“Lookup there! It’s Microsoft and Amazon inventory!” Nationwide Archives, 1962.
In a current chat I had on a local TV network on this 12 months’s respiratory virus season, the host talked about that “this 12 months felt very post-pandemic”, prompting me reflexively to knock wooden — and I’m not a superstitious individual.
However even we ID docs should acknowledge the dramatic enchancment in COVID severity this winter in comparison with the final two, each of which had been extreme sufficient to make the Convention on Retroviruses and Opportunistic Infections, or CROI, persist with the virtual-only format. And, in fact, traditionally, CROI was the very first scientific convention to go this route, method again in March 2020, a interval about which the much less mentioned the higher.
(Involuntary shudder.)
However on to this 12 months’s CROI, which was obtainable in-person or digital, happening as soon as once more in Seattle, a spot it’s been a number of occasions earlier than. It’s our premiere scientific convention, protecting not simply HIV, but additionally sexually transmitted infections (STIs), hepatitis, and now SARS-CoV-2, with many glorious research on all these scourges.
This week, on this Actually Fast Assessment™, I’ll cowl the non-COVID research, with take-home messages and typically a quick remark. You’ll see the summary numbers in brackets and hyperlinks to both the summary (if obtainable) or to the invaluable NATAP web site, which in some way continues to mixture lots of the precise slide shows and posters in real-time. Bravo for that, and lengthy could it reside!
- The prognosis for people with HIV has markedly improved since 2012 [870]. This multi-national, massive (n=33,598) cohort research demonstrated a major drop in danger of loss of life throughout this era, no matter trigger. The main reason behind loss of life was non-AIDS-related cancers, an commentary prone to resonate with all HIV suppliers. Amongst HIV components, CD4 <350 and RNA >200 had been the strongest predictors of loss of life.
- After treatment failure with NNRTI + 2NRTIs, DTG plus DRV/r was both noninferior and superior to standard of care [198]. That is the primary time a boosted PI plus an INSTI has bested a routine of recycled NRTIs plus a boosted PI. Given the widespread use of DTG + 2NRTIs as fixed-dose “TLD”, which additionally carried out properly on this research, I think the DRV/r + DTG technique won’t be used a lot. FYI, the research known as “D2EFT” for “Dolutegravir and Darunavir Effectiveness in adults Failing first-line Remedy” — you knew that, proper?
- Switching stable PWH on BIC/FTC/TAF to long-acting injectable CAB-RPV every 2 months resulted in noninferior virologic suppression at 12 months [191]. 670 PWH had been randomized 1:2 to proceed versus swap to 2-monthly CAB-RPV. Whereas the outcomes met the factors for noninferiority, there have been 5 individuals on CAB-RPV (3 with resistance) with viral masses >50 within the injectable group, versus 1 within the BIC/FTC/TAF group (no resistance). Counseling individuals contemplating CAB/RPV that this remedy comes with a small (however non-zero) danger of failure with resistance is vital. Therapy satisfaction improved with the swap. That is the SOLAR research, for “Swap Onto Lengthy-Appearing Routine” — now that’s a very good title!
- Switching from BIC/FTC/TAF to CAB/RPV does not lead to weight loss [146]. Information are from the above scientific trial. Which means — don’t use “perhaps they are going to drop a few pounds” because the motivation for the swap to long-acting injectables. Some individuals achieve weight, some individuals keep secure, some individuals lose.
- What influences switches to either BIC/FTC/TAF or DTG/3TC [532]? The previous is chosen extra for these with low CD4 or danger components for poor adherence; the latter for renal impairment or weight problems. So although these have comparable indications, they aren’t used identically in scientific apply. (Co-author disclosure.)
- Having a detectable viral load in the year preceding a switch to CAB-RPV is a risk factor for detectable viremia following the switch [516]. This research, from the UCSD scientific program that has adopted CAB-RPV extra enthusiastically than another clinic web site I’m conscious of, discovered that 25% of switchers find yourself having detectable viral masses submit swap — I’m certain engendering a lot anxiousness! Importantly, one of many investigators instructed me that failure with resistance of their scientific cohort happens at a fee akin to the scientific trials (roughly 1-2%).
