HIV and ID Observations

Lamington National Park, Queensland.

You’ll find some conference highlights listed below from the 12th International AIDS Society Conference on HIV Science (or IAS 2023), which took place in lovely Brisbane — where the late July weather was delightful, the ubiquitous ibis was the local nuisance bird, and the riverside parks went on and on and on.

Some might wonder if I can still use the patented, trademarked, and copyrighted Really Rapid Review™ title when I’ve been home from Australia for a whole week. I vote yes — after all, I lost a whole day getting there, and deserve some of that time back. No, my Saturday, July 22, did not exist.

Most links will bring you to the invaluable natap.org site, long may it exist in its delightfully retro late-1990s format.

• Pitavastatin reduced cardiovascular events in people with HIV at low- to moderate CV risk. Yes, I already discussed it in detail, but how could I not at least mention this large, randomized clinical trial? It was the biggest story of the conference, which strangely was put in one of the smaller conference venues. People were literally sitting in the aisles, standing outside, clamoring to get in. Go figure.
• Prolonged ART-free HIV suppression occurred in a person treated with a stem cell transplant from a donor with wild-type CCR5 receptor status. Whether this case will be durable or ultimately have virologic rebound like the Boston patients remains to be seen. “Remission” (no detectable replication competent virus in blood or sampled tissues) is now at 20 months off ART and counting.
• Australia continues to be a model for HIV care and prevention. Their HIV care cascade exceeds 90-90-90% (diagnosed, started on treatment, suppressed), and they also have widely adopted preexposure prophylaxis (PrEP). Anecdotally, some HIV specialists in major urban areas say they rarely see new diagnoses. Imagine!
• 78% of the women in a large study of PrEP chose injectable over oral PrEP after the blinded, comparative phase of the trial ended. HPTN 084 compared TDF/FTC to injectable cabotegravir in women at risk for HIV; cabotegravir was significantly more effective. These results raise the question of whether cabotegravir for PrEP would be more widely used here if logistical and cost barriers were lower — I suspect yes.
• Stay tuned for updated information on prevention of gonorrhea with the meningitis B vaccine. In the ANRS DOXYVAC study, the factorial design randomized participants to doxycycline PEP and/or the meningitis B vaccine or neither. Though both interventions were reported at CROI 2023 to be significantly protective against gonorrhea in the interim analysis, investigators observed a discrepancy between the interim meningitis B vaccine results and the complete analysis — hence we await review and reporting of the final results.
• At Fenway Health (an LGBTQ Care Center in Boston), they have started using doxycycline post-exposure prophylaxis (PEP) to prevent sexually transmitted infections (STIs). I suspect most of us have also begun offering this (I have), in particular to those with recent bacterial STIs. Guidelines endorsement coming soon, I hear.
• At 48 weeks, doravirine/islatravir was non-inferior to bictegravir/FTC/TAF as initial therapy. One versus zero participants developed treatment failure and resistance. No differences in weight gain (roughly 3 kilograms). Because the 0.75-mg daily dose of islatravir was used, CD4 response was blunted in that treatment arm. This comparison is now being repeated with 0.25 mg/daily islatravir dose; it will be interesting to see if virologic responses are as good.
• The key doravirine resistance mutations occurring in prospective clinical trials were V106A/M and F227C/L/R. These aren’t the only mutations that lead to doravirine resistance (notably Y188L and M230L do as well), but in the rare patient with virologic failure on doravirine-containing regimens, these two are the most likely to occur — and they don’t lead to cross-resistance with efavirenz or rilpivirine. Memorize these mutations, impress your friends!
• DTG/3TC was non-inferior to DTG + TDF/3TC in treatment-naive PWH, even without baseline resistance testing. 30% had HIV RNA >100,00, 21% CD4 <200. No treatment-emergent resistance. The study was slightly underpowered (n=214), but it highlights how rare transmitted 3TC or DTG resistance is, fortunately enough.
