Alejandro Balazs

Numerous topics were covered in this session including transcriptional programs of HIV silencing, Doxycycline post-exposure prophylaxis for STI prevention, results from a trial of (B/F/TAF) vs (DTG+F/TDF), PrEP inequity by race and census region in the United States and results from the HPTN 084 trial of long acting Cabotegravir.

Eli Boritz presented on memory CD4 T cells harboring HIV from ART-treated PWH and a new technology to characterize these cells, called FIND-Seq (Focused Interrogation of cells by Nucleic acid Detection and Sequencing), which can identify and sort cells that are HIV DNA+ using microfluidics, followed by transcriptional analysis. Genes involved in epigenetic regulation, RNA processing, inhibition of cell death, and anti-proliferative pathways are enriched in memory CD4 T cells that were HIV DNA+ versus HIV DNA-, suggesting HIV silencing and cell survival in HIV-infected memory CD4 T cells under ART. Annie Luetkemeyer presented interim results from a trial of Doxycycline taken as post-exposure prophylaxis showing that it was very effective in reducing sexually transmitted infections in their cohort. Anchalee Avihingsanon showed data from a Phase 3 study comparing B/F/TAF to DTG+F/TDF, demonstrating that the TAF-containing regimen was superior to TDF for suppression of HBV and equivalent in suppression of HIV viral load. Patrick Sullivan found growing inequity over the past two decades in the use of PreP among minorities throughout the United States. Sinead Delany-Moretlwe showed that long-acting injectable Cabotegravir remained superior to daily oral TDF/FTC for HIV prevention in the ongoing HPTN 084 trial.

The signature of memory CD4 T cells harboring HIV could lead to improvements in future cure strategies, including addressing post-transcriptional HIV silencing and potentiating CD4 cell death. The use of doxycycline as post-exposure prophylaxis could be used to substantially reduce the incidence of sexually transmitted infections. B/F/TAF may be a more effective than DTG+F/TDF for treatment of HIV/HBV co-infection. There is a large and growing inequity in the use of PrEP among minorities throughout the United States. Long-acting injectable Cabotegravir is more effective than daily oral TDF/FTC in preventing HIV infection.

Stephane Wen-Wei Ku

1. Regardless of HIV status, doxycycline as PEP was effective to reduce bacterial STI among MSM and TGW. 2. US prevention programs in all regions demonstrated decreasing PrEP equity over time. 3. Long-acting injectable cabotegravir remained superior to TDF/FTC as PrEP among cisgender women in unblinded phase of HPTN 084.

1. Doxycycline used as PEP has been shown reduction in syphilis and chlamydia but not for gonorrhea in previous study. Luetkemeyer et al. presented DOXYPEP, an open-label randomized clinical trial in which doxycycline 200 mg was taken within 72 hours after condomless sex compared to standard care among MSM and TGW living with HIV or on HIV PrEP. There was a substantial decrease in the incidence of bacterial STI, with 62% reduction in PLWH and 66% in those taking PrEP. 2. Sullivan et al. proposed PrEP-to-Need Ratio, defined by the number of PrEP users in a group divided by the number of new diagnoses to evaluate PrEP equity. The US South lagged all regions in PrEP equity. Black and Hispanic people had greater PrEP inequity compared to white people, and the gaps grew larger over time in all US regions. 3. Delany-Moretlwe reported data from the unblinded period of HPTN 084. There remained 89% reduction of HIV infection in cabotegravir group compared to TDF/FTC group, without identifying new safety concerns. Three additional infections were documented in cabotegravir group, likely due to poor adherence. No on-injection breakthrough infections were observed.

1. Doxycycline is effective as PEP in populations with high STI incidence. How doxycycline PEP might impact tetracycline resistance development in gonorrhea mandates larger surveillance studies. 2. Prevention programs should be guided by PrEP equity, i.e. PrEP use relative to epidemic impact or HIV diagnosis proportion in certain population, instead of PrEP equality. 3. Cabotegravir continued to be superior to TDF/FTC as PrEP without new safety issues among cisgender women. Access to cabotegravir should be a priority for populations with greatest need.