Publications by authors named "Philippe Mayaud"

150 Publications

What is the burden of heterosexually-acquired HIV due to HSV-2? Global and regional model-based estimates of the proportion and number of HIV infections attributable to HSV-2 infection.

J Acquir Immune Defic Syndr 2021 Jun 9. Epub 2021 Jun 9.

MRC Centre for Global Infectious Disease Analysis, School of Public Health, Imperial College London. Department of Respiratory Sciences, University of Leicester. London School of Hygiene and Tropical Medicine, London, United Kingdom Department of Sexual and Reproductive Health and Research, World Health Organization, Geneva, Switzerland Department of Epidemiology, Biostatistics, and Occupational Health, McGill University, Montréal (QC), Canada Bristol Veterinary School, University of Bristol, Bristol, United Kingdom Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, United Kingdom.

Background: Biological and epidemiological evidence suggest that herpes simplex virus type 2 (HSV-2) elevates HIV acquisition and transmission risk. We improved previous estimates of the contribution of HSV-2 to HIV infections by using a dynamic-transmission model.

Setting: WHO regions.

Methods: We developed a mathematical model of HSV-2/HIV transmission among 15-49-year-old heterosexual, non-drug-injecting populations, calibrated using region-specific demographic and HSV-2/HIV epidemiological data. We derived global and regional estimates of the contribution of HSV-2 to HIV infection over ten years (the transmission population-attributable fraction, tPAF) under three additive scenarios, assuming: (1) HSV-2 only increases HIV acquisition ("conservative"); (2) HSV-2 also increases HIV transmission ("liberal"); (3) HIV/ART (antiretroviral therapy) also modifies HSV-2 transmission and HSV-2 decreases ART effect on HIV transmission ("fully liberal").

Results: Under the conservative scenario, the predicted tPAF was 37.3% (95% uncertainty interval 33.4-43.2%) and an estimated 5.6 (4.5-7.0) million incident heterosexual HIV infections were due to HSV-2 globally over 2009-2018. The contribution of HSV-2 to HIV infections was largest for the African region (tPAF=42.6% (38.0-51.2%)), and lowest for the European region (tPAF=11.2% (7.9-13.8%)). The tPAF was higher among female sex-workers, their clients, and older populations, reflecting their higher HSV-2 prevalence. The tPAF was ∼50% and 1.3-2.4-fold higher for the liberal/fully liberal than the conservative scenario across regions.

Conclusion: HSV-2 may have contributed to at least 37% of incident HIV infections in the last decade worldwide, and even more in Africa, and may continue to do so despite increased ART access unless future improved HSV-2 control measures, such as vaccines, become available.
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http://dx.doi.org/10.1097/QAI.0000000000002743DOI Listing
June 2021

Vertical transmission of SARS-CoV2 during pregnancy: A high-risk cohort.

Prenat Diagn 2021 Jun 8. Epub 2021 Jun 8.

Disciplina de Obstetrícia, Departamento de Obstetrícia e Ginecologia da FMUSP, São Paulo, Brazil.

Objective: Identify the potential for and risk factors of SARS-CoV-2 vertical transmission.

Methods: Symptomatic pregnant women with COVID-19 diagnosis in whom PCR for SARS-CoV-2 was performed at delivery using maternal serum and at least one of the biological samples: cord blood (CB), amniotic fluid (AF), colostrum and/or oropharyngeal swab (OPS) of the neonate. The association of parameters with maternal, AF and/or CB positivity and the influence of SARS-CoV-2 positivity in AF and/or CB on neonatal outcomes were investigated.

Results: Overall 73.4% (80/109) were admitted in hospital due to COVID-19, 22.9% needed intensive care and there were four maternal deaths. Positive RT-PCR for SARS-CoV-2 was observed in 14.7% of maternal blood, 13.9% of AF, 6.7% of CB, 2.1% of colostrum and 3.7% of OPS samples. The interval between COVID-19 symptoms and delivery was inversely associated with SARS-CoV-2 positivity in the maternal blood (p = 0.002) and in the AF and/or CB (p = 0.049). Maternal viremia was associated with positivity for SARS-CoV-2 in AF and/or CB (p = 0.001). SARS-CoV-2 positivity in the compartments was not associated with neonatal outcomes.

Conclusion: Vertical transmission is possible in pregnant women with COVID-19 and a shorter interval between maternal symptoms and delivery is an influencing factor.
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http://dx.doi.org/10.1002/pd.5980DOI Listing
June 2021

Effect of Internet use for searching information on vaccination on the uptake of human papillomavirus vaccine in France: A path-analysis approach.

Prev Med 2021 Aug 11;149:106615. Epub 2021 May 11.

INSERM CIC 1417, F-CRIN, I REIVAC, Assistance Publique- Hôpitaux de Paris, Hôpital Cochin, Paris, France; Université de Paris, Faculté de médecine Paris Descartes, Paris, France.

Internet is a popular source of information regarding vaccination. This study aimed to determine whether there is a negative association between Internet use among French vaccine-hesitant mothers and HPV vaccine uptake by their daughters, and to gain insight into the pathways that would link Internet use to the lack of HPV vaccine uptake. We conducted a pooled cross-sectional analysis across the 2015, 2016, 2017 and 2018 Vaccinoscopie® Survey. Multivariate logistic regression and path models were used in the analysis. The study sample included a total of 2038 respondent mothers. Of those, 89 (4.4%) declared having never been in the situation of searching for information regarding a vaccination they had hesitated about, leaving 1949 mothers for the present analysis. Approximately 24% (466/1949) of the mothers declared using the Internet as a source of vaccine information. In multivariate logistic regression adjusted for physician recommendation of HPV vaccination, attitudes towards vaccines in general, perception of HPV vaccine usefulness, maternal level of education, region of residence, and the survey year, the use of Internet by the mothers was significantly associated with a lower HPV vaccination among their daughters (adjusted odds ratio (aOR), 0.66; 95% confidence interval (CI), 0.47-0.91). Path analysis further confirmed the negative effect of Internet use (β = -0.10, standard error (SE) = 0.02, P < 0.0001), highlighting how the Internet plays a detrimental role in HPV vaccine uptake through a lower perceived level of HPV vaccine usefulness, a lower perceived level of information on childhood vaccination, and unfavorable attitudes towards vaccination in general.
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http://dx.doi.org/10.1016/j.ypmed.2021.106615DOI Listing
August 2021

Congenital malformations in sub-Saharan Africa-warnings of a silent epidemic?

Lancet Infect Dis 2021 05 25;21(5):594-596. Epub 2021 Mar 25.

Heidelberg Institute of Global Health (HIGH), Heidelberg University Hospital, Heidelberg, Germany; Center for Global Health, Colorado School of Public Health, Aurora, CO, USA.

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http://dx.doi.org/10.1016/S1473-3099(21)00061-XDOI Listing
May 2021

Costs and cost-effectiveness of cervical cancer screening strategies in women living with HIV in Burkina Faso: The HPV in Africa Research Partnership (HARP) study.

PLoS One 2021 25;16(3):e0248832. Epub 2021 Mar 25.

London School of Hygiene & Tropical Medicine, London, United Kingdom.

Introduction: This study estimated the costs and incremental cost per case detected of screening strategies for high-grade cervical intraepithelial neoplasia (CIN2+) in women living with HIV (WLHIV) attending HIV clinics in Burkina Faso.

Methods: The direct healthcare provider costs of screening tests (visual inspection with acetic acid (VIA), VIA combined visual inspection with Lugol's iodine (VIA/VILI), cytology and a rapid HPV DNA test (careHPV)) and confirmatory tests (colposcopy, directed biopsy and systematic four-quadrant (4Q) biopsy) were collected alongside the HPV in Africa Research Partnership (HARP) study. A model was developed for a hypothetical cohort of 1000 WLHIV using data on CIN2+ prevalence and the sensitivity of the screening tests. Costs are reported in USD (2019).

