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. METHODS: We conducted a phase 3 trial at 25 U.S. sites. Persons living with HIV who were 35 years of age or older and who had biopsy-proven anal HSIL were randomly assigned, in a 1:1 ratio, to receive either HSIL treatment or active monitoring without treatment. Treatment included office-based ablative procedures, ablation or excision under anesthesia, or the administration of topical fluorouracil or imiquimod. The primary outcome was progression to anal cancer in a time-to-event analysis. Participants in the treatment group were treated until HSIL was completely resolved. All the participants underwent high-resolution anoscopy at least every 6 months; biopsy was also performed for suspected ongoing HSIL in the treatment group, annually in the active-monitoring group, or any time there was concern for cancer. RESULTS: Of 4459 participants who underwent randomization, 4446 (99.7%) were included in the analysis of the time to progression to cancer. With a median follow-up of 25.8 months, 9 cases were diagnosed in the treatment group (173 per 100,000 person-years; 95% confidence interval [CI], 90 to 332) and 21 cases in the active-monitoring group (402 per 100,000 person-years; 95% CI, 262 to 616). The rate of progression to anal cancer was lower in the treatment group than in the active-monitoring group by 57% (95% CI, 6 to 80; P = 0.03 by log-rank test). CONCLUSIONS: Among participants with biopsy-proven anal HSIL, the risk of anal cancer was significantly lower with treatment for anal HSIL than with active monitoring. (Funded by the National Cancer Institute; ClinicalTrials.gov number, NCT02135419.).

Development and Pilot of an Mpox Severity Scoring System.

Clinical severity scores facilitate comparisons to understand risk factors for severe illness. For the 2022 multinational monkeypox clade IIb virus outbreak, we developed a 7-item Mpox Severity Scoring System (MPOX-SSS) with initial variables refined by data availability and parameter correlation. Application of MPOX-SSS to the first 200 patients diagnosed with mpox revealed higher scores in those treated with tecovirimat, presenting >3 days after symptom onset, and with CD4 counts <200 cells/mm3. For individuals evaluated repeatedly, serial scores were concordant with clinical observations. The pilot MPOX-SSS demonstrated good discrimination, distinguished change over time, and identified higher scores in expected groups.

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. Overall, trial participants exhibited relatively high preventive expectations that may be associated with an increase in risk behaviors among men who have sex with men. In addition, we identified substantial site variability in PM that necessitates future research to uncover its source. This will allow appropriate measures to be taken to mitigate PM and help ensure that participants have an accurate understanding of the potential risks and benefits of trial participation throughout the course of a trial.

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. The responsiveness phase enrolled a separate cohort of ANCHOR participants who were not yet randomized to complete A-HRSI at three time points: prior to randomization (T1), 14-70 (T2), and 71-112 (T3) days following randomization. RESULTS: Confirmatory factor analysis techniques established a three-factor model (i.e., physical symptoms, impact on physical functioning, impact on psychological functioning), with moderate evidence of convergent validity and strong evidence of discriminant validity in the construct validity phase (n = 303). We observed a significant moderate effect for changes in A-HRSI impact on physical functioning (standardized response mean = 0.52) and psychological symptoms (standardized response mean = 0.60) from T2 (n = 86) to T3 (n = 92), providing evidence of responsiveness. CONCLUSION: A-HRSI is a brief PRO index that captures health-related symptoms and impacts related to anal HSIL. This instrument may have broad applicability in other contexts assessing individuals with anal HSIL, which may ultimately help improve clinical care and assist providers and patients with medical decision-making.

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. Percentage change in LS and hip BMD was compared between the tenofovir disoproxil fumarate- and non-tenofovir disoproxil fumarate-containing arms by Wilcoxon rank-sum tests and multiple linear regression adjusting for sex, race and baseline BMI. RESULTS: At baseline (n = 307), the median age was 33 years, 56% male and 43% black. At the hip, the median percentage change in BMD at 48 weeks was -1.05% in the tenofovir disoproxil fumarate arms and 0.0% in the non-tenofovir disoproxil fumarate arms (between group P = 0.001). No interaction by sex was observed. The median percentage change in LS BMD was not different between arms. CONCLUSIONS: Tenofovir disoproxil fumarate-containing PrEP was associated with significantly greater bone loss compared with maraviroc ± emtricitabine PrEP at the hip, but not the LS. The BMD changes at the hip were similar in magnitude in men and women.

