Prevalence and determinants of high-risk human papilloma virus among men who have sex with men in Benin: a cross-sectional study embedded in a demonstration project on pre-exposure prophylaxis against HIV.

OBJECTIVES: This study aims to assess the prevalence and factors associated with anal high-risk human papilloma virus (HR-HPV). DESIGN: A cross-sectional study conducted from 24 August 2020 to 24 November 2020. SETTING: Primary care, Cotonou, Benin. PARTICIPANTS: 204 HIV-negative men who have sex with men initiating oral pre-exposure prophylaxis. PRIMARY OUTCOME MEASURE: Anal HR-HPV genotypes using GeneXpert HPV assay. Fourteen HR-HPV were evaluated: HPV-16 and HPV-18/45 in 2 distinct channels and the 11 other genotypes as a pooled result (31, 33, 35, 39, 51, 52, 56, 58, 59, 66 and 68). The potential independent variables analysed included anal gonorrhoea and chlamydia infections, and sociodemographic and sexual behaviour factors. To assess the determinants of HR-HPV, univariate and multivariate Poisson regression models were performed by using SAS V.9.4. RESULTS: Mean age±SD was 25.9±4.8 years. 131/204 men claimed insertive sex procured more pleasure. Thirty-two participants, accounting for 15.7% of the study sample, had gonorrhoea and/or chlamydia. The prevalence of any HR-HPV genotype was 36.3% (95% CI 30.0% to 43.0%). In total, 7.8% of men had HPV-16 and 7.4% had HPV-18/45. The prevalence for the pooled genotypes (31, 33, 35, 39, 51, 52, 56, 58, 59, 66 and 68) was 29.9%. Receptive anal sex during the last 6 months was strongly associated with prevalent HR-HPV infections. The adjusted proportion ratio (aPR) was 1.93 (95% CI 1.31 to 2.83). Gonorrhoea and chlamydia were also associated with the outcome of interest; p value for both infections was <0.05. The aPR comparing patients who perceived some risk of acquiring HIV to other men was 1.44 (95% CI 1.00 to 2.08). CONCLUSIONS: In Benin, anal HR-HPV was common among HIV-negative men who have sex with men. Among this highly vulnerable population, there is a need for integrated preventive and management strategies targeting HPV and other sexually transmitted infections.

Pre-exposure prophylaxis in real life: experience from a prospective, observational and demonstration project among men who have sex with men in Benin, West Africa.

INTRODUCTION: Since many countries in sub-Saharan Africa are willing to implement HIV oral pre-exposure prophylaxis (PrEP) for men who have sex with men (MSM), data are needed to assess its feasibility and relevance in real life. The study objectives were to assess drug uptake, adherence, condom use and number of sexual partners, HIV incidence and trends in the prevalence of gonorrhoea and chlamydia. METHODS: In this oral PrEP demonstration study conducted prospectively in Benin, a combination of tenofovir disoproxil fumarate-TDF 300 mg and emtricitabine-FTC 200 mg (TDF-FTC) was offered daily or on-demand to MSM. Participants were recruited from 24 August to 24 November 2020 and followed over 12 months. At enrolment, month-6 and month-12, participants answered to a face-to-face questionnaire, underwent a physical examination and provided blood samples for HIV, gonorrhoea and chlamydia. RESULTS: Overall, 204 HIV-negative men initiated PrEP. The majority of them (80%) started with daily PrEP. Retention rates at month-3, 6, 9 and 12 were 96%, 88%, 86% and 85%, respectively. At month-6 and month-12, respectively, 49% and 51% of the men on daily PrEP achieved perfect adherence (self-reported), that is seven pills taken during the last week. For event-driven PrEP, the corresponding proportions for perfect adherence (last seven at-risk sexual episodes covered) were 81% and 80%, respectively. The mean number (standard deviation) of male sexual partners over the last 6 months was 2.1 (1.70) at baseline and 1.5 (1.27) at month-12 (p-value for trend <0.001). Consistent condom use during the last 6 months was 34% (enrolment), 37% (month-6) and 36% (month-12). Three HIV seroconversions (2-daily and 1-event-driven) were recorded. Crude HIV incidence (95% confidence interval) was 1.53 (0.31-4.50)/100 person-years. Neisseria gonorrhoeae and/or Chlamydia trachomatis prevalence at the anal and/or pharyngeal and/or urethral sites was 28% at baseline and 18% at month-12 (p-value = 0.017). CONCLUSIONS: In West Africa, oral PrEP introduction in routine practice as a component of a holistic HIV prevention package is feasible and may not result in a significant increase in condomless sex among MSM. Since HIV incidence was still higher, additional interventions, such as culturally tailored adherence counselling, may be needed to optimize the benefits of PrEP.

Facteurs structurels et communautaires augmentant la vulnérabilité des hommes ayant des relations sexuelles avec des hommes dans la riposte au virus de l'immunodéficience humaine au Burkina Faso.

