ between the drugs.
- High DTG plasma concentrations associated with more neuropsychiatric adverse events . Study done in Japan — could tolerability be linked to BMI or pharmacogenomic issues?
- More adverse events in EFV rapid metabolizers . Study done in Botswana, and runs counter to analysis of suicidality done in (mostly) US-based studies, where those with genotypes associated with slow metabolism appeared to be at higher risk.
- EFV use as a first-line agent in the USA has dropped dramatically . Now less than 10% start it as first line, a stark contrast from the pre-integrase era.
- TAF superior to TDF after 144 weeks . The most important safety finding is that 0/866 on TAF vs 12 (11 if you remove “bladder spasm”)/867 on TDF developed clinically significant renal issues, a difference that is highly statistically significant. ੯ੁૂ‧̀͡u
- Resistance to integrase inhibitors remains extremely rare . In a 9 site survey, baseline (transmitted) integrase resistance was 0.04%; post-treatment was 0.4% — both very good news.
- Should we be sending baseline integrase genotypes before starting therapy ? Based on this modeling study, the answer is a resounding NO, for three reasons: 1) the prevalence of transmitted integrase resistance is fortunately still very low (see above); 2) DTG-based regimens will likely succeed even when resistance to first-generation INSTIs is present; and 3) even if virologic failure occurs, it will delay use of a salvage regimen only briefly. ੯ੁૂ‧̀͡u
- Many novel drugs in various stages of development. These include (deep breath) ibalizumab [449LB] (anti-CD4 monoclonal antibody), PRO140  (different humanized anti-CD4 monoclonal antibody), UB-421 [450LB] (yet another monoclonal antibody that blocks viral entry), elsulfavirine [452LB] (NNRTI with 8-day half-life), MK-8591  (potent and very long acting NRTI), GS-PI1  (an unboosted once-daily protease inhibitor), GS-9131  (NRTI with activity against essentially all NRTI-resistant isolates), and GS-CA1  (capsid inhibitor that in vitro is more potent than any other antiretroviral agents). Wow that’s a lot!
- Even very early HIV treatment does not prevent virologic rebound after stopping ART . Eight started treatment during “Fiebig I acute infection” (VL+, p24-, Ab-), which is known to induce a lower HIV reservoir, yet all rebounded by 9 weeks.
- A prolonged virologic remission in a patient undergoing a stem cell transplant . The patient continued suppressive ART for 784 days after transplant, and had no detectable virus (HIV RNA or DNA) using many techniques. Rebound occurred after 288 days off ART, longer than in the “Boston patients”. Note that donor was CCR5 wild-type, not CCR5 negative.
- Latency-reversing agent plus HIV immunization may induce “viremic control” [119LB]. Strategy tested was “MVA.HIVconsv” vaccination, then three doses of romidepsin, then another vaccination; 5 of 13 maintained low-level viremia after treatment interruption. Importantly, study subjects started ART soon after HIV acquisition, hence were likely to have low viral reservoirs.
- TLR7 agonist induced “viral remission” in two of four Indian Rhesus macaques [338LB]. One of the agents (GS-9620) is currently in human trials.
- Does ART with integrase inhibitors increase the risk of immune reconstitution inflammatory syndrome (IRIS)? The answer is yes, based on two studies conducted in non-TB endemic regions ( and ). As DTG-based regimens are increasingly adopted world-wide, we should expect IRIS incidence to increase. And count me in the group that thinks this is a good thing — IRIS is a marker for faster virologic response and immunologic recovery. (Not everyone agrees.)
- Pre-emptive prednisone reduced the risk of TB IRIS in patients with advanced HIV disease [81LB]. All patients (CD4 < 100, diagnosed with TB) received ART and TB therapy. The study compared prednisone 40 mg/day for 2 weeks then 20 mg/day for 2 weeks versus placebo. Incidence of IRIS was 47% in placebo arm, 33% in prednisone arm (p=0.02). Incidence of infectious complications or malignancies did not differ between study groups.
- In cryptococcal meningitis, a single high dose (10 mg/kg) of liposomal amphotericin reduced CSF fungal burden as fast as standard dosing (3 mg/kg/day for 14 days) . Based on these encouraging early results, this strategy will be evaluated in a randomized clinical endpoint study.
- Researchers intensively studied 5 patients with paradoxical CD4 decline on suppressive ART . 4 of 5 had CD4 < 50 (other was 74). Unlike immuologic non-response, these patients did not have elevated inflammatory markers or immune activation, but did have higher levels of homeostatic cytokine IL-7. The title says it all: “a novel, rare and perplexing immunologic outcome.” (I’ve seen this once in my career, for the record.)
