CROI 2024: The Challenges of Sustained Viral Suppression, Advanced HIV Disease, and Ending the HIV Epidemic Targets.

Data on the HIV care cascade demonstrated challenges in achieving Ending the HIV Epidemic (EHE) targets across all 18 EHE focus metropolitan areas, but innovative adherence interventions using point-of-care tenofovir testing and motivational interviewing support care cascade outcomes in Namibia and South Africa, respectively. Data on treatment with long-acting injectable (LAI) antiretroviral therapy (ART) demonstrated high acceptability, retention, and virologic suppression including in groups that were not well represented in clinical trials including persons born female and persons with detectable viral loads. The adjuvanted hepatitis B vaccine appeared to be safe and appeared to be superior to conventional hepatitis B vaccines in persons with HIV (PWH) who were prior nonresponders to the hepatitis B vaccine.

Expectations of preventative benefits and risk behaviors in a randomized trial evaluating oral HIV preexposure prophylaxis candidates.

When participants enrolled in an HIV prevention trial hold a preventive misconception (PM) - expectations that experimental interventions will confer protection from HIV infection - they may engage in behaviors that increase their risk of acquiring HIV. This can raise ethical concerns about whether those enrolled in the trial understand the nature of participation and their safety. Consequently, we systematically evaluated the prevalence of PM and its association with risk behaviors in a trial examining three candidate regimens for oral HIV pre-exposure prophylaxis in which all participants received at least one antiretroviral agent.

CROI 2023: Advances in Antiviral Therapy in HIV and Viral Hepatitis.

Several innovative methods were presented at the 2023 Conference on Retroviruses and Opportunistic Infections (CROI) targeting different aspects of the HIV care continuum to improve testing, linkage to care, and viral suppression. Some of these approaches were directed at more vulnerable groups, such as pregnant women, adolescents, and individuals who inject drugs. In contrast was the devastating impact of the COVID-19 pandemic, with negative outcomes on HIV viral load suppression and retention in care.

Construct validity and responsiveness of a health-related symptom index for persons either treated or monitored for anal high-grade squamous intraepithelial lesions (HSIL): AMC-A01/-A03.

Purpose: To determine whether treatment of anal high-grade squamous intraepithelial lesions (HSIL), vs active monitoring, is effective in reducing incidence of anal cancer in persons living with HIV, the US National Cancer Institute funded the Phase III ANal Cancer/HSIL Outcomes Research (ANCHOR) clinical trial. As no established patient-reported outcomes (PRO) tool exists for persons with anal HSIL, we sought to estimate the construct validity and responsiveness of the ANCHOR Health-Related Symptom Index (A-HRSI).

Methods: The construct validity phase enrolled ANCHOR participants who were within two weeks of randomization to complete A-HRSI and legacy PRO questionnaires at a single time point.

CROI 2022: advances in antiviral therapy for HIV, COVID-19, and viral hepatitis.

The 2022 Conference on Retroviruses and Opportunistic Infections provided a rich source of new data and comprehensive reviews on antiviral therapy. For COVID-19, intramuscular sotrovimab was noninferior to intravenous sotrovimab, serostatus did not predict the efficacy of sotrovimab, and molnupiravir appeared safe and modestly effective in decreasing hospitalization rates. Trials from low- and middle-income countries provided data to support transitioning those on first-line therapy with or without virologic suppression and those virologically suppressed on second-line therapy to dolutegravir-based regimens.

SARS CoV-2 mRNA vaccination exposes latent HIV to Nef-specific CD8 T-cells.

Efforts to cure HIV have focused on reactivating latent proviruses to enable elimination by CD8 cytotoxic T-cells. Clinical studies of latency reversing agents (LRA) in antiretroviral therapy (ART)-treated individuals have shown increases in HIV transcription, but without reductions in virologic measures, or evidence that HIV-specific CD8 T-cells were productively engaged. Here, we show that the SARS-CoV-2 mRNA vaccine BNT162b2 activates the RIG-I/TLR - TNF - NFκb axis, resulting in transcription of HIV proviruses with minimal perturbations of T-cell activation and host transcription.

Treatment of Anal High-Grade Squamous Intraepithelial Lesions to Prevent Anal Cancer.

Background: The incidence of anal cancer is substantially higher among persons living with the human immunodeficiency virus (HIV) than in the general population. Similar to cervical cancer, anal cancer is preceded by high-grade squamous intraepithelial lesions (HSILs). Treatment for cervical HSIL reduces progression to cervical cancer; however, data from prospective studies of treatment for anal HSIL to prevent anal cancer are lacking.

