Clinical effectiveness and cost-effectiveness of quadrivalent human papillomavirus vaccination in HIV-negative men who have sex with men to prevent recurrent high-grade anal intraepithelial neoplasia

We examined the long-term clinical and economic benefits of quadrivalent human papillomavirus (qHPV) vaccine as a secondary/adjunct prevention strategy in the prevention of recurrent high-grade intraepithelial neoplasia (HGAIN) in HIV-negative men who have sex with men (MSM) and are 27 years or older. We constructed a Markov model to evaluate the clinical effectiveness and cost-effectiveness of two strategies: (1) no qHPV vaccine after treatment for HGAIN versus (2) qHPV vaccine after treatment for HGAIN. Model parameters, including natural history of anal cancer, vaccine efficacy measured in terms of hazard ratio (HR) (decrease in the risk of recurrent HGAIN), HGAIN treatment efficacy, utilities, and costs, were obtained from the literature. The outcomes were measured in terms of lifetime risk of anal cancer, lifetime cost, quality-adjusted life years, and incremental cost-effectiveness ratios (ICERs). Sensitivity analysis was conducted on all model parameters. We found that vaccinating HIV-negative MSM reduced the lifetime risk of anal cancer by 60.77% at an ICER of US$87,240 per quality-adjusted life-year. The results were highly sensitive to vaccine efficacy, transition of HGAIN to anal cancer, cost of treatment for HGAIN, vaccine degree of protection over time, and the vaccine duration of protection and less sensitive to HPV clearance, cost of qHPV vaccine, and the transitions from normal to low-grade anal intraepithelial neoplasia (LGAIN) and normal to HGAIN. With an HR of 0.3, the ICER was well below a $50,000 willingness-to-pay threshold; with an HR of 0.5, the ICER was still below a threshold of $100,000. The most critical disease-related factor influencing the cost-effectiveness was the progression of HGAIN to anal cancer. At an annual transition probability below 0.001, the ICER was below $50,000. Vaccinating HIV-negative MSM treated for HGAIN decreases the lifetime risk of anal cancer and is likely to be a cost-effective intervention.     

Targeted human papillomavirus vaccination for young men who have sex with men in Australia yields significant population benefits and is cost-effective

BackgroundWe investigated the effectiveness and cost-effectiveness of a targeted human papillomavirus (HPV) vaccination program for young (15–26) men who have sex with men (MSM).MethodsWe developed a compartmental model to project HPV epidemic trajectories in MSM for three vaccination scenarios: a boys program, a targeted program for young MSM only and the combination of the two over 2017–2036. We assessed the gain in quality-adjusted-life-years (QALY) in 190,000 Australian MSM.ResultsA targeted program for young MSM only that achieved 20% coverage per year, without a boys program, will prevent 49,283 (31,253–71,500) cases of anogenital warts, 191 (88–319) person-years living with anal cancer through 2017–2036 but will only stablise anal cancer incidence. In contrast, a boys program will prevent 82,056 (52,100–117,164) cases of anogenital warts, 447 (204–725) person-years living with anal cancers through 2017–2036 and see major declines in anal cancer. This can reduce 90% low- and high-risk HPV in young MSM by 2024 and 2032, respectively, but will require vaccinating ≥84% of boys. Adding a targeted program for young MSM to an existing boys program would prevent an additional 14,912 (8479–21,803) anogenital wart and 91 (42–152) person-years living with anal cancer. In combination with a boys’ program, a catch-up program for young MSM will cost an additional $AUD 6788 ($4628–11,989) per QALY gained, but delaying its implementation reduced its cost-effectiveness.ConclusionsA boys program that achieved coverage of about 84% will result in a 90% reduction in HPV. A targeted program for young MSM is cost-effective if timely implemented.     

Should I or shouldn't I: decision making, knowledge and behavioral effects of quadrivalent HPV vaccination in men who have sex with men

Prior to FDA licensure in men, a surgical practice (SG) offered the quadrivalent HPV vaccine (qHPV) off-label to men who have sex with men (MSM). We administered a written or telephone survey to MSM to elicit drivers and barriers to vaccination, sexual behavior changes post-vaccination, and knowledge. 191 subjects enrolled: 68 refused qHPV, 71 received qHPV <1 year ago, and 52 received qHPV >1 year ago. History of HPV infection (86%, n = 164) and level of HPV and qHPV knowledge were high, with a mean of 10.8 of 13 knowledge questions correct. Ninety-seven percent of participants understood that qHPV does not cure present infection or disease. MSM refused qHPV for reasons including cost and not FDA approved; prevention of future HPV infection was the paramount driver for immunization. Vaccination did not affect sexual behavior.     