- For neurosyphilis, intravenous penicillin and procaine penicillin plus probenecid achieved similar clinical outcomes . Although limited by the observational design, there is so little modern data on treatment of neurosyphilis this poster is still of great interest.
- Widespread use of HCV therapy in Holland has reduced the incidence of acute HCV [137LB]. An excellent example of treatment as prevention.
- No dose adjustment should be required when glecaprevir and pibrentasvir are administered with either ECF-TAF or ABC/3TC/DTG . Approval of this pan-genotypic HCV treatment is expected soon.
- American ginseng did not reduce HIV-related fatigue . We can add this to the (long) list of studies that fail to show benefits from
homeopathicnon-FDA approved herbal remedies. Plus, I just like typing “American ginseng.”
If you’re interested in watching webcasts of interesting plenary or symposium talks, I can strongly recommend Demetre Daskalakis on ending the HIV epidemic in NYC (he has more energy than the rest of the 4199 CROI attendees combined), Charlie Flexner on long-acting ART (he dispelled several “myths”), and Carl June on how cellular treatments of cancer might apply to the HIV cure effort.
One caveat to this last talk is that Dr. June neglected to mention that there’s huge difference in acceptable risk between someone with refractory metastatic cancer versus stable HIV infection. So I’m mentioning it for him.
See you at next year’s CROI in Boston!
February 13th, 2017
The people researching cardiovascular disease in HIV have quite the challenge.
Because when you think about it for a second, we HIV treaters are a pretty spoiled bunch when it comes to therapeutic success.
We saw the transformation of a terrifying, incurable, and rapidly progressive disease (AIDS) into something that can be managed for decades — usually with just a pill or two each day.
Or, if you prefer a quantitative description, here’s the slide Tony Fauci uses when he cites my friend Rochelle Walensky’s 2006 landmark paper in his talks:
Remember, these impressive numbers were estimated before we had the great advances in antiretroviral therapy in the late 2000s. The benefits are undoubtedly even greater over the last decade, since virtually everyone who takes HIV medications regularly now is virologically suppressed.
Pretty much any medical intervention for a non-HIV problem might seem a bit ho-hum compared to the miracle of antiretroviral therapy, meaning the people researching non-HIV related problems have their work cut out for them to get our attention. This is despite the fact that these non-HIV problems (especially the problems of aging) are more important than ever.
So when Steve Grinspoon contacted me recently about mentioning the REPRIEVE study on this site in honor of “Heart Month”, I readily agreed. Steve is leading this large NIH-funded trial, which asks this important question:
If people with HIV are intrinsically greater risk of heart disease, would they benefit from taking a statin drug even if we would not ordinarily prescribe it based on standard risk assessments?
REPRIEVE is actively enrolling at clinics and hospitals around the world, including at our site here in Boston.
As demonstrated in multiple studies (and reviewed here), people with HIV do appear to be at higher risk for heart disease even when their virus is well controlled with ART. “Lifestyle” issues (especially smoking), current and past immunosuppression, duration of uncontrolled viral replication, cardiotoxic drugs, and immune activation and inflammation all likely play a role. Related to the issue of inflammation, Steve’s research group just published a paper demonstrating that abnormal arterial inflammation — a risk factor for coronary disease — continues despite effective ART, at least in the short term.
So why not just recommend a statin for all people with HIV above a certain age? While it’s theoretically possible that statins will improve this abnormal inflammatory state, we don’t know that statins will provide a clinical benefit. And perhaps not all people with HIV are at higher CV risk — the most recent look at MI incidence in the Kaiser HIV cohort did not find an excess risk in a group of very healthy (high CD4, modern ART regimens, low rates of smoking) HIV patients compared to HIV negative controls.
Which brings us back to REPRIEVE — statins might be beneficial, they might not, and there’s enough equipoise that it’s appropriate to conduct a real randomized trial.
Eligible patients must have stable HIV, be older than 40, and not have a high risk for heart attacks or stroke (otherwise they should be on a statin). If you want to check, you can enter patient information into the American College of Cardiology/American Heart Association heart risk calculator. Those with a 10-year risk of heart disease or stroke < 15% may be eligible, depending on LDL cholesterol levels.
Participants are then randomized to pitavastatin (chosen because it doesn’t interact with any HIV drugs) or placebo. The primary endpoint is time to atherosclerosis-related clinical event.
