HIV and ID Observations

National Library of Congress, 1970.

The International AIDS Conference — or AIDS 2020 — shifted from its Bay Area dual locations of San Francisco and Oakland to be entirely online.

Digital. In the cloud. Virtual.

The primary motivation for the switch was to show off what the numerous tech giants in the region could do with this fancy thing called the World Wide Web.

You know — Google, Apple, Facebook, Oracle, Intel, Hewlett-Packard, Cisco, Twitter, Zoom, and the whole gang — flexing their digital muscles.

Ha, ha.

With that silly preface out of the way, here’s a Really Rapid Review™ of some highlights — which encouragingly included some very important HIV research. Off we go with some highlights:

• Long-acting injectable cabotegravir is superior to TDF/FTC for pre-exposure prophylaxis in MSM and transgender women. Sure, we’ve known some of these results of HPTN 083 for ages — that’s May 2020, isn’t time strange these days? But seeing the data makes the results even more impressive, especially since 1) the study enrolled the demographics at highest risk for HIV; 2) both strategies were highly effective, CAB just more so; and 3) based on when incident HIV occurred, it looks like only 5 out of 2200 acquired HIV while actually receiving injectable cabotegravir. That’s an incredibly small number, regardless of what subsequent resistance studies show. Those are strangely not yet available — blame COVID-19.
• People in Boston stopped PrEP due to COVID-19. Completely understandable — why take PrEP if you’re social distancing? Similar COVID-19 effect in Australia. Some things definitely cannot happen with a 6-foot space between you and another person. And the virtual version of this activity does not require PrEP — unless those tech giants mentioned above have figured out something very novel. Jokes aside, this trend will bear watching as COVID-19 recedes in some areas.
• The occurrence of neural tube defects in babies born to mothers receiving dolutegravir at conception continues to drop. From an estimate of 1/100 exposures after the first report 2 years ago, to 2/1000 now, this decline suggests that the initial case cluster (n=4) may have occurred by chance. Good news! Note that the difference in neural tube defects between dolutegravir and other ART exposure at conception is no longer statistically significant.
• Despite a faster viral load decline, DTG-based regimens in pregnancy do not appear to prevent maternal-to-child transmission better than treatment with EFV. An unexpected finding is that among the 1074 pregnancies, there were 5 transmissions to the newborn — and all occurred in dolutegravir-treated moms. Though not statistically significant, this numeric imbalance is something worth watching as tenofovir-lamivudine-dolutegravir rolls out globally.
• Treatment-related obesity may increase the risk of adverse pregnancy and infant outcomes, especially with TAF/FTC + DTG. This modeling study used incident obesity from the ADVANCE trial, where 14% of women on this regimen developed obesity at 96 weeks, to predict the occurrence of varous complications. Examples include gestational diabetes, preeclampsia, large for gestational age, and macrosomia (among others). Note that these adverse outcomes were not seen in the IMPAACT 2010 study, which tested this exact regimen in women starting HIV treatment during pregnancy — and conversely found TAF/FTC + DTG to be the safest treatment.
• In South Africa, people with HIV with COVID-19 experienced a twofold increased risk for death compared to those without HIV. As I noted before, this giant study contrasts with most U.S. and European cohorts both in its sheer size — 4016 people with HIV, if I did my math right — and conclusions about the negative impact of HIV on outcome. An important unmeasured contributor is likely to be social determinants of health — especially poverty.
• A cohort study of 100 people with HIV in the Bronx showed no effect of HIV on mortality. This reassuring result is much more typical of the European and U.S. studies of HIV and COVID-19. An interesting observation is that none of the viremic people with HIV required intubation, further suggesting that immune responses to the virus contribute to the most severe outcomes.
• In this VA cohort study, people with HIV were no more likely to test positive for COVID-19 than HIV-negative controls. Disease outcomes similar as well. Results imply that HIV does not predispose to acquiring COVID-19, nor worsens severity of disease.
• Could the HCV drugs sofosbuvir and daclatasvir be effective treatment for COVID-19? Pooled results from three studies in Iran demonstrated a faster recovery time in those receiving these drugs. Results should be considered hypothesis-generating rather than definitive given the small number of patients treated; a 600-person randomized trial is ongoing. If effective, let’s hope the price comes down, as the price of 14 days of this combination in the USA is nearly $19,000.
• One person (out of five) who intensified treatment of with maraviroc, dolutegravir, and nicotinamide (?) is now off therapy with no viral rebound. His baseline regimen was TDF/FTC/EFV, and he’s been off treatment for 66 weeks; HIV antibody titers are also declining. Could this be the next HIV cure? Or just a very small reservoir, potentially primed to rebound, as in the “Boston” patients after stem cell transplants? Only time will tell.
• In a retrospective study of first-line failure with TDF/FTC and an NNRTI, an strategy of recycling tenofovir versus switching to zidovudine favors the tenofovir approach. Note that this is despite a high proportion of K65R resistance mutations among viral isolates after first-line failure. The results were attributed to better adherence on the TDF, which is much better tolerated than ZDV. Agree 100%, and worth studying prospectively since they contradict WHO guidelines.