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.

ABSTRACT: 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. To guide optimization of HPV-based cervical cancer screening among WHIV in Latin America/Caribbean, review of current literature was completed to assess HPV genotype distribution by cervical disease grade in WHIV in this region; and further expanded globally for comparison across regions.A systematic review of the literature from June 2016 to January 2020 revealed 15 studies reporting human papillomavirus (HPV) genotype distribution by cervical disease state (normal, low-grade disease, high-grade disease, and invasive cervical cancer) across different global regions.Across all studies, there were 6928 WHIV from 4 global regions, 3952 of whom were HPV-positive. Three studies from Latin America/Caribbean (LAC) countries were reviewed, with 1 providing enough detail to describe HPV genotypes by cervical disease grade and identified types 31 and 35 in high-grade cervical lesions. Of the studies included, 4 from Africa and Europe/North America each, and 1 from Asia included data that were able to be summarized.Latin America, a region which experiences high rates of HPV, human immunodeficiency virus (HIV), and cervical disease, had few published studies reporting HPV genotypes by cervical disease grade, with 1 reporting individual HPV genotype and specific cervical disease grade. Identifying HPV types associated with CIN2+ in WHIV in this region has the potential to improve screening and treatment for cervical cancer prevention and should be the focus of future research.

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., internal consistency, test-retest) and between-group stability of a 25-item ANCHOR Health-Related Symptom Index (A-HRSI). METHODS: ANCHOR participants at least 1-month post-randomization to treatment or active surveillance completed the A-HRSI via telephone. Participants were contacted 7-10 days later to complete the A-HRSI and a participant global impression of change (PGIC) item. RESULTS: Participants (n = 100) were enrolled (mean age = 51.4, 79% cisgender-male, 73% African American, 9% Hispanic) from five ANCHOR sites. Cronbach's α was good for the physical symptoms (0.82) domain and fair for the physical impacts (0.79) and psychological symptoms (0.73) domains. Intraclass correlation coefficients were good for each of respective domains (i.e., 0.80, 0.85, and 0.82). There were no significant differences in PGIC between the treatment (n = 56) and active surveillance (n = 44) groups (F(1,98) = 2.03, p = 0.16). CONCLUSIONS: The A-HRSI is able to reliably assess participant-reported symptoms and impacts of anal HSIL across a 7-10 days of timeframe. Future work will involve the establishment of construct and discriminant validity prior to inclusion in the full ANCHOR trial.

A Randomized, Placebo-Controlled Trial of the Quadrivalent Human Papillomavirus Vaccine in Human Immunodeficiency Virus-Infected Adults Aged 27 Years or Older: AIDS Clinical Trials Group Protocol A5298.

Background: Adults living with human immunodeficiency virus (HIV) are at increased risk for anal and oropharyngeal cancer caused by human papillomavirus (HPV). The efficacy of HPV vaccines in this population is unknown. Methods: In this phase 3, double-blind, randomized, controlled trial, we assigned HIV-infected adults aged ≥27 years to the quadrivalent HPV (types 6, 11, 16, 18) vaccine or placebo (1:1) stratified by sex and presence of anal high-grade squamous intraepithelial lesions on biopsy (bHSIL). The primary endpoint was vaccine efficacy against incident persistent anal infection with quadrivalent vaccine types or single detection at the final visit that were not present at baseline. Secondary endpoints included vaccine efficacy for anal bHSIL after week 52, persistent oral HPV infection. Results: A total of 575 participants were randomized. The Data and Safety Monitoring Board stopped the study early due to futility. Vaccine efficacy was 22% (95.1% confidence interval [CI], -31%, 53%) for prevention of persistent anal infection or single detection at the final visit, 0% (95% CI -44%, 31%) for improving bHSIL outcomes and 88% (95.1% CI 2%, 98%) for preventing persistent oral HPV infection, but was 32% (95.1% CI -80%, 74%) for 6-month persistent oral HPV infection or single detection at the final visit. Conclusions: These results do not support HPV vaccination of HIV-infected adults aged ≥27 years to prevent new anal HPV infections or to improve anal HSIL outcomes. However, our data suggest a role for prevention of oral HPV infections, but this finding should be confirmed in future studies. Clinical Trials Registration: NCT01461096.