I think it’s an excellent study, not just because I’ve known Steve for ages and he’s been a leading figure researching metabolic complications of HIV disease longer than just about anyone. A clinical trial that evaluates a critical non-HIV related complication makes abundant sense in a population where infectious complications are increasingly rare. The results will have great importance to patients, in particular the increasing proportion over the age of 50 (which now exceeds 50% in many urban areas).
Plus, if I mention REPRIEVE here, maybe I’ll get him to read this blog — which he obviously had never done before he called me. “I’ve been really busy,” he said.
“Really busy”? — not sure I’m buying that excuse!
February 5th, 2017
The New England Journal of Medicine has published the first well-documented case of HIV pre-exposure prophylaxis (PrEP) failure despite good medication adherence.
We heard lots of this information at CROI last year, and again I’m impressed at the extraordinary degree of virologic investigation done on a case from clinical practice.
To refresh your memory, here are the critical details from the published case report and the supplementary appendix:
- A 43-year-old man began PrEP with TDF/FTC in April 2013, and had multiple negative 4th generation HIV screening tests over the next 21 months.
- Pharmacy refill records indicated excellent adherence. (Side note to young clinicians: Refill frequency is an amazingly powerful tool to monitor adherence.)
- Prior to diagnosis, he had multiple sexual exposures, including receptive anal intercourse without the use of condoms.
- A couple of weeks before his first positive HIV screening test (antigen positive, antibody negative — Day 0), he developed abdominal pain which waxed and waned over the next 3 weeks. A CT scan demonstrated thickening of the sigmoid colon, ascending colon and rectum. Endoscopy revealed erythematous patches of the sigmoid colon.
- Adherence was confirmed by analysis of a plasma sample obtained on Day 0 revealing tenofovir concentrations consistent with recently taking the drug.
- HIV RNA peaked at 28,000, and became undetectable with the addition of boosted-darunavir and raltegravir.
- His viral isolate had extensive multi-class resistance, including to FTC (M184V), TDF (multiple thymidine-associated mutations), NNRTIs (Y181C), and first-generation integrase inhibitors (92Q).
- He’s now virologically suppressed on DRV/c, RPV, and DTG.
The supplementary appendix has an excellent figure of the timeline, which I’ve pasted below:
So what can we learn from this single case?
- PrEP is very effective, but it’s not 100% protective. I don’t think clinicians are claiming 100% effectiveness, but PrEP-takers may be hearing this from various “experts”, or may be misunderstanding the data.
- Transmitted drug resistance will weaken PrEP. Although all of the mutations in the case are to drugs not in the TDF/FTC combination — except M184V — the multiple TAMs could have weakened TDF through cross resistance. Furthermore, FTC could have been transmitted, or alternatively selected by period of viral replication after viremia developed. The source patient’s virus was not available for sequencing, unfortunately.
- The symptoms of acute HIV infection are highly variable. The supplement to the case reports states, “The patient did not have classic symptoms of acute HIV seroconversion”, which is true — but he did have GI symptoms, which are quite common in acute HIV. We need to remember this variability when following patients on PrEP.
- The monitoring strategy recommended by the CDC in the guidelines should be followed. Although it might seem like overkill to monitor for HIV and other STIs every 3 months while receiving PrEP, remember that only those at highest risk for getting HIV should be receiving PrEP to begin with. Clinicians may choose to recommend more frequent monitoring if clinically warranted.
- Integrase resistance is rare in clinical practice, and transmitted integrase resistance is even less common. While some might interpret this case report to indicate a need for baseline integrase testing for newly diagnosed individuals, the detection of transmitted integrase resistance in most studies of newly diagnosed patients is less than 1%, and often 0%. Notably, the transmitted virus was still sensitive to dolutegravir (I’d interpret the genotype as fully susceptible).
Ok, that’s what I learned. Provides a cautionary note to those both prescribing and receiving PrEP, one further reinforced by this additional case report of PrEP failure presented at a recent conference.
As for tonight’s game, below is what I’m going to watch, and here’s why!
January 29th, 2017
This was not a happy or comfortable weekend for ID doctors, given our predilection for inclusiveness, non-judgmental care, global health, and that “safety net” idea that seems to us such an intrinsic part of being a good doctor.
Exclusion of foreigners? Why, we ask, would you do that? People from other countries are our friends, our colleagues, and our patients. Many of our favorite patients, I might add, since they might bring with them exotic, challenging, and treatable problems that are right up our alley.