INTRODUCTION: Worldwide and particularly in Africa, Men who have sex with men (MSM) can play a significant role in response to the Human Immunodeficiency Virus (HIV). In Burkina Faso the fight against HIV within this population seems to be limited by violence towards MSM. PURPOSE OF RESEARCH: The goal of this study was to identify the social obstacles to HIV response among MSM in Burkina Faso. METHODS: It has been a descriptive study with an exploratory aim in a mainly qualitative approach. It was conducted in the two biggest cities as well as two border ones of the country. Nonstructural interviews have been conducted with the help of prevention MSM actors. The data have been thematically analyzed. RESULTS: In the structural level, homosexuality is publically condemned by politicians some of whom seeking its criminalization. According to them it has "come from elsewhere" and is "contrary to morals". Even though there is no legally punishing regulation against it, political and administrative authorities and security forces do not protect MSM against homophobic violence. There is not enough care structures for MSM in the country. At the community level, many religious leaders condemn homosexuality, considered as a sin; they view homosexuality as an "abomination". MSM feel that they are victims of homophobic violence. CONCLUSIONS: The MSM are victims of violence from populations and state institutions too. To reach MSM by activities in response to HIV these obstacles must necessarily be removed.

Incidence of HIV and hepatitis C virus among people who inject drugs, and associations with age and sex or gender: a global systematic review and meta-analysis.

BACKGROUND: Measuring the incidence of HIV and hepatitis C virus (HCV) infection among people who inject drugs (PWID) is key to track progress towards elimination. We aimed to summarise global data on HIV and primary HCV incidence among PWID and associations with age and sex or gender. METHODS: In this systematic review and meta-analysis, we updated an existing database of HIV and HCV incidence studies among PWID by searching MEDLINE, Embase, and PsycINFO, capturing studies published between Jan 1, 2000, and Dec 12, 2022, with no language or study design restrictions. We contacted authors of identified studies for unpublished or updated data. We included studies that estimated incidence by longitudinally re-testing people at risk of infection or by using assays for recent infection. We pooled incidence and relative risk (RR; young [generally defined as ≤25 years] vs older PWID; women vs men) estimates using random-effects meta-analysis and assessed risk of bias with a modified Newcastle-Ottawa scale. This study is registered with PROSPERO, CRD42020220884. FINDINGS: Our updated search identified 9493 publications, of which 211 were eligible for full-text review. An additional 377 full-text records from our existing database and five records identified through cross-referencing were assessed. Including 28 unpublished records, 125 records met the inclusion criteria. We identified 64 estimates of HIV incidence (30 from high-income countries [HICs] and 34 from low-income or middle-income countries [LMICs]) and 66 estimates of HCV incidence (52 from HICs and 14 from LMICs). 41 (64%) of 64 HIV and 42 (64%) of 66 HCV estimates were from single cities rather than being multi-city or nationwide. Estimates were measured over 1987-2021 for HIV and 1992-2021 for HCV. Pooled HIV incidence was 1·7 per 100 person-years (95% CI 1·3-2·3; I2=98·4%) and pooled HCV incidence was 12·1 per 100 person-years (10·0-14·6; I2=97·2%). Young PWID had a greater risk of HIV (RR 1·5, 95% CI 1·2-1·8; I2=66·9%) and HCV (1·5, 1·3-1·8; I2=70·6%) acquisition than older PWID. Women had a greater risk of HIV (RR 1·4, 95% CI 1·1-1·6; I2=55·3%) and HCV (1·2, 1·1-1·3; I2=43·3%) acquisition than men. For both HIV and HCV, the median risk-of-bias score was 6 (IQR 6-7), indicating moderate risk. INTERPRETATION: Although sparse, available HIV and HCV incidence estimates offer insights into global levels of HIV and HCV transmission among PWID. Intensified efforts are needed to keep track of the HIV and HCV epidemics among PWID and to expand access to age-appropriate and gender-appropriate prevention services that serve young PWID and women who inject drugs. FUNDING: Canadian Institutes of Health Research, Fonds de recherche du Québec-Santé, Canadian Network on Hepatitis C, UK National Institute for Health and Care Research, and WHO.

HIV Replication Increases the Mitochondrial DNA Content of Plasma Extracellular Vesicles.

Extracellular vesicles (EVs) and their cargo have been studied intensively as potential sources of biomarkers in HIV infection; however, their DNA content, particularly the mitochondrial portion (mtDNA), remains largely unexplored. It is well known that human immunodeficiency virus (HIV) infection and prolonged antiretroviral therapy (ART) lead to mitochondrial dysfunction and reduced mtDNA copy in cells and tissues. Moreover, mtDNA is a well-known damage-associated molecular pattern molecule that could potentially contribute to increased immune activation, oxidative stress, and inflammatory response. We investigated the mtDNA content of large and small plasma EVs in persons living with HIV (PLWH) and its implications for viral replication, ART use, and immune status. Venous blood was collected from 196 PLWH, ART-treated or ART-naïve (66 with ongoing viral replication, ≥20 copies/mL), and from 53 HIV-negative persons, all recruited at five HIV testing or treatment centers in Burkina Faso. Large and small plasma EVs were purified and counted, and mtDNA level was measured by RT-qPCR. Regardless of HIV status, mtDNA was more abundant in large than small EVs. It was more abundant in EVs of viremic than aviremic and control participants and tended to be more abundant in participants treated with Tenofovir compared with Zidovudine. When ART treatment was longer than six months and viremia was undetectable, no variation in EV mtDNA content versus CD4 and CD8 count or CD4/CD8 ratio was observed. However, mtDNA in large and small EVs decreased with years of HIV infection and ART. Our results highlight the impact of viral replication and ART on large and small EVs' mtDNA content. The mechanisms underlying the differential incorporation of mtDNA into EVs and their effects on the surrounding cells warrant further investigation.

