The CROI 2023 conference, one of the most important international scientific conferences covering HIV, STIs, mpox, hepatitis and COVID, took place on February 19-22, 2023. Our practice-changing highlights are below, and you can check out more summaries from Dr. Paul Sax’s CROI 2023 Really Rapid Review and on NATAP’s website.
- Doxy-PEP: doxycycline post-exposure prophylaxis for STIs is effective for MSM and transwomen but not in a group of ciswomen in Kenya. No marked doxycycline resistance has been found yet.
- The DOXYVAC trial found that doxyPEP reduced bacterial STIs by 65% among MSM and transgender women. In addition, the 4CMenB meningococcal vaccine reduced gonococcal infection by 51%.
- The dPEP Kenya Trial found that doxy-PEP was not effective among cisgender women in Kenya at high risk for STDs. A separate study found that mucosal levels of doxycycline were similar among men and women. Research is ongoing to evaluate why it was not effective in this group of cisgender women.
- The doxy-PEP trial has not found markedly increased doxycycline resistance yet.
- Injectables
- CAB/RPV ART (Cabenuva)
- Thigh injections have drug levels equivalent to gluteal injections. A study among people who had 3+ years of experience with gluteal injections found that thigh injections had equivalent drug levels, acceptable safety and tolerability, and no virologic failures. This data suggests that thigh injections may be a reasonable alternative to gluteal injections.
- CAB/RPV is highly effective even for people with viremia and adherence challenges and is non-inferior to BIK, but baseline viremia and NNRTI or INSTI resistance are associated with CAB/RPV failures.
- One cohort at UCSD found that 25% of 144 PLWH on CAB/RPV had HIV RNA ≥20 copies/mL a month or after starting injections. The incidence was highest (40%) among those with detectable viral loads in the year before starting injections. The impact of low-level viremia on CAB/RPB is not entirely clear.
- The CAB/RPV cohort at UCSF had 2 people with virologic failure out of 133 people (including 57 people with viremia), which is a failure rate (1.5%) similar to ART clinical trials. The 2 people with virologic failure started with NNRTI or INSTI resistance mutations: one had V179I, a rare RPV resistance mutation and the other had T97A, a common INSTI resistance mutation. Both developed additional NNRTI/INSTI resistance mutations on CAB/RPV.
- When you fail CAB/RPV, you fail hard (with NNRTI and INSTI resistance). The SOLAR study randomized people to switch to CAB/RPV-LA (Cabenuva) vs. BIC/F/TAF (Biktarvy) and found that CAB/RPV was non-inferior to BIK. For the 3 people who had virologic failure on CAB/RPV, one had baseline INSTI resistance, one had no known baseline resistance, and the third person’s baseline genotype had an assay failure. All 3 failed with additional NNRTI and/or INSTI resistance mutations.
- CAB-LA PrEP (Apretude)
- CAB-LA PrEP is highly effective. Failures are rare and can be hard to detect. The HPTN 083 study reported 0.3% cases of HIV infection while on CAB-LA PrEP: 18 out of 2,282 cases total, which is a very low failure rate. Half had delayed diagnoses due to labs that were difficult to interpret, such as very low RNA/DNA levels and delayed Ab production. This is dubbed LEVI syndrome (Long-acting Early Viral Inhibition syndrome). 10 developed INSTI resistance mutations. In order to detect failures earlier, we recommend to:
- Get the most sensitive HIV RNA you can get and HIV Ag/Ab tests q2 months while on CAB-LA.
- If someone seroconverts to HIV-positive (positive RNA, DNA or HIV Ag/Ab), get a genotype including INSTI resistance and prescribe a PI-based regimen such as Symtuza as rapid ART.
- If someone stops CAB-LA for PrEP, prescribe daily oral F/TDF or F/TAF within 8 weeks after the last CAB injection (2-1-1 could be a reasonable alternative in some situations) and get quarterly HIV RNA and Ag/Ab testing for a year after stopping CAB-LA.
- There may be some forgiveness with late CAB-LA PrEP injections, at least for people assigned female at birth. The HPTN 084 study found that for people assigned female at birth, CAB-LA injections given 4-6 weeks late had 98% drug concentrations above target; given 6-8 weeks late had 95% concentrations above target; and given 8-10 weeks late had 90% concentrations above target. This data suggests that there may be up to ~6 weeks of forgiveness in CAB-LA injections for people assigned female at birth.
- CAB-LA PrEP is highly effective. Failures are rare and can be hard to detect. The HPTN 083 study reported 0.3% cases of HIV infection while on CAB-LA PrEP: 18 out of 2,282 cases total, which is a very low failure rate. Half had delayed diagnoses due to labs that were difficult to interpret, such as very low RNA/DNA levels and delayed Ab production. This is dubbed LEVI syndrome (Long-acting Early Viral Inhibition syndrome). 10 developed INSTI resistance mutations. In order to detect failures earlier, we recommend to:
- LEN ART (Sunlenca) is effective for treatment-experienced people with MDR-HIV but has a low barrier to resistance and not as effective as BIK for people who are treatment naïve.
- The CAPELLA study of LEN for people with multi-drug resistant (MDR) HIV and viremic on baseline regimens found high rates of virologic suppression (78%) at 52 weeks for LEN + optimized background regimen, suggesting that LEN is an effective option for people with MDR HIV and limited treatment options. However, data presented at IDWeek showed that 10 people on LEN developed capsid resistance mutations, so optimizing the background regimen is critical for success. LEN cannot be used as the sole active agent.
- The CALIBRATE study of LEN among treatment naïve PLWH found 3 out of 157 people (2%) with virologic failure at Week 80, and all 3 people developed capsid resistance mutations. People on BIK had fewer virologic failures.
- Persistent low-level viremia (not blips) raised the risk of non-AIDS illnesses by 25% (cancer or cardiovascular, kidney and liver disease) in the US Military HIV Natural History Study. Low-level viremia is defined by viral loads persistently between 51 and 199 copies per mL whereas blips are viral loads under 1,000 copies/mL that are preceded and followed by virologic suppression.
- Weight changes with ART: Studies presented and discussed at CROI suggest that TDF and EFV reduce weight while TAF and DTG are associated with weight gain. Switches from TAF to TDF have resulted in weight loss, especially among women.
- Mpox in PWLH with advanced immunosuppression can be a disfiguring and life-threatening opportunistic infection with a mortality rate of 27% among PLWH with CD4 <100. Lesions can flare (IRIS-like) when ART is started. Pictures of the severe Mpox lesions (which are quite graphic) are in the published paper. This data shows how important it is to test and treat early and vaccinate people against mpox.