Furthermore, to overstate the obvious, most of us living here in the USA are not that far removed from immigration ourselves.
Fidencio Saldana — he’s a cardiologist, the Dean of Students at Harvard Medical School, and the child of Mexican immigrants — gave medical Grand Rounds at our hospital recently.
He recounted what it was like being a medical student here, and how out of place he sometimes felt. He then movingly described how was made to feel welcome by hearing from one of our senior doctors, Marshall Wolf:
Hey relax. My parents were immigrants too. You belong here.
That was two weeks ago, a brief aside made at a lecture, yet I have thought of it frequently since, especially this weekend.
And this morning, glum and discouraged by recent events, I needed some distraction.
So I turned on the television at 6AM and watched two of the most extraordinary athletes in the world, Roger Federer of Switzerland and Rafael Nadal of Spain, play the fifth and deciding set of tennis at the Australian Open in Melbourne, Australia.
The crowd was cheering, and hanging on every point, and no doubt millions of others all over the world were doing what I was doing — watching and marveling and feeling a sense of global togetherness for this extraordinary event.
And here’s the best part. After Federer won the match, a grueling 5-set affair that lasted over 3 hours, he graciously said:
Tennis is a tough sport, there are no draws. But if there was I’d be happy to share it with Rafa tonight.
Share. No gloating. No petty rivalries. No cheating. No distortion of facts. These are the best players in the world, competing at the highest level for hours, and they can still get along like friends even in the most intense setting imaginable.
You got that?
January 22nd, 2017
Welcome to Fun with Old Medical Images!
Here’s how it works: You’ll see a series of images — old, strange, and perplexing — and each will have a caption that I have created for you at no extra cost.
Accustomed to high-quality and clinically relevant information from your NEJM Journal Watch contributors, you will laugh happily at the contrast between that solid content and this silly exercise, forgetting for a moment the complicated and sometimes contentious world we live in.
See, this will be therapeutic.
Off we go. Here’s the first one:
Poor Perkins! I’m sure he’s also wondering why his doctors didn’t give him a pillow.
That was fun. Ready for #2?
So many promising drugs fail during clinical trials due to side effects! At least dreaming of lamb chops is safer than QT prolongation.
Now, onto #3:
Such stillness in that room! And who’s the uniformed man in the upper right? Is he a scribe?
We’re on a roll! Here’s #4:
The laughs keep coming, so let’s go on to #5:
Here the key question — did medical insurance in mid-19th century France cover the cost of Uber for housecalls? I did a quick search — fascinating result.
Should we finish with a neat half-dozen? Why not, here’s #6:
Nothing but fun at this ophthalmologist’s office! Eye appointments always last too long, so why not get checked for glaucoma and get a bit more stylish at the same time?
Thank you for taking this tour of Old Medical Images, I hope you enjoyed it as much as I did.
Next time, we’ll go back to our usual programming.
January 16th, 2017
- A Las Vegas woman died after infection with a pan-resistant strain of Klebsiella. While CDC receives many isolates of carbapenem-resistant enterobacteriaceae (CRE), 80% are susceptible to at least one aminoglycoside and 90% to tigecycline — not this one, which retained susceptibility only to fosfomycin (a drug not available in this country for systemic use). One critical detail in this case was her multiple recent hospitalizations in India related to a right femur fracture and osteomyelitis of the right femur and hip. As with this case of metronidazole-resistant Bacteroides, the travel appears to be the critical exposure history. Question for those who practice in a Travel Clinic — do you now counsel patients about their risks of acquiring highly resistant organisms during travel to certain countries? Seems this risk is particularly high with travel to Southern Asia — probably higher than many of the more exotic conditions that get more attention.
- A man experienced a delayed diagnosis of TB meningitis due to a false-positive multiplex PCR. A 75-year-old man presented with mental status changes, and the BioFire FilmArray on the CSF was positive for HSV-1. Herpes encephalitis, case closed, right? However, the ultimate diagnosis was tuberculous meningitis, and the HSV-1 was not confirmed by additional PCR testing using another FDA-approved assay. Of course in hindsight, it seems clear that this wasn’t clinically consistent with HSV-1 encephalitis, FilmArray result notwithstanding — onset of confusion and speech difficulties was gradual, not acute; an MRI showed no parenchymal abnormalities, unusual in someone with HSV-1 encephalitis of this duration and severity; there was a neutrophilic pleocytosis and markedly elevated CSF protein; he developed hydrocephalus. Individually, several of these could rarely be seen with HSV-1 encephalitis, but together along with his clinical worsening they appropriately raised the concern that the diagnosis was incorrect. Of course hindsight is 20-20, and the most important message in this case is not to succumb to “premature closure” if the clinical picture does not fit the lab test result — an especially important lesson with new testing modalities.