Results: The study enrolled 554 WLHIV with median age 36 years (inter-quartile range, 31-41) and CIN2+ prevalence of 5.8%. The average cost per screening test ranged from US$3.2 for VIA to US$24.8 for cytology. Compared to VIA alone, the incremental cost per CIN2+ case detected was US$48 for VIA/VILI and US$814 for careHPV. Despite higher costs, careHPV was more sensitive for CIN2+ cases detected compared to VIA/VILI (97% and 56%, respectively). The cost of colposcopy was US$6.6 per person while directed biopsy was US$33.0 and 4Q biopsy was US$48.0.

Conclusion: Depending on the willingness to pay for the detection of a case of cervical cancer, decision makers in Burkina Faso can consider a variety of cervical cancer screening strategies for WLHIV. While careHPV is more costly, it has the potential to be cost-effective depending on the willingness to pay threshold. Future research should explore the lifetime costs and benefits of cervical cancer screening to enable comparisons with interventions for other diseases.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0248832PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7993811PMC
March 2021

Diagnostic accuracy of cervical cancer screening and screening-triage strategies among women living with HIV-1 in Burkina Faso and South Africa: A cohort study.

PLoS Med 2021 Mar 4;18(3):e1003528. Epub 2021 Mar 4.

London School of Hygiene & Tropical Medicine, London, United Kingdom.

Background: Cervical cancer screening strategies using visual inspection or cytology may have suboptimal diagnostic accuracy for detection of precancer in women living with HIV (WLHIV). The optimal screen and screen-triage strategy, age to initiate, and frequency of screening for WLHIV remain unclear. This study evaluated the sensitivity, specificity, and positive predictive value of different cervical cancer strategies in WLHIV in Africa.

Methods And Findings: WLHIV aged 25-50 years attending HIV treatment centres in Burkina Faso (BF) and South Africa (SA) from 5 December 2011 to 30 October 2012 were enrolled in a prospective evaluation study of visual inspection using acetic acid (VIA) or visual inspection using Lugol's iodine (VILI), high-risk human papillomavirus DNA test (Hybrid Capture 2 [HC2] or careHPV), and cytology for histology-verified high-grade cervical intraepithelial neoplasia (CIN2+/CIN3+) at baseline and endline, a median 16 months later. Among 1,238 women (BF: 615; SA: 623), median age was 36 and 34 years (p < 0.001), 28.6% and 49.6% ever had prior cervical cancer screening (p < 0.001), and 69.9% and 64.2% were taking ART at enrolment (p = 0.045) in BF and SA, respectively. CIN2+ prevalence was 5.8% and 22.4% in BF and SA (p < 0.001), respectively. VIA had low sensitivity for CIN2+ (44.7%, 95% confidence interval [CI] 36.9%-52.7%) and CIN3+ (56.1%, 95% CI 43.3%-68.3%) in both countries, with specificity for ≤CIN1 of 78.7% (95% CI 76.0%-81.3%). HC2 had sensitivity of 88.8% (95% CI 82.9%-93.2%) for CIN2+ and 86.4% (95% CI 75.7%-93.6%) for CIN3+. Specificity for ≤CIN1 was 55.4% (95% CI 52.2%-58.6%), and screen positivity was 51.3%. Specificity was higher with a restricted genotype (HPV16/18/31/33/35/45/52/58) approach (73.5%, 95% CI 70.6%-76.2%), with lower screen positivity (33.7%), although there was lower sensitivity for CIN3+ (77.3%, 95% CI 65.3%-86.7%). In BF, HC2 was more sensitive for CIN2+/CIN3+ compared to VIA/VILI (relative sensitivity for CIN2+ = 1.72, 95% CI 1.28-2.32; CIN3+: 1.18, 95% CI 0.94-1.49). Triage of HC2-positive women with VIA/VILI reduced the number of colposcopy referrals, but with loss in sensitivity for CIN2+ (58.1%) but not for CIN3+ (84.6%). In SA, cytology high-grade squamous intraepithelial lesion or greater (HSIL+) had best combination of sensitivity (CIN2+: 70.1%, 95% CI 61.3%-77.9%; CIN3+: 80.8%, 95% CI 67.5%-90.4%) and specificity (81.6%, 95% CI 77.6%-85.1%). HC2 had similar sensitivity for CIN3+ (83.0%, 95% CI 70.2%-91.9%) but lower specificity compared to HSIL+ (42.7%, 95% CI 38.4%-47.1%; relative specificity = 0.57, 95% CI 0.52-0.63), resulting in almost twice as many referrals. Compared to HC2, triage of HC2-positive women with HSIL+ resulted in a 40% reduction in colposcopy referrals but was associated with some loss in sensitivity. CIN2+ incidence over a median 16 months was highest among VIA baseline screen-negative women (2.2%, 95% CI 1.3%-3.7%) and women who were baseline double-negative with HC2 and VIA (2.1%, 95% CI 1.3%-3.5%) and lowest among HC2 baseline screen-negative women (0.5%, 95% CI 0.1%-1.8%). Limitations of our study are that WLHIV included in the study may not reflect a contemporary cohort of WLHIV initiating ART in the universal ART era and that we did not evaluate HPV tests available in study settings today.

Conclusions: In this cohort study among WLHIV in Africa, a human papillomavirus (HPV) test targeting 14 high-risk (HR) types had higher sensitivity to detect CIN2+ compared to visual inspection but had low specificity, although a restricted genotype approach targeting 8 HR types decreased the number of unnecessary colposcopy referrals. Cytology HSIL+ had optimal performance for CIN2+/CIN3+ detection in SA. Triage of HPV-positive women with HSIL+ maintained high specificity but with some loss in sensitivity compared to HC2 alone.
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http://dx.doi.org/10.1371/journal.pmed.1003528DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7971880PMC
March 2021

The dapivirine vaginal ring from the perspective of married men in Uganda.

Afr J AIDS Res 2021 Mar 25;20(1):53-60. Epub 2021 Feb 25.

London School of Hygiene and Tropical Medicine, London, United Kingdom.

: Men play a key role in influencing uptake of women's health products, such as female condoms and vaginal microbicides used for family planning and HIV prevention.: We explored men's perceptions of the dapivirine vaginal ring (DVR), a vaginal microbicide, in Kalungu District, rural south-western Uganda. In June/July 2018, we conducted in-depth interviews with 10 partners of women participating in the DREAM study, a phase 3B open-label extension trial of the DVR. Data were analysed thematically, drawing on the socio-ecological model theoretical framework.: Influencing factors such as individual and interpersonal characteristics, perception of HIV risk, lack of knowledge about the DVR, misconceptions, and product characteristics acting at different levels (individual, societal and organisational) affected men's knowledge, attitudes and perceptions towards the DVR, which in turn impacted on their willingness to allow their partners to use it. Above all, men wanted to be involved in the decision- making process about the use of the DVR. All the men were happy that there was a new HIV prevention option in the pipeline and were not concerned about the degree of effectiveness, saying it was better than nothing.: The use of the DVR in an environment where men expect to make decisions about sex on behalf of women may affect its usage and success. Given this context, women may not always be able to independently choose to use it. If the DVR is approved and rolled out, increased sensitisation of men about it will be critical to ensure its uptake.
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http://dx.doi.org/10.2989/16085906.2020.1866043DOI Listing
March 2021

Online mis/disinformation and vaccine hesitancy in the era of COVID-19: Why we need an eHealth literacy revolution.

Hum Vaccin Immunother 2021 Feb 24:1-3. Epub 2021 Feb 24.