Longitudinal study of pregnancy intention and its association with pregnancy occurrence among female sex workers in Benin and Mali.

BACKGROUND: The intention of becoming pregnant has an evident impact on the prenatal and postnatal period. For female sex workers (FSWs) in West Africa, among whom pregnancies are frequent as are HIV and sexually transmitted infections, a better understanding of their pregnancy intention and its influence on pregnancy occurrence could help prevent unwanted pregnancies and adverse effects on wanted pregnancies. METHODS: We recruited 330 FSWs in Benin and 322 in Mali and followed them for 12 months. We evaluated their pregnancy intention at recruitment and 6-month follow-up, using a multidimensional prospective measure that we developed. We assessed pregnancy occurrence with a pregnancy test and a retrospective questionnaire at 6 and 12 months. A Cox proportional hazard model was used to estimate the association between intention and pregnancy. We carried out an analysis to take losses to follow-up into account using the inverse of probability of censoring weights and a cluster analysis to corroborate that the multidimensional measure of pregnancy intention fitted the data. RESULTS: 407 FSWs were included in the first 6-month analysis and 284 at 12 months. Mean age was 30.9 years. The pregnancy intention distribution was similar between the two periods: 15.2% in the first period and 16.3% in the second had a positive intention. One out of four were ambivalent and almost 60% (57.7% and 56.3%) had a negative intention. For 38.2% of the FSWs, the intention changed between the two periods. The global incidence rate (to first event) was 19.1 pregnancies per 100 person-years. There was a borderline significant trend (p = 0.0529) of decreased pregnancy incidence with decreasing intention. Compared to positive intention, the adjusted hazard ratio (aHR) for ambivalent and negative intentions were 0.71 [95% confidence interval (95% CI) 0.32-1.60] and 0.46 (95% CI 0.21-1.01), respectively. CONCLUSION: The level of pregnancy intention influences its occurrence among FSWs and nearly one out of six wants a baby despite working in the sex trade. Programmatically, early identification of these women could facilitate provision of quality antenatal and postnatal care. Given other health risks associated with sex work this care may decrease potential risks of adverse maternal, fetal and neonatal outcomes.

The intention of becoming pregnant has an evident impact on the prenatal and postnatal period. For female sex workers (FSWs) in West Africa, among whom pregnancies are frequent, a better understanding of their pregnancy intention and its influence on pregnancy occurrence could help prevent unwanted pregnancies and adverse effects of wanted pregnancies. We recruited 330 FSWs in Benin and 322 in Mali and we followed them for 12 months. We evaluated their pregnancy intention at recruitment and at 6-month follow-up. We assessed pregnancy occurrence with a pregnancy urine test and with a retrospective questionnaire asking on pregnancy occurrence at 6 and 12 months. With these data we estimated the association between intention and pregnancy. 407 FSWs were included in the first 6-month analysis and 284 at 12 months. Sixteen percent of the FSWs had a positive intention of having a pregnancy in the next 6 months in both the first 6-month and 12 months. One out of four were ambivalent and almost 60% had a negative intention. For 38.2% of the FSWs the intention changed between the two periods. Women with an ambivalent intention compared to those with positive intention, had 30% less pregnancies whereas for negative intention, women had 54% less pregnancies during the study follow-up. As for any woman, the level of pregnancy intention influences its occurrence. Moreover, nearly one out of six FSWs wants a baby despite working in the sex trade. Programmatically, early identification of these women could facilitate provision of quality antenatal and postnatal care.

[Prevalence of viral hepatitis B and C in men who have sex with men enrolled in a demonstration study of pre-exposure prophylaxis for HIV in Cotonou, Benin]. / Prévalence des hépatites virales B et C chez les hommes ayant des rapports sexuels avec d'autres hommes mobilisés pour une étude de démonstration de la prophylaxie préexposition au VIH à Cotonou, au Bénin.

Introduction: men who have sex with men (MSM) are disproportionately affected by hepatitis B virus (HBV) and hepatitis C virus (HCV) worldwide. In Benin, there are no data on MSM. The purpose of this study was to estimate HBV and HCV prevalence and HBV-associated factors in MSM who were HIV negative. Methods: we conducted an analytical cross-sectional study. A two-degree random sampling was used to recruit 204 MSM. An immunochromatographic rapid test and enzyme immunoassays were used to detect HBV and HCV antigens/antibodies. Log-binomial regression was used to identify factors associated with HBV. Results: HbsAg positivity, history of hepatitis B infection and hepatitis C prevalences were 37.7%, 8.8 %, and 0.9 %, respectively. HBsAg positivity and history of hepatitis B were more prevalent in MSM aged ≥30 years compared to younger subjects: 16.7% versus 6.4% (p<0.0001) and 66.7% versus 28.8% (p<0.0001), respectively. Sexual intercourse under the effect of drug or alcohol and living in couple were also associated with HBV. conclusion: the prevalence of hepatitis C was low, but hepatitis B was common, especially among older MSM. Screening and vaccination against hepatitis B should be strengthened in this population.

Plasma vesicular miR-155 as a biomarker of immune activation in antiretroviral treated people living with HIV.