The Association between Smoking and Anal Human Papillomavirus in the HPV Infection in Men Study.

Background: Previous studies show an association between smoking and anal cancer. The objective of this study was to assess the association between smoking and anal HPV (human papillomavirus) prevalence, incidence, and persistence in men.

Methods: The HPV Infection in Men (HIM) Study is a multinational study that enrolled HIV-negative men.

Review of human papillomavirus (HPV) burden and HPV vaccination for gay, bisexual, and other men who have sex with men and transgender women in the United States.

Gay, bisexual, and other men who have sex with men (MSM) and transgender women, particularly those who are living with HIV, are disproportionately affected by human papillomavirus (HPV). For this narrative review of HPV health outcomes and vaccination for gay, bisexual, and other MSM and transgender women in the United States, we highlighted 71 publications regarding 1) burden of HPV infections and related diseases; 2) HPV vaccine efficacy; 3) HPV vaccination recommendations; 4) HPV vaccination coverage; 5) real-world vaccine effectiveness and health impacts; and 6) HPV vaccination acceptability. Vaccination is effective at reducing HPV infections among MSM; in the United States, routine HPV vaccination is recommended for all adolescents at age 11-12 years and for all persons through age 26 years.

Design of the ANal Cancer/HSIL Outcomes Research study (ANCHOR study): A randomized study to prevent anal cancer among persons living with HIV.

It is well established that persons living with HIV (PLWH) have highly elevated rates of anal HSIL and anal cancer compared with those who are not living with HIV. The 5-year risk of anal cancer following anal HSIL has been reported to be as high as 14.1% among PLWH compared with 3.

Bone changes with candidate PrEP regimens containing tenofovir disoproxil fumarate and/or maraviroc and/or emtricitabine in US men and women: HPTN 069/ACTG A5305.

Background: Tenofovir disoproxil fumarate-containing pre-exposure prophylaxis (PrEP) has been associated with decreases in bone mineral density (BMD), but the bone effects of other non-tenofovir disoproxil fumarate candidate PrEP regimens are not well described.

Methods: The HPTN 069/ACTG A5305 study randomized 406 US cisgender men and transgender women, and 188 cisgender women at risk for HIV infection to one of four double-blinded regimens: (i) maraviroc; (ii) maraviroc + emtricitabine; (iii) maraviroc + tenofovir disoproxil fumarate; or (iv) tenofovir disoproxil fumarate + emtricitabine. BMD was measured in a subset of participants at the lumbar spine (LS) and hip by dual-energy X-ray absorptiometry (DXA) at baseline and 48 weeks.

CROI 2021: Advances in Antiretroviral Therapy for HIV and Antiviral Therapy for COVID-19.

The 2021 Conference on Retroviruses and Opportunistic Infections included advances in therapy for HIV as well as for SARS-CoV-2. Data presented on COVID-19 therapies included trials showcasing the use of monoclonal antibodies for prevention and treatment of COVID-19. Promising new data were presented on lenacapavir, an investigational HIV capsid inhibitor given as a subcutaneous injection every 6 months.

An Updated Systematic Review of Human Papillomavirus Genotype Distribution by Cervical Disease Grade in Women Living With Human Immunodeficiency Virus Highlights Limited Findings From Latin America.

Cervical cancer is 5 times more likely among women living with human immunodeficiency virus (WHIV), likely due to higher prevalence of human papillomavirus (HPV). Despite evidence of higher rates with multiple HPV genotypes in WHIV, there are no recommendations for triage by HPV genotyping specific to WHIV. In Latin America/Caribbean rates are high and vary significantly.

Xpert HPV as a Screening Tool for Anal Histologic High-Grade Squamous Intraepithelial Lesions in Women Living With HIV.

Background: Women living with HIV (WLWH) experience high rates of anal cancer. Screening using anal cytology, high-resolution anoscopy (HRA) with biopsies, can histologically diagnose anal cancer precursors called high-grade squamous intraepithelial lesions (HSIL). The low specificity of screening using anal cytology results in HRA referral for many WLWH without HSIL.

Higher colorectal tissue HIV infectivity in cisgender women compared with MSM before and during oral preexposure prophylaxis.

Objective: The objective of this study was to compare HIV-negative cisgender women (CGW) with MSM for mucosal tissue differences in pharmacokinetics, HIV infectivity and cell phenotype.