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. METHODS: Expert consultation was used to guide one-on-one concept elicitation interviews with participants to identify HRQOL aspects they attribute to their anal HSIL and its treatment. This resulted in a draft instrument, which was administered to an independent participant sample, where cognitive interview techniques assessed comprehension. RESULTS: Eighteen anal HSIL-related concepts were identified by the expert panel. Across the 41 concept elicitation interviews, 23 items representing physical symptoms, physical impacts, and psychological symptoms were identified to comprise the initial measure, which was then evaluated during three rounds of cognitive interviews (n = 45). Several questionnaire aspects were refined on the basis of participant input, with three additional items added per expert/participant recommendation. One item was removed because of poor comprehension, resulting in a 25-item measure. CONCLUSIONS: Using state-of-the-art qualitative methodology, we have established the content validity of this new instrument, the ANCHOR Anal HSIL Health-Related Symptom Index. Quantitative validation efforts are currently underway. The participant-driven process of developing this tool will facilitate a participant-centered evaluation of the impact on morbidity for treatment of anal HSIL or observation without treatment.

Safety and Tolerability of Maraviroc-Containing Regimens to Prevent HIV Infection in Women: A Phase 2 Randomized Trial.

BACKGROUND: Maraviroc (MVC) is a candidate drug for HIV preexposure prophylaxis (PrEP). OBJECTIVE: To assess the safety and tolerability of MVC-containing PrEP over 48 weeks in U.S. women at risk for HIV infection. DESIGN: Phase 2 randomized, controlled, double-blinded study of 4 antiretroviral regimens used as PrEP. (ClinicalTrials.gov: NCT01505114). SETTING: 12 clinical research sites of the HIV Prevention Trials Network and AIDS Clinical Trials Group. PARTICIPANTS: HIV-uninfected women reporting condomless vaginal or anal intercourse with at least 1 man with HIV infection or unknown serostatus within 90 days. INTERVENTION: MVC only, MVC-emtricitabine (FTC), MVC-tenofovir disoproxil fumarate (TDF), and TDF-FTC (control). MEASUREMENTS: At each visit, clinical and laboratory (including HIV) assessments were done. Primary outcomes were grade 3 and 4 adverse events and time to permanent discontinuation of the study regimen. All randomly assigned participants were analyzed according to their original assignment. RESULTS: Among 188 participants, 85% completed follow-up, 11% withdrew early, and 4% were lost to follow-up; 19% discontinued their regimen prematurely. The number discontinuing and the time to discontinuation did not differ among regimens. Grade 3 or 4 adverse events occurred in 5 (MVC), 13 (MVC-FTC), 9 (MVC-TDF), and 8 (TDF-FTC) participants; rates did not differ among regimens. One death (by suicide) occurred in the MVC-TDF group but was judged not to be related to study drugs. Of available plasma samples at week 48 (n = 126), 60% showed detectable drug concentrations. No new HIV infections occurred. LIMITATIONS: Participants were not necessarily at high risk for HIV infection. The regimen comprised 3 pills taken daily. The study was not powered for efficacy. CONCLUSION: Maraviroc-containing PrEP regimens were safe and well-tolerated compared with TDF-FTC in U.S. women. No new HIV infections occurred, although whether this was due to study drugs or low risk in the population is uncertain. Maraviroc-containing PrEP for women may warrant further study. PRIMARY FUNDING SOURCE: National Institutes of Health.

Phase 2 Study of the Safety and Tolerability of Maraviroc-Containing Regimens to Prevent HIV Infection in Men Who Have Sex With Men (HPTN 069/ACTG A5305).

BACKGROUND: Maraviroc (MVC) is a candidate for human immunodeficiency virus (HIV) pre-exposure prophylaxis. METHODS: Phase 2 48-week safety/tolerability study was conducted, comparing 4 regimens: MVC alone, MVC plus emtricitabine (FTC), MVC plus tenofovir disoproxil fumarate (TDF), and TDF plus FTC. Eligible participants were HIV-uninfected men and transgender women reporting condomless anal intercourse with ≥1 HIV-infected or unknown-serostatus man within 90 days. At each visit, assessments, laboratory testing, and counseling were done. Analyses were intention to treat. RESULTS: Among 406 participants, 84% completed follow-up, 7% stopped early, and 9% were lost to follow-up; 9% discontinued their regimen early. The number discontinuing and the time to discontinuation did not differ among study regimens (P = .60). Rates of grade 3-4 adverse events did not differ among regimens (P = .37). In a randomly selected subset, 77% demonstrated detectable drug concentrations at week 48. Five participants acquired HIV infection (4 MVC alone, 1 MVC + TDF; overall annualized incidence, 1.4% [95% confidence interval, .5%-3.3%], without differences by regimen; P = .32); 2 had undetectable drug concentrations at every visit, 2 had low concentrations at the seroconversion visit, and 1 had variable concentrations. CONCLUSIONS: MVC-containing regimens were safe and well tolerated compared with TDF + FTC; this study was not powered for efficacy. Among those acquiring HIV infection, drug concentrations were absent, low, or variable. MVC-containing regimens may warrant further study for pre-exposure prophylaxis. CLINICAL TRIALS REGISTRATION: NCT01505114.