People living with HIV (PLWH), despite suppression of viral replication with antiretroviral therapy (ART), have high morbidity and mortality due to immune activation and chronic inflammation. Discovering new biomarkers of immune activation status under ART will be pertinent to improve PLWH quality of life when the majority will be treated. We stipulate that plasma large and small extracellular vesicle (EVs) and their microRNA content could be easily measured biomarkers to monitor immune activation in PLWH. Venous blood samples from n = 128 ART-treated PLWH with suppressed viral load (≤ 20 copies/mL) and n = 60 HIV-uninfected participants were collected at five testing or treatment centers of PLWH in Burkina Faso. Large and small plasma EVs were purified, counted, and the mature miRNAs miR-29a, miR-146a, and miR-155 were quantified by RT-qPCR. Diagnostic performances of large and small EVs miRNAs level were evaluated by receiver operating characteristic (ROC) curve analysis and principal component analysis (PCA). Among the EVs microRNA measured, only large EVs miR-155 copies distinguished PLWH with immune activation, with AUC of 0.75 for CD4/CD8 < 1 (95% CI: 0.58-0.91, P = 0.0212), and 0.77 for CD8 T cells ≥ 500/µL (95% CI: 0.63-0.92, P = 0.0096). In addition, PCA results suggest that large EVs miR-155 copies may be a biomarker of immune activation. Since miR-155 may influence immune cell function, its enrichment in large EV subpopulations could be a functional biomarker of immune activation in PLWH on ART. This measure could help to monitor and diagnose the immune activation with more accuracy.

Measuring progress towards reaching zero new HIV acquisitions among key populations in Québec (Canada) using routine surveillance data: a mathematical modelling study.

INTRODUCTION: Men who have sex with men (MSM) and people who inject drugs (PWID) are disproportionately impacted by the HIV epidemic in Canada. Having the second-highest provincial diagnosis rate, an improved understanding of the epidemic among these populations in Québec could aid ongoing elimination efforts. We estimated HIV incidence and other epidemic indicators among MSM and PWID in Montréal and across Québec using a back-calculation model synthesizing surveillance data. METHODS: We developed a deterministic, compartmental mathematical model stratified by age, HIV status and disease progression, and clinical care stages. Using AIDS and HIV diagnoses data, including self-reported time since the last negative test and laboratory results of CD4 cell count at diagnosis, we estimated HIV incidence in each population over 1975-2020 by modelling a cubic M-spline. The prevalence, undiagnosed fraction, fraction diagnosed that started antiretroviral treatment (ART) and median time to diagnosis were also estimated. Since the COVID-19 pandemic disrupted testing, we excluded 2020 data and explored this in sensitivity analyses. RESULTS: HIV incidence in all populations peaked early in the epidemic. In 2020, an estimated 97 (95% CrI: 33-227) and 266 (95% CrI: 103-508) HIV acquisitions occurred among MSM in Montréal and Québec, respectively. Among PWID, we estimated 2 (95% CrI: 0-14) and 6 (95% CrI: 1-26) HIV acquisitions in those same regions. With 2020 data, unless testing rates were reduced by 50%, these estimates decreased, except among Québec PWID, whose increased. Among all, the median time to diagnosis shortened to <2 years before 2020 and the undiagnosed fraction decreased to <10%. This fraction was higher in younger MSM, with 22% of 15-24 year-olds living with HIV in Montréal (95% CrI: 9-39%) and 31% in Québec (95% CrI: 17-48%) undiagnosed by 2020 year-end. Finally, ART access neared 100% in all diagnosed populations. CONCLUSIONS: HIV incidence has drastically decreased in MSM and PWID across Québec, alongside significant improvements in diagnosis and treatment coverage-and the 2013 introduction of pre-exposure prophylaxis. Despite this, HIV transmission continued. Effective efforts to halt this transmission and rapidly diagnose people who acquired HIV, especially among younger MSM, are needed to achieve elimination. Further, as the impacts of the COVID-19 pandemic on HIV transmission are understood, increased efforts may be needed to overcome these.

HIV self-testing implementation, distribution and use among female sex workers in Cotonou, Benin: a qualitative evaluation of acceptability and feasibility.

BACKGROUND: In Benin, the burden of HIV is disproportionately high among female sex workers (FSWs). HIV testing and knowledge of status are starting points for HIV treatment and prevention interventions. Despite the importance given to testing services in HIV control, its uptake among FSWs remains suboptimal in Benin. HIV self-testing (HIVST) may be useful for increasing testing rates in FSWs. METHODS: We conducted a pilot study of the distribution of saliva-based HIVST among FSWs in Cotonou and its surroundings, Benin. The HIVST promotion and distribution model included three complementary strategies: community-based, facility-based and secondary distribution. In this qualitative study, we explored the elements influencing HIVST implementation, distribution and use among FSWs. We assessed HIVST acceptability and feasibility in this population. We conducted 29 semi-structured individual interviews with FSWs. Data were interpreted with a thematic analysis method, using the Theoretical Domains Framework. RESULTS: Only two FSWs (6.9%) were aware of HIVST before participating in the study. All participants were interested in using HIVST if available in Benin. Many advantages of HIVST were mentioned, including: autonomy, privacy, accessibility, time saving, and the fact that it is a painless test. Barriers to the use of HIVST included: the fear of unreliability, the lack of psychological support and medical follow-up and the possibility of result dissimulation. Participants thought HIVST was easy to use without assistance. HIVST enabled linkage to care for a few FSWs in denial of their HIV-positive status. No case of suicide or violence associated with HIVST was reported. HIVST secondary distribution within FSWs social network was well received. FSWs' boyfriends and clients showed interest in using the device. Some FSWs reported using HIVST to practice serosorting or to guide their decisions regarding condom use. CONCLUSIONS: Our study shows a very high level of acceptability for HIVST among FSWs in Cotonou and its surroundings. Results also demonstrate the feasibility of implementing HIVST distribution in Benin. HIVST should be implemented in Benin quickly and free of charge for all individuals at risk of HIV. HIVST offer should be integrated with comprehensive sexual health and prevention services.