Inserm Cic 1417, F-crin, I Reivac; Assistance Publique- Hôpitaux de Paris, Hôpital Cochin, Paris, France.

The quality of online health information is cause for concern in general, and the spread of mis/disinformation on the benefits and risks of vaccines has certainly been fueling vaccine hesitancy. In the wake of the COVID-19 pandemic, we have entered an era of unprecedented "infodemic." There has never been a more urgent time to address the long-standing question of how to overcome the deleterious influence of exposure to online mis/disinformation on vaccine uptake. eHealth literacy, a skill set including media literacy, is key to navigating the web in search for health information and processing the one encountered through social media. Studies assessing the impact of increasing eHealth literacy on behavioral attitudes and health outcomes in the general population are relatively scarce to date. Yet for many reasons, leveraging eHealth literacy skills, and more specifically, media literacy, could be of great value to help mitigate the detrimental effects of erroneous information on vaccination decision-making. In this paper, we make the case that eHealth and media literacies should be viewed as fundamental skills that have the potential to empower citizens to better recognize online mis/disinformation and make informed decisions about vaccination as any other health matters.
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http://dx.doi.org/10.1080/21645515.2021.1874218DOI Listing
February 2021

Clinical features and natural history of the first 2073 suspected COVID-19 cases in the Corona São Caetano primary care programme: a prospective cohort study.

BMJ Open 2021 01 12;11(1):e042745. Epub 2021 Jan 12.

Instituto de Medicina Tropical (LIM-52, LIM-46, LIM-49) and Departamento de Moléstias Infecciosas e Parasitarias, Universidade de São Paulo, São Paulo, Brazil.

Background: Despite most cases not requiring hospital care, there are limited community-based clinical data on COVID-19.

Methods: The Corona São Caetano programme is a primary care initiative providing care to all residents with COVID-19 in São Caetano do Sul, Brazil. It was designed to capture standardised clinical data on community COVID-19 cases. After triage of potentially severe cases, consecutive patients presenting to a multimedia screening platform between 13 April and 13 May 2020 were tested at home with SARS-CoV-2 reverse transcriptase (RT) PCR; positive patients were followed up for 14 days with phone calls every 2 days. RT-PCR-negative patients were offered additional SARS-CoV-2 serology testing to establish their infection status. We describe the clinical, virological and natural history features of this prospective population-based cohort.

Findings: Of 2073 suspected COVID-19 cases, 1583 (76.4%) were tested by RT-PCR, of whom 444 (28.0%, 95% CI 25.9 to 30.3) were positive; 604/1136 (53%) RT-PCR-negative patients underwent serology, of whom 52 (8.6%) tested SARS-CoV-2 seropositive. The most common symptoms of confirmed COVID-19 were cough, fatigue, myalgia and headache; whereas self-reported fever (OR 3.0, 95% CI 2.4 to 3.9), anosmia (OR 3.3, 95% CI 2.6 to 4.4) and ageusia (OR 2.9, 95% CI 2.3 to 3.8) were most strongly associated with a positive COVID-19 diagnosis by RT-PCR or serology. RT-PCR cycle thresholds were lower in men, older patients, those with fever and arthralgia and closer to symptom onset. The rates of hospitalisation and death among 444 RT-PCR-positive cases were 6.7% and 0.7%, respectively, with older age and obesity more frequent in the hospitalised group.

Conclusion: COVID-19 presents in a similar way to other mild community-acquired respiratory diseases, but the presence of fever, anosmia and ageusia can assist the specific diagnosis. Most patients recovered without requiring hospitalisation with a low fatality rate compared with other hospital-based studies.
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http://dx.doi.org/10.1136/bmjopen-2020-042745DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7805372PMC
January 2021

A dose-reduction HPV vaccine immunobridging trial of two HPV vaccines among adolescent girls in Tanzania (the DoRIS trial) - Study protocol for a randomised controlled trial.

Contemp Clin Trials 2021 02 6;101:106266. Epub 2021 Jan 6.

Clinical Research Department, London School of Hygiene and Tropical Medicine, Keppel Street, London, UK; Mwanza Intervention Trials Unit, National Institute for Medical Research, Mwanza, Tanzania.

Background: Human papillomavirus (HPV) infection is the primary cause of cervical cancer. In 2018, the World Health Organization (WHO) Director General announced his commitment to eliminate cervical cancer, with HPV vaccination as a priority. However, the costs of setting up a multi-dose HPV vaccination programme remain a barrier to its introduction.

Methods/design: We are conducting a randomised-controlled trial of reduced dose schedules of HPV vaccine in Tanzania to establish whether a single dose produces immune responses that will be effective in preventing cervical cancer. 930 girls aged 9-14 years in Mwanza, Tanzania, were randomised to one of 6 arms, comprising 3 different dose schedules of the 2-valent (Cervarix) and 9-valent (Gardasil-9) HPV vaccines: 3 doses; 2 doses given 6 months apart; or a single dose. All participants will be followed for 36 months; those in the 1 and 2 dose arms will be followed for 60 months. Trial outcomes focus on vaccine immune responses including HPV 16/18-specific antibody levels, antibody avidity, and memory B cell responses. Results will be immunobridged to historical cohorts of girls and young women in whom efficacy has been demonstrated.

Discussion: This is the first randomised trial of the single dose HPV vaccine schedule in the target age group. The trial will allow us to examine the quality and durability of immune responses of reduced dose schedules in a population with high burden of malaria and other infections that may affect vaccine immune responses. Initial results (24 months) are expected to be published in early 2021.
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http://dx.doi.org/10.1016/j.cct.2021.106266DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7970022PMC
February 2021

Performance of the Swede score to predict cervical intraepithelial neoplasia in women with HIV-1 in Johannesburg, South Africa.

Int J Gynaecol Obstet 2021 Feb 22;152(2):188-195. Epub 2020 Oct 22.

Department of Obstetrics and Gynecology, Chris Hani Baragwanath Academic Hospital, Johannesburg, South Africa.

Objective: To evaluate the performance of the Swede score to detect cervical intraepithelial neoplasia (CIN) in women with HIV-1 in Johannesburg, South Africa.

Methods: A cross-sectional study using secondary data analysis from the HPV in Africa Research Partnership (HARP) study that compared the performance of three different screening tests to detect CIN. Colposcopy was performed on any woman who screened positive and findings were recorded using the Swede score. A biopsy of any lesion and a four-quadrant biopsy was taken. The score was evaluated against a histological diagnosis of >CIN1. The sensistivity, specificity, PPV and NPV for each score was calculated.

Results: Median age and CD4+ count of the 576 women eligible from the Johannesburg cohort was 34 years (IQR, 30-39) and 427 cells/mm (IQR, 323-579), respectively. Almost two-thirds (64%) were on ART and about 21% had CIN 2+ on histology. A Swede score of 5 or greater had the best combination of sensitivity and specificity for CIN 2+ with an AUC of 0.72 (95% CI, 0.68-0.76) corresponding to a sensitivity of 72.1 (95% CI, 63.5-79.6) and specificity of 71.8 (95% CI, 67.4-75.9).

Conclusion: The Swede score can assist in determining whether women with HIV/AIDS should have treatment at the first colposcopy visit versus those who may be followed up, thereby individualizing treatment.
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http://dx.doi.org/10.1002/ijgo.13392DOI Listing
February 2021

Prevalence and determinants of genital among school-going, sexually experienced adolescents in urban and rural Indigenous regions of Panama.

Sex Transm Infect 2021 Jun 28;97(4):304-311. Epub 2020 Aug 28.

Dirección General, Gorgas Memorial Institute for Health Studies, Panama City, Panama.

Objectives: To determine the prevalence and risk factors of genital (CT) among school-going sexually experienced male and female adolescents in Panama.

