Like cervical cancer, anal cancer is often caused by a human papillomavirus and has a premalignant stage called high-grade squamous intraepithelial lesion or anal intraepithelial neoplasia. A ...randomized trial showed that treating HSIL led to a 57% reduction in progression to anal cancer as compared with active surveillance.
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.
Background. Vicriviroc, an investigational CCR5 inhibitor, demonstrated short-term antiretroviral activity in a phase 1 study. Methods. The present study was a double-blind, randomized phase 2 study ...of vicriviroc in treatment-experienced, human immunodeficiency virus (HIV)–infected subjects experiencing virologic failure while receiving a ritonavir-containing regimen with an HIV-1 RNA level ⩾5000 copies/mL and CCR5-using virus. Vicriviroc at 5, 10, or 15 mg or placebo was added to the failing regimen for 14 days, after which the antiretroviral regimen was optimized. The primary end point was the change in plasma HIV-1 RNA levels at day 14; secondary end points included safety/tolerability and HIV-1 RNA level changes at week 24. Results. One hundred eighteen subjects were randomized with a median HIV-1 RNA level of 36,380 (4.56 log10) copies/mL and a median CD4 cell count of 146 cells/mm3. At 14 days and 24 weeks, mean changes in HIV-1 RNA level (log10 copies/mL) were greater in the vicriviroc groups (−0.87 and −1.51 5 mg, −1.15 and −1.86 10 mg, and −0.92 and −1.68 15 mg), than in the placebo group (+0.06 and −0.29) (P<.01). Grade 3/4 adverse events were similar across groups. Malignancies occurred in 6 subjects randomized to vicriviroc and in 2 to placebo. Conclusions. In HIV-1–infected, treatment-experienced patients, vicriviroc demonstrated potent virologic suppression through 24 weeks. The relationship of vicriviroc to malignancy is uncertain. Further development of vicriviroc in treatment-experienced patients is warranted.
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.
Anal cancer is common in human immunodeficiency virus-infected adults. This randomized trial did not find a benefit from human papillomavirus (HPV) vaccination to prevent anal HPV infection or anal ...high-grade squamous intraepithelial lesions. There may be a benefit for prevention of oral HPV infections.
Abstract
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.
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. Although anal cancer screening is not recommended by all authorities, there is a least some evidence that screening and treatment of anal high-grade squamous intraepithelial lesions may prevent progression to cancer. However, more definitive evidence is needed. Early initiation of ART reduces the risk of infection-related cancers, with some evidence of benefit in preventing HPV-associated cancer in individuals with HIV infection. This article summarizes a presentation by Timothy J. Wilkin, MD, MPH, at the IAS-USA continuing education program held in Los Angeles, California in April 2018.
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. women and men.
QOL was measured at baseline (before starting medications) and every 8 weeks through week 48 using the EQ-5D-3L. Responses were converted to a scale from 0.0 (death) to 1.0 (perfect health), using published valuation weights. Mean scores were compared between groups at each time point using nonparametric testing. Multivariable linear regression was used to adjust for potential confounders.
We analyzed 186 women (median age 35 years, 65% black, 17% Hispanic) and 405 men (median age 30 years, 28% black, 22% Hispanic), including 9 transgender participants analyzed based on sex-at-birth. Mean baseline QOL was 0.91 for women and 0.95 for men. There were minimal changes in mean QOL over time for any regimen (women: p = 0.29; men: p = 0.14). There were no significant differences between participants who continued the regimen compared to participants who discontinued early (women: p = 0.61; men: p = 0.1). Mean QOL did not differ significantly by regimen at any time point, both unadjusted and after adjustment for age, race/ethnicity, adherence, and use of alcohol, marijuana, opiates, and other substances.
QOL in at-risk individuals starting candidate PrEP regimens in a clinical trial is similar to the general population and maintained over time. This finding did not vary among regimens or when adjusted for demographics, adherence, and substance use. Our findings are the first to show that starting a candidate PrEP regimen in at-risk HIV-uninfected U.S. women and men was not associated with significant changes in QOL.
Clinicaltrials.gov NCT01505114.
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.
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.
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.
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.
Prevention initiatives should raise awareness about smoking and the risk factor of anal HPV infection and anal cancer.
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.
PDF