Vesicular MicroRNA as Potential Biomarkers of Viral Rebound.

Changes in the cellular microRNA (miRNA) expression profile in response to HIV infection, replication or latency have been reported. Nevertheless, little is known concerning the abundance of miRNA in extracellular vesicles (EVs). In the search for a reliable predictor of viral rebound, we quantified the amount of miR-29a, miR-146a, and miR-155 in two types of plasma extracellular vesicles. Venous blood was collected from 235 ART-treated and ART-naive persons living with HIV (85 with ongoing viral replication, ≥20 copies/mL) and 60 HIV-negative participants at five HIV testing or treatment centers in Burkina Faso. Large and small plasma EVs were purified and counted, and mature miRNA miR-29a, miR-146a, and miR-155 were measured by RT-qPCR. Diagnostic performance of miRNA levels in large and small EVs was evaluated by a receiver operating characteristic curve analysis. The median duration of HIV infection was 36 months (IQR 14-117). The median duration of ART was 34 months (IQR 13-85). The virus was undetectable in 63.8% of these persons. In the others, viral load ranged from 108 to 33,978 copies/mL (median = 30,032). Large EVs were more abundant in viremic participants than aviremic. All three miRNAs were significantly more abundant in small EVs in persons with detectable HIV RNA, and their expression levels in copies per vesicle were a more reliable indicator of viral replication in ART-treated patients with low viremia (20-1000 copies/mL). HIV replication increased the production of large EVs more than small EVs. Combined with viral load measurement, quantifying EV-associated miRNA abundance relative to the number of vesicles provides a more reliable marker of the viral status. The expression level as copies per small vesicle could predict the viral rebound in ART-treated patients with undetectable viral loads.

Monocyte Gene and Molecular Expression Profiles Suggest Distinct Effector and Regulatory Functions in Beninese HIV Highly Exposed Seronegative Female Commercial Sex Workers.

We have previously reported that the female genital tract (FGT) of Beninese HIV highly-exposed seronegative (HESN) commercial sex workers (CSWs), presented elevated frequencies of a myeloid HLA-DR+CD14+CD11c+ population presenting "tolerogenic" monocyte derived dendritic cells (MoDC) features. In order to assess whether a differential profile of monocytes may be involved in the generation of these genital MoDCs, we have herein characterized the blood monocyte compartment of Beninese HESNs (HIV-uninfected ≥ 10 years CSWs) and relevant controls (HIV-uninfected 2.5-5 years CSWs herein termed "early HESNs"), HIV-infected CSWs, and low-risk HIV-uninfected women from the general population. Transcriptomic analyses by RNA-Seq of total sorted blood monocytes demonstrate that in comparison to the control groups, HESNs present increased expression levels of FCGR2C, FCAR, ITGAX, ITGAM, CR2, CD68, and CD163 genes, associated with effector functions. Moreover, we found increased expression levels of genes associated with protection/control against SHIV/HIV such as CCL3, CCL4, CCL5, BHLHE40, and TNFSF13, as well as with immune regulation such as IL-10, Ahr, CD83, and the orphan nuclear receptor (NR)4A1, NR4A2, and NR4A3. Through multicolor flow cytometry analyses, we noticed that the frequencies of intermediate and non-classical monocyte populations tended to be elevated in the blood of HESNs, and exhibited increased expression levels of effector CD16, CD11c, CD11b, as well as regulatory HLA-G, IL-10, and IFN-α markers when compared to HIV-uninfected women and/or HIV-infected CSWs. This profile is compatible with that previously reported in the FGT of HESNs, and likely confers an enormous advantage in their resistance to HIV infection.

Optimal human papillomavirus vaccination strategies to prevent cervical cancer in low-income and middle-income countries in the context of limited resources: a mathematical modelling analysis.