Now, to enlist your support for vaccines, for which there is the highest level of evidence for efficacy and safety. At the kind invitation of Carey Goldberg, the skillful editor of WBUR’s CommonHealth blog, I wrote a piece about the possible appointment of Robert F. Kennedy Jr. by Trump to lead a commission on vaccine safety and scientific integrity.
Kennedy, you may be aware, has a lengthy history of pushing anti-vaccine propaganda.
To you, loyal readers of an ID/HIV blog, I am going to state with 99.9% confidence that you will agree with my views — but please read the piece anyway. This debate about the risks and benefits of childhood immunizations is still (amazingly), a thing — just read the comments if you can stand it — and we need all the support we can get.
But I have a query. Here’s the NPR Facebook page on the piece, with one section highlighted for discussion:
Not sure exactly what they meant by “oddly delightful”, but I’m pretty sure it’s better than the converse — “delightfully odd.”
Happy MLK Day.
January 8th, 2017
A few medicine and family practice residency programs around the country have a dedicated track that focuses on HIV care. Though the programs naturally differ somewhat in structure — here are two examples from University of Washington and Yale — they generally involve placing the resident into an HIV clinic for their longitudinal outpatient experience.
We don’t have such a program here, though I’ve been asked about it several times over the years. I can certainly think of advantages and disadvantages to this specialized track.
And since we’re in the midst of residency interview season — plenty of young, bright people wandering around the hospital in dark suits they might not wear again for a couple of years — it seems a good time to consider the issue.
On the plus side for the HIV track:
- Residents with a stated interest in HIV care can get a head start on their career choice.
- There’s a projected shortage of HIV clinicians, and this training will help provide a capable and interested group of young doctors in the field. Residents can skip specialty training in ID and transition right to primary care with a panel of HIV patients.
- Under current training standards, program directors report a high proportion of internal medicine residency graduates are not adequately trained to provide primary HIV care.
- People with HIV are more likely to be poor, from minority or other traditionally marginalized communities (gay men or people with addiction), and having more clinicians sensitive to their needs certainly is a plus.
On the minus side:
- A focused HIV track arguably limits both the breadth of patient experiences and the ambulatory clinical challenges for the resident. Shouldn’t residents get as broad an education as possible at this early stage of their training? This is especially important if they change their minds and choose to do something else.
- If there’s going to be an HIV track, why aren’t there specialty tracks for other diseases? How about more common conditions, such as the primary care needs of cancer survivors, or people with mental illness, or diabetes? Or to choose a couple of problems with comparable numbers in the USA to HIV — how about adults with congenital heart disease, or those with lupus?
- Since so many patients with HIV today are completely stable from the HIV perspective, a dedicated HIV track isn’t necessary. The focus of residency should be learning how to manage problems of aging (hypertension, diabetes, COPD, cancer screening) since these are the most important issues for many HIV patients anyway. Data are emerging that a primary care/specialty collaboration works well — here’s a good recent paper evaluating this issue.
- Doctors who want to manage the most complex HIV issues — multi-class resistance, knotty metabolic abnormalities, opportunistic infections, challenging drug interactions — should do additional subspecialty training Infectious Diseases. In most clinical settings, these situations would prompt a specialty referral regardless of how a resident was trained.
I’m not going to pretend to have the answer to this one. That’s why there’s a poll, and the comments section!
January 1st, 2017
A lot of these “Best of …” or “Top Stories in …” lists have already been published, as they seem to be appearing earlier and earlier each year. Pretty soon we’ll start reading them around the same time they sell Halloween Candy — and that’s just too early, sorry.
Now this list, however, appears just as 2016 is in the books, all 365 days accounted for and scrupulously reviewed. And I chose five because, well, five follows the rules.
(I just finished a block on service and can’t resist linking that post, since the rules came up literally every day.)
Of course by choosing only 5, I’ve necessarily had to leave off some big HIV stories this year in research, clinical care, or policy, so feel free to enter your top story in the comments section.
Drum roll, please.
Number 5. TAF/FTC Approved.
