Human Immunodeficiency Virus Type 1 RNA Levels in Rectal and Seminal Compartments After Switching to Long-Acting Cabotegravir Plus Rilpivirine: A Longitudinal Study.

Human immunodeficiency virus type 1 RNA levels were longitudinally evaluated in 211 rectal and 152 seminal samples from 12 virologically suppressed participants switching to monthly long-acting cabotegravir plus rilpivirine or continuing with daily dolutegravir-abacavir-lamivudine. Maintenance of viral suppression in rectal and seminal compartments was comparable, and blips occurred with similar frequency with both treatment regimens. CLINICAL TRIALS REGISTRATION: NCT02938520.

Invaplex functions as an intranasal adjuvant for subunit and DNA vaccines co-delivered in the nasal cavity of nonhuman primates.

Development of intranasal vaccines for HIV-1 and other mucosal pathogens has been hampered by the lack of adjuvants that can be given safely to humans. We have found that an intranasal Shigella vaccine (Invaplex) which is well tolerated in humans can also function as an adjuvant for intranasal protein and DNA vaccines in mice. To determine whether Invaplex could potentially adjuvant similar vaccines in humans, we simultaneously administered a simian immunodeficiency virus (SIV) envelope (Env) protein and DNA encoding simian-human immunodeficiency virus (SHIV) with or without Invaplex in the nasal cavity of female rhesus macaques. Animals were intranasally boosted with adenoviral vectors expressing SIV env or gag,pol to evaluate memory responses. Anti-SIV antibodies in sera and nasal, genital tract and rectal secretions were quantitated by ELISA. Intracellular cytokine staining was used to measure Th1-type T cells in blood. Macaques given DNA/protein immunizations with 0.5 mg Invaplex developed greater serum IgG, nasal IgA and cervicovaginal IgA responses to SIV Env and SHIV Gag,Pol proteins when compared to non-adjuvanted controls. Rectal IgA responses to Env were only briefly elevated and not observed to Gag,Pol. Invaplex increased frequencies of IFNγ-producing CD4 and CD8 T cells to the Env protein, but not T cell responses induced by the DNA. Ad-SIV boosting increased Env-specific polyfunctional T cells and Env- and Gag,Pol-specific antibodies in serum and all secretions. The data suggest that Invaplex could be highly effective as an adjuvant for intranasal protein vaccines in humans, especially those intended to prevent infections in the genital or respiratory tract.

Short Communication: Discordance in Drug Resistance Mutations Between Blood Plasma and Semen or Rectal Secretions Among Newly Diagnosed HIV-1-Infected Thai Men Who Have Sex with Men.

Human immunodeficiency virus 1 (HIV-1) infection is most commonly transmitted by sexual contact across mucosal surfaces. Information on concordance in drug resistance profile between blood plasma and anogenital compartments in resource-limited settings is limited. We aimed to determine discordances in genotypic drug resistance-associated mutations (DRAMs) between blood plasma and semen or rectal secretions among newly diagnosed, antiretroviral therapy (ART)-naive, HIV-1-infected Thai men who have sex with men (MSM). Blood plasma, semen, and rectal secretions of HIV-1-infected Thai MSM enrolled from the Test and Treat cohort were tested for genotypic mutations in the reverse transcriptase and protease genes. Seven participants with baseline DRAMs in blood plasma were included in this analysis. In anogenital samples, HIV-1 RNA could be fully amplified for DRAMs assessment in semen from three participants and in rectal secretions from four participants. DRAMs were identified in semen from two of three participants and in rectal secretions from four of four participants. Three participants had DRAMs in anogenital compartments that were not detected in blood plasma-one had DRAMs in semen that was not detected in blood plasma (I54FI) and two had DRAMs in rectal secretions that was not detected in blood plasma (I47IM; K70N, L74I, Y115F, M184V, K103N, V108I, and H221Y). Discordance in DRAMs between blood plasma and anogenital compartments is not uncommon among newly diagnosed, ART-naive, HIV-1-infected Thai MSM. Monitoring of drug-resistant virus in these vector compartments is warranted particularly as pre-exposure prophylaxis and treatment as prevention are increasingly used as the mainstay strategies to end the AIDS epidemic.