BACKGROUND: Introduction of human papillomavirus (HPV) vaccination has been slow in low-income and middle-income countries (LMICs) because of resource constraints and worldwide shortage of vaccine supplies. To help inform WHO recommendations, we modelled various HPV vaccination strategies to examine the optimal use of limited vaccine supplies and best allocation of scarce resources in LMICs in the context of the WHO global call to eliminate cervical cancer as a public health problem. METHODS: In this mathematical modelling analysis, we developed HPV-ADVISE LMIC, a transmission-dynamic model of HPV infection and diseases calibrated to four LMICs: India, Vietnam, Uganda, and Nigeria. For different vaccination strategies that encompassed use of a nine-valent vaccine (or a two-valent or four-valent vaccine assuming high cross-protection), we estimated three outcomes: reduction in the age-standardised rate of cervical cancer, number of doses needed to prevent one case of cervical cancer (NNV; as a measure of efficiency), and the incremental cost-effectiveness ratio (ICER; in 2017 international $ per disability-adjusted life-year [DALY] averted). We examined different vaccination strategies by varying the ages of routine HPV vaccination and number of age cohorts vaccinated, the population targeted, and the number of doses used. In our base case, we assumed 100% lifetime protection against HPV-16, HPV-18, HPV-31, HPV-33, HPV-45, HPV-52, and HPV-58; vaccination coverage of 80%; and a time horizon of 100 years. For the cost-effectiveness analysis, we used a 3% discount rate. Elimination of cervical cancer was defined as an age-standardised incidence of less than four cases per 100 000 woman-years. FINDINGS: We predicted that HPV vaccination could lead to cervical cancer elimination in Vietnam, India, and Nigeria, but not in Uganda. Compared with no vaccination, strategies that involved vaccinating girls aged 9-14 years with two doses were predicted to be the most efficient and cost-effective in all four LMICs. NNV ranged from 78 to 381 and ICER ranged from $28 per DALY averted to $1406 per DALY averted depending on the country. The most efficient and cost-effective strategies were routine vaccination of girls aged 14 years, with or without a later switch to routine vaccination of girls aged 9 years, and routine vaccination of girls aged 9 years with a 5-year extended interval between doses and a catch-up programme at age 14 years. Vaccinating boys (aged 9-14 years) or women aged 18 years or older resulted in substantially higher NNVs and ICERs. INTERPRETATION: We identified two strategies that could maximise efforts to prevent cervical cancer in LMICs given constraints on vaccine supplies and costs and that would allow a maximum of LMICs to introduce HPV vaccination. FUNDING: World Health Organization, Canadian Institute of Health Research, Fonds de recherche du Québec-Santé, Compute Canada, PATH, and The Bill & Melinda Gates Foundation. TRANSLATIONS: For the French and Spanish translations of the abstract see Supplementary Materials section.

Can hepatitis C elimination targets be sustained among people who inject drugs post-2030?

BACKGROUND: In high-income countries, people who inject drugs (PWID) are a priority population for eliminating hepatitis C virus (HCV) by 2030. Despite evidence informing micro-elimination strategies, little is known regarding efforts needed to maintain elimination targets in populations with ongoing acquisition risks. This model-based study investigates post-elimination transmission dynamics of HCV and HIV among PWID under different scenarios where harm reduction interventions and HCV testing and treatment are scaled-down. METHODS: We calibrated a dynamic compartmental model of concurrent HCV and HIV transmission among PWID in Montréal (Canada) to epidemiological data (2003-2018). We then simulated achieving the World Health Organization elimination targets by 2030. Finally, we assessed the impact of four post-elimination scenarios (2030-2050): 1) scaling-down testing, treatment, opioid agonist therapy (OAT), and needle and syringe programs (NSP) to pre-2020 levels; 2) only scaling-down testing and treatment; 3) suspending testing and treatment, while scaling down OAT and NSP to pre-2020 levels; 4) suspending testing and treatment and maintaining OAT and NSP coverage required for elimination. RESULTS: Scaling down interventions to pre-2020 levels (scenario 1) leads to a modest rebound in chronic HCV incidence from 2.4 to 3.6 per 100 person-years by 2050 (95% credible interval - CrI: 0.8-7.2). When only scaling down testing and treatment (scenario 2), chronic HCV incidence continues to decrease. In scenario 3 (suspending treatment and scaling down OAT and NSP), HCV incidence and mortality rapidly increase to 11.4 per 100 person-years (95%CrI: 7.4-15.5) and 3.2 per 1000 person-years (95%CrI: 2.4-4.0), respectively. HCV resurgence was mitigated in scenario 4 (maintaining OAT and NSP) as compared to scenario 3. All scenarios lead to decreases in the proportion of reinfections among incident cases and have little impact on HIV incidence and HIV-HCV coinfection prevalence. CONCLUSION: Despite ongoing transmission risks, HCV incidence rebounds slowly after 2030 under pre-2020 testing and treatment levels. This is heightened by maintaining high-coverage harm reduction interventions. Overall, sustaining elimination would require considerably less effort than achieving it.

Plasma Extracellular Vesicle Subtypes May be Useful as Potential Biomarkers of Immune Activation in People With HIV.

BACKGROUND: Extracellular vesicles (EVs) are intercellular messengers with epigenetic potential since they can shuttle microRNA (miRNA). EVs and miRNA play a role in human immunodeficiency virus (HIV) infection immunopathogenesis. Chronic immune activation and systemic inflammation during HIV infection despite effective antiretroviral therapy (ART) are associated with non-acquired immunodeficiency syndrome (AIDS) comorbidities in people living with HIV (PLWH). Analysis of plasma EVs and their miRNA content may be useful as immune activation or inflammatory biomarkers in PLWH receiving ART. In this study, we hypothesized that the number, size, and miRNA of large and small EVs could reflect immune activation associated with an elevated CD8 T-cell count or a low CD4/CD8 ratio in PLWH. METHODS: Plasma EVs subtype purified from PLWH and uninfected controls were sized using dynamic light scattering and quantified using flow cytometry and acetylcholine esterase (AChE) activity. Expression of mature miRNAs miR-92, miR-155, miR-223 was measured by quantitative reverse-transcriptase polymerase chain reaction in EVs and leucocytes. RESULTS: HIV infection induces increased production of small EVs in plasma. EV subtypes were differentially enriched in miR-92, miR-155, and miR-223. Positive correlations between CD8 T-cell count and large EVs abundance and small EVs AChE activity were observed. CD4/CD8 ratio was negatively correlated with small EV AChE activity, and miRNA-155 level per small EV was negatively correlated with CD8 T-cell count. CONCLUSIONS: These findings suggest that quantifying large or small EVs and profiling miRNA content per EV might provide new functional biomarkers of immune activation and inflammation.