我国男男性行为人群中人乳头瘤病毒疫苗接种的需求与建议

MSM是HPV感染与相关疾病发生的高危人群,四价和九价HPV疫苗能够为MSM提供有效的保护。本文综述了为MSM提供HPV疫苗接种的重要性,综合了关于MSM接种HPV疫苗的依据并提出建议:我国应加快HPV疫苗在男性中使用的适应症研究及审批;尽快为HIV阳性的MSM接种HPV疫苗;优先为 ≤ 26岁MSM接种HPV疫苗;在HPV疫苗资源充分的情况下,为>26岁的MSM进行补接种或机会性接种。采用这种接种策略能够为MSM提供保护,控制性病和艾滋病的传播。     

Anal human papillomavirus among men who have sex with men in three metropolitan cities in southern China: implications for HPV vaccination

IntroductionMen who have sex with men (MSM), especially those infected with human immunodeficiency virus (HIV), are at disproportionate risk for human papillomavirus (HPV) infection. Data about anal HPV prevalence among MSM in southern China are limited.MethodsMSM were recruited between January 1 and August 31, 2017 in three metropolitan cities: Guangzhou, Shenzhen and Wuxi. A self-completed tablet-based questionnaire was used to collect information about socio-demographic/sexual behavioral characteristics, history of sexually transmitted infections (STIs) and recreational drug use. An anal brush was used to collect exfoliated cells for HPV DNA testing and genotyping, and a blood sample was taken for HIV testing. Penile/anal warts were checked by a clinician.ResultsA total of 536 MSM were enrolled, including 39 HIV-positive and 497 HIV-negative individuals. Compared with HIV-negative MSM, prevalence of any HPV genotype (79.5% vs 46.7%), any high-risk genotype (64.1% vs 36.6%) and any nonavalent vaccine-preventable genotype (53.9% vs 31.6%) was significantly higher in HIV-positive MSM, with all P < 0.01. HIV infection (adjusted odds ratio [AOR], 4.28; 95% confidence interval [CI], 1.87–9.80), using recreational drugs (AOR, 1.87; 95% CI, 1.22–2.87), having ≥ 3 years of sexual experience (AOR, 1.52; 95% CI, 1.01–2.28), having ≥ 6 lifetime male partners (AOR, 1.92; 95% CI, 1.29–2.86), and engaging receptive anal intercourse (AOR, 2.30; 95% CI, 1.48–3.57) were associated with higher anal HPV prevalence. Any HPV prevalence increased with age, from 24.5% at < 20 years to 55.8% at ≥ 40 years.ConclusionsAnal HPV prevalence was high among MSM in southern China, significantly associated with HIV status and sexual experience. HPV prevalence increased with age among MSM. A targeted HPV vaccination program for teenage MSM might be necessary. Our findings will inform targeted HPV modelling among MSM in China.     

Anal human papillomavirus infections in young unvaccinated men who have sex with men attending a sexual health clinic for HPV vaccination in Melbourne,Australia

The Victorian Government introduced a time-limited quadrivalent human papillomavirus (HPV) vaccination catch-up program targeting gay and bisexual men who have sex with men (MSM) aged up to 26 years in 2017. As of 2017, men aged ≥20 years were not eligible for the school-based HPV vaccination program. This study examined the prevalence of anal HPV among 496 MSM aged 20–26 years before they received the first dose of the HPV vaccine at the Melbourne Sexual Health Centre, Australia. More than half (56.5%) had any high-risk HPV genotypes detected in the anus. Almost half (43.1%) had at least one quadrivalent HPV vaccine-preventable genotype (6, 11, 16 or 18) and one-fifth (21.0%) had HPV 16 detected in the anus. These findings suggest that a targeted catch-up HPV vaccination program for MSM is still beneficial to protect against high-risk HPV genotypes associated with anal cancer, as well as low-risk HPV genotypes.     