• In NAMSAL study, DTG remains non-inferior to EFV at 96 weeks. The importance of this clinical trial, conducted in Cameroon, is that it included a very high proportion of participants with high viral loads (66% > 100K) and/or low CD4-cell counts (33% < 200). DTG treated patients experienced less emergent resistance, but EFV did surprisingly well given what is considered a region with high transmitted NNRTI resistance. Both strategies did worse in the high viral load stratum — something I’d expect we’d see more often if our other treatment-naive studies enrolled a comparable population.
• In the NIX-TB study of bedaquiline, pretomanid, and linezolid for drug-resistant TB, HIV status did not worsen outcomes. The most important toxicity of this regimen — so transformative for treatment of such a difficult infection — is linezolid-related neuropathy.
• In a longitudinal clinic-based analysis, a switch from TDF to TAF leads to a 9-month period of weight gain (1–4 kg). Change in weight then resumes at roughly the same slope as before the switch. Whether this is due to the weight suppressive effects of TDF versus a direct effect of TAF — or both — remains an unanswered question. In support of the former hypothesis, weight change in the HPTN 083 study was less in the TDF/FTC than the CAB arm, just as it was versus the placebo arm of iPrEx and TAF/FTC arm of DISCOVER.
• People with HIV starting treatment gain more weight over time than matched HIV negative controls. This large comparative cohort study from Kaiser demonstrates both a “return to health” phenomenon for those starting treatment with low body weight, and an eventual “overshoot” for those with normal or above-normal weight at baseline.
• Metabolic parameters improved when switching from TAF-based regimens to DTG/3TC in the TANGO study. Importantly, a high proportion of the enrolled participants were receiving “boosted” regimens, mostly elvitegravir/cobicistat/FTC/TAF — the bulk of the benefit came from these switches. No significant differences in weight.
• Standard risk calculators appear to underestimate cardiovascular risk in people with HIV. Data derived from two large clinical databases, one from Kaiser and the other from our health system — which has been newly named “Mass General Brigham” (R.I.P., Partners).
• Patients switched to DTG/3TC did not experience more low-level viremia than those remaining on a three-drug TAF-based regimen. Another analysis from TANGO, this time using “target not detected” as the endpoint of interest.
• People with NRTI resistance do not have more more “blips” if suppressed on BIC/FTC/TAF or DTG plus FTC/TAF. Guess if you’re suppressed on these high resistance-barrier integrase inhibitors, you’re really suppressed.
• Participants with virologic failure on doravirine plus islatravir as initial therapy experienced only low-level viremia. In these data from the Phase 2 study, all confirmatory viral load values were <80, so none met criteria for resistance testing. The presentation included a table with the research plans for this DOR/ISL combination, which includes fully powered studies in treatment-naive patients (vs. BIC/FTC/TAF) and switch studies.
• Among NNRTIs, doravirine was most likely to be active against over 4000 viral isolates sent for HIV drug resistance testing. At a biologic cut-off of threefold change, 92.5% of the isolates retained doravirine susceptibility, including 45–62% of those resistant to other NNRTIs. Isolates with single mutations (e.g., K103N or Y181C or V106I) generally remained susceptible.
• The pharmacokinetics of subcutaneous injections of lenacapavir support an every 6-month dosing interval. Introducing a new antiretroviral name for this investigational CAPsid inhibitor (note the third syllable)! A key question is what partner should accompany such an infrequent administration, and at what intervals.
• There is no significant drug interaction between darunavir/ritonavir and dolutegravir. Good thing, too — it’s a very commonly used combination in patients with resistance.
• Among those older than 65, a switch to BIC/FTC/TAF maintains viral suppression and is well tolerated. Raises my spirits to see the age threshold for “older” people with HIV to be moved up from 50 to 65!
• A compassionate use program offers injectable cabotegravir plus rilpivirine to people who cannot or will not take oral antiretrovirals. Of the 35 patients in this program, 28 were viremic — and hence received CAB/RPV treatment not as a switch-strategy, which is how it will be licensed. Still, a remarkable 63% of the total population achieved viral suppression despite enormous challenges.

At this point in these Really Rapid Reviews™, I often comment a bit on the host city’s cuisine, or sites, or weather, or something local. (Sharon Lewin says I captured Melbourne perfectly. Very proud of that comment.)

But since this was a virtual meeting, what can I discuss? The conference website? Acknowledging that it must be a huge challenge to put these meetings on this way, I confess to finding the AIDS 2020 site rather baffling. Fortunately, several people (including one of the conference chairs, Monica Gandhi) circulated brief tutorials. Here’s a nice guide, too.

Still, the search function was wonky, and I couldn’t figure out a way to share the URLs from the abstracts; as a result, the links in the above summary refer to outside sources.

And yes, it’s mostly NATAP, which remains the most reliable place to find conference results — despite a web design that hasn’t been updated since 1999 (my estimate). Thank you, Jules Levin and Mark Mascolini!

As usual, if I missed something important, put it in the comments section. Also — will we meet in person next year in Berlin? What do you think?