Type-specific incidence, persistence and factors associated with human papillomavirus infection among female sex workers in Benin and Mali, West Africa.

OBJECTIVES: This study in female sex workers (FSWs) aimed to: (1) estimate type-specific incidence and persistence of human papillomavirus (HPV) infection in Cotonou (Benin) and Bamako (Mali); and (2) identify the factors associated with type-specific incidence and persistence of high-risk HPV (HR-HPV) infection. METHODS: A 1-year prospective cohort study on cervical cancer screening, and HPV and human immunodeficiency virus (HIV) infections was conducted among FSWs in Cotonou and Bamako from 2017 to 2019. Poisson regression models assessed factors associated with the incidence of HR-HPV infection, while log-binomial regression was performed to identify factors associated with the persistence of HR-HPV infection. Adjusted relative risks (ARR) and 95% confidence intervals (95% CI) were estimated. RESULTS: The incidence of HR-HPV infection was 46.98 per 1000 women-months (predominant types HPV16, HPV35 and HPV59). Factors associated with the incidence of HR-HPV infection were age <20 years (ARR 15.10; 95% CI 3.29-69.19), age at sexual debut <18 years (ARR 6.92; 95% CI 1.97-24.27) and sex work duration ≤1 year (ARR 7.40; 95% CI 1.84-29.69). The persistence of HR-HPV infection at 12 months was 38.7% (most persistent types HPV59, HPV52 and HPV51). Persistence of HR-HPV infection was higher in women with chlamydia (P = 0.031), HIV infection (P < 0.001) and multiple-type HPV infections (P < 0.001). CONCLUSION: FSWs in West Africa are at high risk of incident and persistent HR-HPV infection, suggesting an urgent need for cervical cancer screening in this population.

Diurnal Variation of Plasma Extracellular Vesicle Is Disrupted in People Living with HIV.

BACKGROUND: Several types of extracellular vesicles (EVs) secreted by various immune and non-immune cells are present in the human plasma. We previously demonstrated that EV abundance and microRNA content change in pathological conditions, such as HIV infection. Here, we investigated daily variations of large and small EVs, in terms of abundance and microRNA contents in people living with HIV (PLWH) receiving antiretroviral therapy (HIV+ART) and uninfected controls (HIV-). METHODS: Venous blood samples from n = 10 HIV+ART and n = 10 HIV- participants were collected at 10:00 and 22:00 the same day. Large and small plasma EVs were purified, counted, and the mature miRNAs miR-29a, miR-29b, miR-92, miR-155, and miR-223 copies were measured by RT-PCR. RESULTS: Large EVs were significantly bigger in the plasma collected at 10:00 versus 22:00 in both groups. There was a significant day-night increase in the quantity of 5 miRNAs in HIV- large EVs. In HIV+ART, only miR-155 daily variation has been observed in large EVs. Finally, EV-miRNA content permits to distinguish HIV- to HIV+ART in multivariate analysis. CONCLUSION: These results point that plasma EV amount and microRNA contents are under daily variation in HIV- people. This new dynamic measure is disrupted in PLWH despite viral-suppressive ART. This study highlights a significant difference concerning EV abundance and their content measured at 22:00 between both groups. Therefore, the time of blood collection must be considered in the future for the EV as biomarkers.

Assessing the Potential Impact of Disruptions Due to COVID-19 on HIV Among Key and Lower-Risk Populations in the Largest Cities of Cameroon and Benin.

BACKGROUND: The COVID-19 pandemic indirectly impacts HIV epidemiology in Central/West Africa. We estimated the potential impact of COVID-19-related disruptions to HIV prevention/treatment services and sexual partnerships on HIV incidence and HIV-related deaths among key populations including female sex workers (FSW), their clients, men who have sex with men, and overall. SETTING: Yaoundé (Cameroon) and Cotonou (Benin). METHODS: We used mathematical models of HIV calibrated to city population-specific and risk population-specific demographic/behavioral/epidemic data. We estimated the relative change in 1-year HIV incidence and HIV-related deaths for various disruption scenarios of HIV prevention/treatment services and decreased casual/commercial partnerships, compared with a scenario without COVID-19. RESULTS: A 50% reduction in condom use in all partnerships over 6 months would increase 1-year HIV incidence by 39%, 42%, 31%, and 23% among men who have sex with men, FSW, clients, and overall in Yaoundé, respectively, and 69%, 49%, and 23% among FSW, clients, and overall, respectively, in Cotonou. Combining a 6-month interruption of ART initiation and 50% reduction in HIV prevention/treatment use would increase HIV incidence by 50% and HIV-related deaths by 20%. This increase in HIV infections would be halved by a simultaneous 50% reduction in casual and commercial partnerships. CONCLUSIONS: Reductions in condom use after COVID-19 would increase infections among key populations disproportionately, particularly FSW in Cotonou, who need uninterrupted condom provision. Disruptions in HIV prevention/treatment services have the biggest impacts on HIV infections and deaths overall, only partially mitigated by equal reductions in casual/commercial sexual partnerships. Maintaining ART provision must be prioritized to minimize short-term excess HIV-related deaths.