- PWH with uncontrolled viremia achieved high rates of virologic suppression on CAB-RPV [518]. Extra from the UCSF Ward 86 cohort, utilizing CAB/RPV in a non-FDA-approved technique. Out of 133 PWH who had been very a lot not the same old candidates for this remedy, 57 had viremia. Suppression was achieved in 55 — astoundingly good — with solely 2 creating remedy failure. A corresponding modeling study [517] confirmed this technique would enormously extend survival, even with conservative estimates about efficacy (co-author disclosure). We’d like this success with IM CAB/RPV in individuals with viremia replicated elsewhere! Whether it is, I think it might enter remedy tips, in fact with all types of caveats and cautionary language.
- Lenacapavir plus two long-acting broadly neutralizing antibodies (bNAbs) given every 6 months maintained virologic suppression for 26 weeks [193]. Out of 20 contributors, 1 rebounded — unclear why. A research entry requirement was pre-treatment resistance testing displaying susceptibility to the bNAbs — a giant hurdle if this type of remedy is ever going to be virtually deployed. One other hurdle — saying the names of the bNAbs. From an at all times amusing good friend:
- Islatravir (ISL) causes a dose-related drop in lymphocytes that resolves over several months [192]. Welcome again, islatravir! The suspected mechanism of this drop is intracellular accumulation of ISL-triphosphate, resulting in apoptosis — not mitochondrial toxicity. The dose shifting ahead might be 0.25 mg day by day, which should be active in opposition to wild-type and M184V-containing viruses; the weekly dose (when mixed with lenacapavir) might be 2 mg. These knowledge preceded shows on two section 3 swap research of doravirine/islatravir (DOR/ISL) in stably suppressed PWH.
- Stable PWH on any regimen maintained virologic suppression comparable to their baseline treatment when switching to daily DOR/ISL [196]. There have been no remedy failures on DOR/ISL versus 3 within the continued baseline routine on this open-label research.
- Stable PWH on BIC/FTC/TAF maintained virologic suppression when switching to daily DOR/ISL [197]. This was a blinded research and encouragingly confirmed no distinction in treatment-related unwanted side effects aside from a drop in lymphocytes. (0.75 mg day by day of ISL used.) There was a query from the viewers about weight adjustments, which weren’t introduced, but are in the public domain — no vital adjustments at 48 weeks after the swap. For the report, I’ve it on good authority that we’re not speculated to name this routine “door-isil”.
- The weight trajectory of over 20,000 PWH in Kenya switching to dolutegravir differed by baseline regimen [617]. Folks switching off efavirenz had a pointy enhance in weight, one not noticed with baseline nevirapine — a reminder that weight results inside drug courses will not be uniform, as solely efavirenz (among the many NNRTIs) seems to have this weight-suppressive impact.
- Weight decreases when TAF/FTC + DTG is switched to “TLD” and increases when the switch is from TDF/FTC/EFV [671]. These adjustments are precisely as one would predict, because the “T” stands for TDF — which has been proven in a number of research to suppress weight, particularly when mixed with EFV. The mechanism stays unclear. Linked the published clinical study from CID.
- An in vitro mannequin confirmed that dolutegravir, however not doravirine or efavirenz, disrupted estrogen-mediated fats differentiation [147]. Is that this the reason for the better weight achieve on INSTIs for ladies than males? By the way in which, the complete title of the presentation was A LOSS OF ERα ATTENUATES DTG-MEDIATED DISRUPTION OF THERMOGENESIS IN BROWN ADIPOCYTES, in case you had been questioning. (Summary not obtainable.)
- Could alteration in GI microflora explain the weight differences between regimens [248]? Intestine microbiota amongst 27 PWH switching remedy from TDF/FTC/EFV to BIC/FTC/TAF confirmed elevated variety (typically an indication of well being), but additionally elevated sC163 (an inflammatory marker related to weight problems) — trigger versus impact? There have been no controls on this research.
- When controlling for baseline risk factors, integrase-inhibitor-based regimens were not associated with elevated cardiovascular risk [149]. That is reassuring knowledge from the Swiss HIV Cohort research, contrasting with published data from a different cohort. I confess I held my breath when studying the title of the presentation, as this class of medicine is now vital to HIV remedy worldwide.