Methods: We conducted two multisite cross-sectional studies using two-stage cluster sampling to select adolescents aged 14-19 years attending urban public high schools (URB) in Panama City, San Miguelito, Colón and Panama Oeste from 2015 to 2018, and in the rural Indigenous Comarca Ngäbe-Buglé (CNB) from July-November 2018. CT testing was performed by real-time PCR on urine samples. Random-effects logistic regression accounting for sample clustering was used to identify risk factors.

Results: We enrolled 3166 participants (54.3% females), median age 17 years (IQR: 15.9-18.1), with no difference by sex. Sexual experience was reported by 1954 (61.7%) participants. Combined CT prevalence was 15.8% (95% CI: 14.2 to 17.4), with no significant differences by region (URB=16.5%, 95% CI: 14.7% to 18.6%; CNB=13.6%, 95% CI: 10.9% to 16.8%; p=0.12). In an age-and-region-adjusted analysis, CT prevalence was higher among female participants compared with males (21.6% vs 9.1%, adjusted OR (AOR)=2.87, 95% CI: 1.62 to 5.10). Among sexually experienced females, CT prevalence was higher among those who reported ≥3 lifetime sex partners compared with one partner (33.5% vs 15.3%, AOR=2.20, 95% CI: 1.09 to 4.07); and among those reporting at least one pregnancy compared with nulligravidae participants (30.9% vs 13.8%, AOR=1.89, 95% CI: 1.05 to 3.43). In unadjusted analyses among males, CT was associated with older age (11.5% among those aged 18-19 years vs 3.4% among those aged 14-15 years, OR=3.69, 95% CI: 1.10 to 12.33).

Conclusions: We report high CT prevalence among sexually experienced, school-going adolescents in Panama. Female adolescents, particularly those with multiple sex partners and a history of pregnancy, were at highest risk. Adolescent-targeted CT screening should be implemented in Panama. Additionally, evidence-based comprehensive sexuality education will be imperative.
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http://dx.doi.org/10.1136/sextrans-2019-054395DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8165139PMC
June 2021

Epidemiological and clinical characteristics of the COVID-19 epidemic in Brazil.

Nat Hum Behav 2020 08 31;4(8):856-865. Epub 2020 Jul 31.

Secretariat of Health Surveillance, Department of Immunization and Communicable Diseases, Brazilian Ministry of Health, Brasília, Brazil.

The first case of COVID-19 was detected in Brazil on 25 February 2020. We report and contextualize epidemiological, demographic and clinical findings for COVID-19 cases during the first 3 months of the epidemic. By 31 May 2020, 514,200 COVID-19 cases, including 29,314 deaths, had been reported in 75.3% (4,196 of 5,570) of municipalities across all five administrative regions of Brazil. The R value for Brazil was estimated at 3.1 (95% Bayesian credible interval = 2.4-5.5), with a higher median but overlapping credible intervals compared with some other seriously affected countries. A positive association between higher per-capita income and COVID-19 diagnosis was identified. Furthermore, the severe acute respiratory infection cases with unknown aetiology were associated with lower per-capita income. Co-circulation of six respiratory viruses was detected but at very low levels. These findings provide a comprehensive description of the ongoing COVID-19 epidemic in Brazil and may help to guide subsequent measures to control virus transmission.
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http://dx.doi.org/10.1038/s41562-020-0928-4DOI Listing
August 2020

Design and content validation of a survey questionnaire assessing the determinants of human papillomavirus (HPV) vaccine hesitancy in France: A reactive Delphi study.

Vaccine 2020 09 25;38(39):6127-6140. Epub 2020 Jul 25.

INSERM, Sorbonne Université, Institut Pierre Louis d'Épidémiologie et de Santé Publique, Paris, France.

Introduction: This study aimed to develop and undertake a preliminary validation of a French Survey Questionnaire for the Determinants of HPV Vaccine Hesitancy (FSQD-HPVH).

Methods: We undertook an electronic-based Delphi consultation among a panel of Francophone experts in two rounds. Round 1 consisted of the assessment of a structured questionnaire comprising of three parts ((i) Contextual influences, (ii) Individual and group influences, and (iii) Vaccine/vaccination-specific issues), in line with the WHO Strategic Advisory Group of Experts (SAGE) Vaccine Hesitancy (VH) Model of Determinants. Items included in this questionnaire were based on a literature review. Definitions of the factors included in the SAGE model were provided in the questionnaire. The panel of experts was asked to score each item using a 3-point Likert scale, in which 1 meant "Essential", 2 "Useful but not essential", and 3 "Not necessary". The panel was also invited to comment on the clarity/comprehension of the questions and suggest reformulations/additional items. Lawshe's Content Validity Ratio (CVR) was computed to assess the level of consensus for each statement. Only items upon which agreement was not reached in Round 1 (CVR < 0.6) and newly proposed items were submitted for evaluation in Round 2, using the same procedure.

Results: Fifteen experts completed the two rounds. Of 83 items evaluated in Round 1, 35 (42%) had a CVR ≥ 0.6 and were accepted without modification. In Round 2, 66 items were submitted to the same panel and consensus was reached for 22 (33%) items using the threshold of 0.6. The final FSQD-HPVH version includes 57 items.

Conclusion: This study developed a survey instrument for the evaluation of HPV VH in France with good content validity. It will be used to assess the determinants of HPV VH, the first step towards an evidence-based approach to improving HPV vaccination rates in France.
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http://dx.doi.org/10.1016/j.vaccine.2020.07.027DOI Listing
September 2020

Pathobionts in the Vaginal Microbiota: Individual Participant Data Meta-Analysis of Three Sequencing Studies.

Front Cell Infect Microbiol 2020 15;10:129. Epub 2020 Apr 15.

London School of Hygiene and Tropical Medicine, London, United Kingdom.

Sequencing studies have shown that optimal vaginal microbiota (VMB) are lactobacilli-dominated and that anaerobes associated with bacterial vaginosis (BV-anaerobes) are commonly present. However, they overlooked a less prevalent but more pathogenic group of vaginal bacteria: the pathobionts that cause maternal and neonatal infections and pelvic inflammatory disease. We conducted an individual participant data meta-analysis of three VMB sequencing studies that included diverse groups of women in Rwanda, South Africa, and the Netherlands (2,044 samples from 1,163 women in total). We identified 40 pathobiont taxa but only six were non-minority taxa (at least 1% relative abundance in at least one sample) in all studies: (54% of pathobionts reads), and . When all pathobionts were combined into one bacterial group, the VMB of 17% of women contained a relative abundance of at least 1%. We found a significant negative correlation between relative abundances (ρ = -0.9234), but not estimated concentrations ( = 0.0031), of lactobacilli and BV-anaerobes; and a significant positive correlation between estimated concentrations of pathobionts and BV-anaerobes ( = 0.1938) but not between pathobionts and lactobacilli ( = 0.0436; although lactobacilli declined non-significantly with increasing pathobionts proportions). VMB sequencing data were also classified into mutually exclusive VMB types. The overall mean bacterial load of the ≥20% pathobionts VMB type (5.85 log cells/μl) was similar to those of the three lactobacilli-dominated VMB types (means 5.13-5.83 log cells/μl) but lower than those of the four anaerobic dysbiosis VMB types (means 6.11-6.87 log cells/μl). These results suggest that pathobionts co-occur with both lactobacilli and BV-anaerobes and do not expand as much as BV-anaerobes do in a dysbiotic situation. Pathobionts detection/levels were increased in samples with a Nugent score of 4-6 in both studies that conducted Nugent-scoring. Having pathobionts was positively associated with young age, non-Dutch origin, hormonal contraceptive use, smoking, antibiotic use in the 14 days prior to sampling, HIV status, and the presence of sexually transmitted pathogens, in at least one but not all studies; inconsistently associated with sexual risk-taking and unusual vaginal discharge reporting; and not associated with vaginal yeasts detection by microscopy. We recommend that future VMB studies quantify common vaginal pathobiont genera.
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http://dx.doi.org/10.3389/fcimb.2020.00129DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7174631PMC
April 2020

Feasibility of establishing an HIV vaccine preparedness cohort in a population of the Uganda Police Force: Lessons learnt from a prospective study.