Going social: Success in online recruitment of men who have sex with men for prevention HIV vaccine research

ObjectiveTo compare the use of four different social media sites to recruit men who have sex with men (MSM) and transgender women to a phase 2b HIV prevention vaccine trial, HVTN 505.DesignRetrospective, observational study.MethodsThe University of Pennsylvania HIV Vaccine Trials Unit (Penn HVTU) employed street outreach and online recruitment methods to recruit participants for HVTN 505 using a combination of national recruitment images/messages with Philadelphia-specific language and imagery. We compared the efficiency (number of enrolled participants per number of completed phone screens) and effectiveness (number of enrolled participants per time interval employed) of each strategy, as well as the demographics and risk behaviors of the populations.ResultsOnline recruitment strategies populated 37% (71/191) of trial participants at our site. Among the four social media strategies employed, 45.1% (32/71) were enrolled through Facebook, 16.9% (12/71) through Craigslist, 15.5% (11/71) through a web-based marketing company (WBMC), and 22.5% (16/71) via GRINDR. The number of participants enrolled per month of strategy and the months the strategy was employed were Facebook - 32(33 months), Craigslist - 12(33 months), WBMC - 11(6 months), and GRINDR - 16(0.56 months). In-person and online recruitment strategies yielded participants of similar demographics and levels of risk behavior.ConclusionUse of several social media recruitment modalities produced large numbers of MSM engaging in high risk behavior and willing to participate in an HIV prevention vaccine trial. In comparison to other social media and online strategies, recruitment via GRINDR was the most effective.     

The impact of serostatus disclosure on spousal relationships between wives and HIV-positive husbands who have sex with men in China

ABSTRACT

This study explored the impact of serostatus disclosure on the spousal relationship between wives and their HIV-positive husbands who have had sex with men. A qualitative study using semi-structured interviews was conducted in Sichuan, China in 2017 with wives (n = 31) who had known their husbands’ HIV-positive status. Participants were identified by local governmental and non-governmental organizations that provide routine services for people living with HIV and their family members. Qualitative data underwent a detailed content analysis. Both positive and negative impacts on the spousal relationship were expressed by wives. Six themes were identified: (1) reduced sexual activities; (2) changes in intimacy; (3) limited communication on HIV-related issues but improved communication on other topics; (4) increased instrumental support but decreased emotional support; (5) improved resilience in the spousal relationship; and (6) shared privacy management rules regarding HIV-positive status. Moreover, the acknowledgment of the husband’s homosexual behavior hurt the spousal relationship more seriously than the disclosure of the husband’s HIV-positive status, and irremediable marriages were observed among wives who knew both. Disclosure of HIV-positive status had a great impact on the spousal relationship, though such impact varied across individuals.     

HIV epidemic and human rights among men who have sex with men in sub-Saharan Africa: Implications for HIV prevention,care, and surveillance

Recent research has presented evidence that men who have sex with men (MSM) bear a disproportionate burden of HIV and are at increased risk for HIV in sub-Saharan Africa (SSA). However, many countries in SSA have failed to address the needs of MSM in national HIV/AIDS programmes. Furthermore, many MSM face structural barriers to HIV prevention and care, the most significant of which include laws that criminalise male-to-male sexual contact and facilitate stigma and discrimination. This in turn increases the vulnerability of MSM to acquiring HIV and presents barriers to HIV prevention, care, and surveillance. This relationship illustrates the link between human rights, social justice, and health outcomes and presents considerable challenges to addressing the HIV epidemic among MSM in SSA. The response to the HIV epidemic in SSA requires a non-discriminatory human rights approach to all at-risk groups, including MSM. Existing international human rights treaties, to which many SSA countries are signatories, and a ‘health in all policies’ approach provides a strong basis to reduce structural barriers to HIV prevention, care, surveillance, and research, and to ensure that all populations in SSA, including MSM, have access to the full range of rights that help ensure equal opportunities for health and wellness.     