With approval this year of co-formulated TAF/FTC, we now have the ideal NRTI pair to use in treatment of, well, pretty much everyone. Yes, we already had TAF/FTC as part of the single tablet treatments of TAF/FTC/RPV and TAF/FTC/EVG/c, but those aren’t appropriate for all patients — both must be taken with food, RPV has high viral load and low CD4 restrictions, and EVG/c has a long list of drug interactions. The availability of TAF/FTC provides greater flexibility when, for example, you want to use it with a different 3rd drug — dolutegravir, or raltegravir, or yes even efavirenz — or as part of a more complex salvage regimen, where it’s generally given with DRV/r.
Number 4. HIV cure research inches forward.
Admittedly, we’re still stuck on 1 person cured — the famous Timothy Ray Brown, he of the CCR5-negative stem cell transplant (and cute dog). But that “n of 1” has led to extensive pre-clinical and clinical research on HIV cure, with lots of very smart people working on the problem. Here’s one notable (and surprising) example — antibodies directed against alpha4/beta7 integrin given to SIV-infected primates led to sustained viral suppression after stopping ART. This finding led to rapid initiation of a human study at the NIH using the drug anti-alpha4/beta7 drug vedolizumab, which is already approved by FDA. One caveat on all this research — HIV cure studies are notorious click-bait, as demonstrated here.
Number 3. First large HIV vaccine study in 7 years starts in South Africa.
It’s called HVTN 702, and it will enroll 5400 seronegative people in South Africa, arguably the country in greatest need of an HIV vaccine. Participants will be randomized to receive either placebo or a vaccine series modeled after the RV144 clinical trial in Thailand. The HVTN 702 strategy, however, modifies the vaccine to provide greater and more sustained immunogenecity than RV144, and has been further adapted to the HIV subtype that predominates in southern Africa. Fingers crossed!
Number 2. PrEP gains traction — but it isn’t perfect.
When TDF/FTC for pre-exposure prophylaxis (PrEP) was approved in 2012, I thought it was going to remain a niche intervention, rarely requested by patients or ordered by clinicians. However, since the presentation of the PROUD and IPERGAY studies in early 2014, and the release of guidelines by the CDC, use of PrEP has taken off — around 80,000 people in the USA are now receiving PrEP, a more than 700% increase since 2012. Most of the use, not surprisingly, is in MSM from affluent urban areas. Two cautionary notes: First, the highest risk patients — young MSM of color, especially in the south — aren’t getting it nearly enough; second, PrEP isn’t perfect, with two failures (here and here) despite good adherence, likely due to transmission of NRTI-resistant strains.
Number 1. Treatment as prevention really really REALLY works.
Did I make that clear enough? Publication of two major papers proved this point: 1) The final results of HPTN 052 showed ZERO transmissions from an HIV-infected study subject to his seronegative partner if the blood HIV RNA was undetectable, and; 2) The PARTNERS study, which explicitly recruited serodiscordant couples not using condoms, again demonstrated ZERO transmissions. We all thought that ART would be effective in preventing HIV transmission — but the degree of protection is way beyond what any of us could have hoped. It’s this effect that’s probably leading to a decline in new HIV diagnoses in certain major cities that have a high proportion of patients on treatment, such as San Francisco, New York, and London.
Happy New Year, everyone!
And in honor of the setting for HVTN 702 (see #3 above), here’s 2016’s most popular Youtube video in South Africa.
(Thanks to NPR.org for the video reference.)
December 18th, 2016
- Holiday parties.
- Travel plans — specifically, should we go with DEET or picaridin?
- Lots of high-carb, high-calorie foods stealing blood from our brains. Maybe too much eggnog or punch doing the same thing.
- Kids on vacation, with their demands for sustenance, adult supervision, and entertainment.
- Many critical work support people already away, with out-of-office messages implying that they’re not reading their email (but you know that they are).
Even our pets are distracted. After a crazy weekend of New England weather, starting with bitter cold, then a day of wet snow, and now a Spring-like thaw, Boston dogs and cats who ventured outside today are in bad need of bath.
(And yes, that was just an excuse to show off that magnificent picture of Louie. Click on it for full effect, I dare you.)
Plus, you have the distraction of our latest ID Cartoon Caption Contest, which generated so many outstanding entries that our powerful advanced humor algorithm was unable to limit the finalists to just three candidates this time. Even after we tweaked the settings, the powerful supercomputer churning through the entries kept overheating. We almost had to cancel today’s post and substitute a lengthy rumination on whether you should say Mycobacterium avium complex (MAC) or Mycobacterium avium-intracellulare (MAI).
(Short answer: the former.)
So here’s the cartoon, plus the top four choices. Vote now before 2016 is no more!
(Drawing by Anne Sax.)