• People with virologic failure on DTG-based three-drug regimens had a high level of resuppression after adherence counseling. The exceedingly low rate of resistance selection with these DTG-based regimens likely explains the favorable results, which obviate the need to switch treatment. Suspect strongly these results apply similarly to BIC/FTC/TAF treatment, at least based on similarly low incident resistance and anecdotal experience.
• In treatment-experienced persons with HIV (PWH) with a history of treatment failure but current virologic suppression, switching to DTG/3TC was successful even with known 3TC resistance. 50/100 participants had documented M184V mutations. These results notwithstanding, until there’s a fully powered study evaluating this question — and why would we do that? — my view is that DTG/3TC has been extensively tested in people without M184V, and this is the population best suited to this switch strategy. By the way, this study is called SOLAR-3D, not to be confused with the SOLAR study of CAB-RPV.
• Switching stable PWH with integrase-inhibitor weight gain to darunavir/cobicistat/FTC/TAF did not reduce weight. Right now, it’s looking like the only regimen switches that may induce weight loss must involve a TDF-based treatment — which has its own toxicity issues (renal, bone), especially in older patients.
• For treatment of hepatitis B and HIV co-infection, BIC/FTC/TAF and DTG + TDF/FTC were both effective. These 96-week results continue to show certain endpoints favoring BIC/FTC/TAF, most notably HBEAg loss and seroconversion. But the DTG + TDF/FTC arm has “caught up” to the BIC/FTC/TAF arm in hepatitis B viral suppression, which happened faster in the TAF treatment arm.
• In a randomized trial comparing BIC/FTC/TAF to CAB-RPV, patient-reported outcomes favored long-acting injectable treatment. These results recapitulate several prior analyses with similar findings, which show that if people want to take injectable therapy, they’re happier once they do so. We could interpret these findings as either reassuring or a “self-fulfilling prophecy” — but how about both? And this, by the way, is the other SOLAR study.
• In a heterogeneous population (735) of PWH with viral suppression on three-drug therapy, switching to DTG plus either 3TC or RPV was safe and effective. Unlike in the phase 3 studies of these treatments, 50% of the population had a history of drug resistance mutations, so this expands the population potentially eligible for using two-drug therapy. Assume (hope) that they did not have primary mutations to either of the two drugs in the given strategy!
• In a small, comparative, matched study, PWH and diabetes mellitus (DM) lost significantly more weight on GLP-1 receptor agonists than people with DM alone. Our limited experience in clinical practice certainly shows this class of drugs leads to weight-loss in PWH. Could GLP-1 agonists be particularly effective in our patient population?
• In treatment-naive people starting antiretroviral therapy (ART), DTG-based regimens were associated with incident hypertension, especially when combined with TAF. This analysis from the NAMSAL and ADVANCE studies also showed that hypertension treatment (available to the ADVANCE study participants) was quite effective. As noted here and in a bunch of other studies looking at hypertension and association with specific ART, it’s tricky to disentangle this effect from differences in weight gain — a well-known trigger of high blood pressure.
• New onset diabetes was associated with current integrase strand inhibitor (INSTI) use, even when controlling for BMI. As noted by some HIV specialists, this same cohort found an association between INSTI use and cardiovascular disease — an association later refuted by an analysis controlling for baseline CV risk factors.
• Bictegravir exposure was reduced in pregnant women taking BIC/FTC/TAF during the second and third trimesters. The median trough was still 6-7 times higher than the inhibitory quotient, and none of the women experienced virologic rebound or failure; the only participant with notably low levels was taking concomitant calcium and iron supplements. These results support the decision to continue BIC/FTC/TAF in women who are found to be pregnant while receiving this regimen.

That’s a wrap! What did I miss?

After the conference, we went hiking in Lamington (see picture above) and Springbrook National Parks. So beautiful! Saw wallabies and cockatoos and kookaburras!

Now, if only someone could come up with a cure for jet lag …