PLoS One 2020 17;15(4):e0231640. Epub 2020 Apr 17.

Medical Research Council/Uganda Virus Research Institute Uganda Research Unit & London School of Hygiene and Tropical Medicine (MRC/UVRI & LSHTM) Uganda Research Unit, Entebbe, Uganda.

Background: Members of uniformed armed forces are considered to be at high risk for HIV infection and have been proposed as suitable candidates for participation in HIV intervention studies. We report on the feasibility of recruitment and follow up of individuals from the community of the Uganda Police Force (UPF) for an HIV vaccine preparedness study.

Methods: HIV-negative volunteers aged 18-49 years, were identified from UPF facilities situated in Kampala and Wakiso districts through community HIV counselling and testing. Potential volunteers were referred to the study clinic for screening, enrolment and quarterly visits for one year. HIV incidence, retention rates were estimated and expressed as cases per 100 person years of observation (PYO). Rate ratios were used to determine factors associated with retention using Poisson regression models.

Results: We screened 560 to enroll 500 volunteers between November 2015 and May 2016. One HIV seroconversion occurred among 431 PYO, for an incidence rate of 0.23/100 PYO (95% confidence interval [CI]: 0.03-1.64). Overall, retention rate was 87% at one year, and this was independently associated with residence duration (compared to <1 year, 1 to 5 years adjusted rate ratio (aRR) = 1.19, 95%CI: 1.00-1.44); and >5 years aRR = 1.34, 95%CI: 0.95-1.37); absence of genital discharge in the last 3 months (aRR = 1.97, 95% CI: 1.38-2.83, absence of genital ulcers (aRR = 1.90, 95%CI: 1.26-2.87, reporting of new sexual partner in the last month (aRR = 0.57, 95%CI: 0.45-0.71, being away from home for more than two nights (aRR = 1.27, 95%CI: 1.04-1.56, compared to those who had not travelled) and absence of knowledge on HIV prevention (aRR = 2.67, 95%CI: 1.62-4.39).

Conclusions: While our study demonstrates the feasibility of recruiting and retaining individuals from the UPF for HIV research, we did observe lower than anticipated HIV incidence, perhaps because individuals at lower risk of HIV infection may have been the first to come forward to participate or participants followed HIV risk reduction measures. Our findings suggest lessons for recruitment of populations at high risk of HIV infection.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0231640PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7164600PMC
July 2020

Gonorrhoea: tackling the global epidemic in the era of rising antimicrobial resistance.

Sex Health 2019 09;16(5):397-400

Central Clinical School, Monash University, Melbourne, Vic. 3053, Australia; and Melbourne Sexual Health Centre, Alfred Health, Carlton, Vic. 3053, Australia.

This Special Issue of Sexual Health aims to collate the latest evidence base focussed on understanding the current epidemic and transmission of gonorrhoea, choice of treatment, molecular epidemiology application, concerns about antimicrobial resistance and alternative prevention and control for gonorrhoea.
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http://dx.doi.org/10.1071/SH19121DOI Listing
September 2019

Antiretroviral Therapy and Detection of High-grade Cervical Intraepithelial Neoplasia (CIN2+) at Post-CIN Management Follow-up Among Women Living With Human Immunodeficiency Virus: A Systematic Review and Meta-Analysis.

Clin Infect Dis 2020 12;71(10):e540-e548

Clinical Research Department, London School of Hygiene and Tropical Medicine, London, United Kingdom.

Background: We evaluated the association of antiretroviral therapy (ART), CD4+ count and human immunodeficiency virus (HIV) plasma viral load (PVL) on high-grade cervical intraepithelial neoplasia (CIN2+) detection at follow-up after CIN management among women living with HIV (WLHIV).

Methods: Medline, Embase, Global Health, and PubMed were searched from 1 January 1996 to 15 January 2020. Eligible studies investigated the association of ART, CD4+ count, or HIV PVL on histology-confirmed CIN2+ detection at follow-up. Summary estimates were obtained using random-effects meta-analyses; heterogeneity was examined using I2 statistic. PROSPERO registration: CRD42018115631.

Results: Eight studies representing 9 populations were identified, including 1452 WLHIV followed between 6 and 33 months post-CIN management. Pooled data from 8 populations (n = 1408) suggested weak evidence of a decreased risk of CIN2+ detection at follow-up among ART users compared to ART-naive women (crude odds ratio [cOR] = 0.70, 95% confidence interval [CI]: .36-1.36; I2 = 64.5%, P = .006; adjusted risk ratio [aRR] from 3 studies = 0.66, 95% CI: .20-2.24; I2 = 78.7%, P = .009). A significant association was observed in high-income countries (cOR = 0.24, 95% CI: .13-.45; I2 = 0.0%, P = .77) but not in low and middle-income countries (cOR = 1.13, 95% CI: .67-1.92; I2 = 18.8%, P = .30).In 3 populations, ART users with HIV PVL <50 copies/ml were less likely to have CIN2+ detection at follow-up (vs ≥50 copies/mL: cOR = 0.55, 95% CI: .32-.94; I2 = 0.0%, P = .23).There was weak evidence of decreased CIN2+ detection at follow-up among WLHIV with higher contemporary CD4+ cell counts (≥200 cells/µL vs <200 cells/µL [cOR = 0.36, 95% CI: .04-3.13; I2 = 81.3%, P = .021]) and significant evidence among women with a higher nadir CD4+ count (≥350 cells/µl vs <200 cells/µl [adjusted hazard ratio [aHR] = 0.35, 95% CI: .15-.84; I2 = 0%, P = .64]).

Conclusion: ART may reduce the risk of CIN2+ detection at follow-up; this effect is most likely enhanced by a combination of adequate HIV control and excisional CIN treatment. Our findings support recommendations of early ART and the integration of CIN2+ screening and management into HIV care.
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http://dx.doi.org/10.1093/cid/ciaa238DOI Listing
December 2020

Association of antiretroviral therapy with anal high-risk human papillomavirus, anal intraepithelial neoplasia, and anal cancer in people living with HIV: a systematic review and meta-analysis.

Lancet HIV 2020 04 25;7(4):e262-e278. Epub 2020 Feb 25.

Clinical Research Department, London School of Hygiene & Tropical Medicine, London, UK.

Background: The effect of antiretroviral therapy (ART) on the natural history of anal high-risk HPV and anal lesion progression is not well established. We reviewed the association of ART and other HIV-related factors on anal HPV infection, anal intraepithelial neoplasia (AIN), and anal cancer among people living with HIV.

Methods: For this systematic review and meta-analysis, we searched MEDLINE and EMBASE for studies published between Jan 1, 1996, and Oct 30, 2019, that reported the association of HIV-related exposures (ART or highly active ART [HAART], HIV-RNA plasma viral load [PVL], and nadir or current CD4 cell count) with outcomes of anal high-risk HPV prevalence, incidence, and persistence; prevalence, incidence, progression, or regression of anal histological and cytological abnormalities; and anal cancer incidence. Effect estimates were extracted whenever available; otherwise, they were calculated from raw data. We assessed the risk of bias of included studies using the Newcastle-Ottawa scale, and random-effects meta-analyses were done to examine heterogeneity using the I statistic. This study is registered on the PROSPERO database, CRD42018007271.