Design: A substudy of HPTN 069/ACTG A5305, 48-week study of three oral candidate preexposure prophylaxis regimens: maraviroc, maraviroc/emtricitabine and maraviroc/tenofovir disoproxil fumarate (TDF) compared with a TDF/emtricitabine control group.

Methods: Plasma, peripheral blood mononuclear cells and cervical and colorectal tissue biopsies were collected at Baseline (no drug), Week 24 and 48 (on drug), and Week 49 (1-week postdrug).

Importance of anal cytology and screening for anal dysplasia in individuals living with HIV with an emphasis on women.

Background: The incidence of squamous cell carcinoma of the anal canal has been increasing in high-risk populations. To the authors' knowledge, there is no international consensus regarding screening for squamous cell carcinoma of the anal canal, but screening is commonly comprised of a Papanicolaou (Pap) test in combination with digital anorectal examination followed by high-resolution anoscopy if necessary. The current study focused on individuals living with HIV and particularly on women living with HIV.

CROI 2019: advances in antiretroviral therapy.

The 2019 Conference on Retroviruses and Opportunistic Infections included many exciting advances in antiretroviral therapy (ART). Investigators presented a case report of a second patient possibly cured of HIV through an allogeneic hematopoietic stem cell transplant from a CC chemokine receptor 5-delta 32 donor. Two clinical trials of long-acting injectable cabotegravir and rilpivirine showed promising safety, efficacy, and tolerability as maintenance ART.

Oral and systemic HPV antibody kinetics post-vaccination among HIV-positive and HIV-negative men.

Duration and functional aspects of the oral and systemic antibody responses following HPV vaccination in HIV-negative (HIV) and HIV-positive (HIV) men are not well characterized. Oral and systemic HPV-16 and HPV-18-specific antibody levels were evaluated over 18-months of follow-up, in HIV and HIV men. Sera and oral gargles from 147 HIV men, ages 27-45 and 75 HIV men, ages 22-61, who received 3-doses of quadrivalent HPV vaccine were tested for HPV-16 and HPV-18 antibodies at Day 1, Month 7 (1 month post-dose 3), and Month 18 (12 months post-dose 3) and HPV avidity (Day 1, and Month 7) using L1-VLP ELISA.

Reliability and between-group stability of a health-related quality of life symptom index for persons with anal high-grade squamous intraepithelial lesions: an AIDS Malignancy Consortium Study (AMC-A03).

Purpose: The Anal Cancer HSIL Outcomes Research (ANCHOR) trial aims to determine whether treating precancerous anal high-grade squamous intraepithelial lesions (HSIL), versus active surveillance, is effective in reducing anal cancer incidence in HIV-infected individuals. We evaluated the reliability (i.e.

No change in health-related quality of life for at-risk U.S. women and men starting HIV pre-exposure prophylaxis (PrEP): Findings from HPTN 069/ACTG A5305.

Introduction: Tenofovir (TDF)-containing PrEP is effective for HIV prevention, but its effect on health-related quality of life (QOL) is unknown. Using data from HPTN 069/ACTG A5305, a randomized study of potential PrEP regimens comparing maraviroc alone, or together with TDF or emtricitabine (FTC), to TDF + FTC (control), we evaluated the impact of these regimens on QOL in at-risk HIV-uninfected U.S.

Human papillomavirus-related malignancies in HIV infection: anal and oropharyngeal cancers.

Human papillomavirus (HPV)-related cancers, including anal cancer and oropharyngeal cancer, occur more frequently in individuals living with HIV infection than in the general population. Strategies for prevention among individuals with HIV infection include HPV vaccination, anal cancer screening programs, and early initiation of antiretroviral therapy (ART). HPV vaccination is not yet optimally used; a stronger and more persistent effort is needed to increase vaccination rates.

Initial Development and Content Validation of a Health-Related Symptom Index for Persons either Treated or Monitored for Anal High-Grade Squamous Intraepithelial Lesions.

Background: Anal cancer, caused by oncogenic types of human papillomavirus, is a growing problem in the United States. A key focus of anal cancer prevention has been screening for and treating precancerous high-grade squamous intraepithelial anal lesions (HSILs).

Objectives: To develop a health-related symptom index for HSIL using qualitative techniques because anal HSIL and its treatment may have a negative impact on health-related quality of life (HRQOL), and no HRQOL measure specific to this condition and treatment currently exists.