Men who have sex with men in Southeastern Europe: Underground and at increased risk for HIV/STIs

This paper reports on research that aimed to identify risk factors and preventive behaviours for HIV/STIs among men who have sex with men in Bulgaria, Kosovo, Macedonia and Romania. Twelve peer researchers conducted interviews on sexual behaviour, condom use and HIV/STI awareness. Data analysis revealed common themes across countries. Sexual activity takes place both in public spaces and private homes. Many men believe that careful partner selection and closing sexual networks to outsiders mitigate risk. Risk behaviours include unprotected sex within multiple partnerships, inconsistent condom use and the use of oil‐based lubricants that compromise the integrity of condoms. Perceived susceptibility for infection is low and misconceptions exist about modes of transmission. Stigma and discrimination force men into clandestine settings and relationships where safer sexual behaviour is difficult. HIV prevention programmes should convey messages through the internet and peer networks, improve access to condoms and water‐based lubricant, raise awareness about STIs, link men who have sex with men to appropriate services and reduce stigma to enable safer behaviour.     

Prevalence of type-specific human papillomavirus infection among women in France: Implications for screening, vaccination, and a future generation of multivalent HPV vaccines

To assess human papillomavirus (HPV) prevalence and genotype distribution by age and cervical cytology/histology status among women undergoing routine gynecological examinations, and to discuss the possible impact on preventive strategies. Liquid-based cytology (LBC) samples were tested for HPV DNA, mRNA, and HPV genotypes. Women with atypical squamous cells of undetermined significance or greater (ASC-US+) and/or at least one positive HPV test were referred to colposcopy. Those with normal colposcopy results had biopsies taken at the 6 and 12 O'clock positions of the normal transformation zone. Of the 5002 women, 515 (10.3%) were <25 and 4487 (89.7%) were ≥25years old. Overall HPV prevalence varied between 10.1% and 16.1% depending on the assay. Risk factors for HPV infection included greater number of recent sexual partners, history of abnormal cervical pathology, age <25years, and smoking. HPV prevalence increased with the cytological and histological severity of cervical lesions. Prevalence of HPV 16/18 was 5.2% and 2.7% in women <25 and ≥25years old, respectively. HPV 16 was the type most strongly associated with a diagnosis of cervical intraepithelial neoplasia grade 3 or higher (CIN3+) (odds ratio=11.64 vs. HPV 16 absent, P<0.001). A high proportion of high-grade cervical lesions (60.6% of genotyping assay-positive CIN2+) were associated with HPV types 31, 33, 45, 52, or 58. These data indicate that almost all young women could benefit from HPV prophylactic vaccination, but confirm the need for continued cervical screening and highlight the potential benefit of future vaccines targeting a wider range of HPV types.     

Prevalence and associated factors of intention to participate in HIV voluntary counseling and testing for the first time among men who have sex with men in Hong Kong,China

Objective

We investigated the prevalence and associated factors of men who have sex with men (MSM) and had never participated in Human Immunodeficiency Virus (HIV) voluntary counseling and testing (VCT) but intended to do so in the next six months.

Method

An anonymous cross-sectional survey interviewed 577 MSM in Hong Kong, China, face-to-face or through an electronic questionnaire.

Results

We identified 245 MSM who had never participated in VCT (never-testers), among whom 12.7% intended to do so in the next six months. Factors associated positively with high behavioral intention were: 1) perceived necessity to participate in HIV test regularly (multivariate odds ratios (ORm) = 4.54, 95% confidence interval (CI): 1.30–15.83), 2) perception that > 20% of the local MSM had participated in VCT (ORm = 17.86, 95% CI: 1.89–169.08) and 3) perceived higher chance to have sex with people living with HIV (PLWH) in the next six months (ORm = 2.92, 95% CI: 1.08–7.93). Negatively associated factors were: local residency (ORm = 0.06, 95% CI: 0.01–0.34) and perceived higher chance of having unprotected anal intercourse (UAI) in the next six months (ORm = 0.27, 95% CI: 0.09–0.84). In addition, no interaction term between the independent variable and UAI status was found to be statistically significant.

Conclusion

Many sampled never-testers had low intention to take up VCT and were in the pre-contemplation stage of the Transtheoretical Model. Stage-matched promotions are warranted.     