- Multivariable analysis of a clinical trial comparing BIC/FTC/TAF and DTG+F/TDF showed that TAF looks better for HBV [116]. Predictors of HBV suppression had been HBeAg-, HBV DNA <8 log, ALT >ULN and remedy w BIC/FTC/TAF. Longer follow-up of this research, presented originally at the AIDS 2022 meeting, might be vital because the TDF-based routine could ultimately catch up.
- Doxycycline given as post-exposure prophylaxis after sex reduced the incidence of syphilis, chlamydia, and gonorrhea in MSM [119]. In a second randomization, the meningococcal B vaccine lowered the incidence of gonorrhea. Referred to as the DOXYVAC research, this was one among a number of key shows on the doxycycline preventive technique through the convention.
- An analysis of bacterial resistance from the Doxy-PEP study found no increase in resistance to GC, Staph aureus, or commensal Neisseria species with PEP [120]. Reassuring knowledge! One caveat is that resistance might occur ultimately if this technique had been extensively adopted. As a reminder, Doxy-PEP also found that bacterial STIs declined in MSM and trans ladies who took PEP, as did the original ANRS study (albeit not for GC). That makes 3 favorable research for doxy-PEP and STI prevention in MSM.
- In women at high risk in Kenya, doxycycline PEP did not reduce bacterial STIs [121]. It’s unsure why this intervention was not efficient in cisgender ladies — adherence was good, and a separate PK research [118] implied that it ought to have labored.
- A modeling study applying favorable data on doxycycline PEP to MSM and trans women found that adopting this strategy for those with prior STIs would avert a substantial number of future infections [122]. Not surprisingly, a sturdy dialogue ensued at this session about whether or not tips ought to advocate doxycycline PEP for sure populations. Although I’m not on tips committees for STIs, I’d vote sure — with ongoing surveillance research for evaluation of resistance. Though we use doxy-PEP for tick bites for Lyme areas, this intervention for STIs is prone to be way more frequent.
- Mpox in PWH who have advanced HIV-related immunosuppression can be a severe, disfiguring, and life-threatening opportunistic infection [173]. Mortality was 27% (!) in these with CD4 <100, and the scientific course suggests an IRIS-like phenomenon when ART is began. There’s a graphic (and unsettling) show of the Mpox lesions in the published paper. These circumstances underscore how vital it’s for PWH to get on HIV remedy earlier than the illness progresses and likewise to get at-risk individuals vaccinated.
- A study of over 6000 women receiving TDF/FTC for PrEP found that the adherence correlates with protection were similar to what’s observed in men [516]. Effectiveness elevated steeply with 4 or extra drugs/week. Earlier research steered that girls required increased ranges of adherence than males.
- HIV acquired while receiving PrEP with cabotegravir may be clinically silent and difficult to diagnose [149]. The investigators described delayed detection, damaging antigen/antibody assessments, and a paucity of signs. They even gave this syndrome a reputation — LEVI, for “Lengthy-acting Early Viral Inhibition” syndrome. Not unhealthy. The secret is to make use of HIV RNA for prognosis, however these are nonetheless going to be very difficult. Right here’s a real-life case, occurring in scientific apply.
Had an incredible time at #CROI2023! We had been in a position to share our actual world case of breakthrough HIV-1 an infection within the setting of on-time, appropriately monitored CAB-LA for PrEP @howardbrownhc.
We enormously appreciated the insightful discussions which I’ll attempt to summarize beneath. pic.twitter.com/iLI7WtJSMj
— Anu Hazra (@AnuHazraMD) February 22, 2023
After all, there have been quite a few further attention-grabbing research not talked about right here, apologies if I ignored your favorites — be happy to quote them within the feedback.
And it was actually enjoyable to go to Seattle once more, a spot with a strong familial connection. Plus, the glowing new wing of the conference heart hosted the convention.
The climate? Chilly and wet — winter in Seattle, you understand — and it even snowed a bit the final day. Nobody ever accused the CROI organizers of choosing their winter areas in tropical paradise, that’s for certain.