Homelessness, unstable housing, and risk of HIV and hepatitis C virus acquisition among people who inject drugs: a systematic review and meta-analysis.

BACKGROUND: People who inject drugs (PWID) are at increased risk for HIV and hepatitis C virus (HCV) infection and also have high levels of homelessness and unstable housing. We assessed whether homelessness or unstable housing is associated with an increased risk of HIV or HCV acquisition among PWID compared with PWID who are not homeless or are stably housed. METHODS: In this systematic review and meta-analysis, we updated an existing database of HIV and HCV incidence studies published between Jan 1, 2000, and June 13, 2017. Using the same strategy as for this existing database, we searched MEDLINE, Embase, and PsycINFO for studies, including conference abstracts, published between June 13, 2017, and Sept 14, 2020, that estimated HIV or HCV incidence, or both, among community-recruited PWID. We only included studies reporting original results without restrictions to study design or language. We contacted authors of studies that reported HIV or HCV incidence, or both, but did not report on an association with homelessness or unstable housing, to request crude data and, where possible, adjusted effect estimates. We extracted effect estimates and pooled data using random-effects meta-analyses to quantify the associations between recent (current or within the past year) homelessness or unstable housing compared with not recent homelessness or unstable housing, and risk of HIV or HCV acquisition. We assessed risk of bias using the Newcastle-Ottawa Scale and between-study heterogeneity using the I2 statistic and p value for heterogeneity. FINDINGS: We identified 14 351 references in our database search, of which 392 were subjected to full-text review alongside 277 studies from our existing database. Of these studies, 55 studies met inclusion criteria. We contacted the authors of 227 studies that reported HIV or HCV incidence in PWID but did not report association with the exposure of interest and obtained 48 unpublished estimates from 21 studies. After removal of duplicate data, we included 37 studies with 70 estimates (26 for HIV; 44 for HCV). Studies originated from 16 countries including in North America, Europe, Australia, east Africa, and Asia. Pooling unadjusted estimates, recent homelessness or unstable housing was associated with an increased risk of acquiring HIV (crude relative risk [cRR] 1·55 [95% CI 1·23-1·95; p=0·0002]; I2= 62·7%; n=17) and HCV (1·65 [1·44-1·90; p<0·0001]; I2= 44·8%; n=28]) among PWID compared with those who were not homeless or were stably housed. Associations for both HIV and HCV persisted when pooling adjusted estimates (adjusted relative risk for HIV: 1·39 [95% CI 1·06-1·84; p=0·019]; I2= 65·5%; n=9; and for HCV: 1·64 [1·43-1·89; p<0·0001]; I2= 9·6%; n=14). For risk of HIV acquisition, the association for unstable housing (cRR 1·82 [1·13-2·95; p=0·014]; n=5) was higher than for homelessness (1·44 [1·13-1·83; p=0·0036]; n=12), whereas no difference was seen between these outcomes for risk of HCV acquisition (1·72 [1·48-1·99; p<0·0001] for unstable housing, 1·66 [1·37-2·00; p<0·0001] for homelessness). INTERPRETATION: Homelessness and unstable housing are associated with increased risk of HIV and HCV acquisition among PWID. Our findings support the development of interventions that simultaneously address homelessness and unstable housing and HIV and HCV transmission in this population. FUNDING: National Institute for Health Research, National Institute on Drug Abuse, National Institute of Allergy and Infectious Diseases, and Commonwealth Scholarship Commission.

HIV Prevention and Treatment Cascades Among Female Sex Workers in Benin, West Africa.

BACKGROUND: Benin has a long-standing history of HIV prevention programs aimed at female sex workers (FSWs). We used data from a national survey among FSWs (2017) to assess the prevention and care cascades in this population. METHODS: Female sex workers were recruited through cluster sampling of sex work sites. A questionnaire was administered, and HIV tested. HIV-positive participants were asked to provide dried blood spots and were tested for antiretroviral and viral load. We assessed 2 prevention cascades (HIV testing and safer sex) and the treatment cascade, using a combination of self-reported and biological variables. RESULTS: Mean age of the 1086 FSWs was 30 years. Half of them were Beninese, and two-thirds had a primary school education level or less. Almost all FSWs had ever heard of HIV/AIDS. More than half (79.1%) had ever been tested, and 84.1% of the latter had been tested in the last year. In the previous 6 months, 90.1% were exposed to prevention messages. Women exposed to any HIV prevention message reported a higher level of consistent condom use in the last month (69.0%) than those who were not (48.5%, P < 0.0001). HIV prevalence was 7.7%. Among HIV-positive women, 60.6% knew their status; among those, 90.5% were on antiretroviral and 81.8% of them had a suppressed viral load. CONCLUSIONS: Despite long-standing HIV prevention programs for FSWs, the prevention indicators were often low. Linkage to care was good, viral suppression was suboptimal, but knowledge of HIV-positive status was low. Exposing women to prevention messages is necessary, as to increase HIV testing.