Adjuvant Systems for vaccines: 13 years of post-licensure experience in diverse populations have progressed the way adjuvanted vaccine safety is investigated and understood

Adjuvant Systems (AS) are combinations of immune stimulants that enhance the immune response to vaccine antigens. The first vaccine containing an AS (AS04) was licensed in 2005. As of 2018, several vaccines containing AS04, AS03 or AS01 have been licensed or approved by regulatory authorities in some countries, and included in vaccination programs. These vaccines target diverse viral and parasitic diseases (hepatitis B, human papillomavirus, malaria, herpes zoster, and (pre)pandemic influenza), and were developed for widely different target populations (e.g. individuals with renal impairment, girls and young women, infants and children living in Africa, adults 50 years of age and older, and the general population). Clearly, the safety profile of one vaccine in one target population cannot be extrapolated to another vaccine or to another target population, even for vaccines containing the same adjuvant. Therefore, the assessment of adjuvant safety poses specific challenges. In this review we provide a historical perspective on how AS were developed from the angle of the challenges encountered on safety evaluation during clinical development and after licensure, and illustrate how these challenges have been met to date. Methods to evaluate safety of adjuvants have evolved based on the availability of new technologies allowing a better understanding of their mode of action, and new ways of collecting and assessing safety information. Since 2005, safety experience with AS has accumulated with their use in diverse vaccines and in markedly different populations, in national immunization programs, and in a pandemic setting. Thirteen years of experience using antigens combined with AS attest to their acceptable safety profile. Methods developed to assess the safety of vaccines containing AS have progressed the way we understand and investigate vaccine safety, and have helped set new standards that will guide and support new candidate vaccine development, particularly those using new adjuvants.Focus on the patientWhat is the context? Adjuvants are immunostimulants used to modulate and enhance the immune response induced by vaccination. Since the 1990s, adjuvantation has moved toward combining several immunostimulants in the form of Adjuvant System(s) (AS), rather than relying on a single immunostimulant. AS have enabled the development of new vaccines targeting diseases and/or populations with special challenges that were previously not feasible using classical vaccine technology.What is new? In the last 13 years, several AS-containing vaccines have been studied targeting different diseases and populations. Over this period, overall vaccine safety has been monitored and real-life safety profiles have been assessed following routine use in the general population in many countries. Moreover, new methods for safety assessment, such as a better determination of the mode of action, have been implemented in order to help understand the safety characteristics of AS-containing vaccines.What is the impact? New standards and safety experience accumulated over the last decade can guide and help support the safety assessment of new candidate vaccines during development.     

Efficacy of quadrivalent human papillomavirus vaccine against persistent infection and genital disease in Chinese women: A randomized,placebo-controlled trial with 78-month follow-up

BackgroundA quadrivalent human papillomavirus vaccine (qHPV; HPV6/11/16/18) has demonstrated efficacy and effectiveness worldwide. We report qHPV vaccine efficacy for up to 6.5 years after first administration among Chinese women 20–45 years of age.MethodsIn this randomized, double-blind, placebo-controlled, multicenter, Phase 3 study (NCT00834106), women were randomized 1:1 to receive 3 doses of qHPV vaccine or placebo (Day 1, Month 2, Month 6). Endo-ecto-cervical and external genital swabs were collected for HPV testing and gynecologic examinations, and cervical cytology testing were performed at Day 1 and Months 7, 12, 18, 24, 30, 42, 54, 66, and 78. Any abnormality in cytology testing would trigger colposcopy examination and cervical biopsy, if necessary. Efficacy against genital disease, persistent infection, and the composite endpoint was assessed. Primary efficacy analyses were conducted in the per-protocol efficacy (PPE) population.ResultsOf 3006 participants randomized, 2759 (91.8%) and 2374 (79%) completed the Month 30 and Month 78 visits, respectively. At Month 78, efficacy among women aged 20–45 years was 100% (95% CI: 32.3, 100; 0 vs 7 cases) and 100% (95% CI: 70.9, 100; 0 vs 14 cases) against HPV16/18-related cervical intraepithelial neoplasia Grade 2 or 3, adenocarcinoma in situ, and cervical cancer (CIN 2+) and HPV6/11/16/18-related CIN 1+, respectively, in the PPE population. The efficacy against cervical 6-month and 12-month persistent infection was 91.6% (95% CI: 66.0, 99.0) and 97.5% (95% CI: 85.1, 99.9) at Month 30 and Month 78, respectively, in the PPE population. The vaccine also reduced the rate of cervical cytology abnormalities associated with HPV6/11/16/18, with an efficacy of 94.0% (95% CI: 81.5, 98.8). The vaccine was generally well tolerated (reported separately).ConclusionThe qHPV vaccine is efficacious against endpoints of persistent infection and genital precancerous lesions in Chinese women aged 20–45 years.