CCR5 antagonism in HIV infection: current concepts and future opportunities.

CCR5 antagonists inhibit HIV-1 entry by blocking the interaction of HIV-1 with the CCR5 cellular receptor. In patients with established HIV-1 infection, some viral strains use an alternative coreceptor for HIV-1 entry, CXCR4; CCR5 antagonists are not effective in patients harboring these viral strains. Coreceptor tropism testing of viral strains in an individual patient is necessary prior to treating with a CCR5 antagonist. There is one CCR5 antagonist, maraviroc, that is FDA-approved for treatment of HIV-1 infection. This drug is used most commonly for the treatment of HIV-1 infection in patients who have failed other antiretroviral regimens. In addition to virologic effects, CCR5 antagonists are under investigation for immune-modulating effects and for HIV-1 prevention. Ongoing research will further elucidate the role of CCR5 antagonists in combating HIV disease.

A pilot trial of adding maraviroc to suppressive antiretroviral therapy for suboptimal CD4⁺ T-cell recovery despite sustained virologic suppression: ACTG A5256.

BACKGROUND: Despite viral suppression, antiretroviral therapy (ART) does not restore CD4(+) T-cell counts in many patients infected with human immunodeficiency virus type 1 (HIV-1). METHODS: In a single-arm pilot trial involving ART recipients with suppressed plasma levels of HIV-1 RNA for at least 48 weeks and stable suboptimal CD4(+) T-cell recovery, subjects added maraviroc, a CCR5 antagonist, to their existing ART for 24 weeks. After stopping maraviroc, they were followed for an additional 24 weeks. A Wilcoxon signed-rank test was used to evaluate whether maraviroc was associated with an increase of at least 20 cells/µL in the CD4(+) T-cell count. RESULTS: A total of 34 subjects were enrolled. The median age was 50 years, and the median baseline CD4(+) T-cell count was 153 cells/µL. The median increase in CD4(+) T-cell count from baseline to week 22/24 was 12 cells/µL (90% confidence interval, 1-22). A CD4(+) T-cell count increase of at least 20 cells/µL was not detected (P = .97). Markers of immune activation and apoptosis decreased during maraviroc intensification; this decline partially reversed after discontinuing maraviroc. CONCLUSIONS: Adding maraviroc to suppressive ART for 24 weeks was not associated with an increase in CD4(+) T-cell counts of at least 20 cells/µL. Further studies of CCR5 antagonists in the dampening of immune activation associated with HIV infection are warranted. Clinical Trials Registration. NCT 00709111.

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. Data were presented on hepatitis B virus (HBV) suppression showing that tenofovir alafenamide (TAF)/emtricitabine (FTC)/bictegravir (BIC) may be superior to tenofovir disoproxil fumarate/FTC plus dolutegravir in suppressing HBV in HIV/HBV-coinfected individuals. A pilot study examining a 4-week trial of direct-acting antiviral therapy to treat hepatitis C in recently infected individuals showed lower rates of sustained virologic response at 12 weeks than longer courses. Additional data were presented on the use of long-acting cabotegravir/rilpivirine, comparing this regimen with oral TAF/FTC/BIC and the use of long-acting cabotegravir/rilpivirine in those with viremia. Data were presented on a novel strategy of lenacapavir with 2 broadly neutralizing antibodies given every 6 months as maintenance antiretroviral therapy (ART). Data were presented on improving HIV care outcomes in adolescents, interventions to prevent mother-to-child transmission, and HIV reservoirs in children and adolescents. Data were also presented on interactions between ART and hormonal contraception, as well as ART-related weight gain and impact on pregnancy. A study examining BIC pharmacokinetics in pregnancy was presented, as well as retrospective data on outcomes of adolescents receiving TAF/FTC/BIC.

