HIV and ID Observations

Having already featured an important non-HIV clinical research study from IDWeek — the amazing ACORN trial — I turn now to a grab bag of HIV-related studies, a veritable Halloween treat bag full of them.

(Note to self: What’s with that “Halloween treat bag” reference? Couldn’t you come up with a less awkward way to link this content with the posting date?)

Note acknowledged. I’ll think of something snappier for next year!

Here are the studies:

Compared to placebo, semaglutide markedly reduced weight and total body fat in PWH with lipohypertrophy (#1984). Interestingly, there was no effect on ectopic fat in the liver and pericardium, locations which correlate with some adverse outcomes. Lead investigator Grace McComsey (who has led several remarkable single-center studies on metabolic issues) cautioned that lipoatrophy might worsen with this treatment, potentially a concern in particular for our older patients who received thymidine analogue drugs (ZDV, d4T) in the distant past.

In a large (n=225) retrospective cohort study, GLP-1 receptor agonists were more likely to lead to > 5% weight loss in those with higher baseline BMI and longer duration of treatment (#1983). Dulaglutide appeared less likely to achieve this weight loss than semaglutide and terzepatide. What does it say about the current state of outpatient HIV management that these two studies of GLP-1 agonists were featured oral abstracts at an ID meeting?

One dose of penicillin is as good as three for early syphilis (#2889). During my ID fellowship, a local expert strongly opined that 3 doses were necessary, especially with concomitant HIV. Not so say the results from this multicenter randomized trial, where response rates were comparable with 1 vs 3 doses, including in the 67% of study participants who also had HIV. Data confirm what is recommended in treatment guidelines.

A bunch of studies looked at various comparisons between BIC/FTC/TAF and DTG/3TC, two highly popular and effective regimens. In an interim analysis of a randomized clinical trial comparing remaining on BIC/FTC/TAF vs. switching to DTG/3TC, the switch strategy was non-inferior at week 24 (#1603). There were more discontinuations in the DTG/3TC arm, explained in part by the open-label nature of the study (ascertainment bias). As with the TANGO and SALSA switch studies, switching to DTG/3TC did not result in weight loss. Interestingly, a person who remained on BIC/FTC/TAF experienced virologic failure at week 12, with detection of M184V and G140S mutations. I believe this is the first report from a prospective study of any participant experiencing virologic failure with INSTI resistance on this regimen — wonder if there was prior treatment failure on RAL or EVG.

Switching to BIC/FTC/TAF (n=3527) or DTG/3TC (n= 2213) in clinical practice maintained virologic suppression, with very rare instances of virologic failure (#1023).  Only two and three cases of virologic failure occurred, respectively, after over a year of follow-up. Since this is a non-randomized study, the patient characteristics differed between those getting BIC/FTC/TAF vs. DTG/3TC: BIC/FTC/TAF recipients were significantly more likely to be Black, on government insurance, have experienced prior virologic failure, and have a lower CD4 count; those on DTG/3TC had a lower eGFR. Regimen discontinuation occurred statistically earlier with DTG/3TC versus BIC/FTC/TAF.

Related to the above, clinicians gave different reasons for switching to BIC/FTC/TAF vs. DTG/3TC (#1570). For BIC/FTC/TAF, these reasons were inconsistent healthcare visit attendance, adherence challenges, substance use, HBV coinfection, or viremic on current regimens. For DTG/3TC, concerns about low eGFR or excess weight gain motivated the switch. For the weight issue, note that none of the switch studies of DTG/3TC have shown any difference between BIC/FTC/TAF and DTG/3TC when it comes to weight — and IDWeek provided another one (see #1603 above).

Out of 1843 PWH who started CAB/RPV in a US-based cohort, 229 (12%) had a detectable viral load at treatment onset, a strategy outside of licensed indications (#1028). For 93 of them, the viral load was > 200, so true virologic failure. Virologic suppression was achieved in 82% overall, with 4% experiencing virologic failure. There was scant data on pre- or post-treatment resistance, or more importantly why the clinicians chose this regimen — especially since the median CD4-cell count was around 500! As noted previously, I strongly believe that if we’re using this treatment for virologic failure, we should limit it to those with low CD4-cell counts at very high risk for disease progression.

Data from a claims database suggests that adherence and persistence on injectable CAB/RPV is better than oral ART (#1024). Adherence was generally high for both strategies, but significantly higher with CAB/RPV using the 90% adherence threshold. Data are both reassuring and perhaps not surprising, given that CAB/RPV requires fewer doses, our generally careful selection of candidates for this strategy, and the intense efforts to keep those who are on it engaged.

In a pilot study, 33 patients successfully received CAB/RPV at home (#1027). Remarkably, a single nurse drove to homes in a 3000 square mile region. The study sent the medications by mail, with instructions for home refrigerator storage and pre-visit preparation by the patients. This is a good proof-of-concept study, but for obvious reasons not sustainable by most healthcare systems. And while I once thought that pharmacies would be a good location for getting CAB/RPV, the commercial pharmacies in our region are now massively understaffed and overwhelmed.

In a prospective cohort study, women with low-level viremia had higher rates of treatment failure, with a trend toward more multi-morbidity (#1025). These results are similar to those observed in cohorts made up of mostly men. Management strategies are still uncertain, aside from redoubling efforts at ensuring adherence and using high resistance barrier regimens.

In large sample of MSM PWH engaged in care at academic HIV clinics with a program for anal cancer screening, only half ever received any screening (#1478). Follow-up was notably low as well. Test performance of the screening anal pap was poor — there were high rates of “unsatisfactory” results, and low rates of detection of high-grade lesions. In other words, the anal pap falls far short of required sensitivity and specificity to be a good cancer screening tool.  Controversial opinion — we should stop doing anal pap smears until we have a better screening test, and in the meantime figure out which MSM with HIV should be referred directly to high-resolution anoscopy.

Hepatitis B reactivation in PWH who have isolated hepatitis B core antibody and switched to non-hepatitis B-active ART is uncommon, but does occur (#1026). These regimens lack any of tenofovir, lamivudine, or emtricitabine. Data came from a large VA cohort study, in which 5,954 were deemed at risk, and 89 (1.5%) experienced reactivation (turning surface antigen positive or having detectable HBV DNA). It’s less likely if surface antibody is also present, and much more likely if they were historically surface antigen positive (20% risk). Studies such as this one become much more clinically relevant in the CAB/RPV era.

In a cohort of PWH at an academic medical center, 23% of those with cirrhosis died during a 3-year follow-up period (#1983). This was 4 times higher than the overall HIV cohort mortality and occurred even though 90% had HIV viral suppression. Although HCV was the most common cause of cirrhosis, the study did not include details on HCV treatment history.

We’ve got PrEP, and PEP, why not PIP (“PEP in Pocket”, #2894)? In this study, 112 people at risk for HIV but with infrequent exposures were provided with 28 days of DTG plus TDF/FTC in case such an exposure occurred. Strategy allows for self-administered prevention and follow-up, a choice made by 35 of the participants, with high rates of follow-up. Some transitioning to PrEP.

That’s a wrap! Am sure I missed something interesting, as IDWeek now has a good portfolio of research studies, in addition to the great lectures, debates, and overall schmoozing.

Speaking of research, I submit the following video of a really fun research job.