Findings: We identified 6777 studies, of which 5377 were excluded before full-text review. 122 studies providing estimates for 130 distinct populations matched the inclusion criteria. The populations comprised 417 006 people living with HIV (women, men who have sex with men, and men who have sex with women). 41 (32%) population estimates were not stratified by sex or sexual orientation. People living with HIV receiving ART had 35% lower high-risk HPV prevalence than ART-naive people (crude odds ratio [OR] 0·65, 95% CI 0·54-0·79; I 12·1%, p=0·31) in 18 studies, and prolonged ART use was associated with a 10% reduction per year in high-risk HPV prevalence in two studies (adjusted OR 0·90, 0·85-0·95; I 0%, p=0·88). People living with HIV with undetectable PVL had lower HSIL-AIN2+ prevalence than those with detectable PVL (crude OR 0·84, 0·72-0·98; I 0%, p=0·80) in 16 studies, particularly if sustained for more than 1 year (crude OR 0·62, 0·47-0·81; I 0%, p=0·51). ART was not associated with anal cancer incidence when adjusted for years living with HIV in three studies (adjusted hazard ratio [HR] 1·11, 95% CI 0·68-1·80; I 0%, p=0·57), but ART users with sustained undetectable HIV PVL had 44% lower risk of anal cancer than those without (adjusted HR 0·56, 0·44-0·70; I 0%, p=0·94) and for each increase in nadir CD4 cell counts of 100 cells per μL, there was a 40% decrease in anal cancer incidence (crude HR 0·60, 0·46-0·78; I 21·7%, p=0·26).

Interpretation: Effective ART use and early initiation at high nadir CD4 counts might reduce anal high-risk HPV infection and anal cancer risk. Although most studies were cross-sectional in design and few adjusted for potential confounders, this analysis provides comprehensive estimates of the effect of ART and HIV-related factors on the natural history of anal HPV-related disease in people living with HIV.

Funding: EU Marie Skłodowska-Curie Actions programme.
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http://dx.doi.org/10.1016/S2352-3018(19)30434-5DOI Listing
April 2020

Human Papillomavirus Seroprevalence and Seroconversion Among Men Living With HIV: Cohort Study in South Africa.

J Acquir Immune Defic Syndr 2020 06;84(2):141-148

Wits RHI, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa.

Background: Men living with HIV (MLHIV) have a high burden of human papillomavirus (HPV)-related cancer. Understanding serological dynamics of HPV in men can guide decisions on introducing HPV vaccination and monitoring impact. We determined HPV seroprevalence and evaluated factors associated with HPV seroconversion among MLHIV in Johannesburg, South Africa.

Methods: We enrolled 304 sexually active MLHIV 18 years and older and collected sociobehavioral data, blood samples (CD4 counts, HIV-1 plasma viral load, and HPV serology), and genital and anal swabs [HPV DNA and HPV viral load (VL)] at enrollment and 6-monthly for up to 18 months. Antibodies to 15 HPV types were measured using HPV pseudovirions. Generalized estimating equations were used to evaluate correlates of HPV seroconversion.

Results: Median age at enrollment was 38 years (IQR: 22-59), 25% reported >1 sexual partner in the past 3 months, and 5% reported ever having sex with other men. Most participants (65%) were on antiretroviral therapy (ART), with median CD4 count of 445 cells/µL (IQR: 328-567). Seroprevalence for any HPV type was 66% (199/303). Baseline seropositivity for any bivalent (16/18), quadrivalent (6/11/16/18), and nonavalent (6/11/16/18/31/33/45/52/58) vaccine types was 19%, 37%, and 60%, respectively. At 18 months, type-specific seroconversion among 59 men whose genital samples were HPV DNA positive but seronegative for the same type at enrollment was 22% (13/59). Type-specific seroconversion was higher among men with detectable HIV plasma viral load (adjusted odds ratio = 2.78, 95% CI: 1.12 to 6.77) and high HPV VL (adjusted odds ratio = 3.32, 95% CI: 1.42 to 7.74).

Conclusions: Seropositivity and exposure to nonavalent HPV types were high among MLHIV. HPV vaccination of boys before they become sexually active could reduce the burden of HPV infection among this at-risk population.
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http://dx.doi.org/10.1097/QAI.0000000000002328DOI Listing
June 2020

Study protocol for the multicentre cohorts of Zika virus infection in pregnant women, infants, and acute clinical cases in Latin America and the Caribbean: the ZIKAlliance consortium.

BMC Infect Dis 2019 Dec 26;19(1):1081. Epub 2019 Dec 26.

Aix-Marseille University, Marseille, France.

Background: The European Commission (EC) Horizon 2020 (H2020)-funded ZIKAlliance Consortium designed a multicentre study including pregnant women (PW), children (CH) and natural history (NH) cohorts. Clinical sites were selected over a wide geographic range within Latin America and the Caribbean, taking into account the dynamic course of the ZIKV epidemic.

Methods: Recruitment to the PW cohort will take place in antenatal care clinics. PW will be enrolled regardless of symptoms and followed over the course of pregnancy, approximately every 4 weeks. PW will be revisited at delivery (or after miscarriage/abortion) to assess birth outcomes, including microcephaly and other congenital abnormalities according to the evolving definition of congenital Zika syndrome (CZS). After birth, children will be followed for 2 years in the CH cohort. Follow-up visits are scheduled at ages 1-3, 4-6, 12, and 24 months to assess neurocognitive and developmental milestones. In addition, a NH cohort for the characterization of symptomatic rash/fever illness was designed, including follow-up to capture persisting health problems. Blood, urine, and other biological materials will be collected, and tested for ZIKV and other relevant arboviral diseases (dengue, chikungunya, yellow fever) using RT-PCR or serological methods. A virtual, decentralized biobank will be created. Reciprocal clinical monitoring has been established between partner sites. Substudies of ZIKV seroprevalence, transmission clustering, disabilities and health economics, viral kinetics, the potential role of antibody enhancement, and co-infections will be linked to the cohort studies.

Discussion: Results of these large cohort studies will provide better risk estimates for birth defects and other developmental abnormalities associated with ZIKV infection including possible co-factors for the variability of risk estimates between other countries and regions. Additional outcomes include incidence and transmission estimates of ZIKV during and after pregnancy, characterization of short and long-term clinical course following infection and viral kinetics of ZIKV. STUDY REGISTRATIONS: clinicaltrials.gov NCT03188731 (PW cohort), June 15, 2017; clinicaltrials.gov NCT03393286 (CH cohort), January 8, 2018; clinicaltrials.gov NCT03204409 (NH cohort), July 2, 2017.
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http://dx.doi.org/10.1186/s12879-019-4685-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6933915PMC
December 2019

Performance of Zika Assays in the Context of Toxoplasma gondii, Parvovirus B19, Rubella Virus, and Cytomegalovirus (TORCH) Diagnostic Assays.

Clin Microbiol Rev 2019 12 11;33(1). Epub 2019 Dec 11.

Erasmus Medical Centre, Department of Viroscience, Rotterdam, The Netherlands

Infections during pregnancy that may cause congenital abnormalities have been recognized for decades, but their diagnosis is challenging. This was again illustrated with the emergence of Zika virus (ZIKV), highlighting the inherent difficulties in estimating the extent of pre- and postnatal ZIKV complications because of the difficulties in establishing definitive diagnoses. We reviewed the epidemiology, infection kinetics, and diagnostic methods used for , parvovirus B19, rubella virus, and cytomegalovirus (TORCH) infections and compared the results with current knowledge of ZIKV diagnostic assays to provide a basis for the inclusion of ZIKV in the TORCH complex evaluations. Similarities between TORCH pathogens and ZIKV support inclusion of ZIKV as an emerging TORCH infection. Our review evaluates the diagnostic performance of various TORCH diagnostic assays for maternal screening, fetal screening, and neonatal screening. We show that the sensitivity, specificity, and positive and negative predictive value of TORCH complex pathogens are widely variable, stressing the importance of confirmatory testing and the need for novel techniques for earlier and accurate diagnosis of maternal and congenital infections. In this context it is also important to acknowledge different needs and access to care for different geographic and resource settings.
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http://dx.doi.org/10.1128/CMR.00130-18DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6927310PMC
December 2019

Global Epidemiologic Characteristics of Sexually Transmitted Infections Among Individuals Using Preexposure Prophylaxis for the Prevention of HIV Infection: A Systematic Review and Meta-analysis.