Cost-effectiveness of adding an agent that improves immune responses to initial antiretroviral therapy (ART) in HIV-infected patients: guidance for drug development.

PURPOSE: Adding an immune-enhancing agent to initial antiretroviral therapy (ART) for HIV is a potential strategy to ensure that patients achieve optimal immune response. METHOD: Using a mathematical model of HIV disease and treatment, we evaluated the treatment benefits and cost-effectiveness of adding a hypothetical immune-enhancing agent to the initial 6 months of ART. We assumed that the additional agent would result in a higher CD4 increase that would provide clinical benefit. The additional cost ($1,900/month) was based on the cost of a drug currently under investigation for immune enhancement. Outcomes included projected life expectancy and cost-effectiveness in 2009 US dollars/quality-adjusted life year (QALY) with costs and QALYs discounted at 3% annually. RESULTS: Compared to standard ART, immune-enhanced ART resulting in an additional 40 CD4 cell/µL increase at 6 months yields a 2.4 month projected undiscounted life expectancy increase with a cost-effectiveness ratio of $107,600/QALY. Achieving a cost-effectiveness ratio <$100,000/QALY requires a >43 CD4 cell/µL improvement, or >19 cells/µL if immune-enhancing agent costs are halved. CONCLUSIONS: In addition to showing clinical efficacy, investigational immune enhancement agents need to increase CD4 counts more than has been previously observed or have a lower cost to be considered cost-effective in the United States.

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. Efforts are ongoing to increase vaccination coverage and monitor health impacts of vaccination. Increasing vaccination coverage before sexual exposure to HPV is expected to reduce the burden of HPV-related disease.

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. Additional data supported the use of lenacapavir as a long-acting antiretroviral drug. Data across the United States demonstrate the negative impact of the COVID-19 pandemic on the HIV care continuum, although enhanced outreach efforts and decentralization of antiretroviral therapy delivery were associated with improvements in care engagement outcomes. Researchers described potential mechanisms for the emergence of integrase strand transfer inhibitor resistance. Studies on proviral genotyping high-lighted the limitations of its use in predicting clinically significant resistance. Several studies looked at the epidemiology and treatment of hepatitis C and B and the status of current hepatitis C virus elimination efforts. Data presented on HIV, COVID-19, and maternal and pediatric health included 2-year virologic outcome data of very early antiretroviral therapy in potentially reducing the latent HIV reservoir in infants with HIV. Data presented on COVID-19 and HIV therapeutics in children included SARS-CoV-2-neutralizing monoclonal antibodies in children younger than 12 years of age, remdesivir in hospitalized infants and children, and long-acting therapies for HIV treatment in children.

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. At baseline and follow-up visits, anal specimens were collected. HPV genotyping was assessed by linear array. Prevalence ratios (PR) were used to assess the association between smoking and anal HPV prevalence. Odds ratios (OR) were used to assess the association between smoking and anal HPV incidence and ≥12-months persistence. RESULTS: Current smokers have a higher prevalence [adjusted PR (aPR), 1.36; 95% confidence interval (CI), 1.06-1.73) and incidence [adjusted OR (aOR), 1.74; 95% CI, 1.26-2.39] and ≥12-months persistence (aOR, 1.67; 95% CI, 1.19-2.33) of any anal HPV compared with never smokers. There were no differences in the prevalence, incidence, or persistence of anal HPV between former and never smokers. Smoking status was not associated with the prevalence or persistence of anal HPV among men who have sex with men but was associated with higher incidence of HR-HPV. Among men that have sex with women (MSW), current smokers had an increased prevalence and incidence of LR-HPV compared with never smokers. CONCLUSIONS: Current smokers had a higher prevalence, persistence, and incidence of HPV compared with never smokers. Further research is needed to assess the role smoking in anal HPV persistence and progression to disease. IMPACT: Prevention initiatives should raise awareness about smoking and the risk factor of anal HPV infection and anal cancer.

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 3.2% among those who are not living with HIV. To address these concerns, the AIDS Malignancy Consortium completed a large-scale, randomized trial to compare strategies for the prevention of anal cancer among PLWH with anal HSIL. The objective of the study was to determine whether treating anal HSIL was effective in reducing the incidence of anal cancer in PLWH compared with active monitoring. This paper describes the design of the ANal Cancer/HSIL Outcomes Research Study (ANCHOR) with respect to estimating the anal cancer event rate in this high risk population.