JAMA Netw Open 2019 12 2;2(12):e1917134. Epub 2019 Dec 2.

Department of Clinical Research, London School of Hygiene and Tropical Medicine, London, United Kingdom.

Importance: Despite a global increase in sexually transmitted infections (STIs), there is limited focus and investment in STI management within HIV programs, in which risks for STIs are likely to be elevated.

Objective: To estimate the prevalence of STIs at initiation of HIV preexposure prophylaxis (PrEP; emtricitabine and tenofovir disoproxil fumarate) and the incidence of STIs during PrEP use.

Data Sources: Nine databases were searched up to November 20, 2018, without language restrictions. The implementers of PrEP were also approached for additional unpublished data.

Study Selection: Studies reporting STI prevalence and/or incidence among PrEP users were included.

Data Extraction And Synthesis: Data were extracted independently by at least 2 reviewers. The methodological quality of studies was assessed using the Joanna Briggs Institute critical assessment tool for prevalence and incidence studies. Random-effects meta-analysis was performed.

Main Outcomes And Measures: Pooled STI prevalence (ie, within 3 months of PrEP initiation) and STI incidence (ie, during PrEP use, after 3 months).

Results: Of the 3325 articles identified, 88 were included (71 published and 17 unpublished). Data came from 26 countries; 62 studies (70%) were from high-income countries, and 58 studies (66%) were from programs only for men who have sex with men. In studies reporting a composite outcome of chlamydia, gonorrhea, and early syphilis, the pooled prevalence was 23.9% (95% CI, 18.6%-29.6%) before starting PrEP. The prevalence of the STI pathogen by anatomical site showed that prevalence was highest in the anorectum (chlamydia, 8.5% [95% CI, 6.3%-11.0%]; gonorrhea, 9.3% [95% CI, 4.7%-15.2%]) compared with genital sites (chlamydia, 4.0% [95% CI, 2.0%-6.6%]; gonorrhea, 2.1% [95% CI, 0.9%-3.7%]) and oropharyngeal sites (chlamydia, 2.4% [95% CI, 0.9%-4.5%]; gonorrhea, 4.9% [95% CI, 1.9%-9.1%]). The pooled incidence of studies reporting the composite outcome of chlamydia, gonorrhea, and early syphilis was 72.2 per 100 person-years (95% CI, 60.5-86.2 per 100 person-years).

Conclusions And Relevance: Given the high burden of STIs among individuals initiating PrEP as well as persistent users of PrEP, this study highlights the need for active integration of HIV and STI services for an at-risk and underserved population.
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http://dx.doi.org/10.1001/jamanetworkopen.2019.17134DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6991203PMC
December 2019

Prevalent, persistent anal HPV infection and squamous intraepithelial lesions: Findings from a cohort of men living with HIV in South Africa.

PLoS One 2019 5;14(12):e0225571. Epub 2019 Dec 5.

Wits RHI, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa.

Objective: To estimate the prevalence, incidence and persistence of anal HPV infection and squamous intra-epithelial lesions (SILs) among men living with HIV (MLHIV), and determine their risk factors.

Methods: We enrolled MLHIV ≥18 years, who attended 6-monthly visits for 18 months. Socio-behavioural data were collected by questionnaire. Clinicians collected blood sample (CD4+ count and HIV plasma viral load), anal swabs (HPV DNA testing) and anal smears (Bethesda classification) at each visit. HPV DNA testing and classification of smears were done at enrolment and last follow-up visit (two time points). Factors associated with persistent anal HPV infection and SILs were evaluated with generalized estimating equations logistic regression and standard logistic regression respectively.

Results: Mean age of 304 participants was 38 (Standard Deviation, 8) years; 25% reported >1 sexual partner in the past 3 months. Only 5% reported ever having sex with other men. Most (65%) participants were taking antiretroviral treatment (ART), with a median CD4+ count of 445 cells/μL (IQR, 328-567). Prevalence of any-HPV infection at enrolment was 39% (88/227). In total, 226 men had anal HPV DNA results at both enrolment and final visits. Persistence of any-anal HPV infection among 80 men who had infection at enrolment was 26% (21/80). Any persistent anal HPV infection was more frequent among MLHIV with low CD4+ count (<200 vs. >500 cells/μL; aOR = 6.58; 95%CI: 2.41-17.94). Prevalence of anal SILs at enrolment was 49% (118/242) while incidence of SILs among MLHIV who had no anal dysplasia at enrolment was 27% (34/124). Of the 118 men who had anal dysplasia at enrolment, 15% had regressed and 38% persisted by month 18. Persistent anal HPV infection was associated with persistent SILs (aOR = 2.95; 95%CI: 1.08-10.89). ART status or duration at enrolment were not associated with persistent anal HPV infection or persistent SILs during follow-up.

Conclusion: In spite of a high prevalence of anal HPV, HIV-positive heterosexual men have a low burden of anal HPV related disease. HPV vaccine and effective ART with immunological reconstitution could reduce this burden of infection.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0225571PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6894774PMC
April 2020

Clinical Characteristics of Mycoplasma genitalium and the Usefulness of Syndromic Management Among Women Living With Human Immunodeficiency Virus.

Sex Transm Dis 2019 12;46(12):801-804

From the Clinical Research Department, Faculty of Infectious and Tropical Diseases, London School of Hygiene & Tropical Medicine, London, United Kingdom.

We report the clinical symptoms and examination findings of Mycoplasma genitalium (MG) in women living with human immunodeficiency virus in South Africa. If we relied on syndromic management alone to treat MG, only 15 of 46 MG-infected women would have received. appropriate treatment: sensitivity of 32.6% (95% confidence interval, 19.5-48.0) and specificity of 67.4% (95% confidence interval, 63.4-71.2).
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http://dx.doi.org/10.1097/OLQ.0000000000001054DOI Listing
December 2019

Knowledge and experience of a cohort of HIV-positive and HIV-negative Ghanaian women after undergoing human papillomavirus and cervical cancer screening.

BMC Womens Health 2019 10 23;19(1):123. Epub 2019 Oct 23.

Department of Clinical Research, Faculty of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London, UK.

Background: Cervical cancer is the most common cancer in women in Ghana, but knowledge and experience of women who have had cervical screening is under-evaluated. This study examined knowledge and understanding of HPV and cervical cancer and evaluated experiences of screening in a cohort of women of mixed HIV status.

Methods: This was a mixed methods study using questionnaires and focus group discussions, with a knowledge score constructed from the questionnaire. HIV-positive and HIV-negative women were recruited from a larger cervical screening study in Ghana and were interviewed 6 months after receiving screening. Quantitative data was analyzed and triangulated with qualitative data following thematic analysis using the framework approach.

Results: A total of 131 women were included (HIV-positive, n = 60). Over 80% of participants had a knowledge score deemed adequate. There was no difference between HIV-status groups in overall knowledge scores (p = 0.1), but variation was seen in individual knowledge items. HIV-positive women were more likely to correctly identify HPV as being sexually-transmitted (p = 0.05), and HIV negative women to correctly identify the stages in developing cervical cancer (p = < 0.0001). HIV-positive women mostly described acquisition of HPV in stigmatising terms. The early asymptomatic phase of cervical cancer made it difficult for women to define "what" cancer was versus "what" HPV infection was. All women expressed that they found it difficult waiting for their screening results but that receiving information and counselling from health workers alleviated anxiety.

Conclusions: Knowledge of women who had participated in a cervical screening study was good, but specific misconceptions existed. HIV-positive women had similar levels of knowledge to HIV-negative, but different misconceptions. Women expressed generally positive views about screening, but did experience distress. A standardized education tool explaining cervical screening and relevance specifically of HPV-DNA results in Ghana should be developed, taking into consideration the different needs of HIV-positive women.
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http://dx.doi.org/10.1186/s12905-019-0818-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6813105PMC
October 2019

Performance of DNA methylation assays for detection of high-grade cervical intraepithelial neoplasia (CIN2+): a systematic review and meta-analysis.

Br J Cancer 2019 11 16;121(11):954-965. Epub 2019 Oct 16.

Queen Mary University of London, Centre for Cancer Prevention, Wolfson Institute of Preventive Medicine, Barts & the London School of Medicine, London, UK.

Background: To conduct a meta-analysis of performance of DNA methylation in women with high-grade cervical intraepithelial neoplasia (CIN2+).

Methods: Medline and Embase databases were searched for studies of methylation markers versus histological endpoints. Pooled sensitivity, specificity and positive predictive value (PPV) for CIN2+ were derived from bivariate models. Relative sensitivity and specificity for CIN2+ compared to cytology and HPV16/18 genotyping were pooled using random-effects models.

Results: Sixteen thousand three hundred thirty-six women in 43 studies provided data on human genes (CADM1, MAL, MIR-124-2, FAM19A4, POU4F3, EPB41L3, PAX1, SOX1) and HPV16 (L1/L2). Most (81%) studies evaluated methylation assays following a high-risk (HR)-HPV-positive or abnormal cytology result. Pooled CIN2+ and CIN3+ prevalence was 36.7% and 21.5%. For a set specificity of 70%, methylation sensitivity for CIN2+ and CIN3+ were 68.6% (95% CI: 62.9-73.8) and 71.1% (95% CI: 65.7-76.0) and PPV were 53.4% (95% CI: 44.4-62.1) and 35.0% (95% CI: 28.9-41.6). Among HR-HPV+ women, the relative sensitivity of methylation for CIN2+ was 0.81 (95% CI: 0.63-1.04) and 1.22 (95% CI: 1.05-1.42) compared to cytology of atypical squamous cells of undetermined significance, or greater (ASCUS+) and HPV16/18 genotyping, respectively, while relative specificity was 1.25 (95% CI: 0.99-1.59) and 1.03 (95% CI: 0.94-1.13), respectively.

Conclusion: DNA methylation is significantly higher in CIN2+ and CIN3+ compared to ≤CIN1. As triage test, DNA methylation has higher specificity than cytology ASCUS+ and higher sensitivity than HPV16/18 genotyping.
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http://dx.doi.org/10.1038/s41416-019-0593-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6889421PMC
November 2019

High Prevalence of Sexually Transmitted Infections, and High-Risk Sexual Behaviors Among Indigenous Adolescents of the Comarca Ngäbe-Buglé, Panama.

Sex Transm Dis 2019 12;46(12):780-787

London School of Hygiene and Tropical Medicine, United Kingdom.

Background: There is scant information on sexually transmitted infection (STI) prevalence and risk factors among Latin American indigenous populations. We investigated STI prevalence and risk factors among adolescents of the Comarca Ngäbe-Buglé indigenous region of Panama.

Methods: A population-based cross-sectional study was conducted among school-going adolescents aged 14 to 19 years. Eligible consenting participants self-completed a questionnaire and provided blood and urine samples. Female participants provided additional self-administered genital swabs. Seroprevalences of human immunodeficiency virus (HIV), syphilis, hepatitis B (HBsAg, anti-HBc), and herpes simplex virus type 2 (HSV-2) were determined in all participants; genital Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG) by PCR among participants who reported sexual experience or were seropositive for HIV/syphilis/HSV2/HBsAg; high-risk human papillomavirus (HPV) by qualitative DNA assay and bacterial vaginosis (BV) by Gram-stain among female participants. Risk factors were identified by estimating adjusted odds ratios (AOR) using random-effects logistic regression.

Results: We enrolled 700 participants (median age, 17 years [female participants]; 18 years [male participants]) from 20 schools. Sexual experience was reported by 536 participants (76.6%). The HIV/STI prevalences among females and males were: HIV 0.4% and 1.0%, high-titer active syphilis 1.3% and 6.6%, HSV-2 16.1% and 16.1%, HBsAg 1.3% and 1.4%, anti-HBc 3.2% and 1.4%, NG 1.8% and 1.7%, CT 17.5% and 10.7%; among females: BV 42.9% and HPV 33.2%. CT was independently associated with being female (AOR, 2.02; 95% confidence interval [CI], 1.20-3.41); high-titer active syphilis with being male (AOR, 4.51; 95% CI, 1.17-17.40). Bacterial vaginosis was associated with sexual behavior (≥3 lifetime sex partners: AOR, 3.81; 95% CI, 1.29-11.26), HPV with sexual experience (AOR, 4.05; 95% CI, 1.62-10.09).

Conclusions: School-going indigenous adolescents in rural Panama have substantial STI burden. Targeted STI screening is required.
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December 2019

Human papillomavirus infection and cervical dysplasia in HIV-positive women: potential role of the vaginal microbiota.

AIDS 2020 01;34(1):115-125

Institute of Infection and Global Health, University of Liverpool, Liverpool, UK Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands Wits Reproductive Health & HIV Institute, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa London School of Hygiene and Tropical Medicine, London, UK National Health Laboratory Services, Johannesburg, South Africa Pathogenesis and Control of Chronic Infections, INSERM, University of Montpellier, Montpellier, France Centre for Genomic Research, University of Liverpool, Liverpool, UK.

Objectives: To assess the associations between microbiological markers of vaginal dysbiosis and incident/cleared/type-swap/persistent high-risk human papillomavirus (hrHPV) infection; and incident/cured/cleared/persistent high-grade cervical intraepithelial neoplasia (CIN2+) while controlling for persistent hrHPV infection.

Design: Two nested case-control studies (N = 304 and 236) within a prospective cohort of HIV-positive women in Johannesburg, South Africa.

Methods: Participants were examined for hrHPV type (INNO-LiPA), cervical dysplasia (histology), and vaginal microbiota (VMB) composition (V3-V4 Illumina HiSeq 2x300 bp) at baseline and endline, a median of 16 months later.

Results: Women with incident hrHPV compared to those who remained hrHPV-negative were less likely to have an optimal Lactobacillus crispatus or jensenii-dominated VMB type at end-line [relative risk ratio (RRR) 0.125, P = 0.019], but not at baseline. Having different hrHPV types at both visits was associated with multiple anaerobic dysbiosis markers at baseline (e.g. increased bacterial vaginosis-associated anaerobes relative abundance: RRR 3.246, P = 0.026). Compared to women without CIN2+, but with hrHPV at both visits, women with incident CIN2+ had increased Simpson diversity (RRR 7.352, P = 0.028) and nonsignificant trends in other anaerobic dysbiosis markers at end-line but not baseline. These associations persisted after controlling for age, hormonal contraception, and CD4 cell count. Current hormonal contraceptive use (predominantly progestin-only injectables) was associated with increased CIN2+ risk over-and-above persistent hrHPV infection and independent of VMB composition.

Conclusions: hrHPV infection (and/or increased sexual risk-taking) may cause anaerobic vaginal dysbiosis, but a bidirectional relationship is also possible. In this population, dysbiosis did not increase CIN2+ risk, but CIN2+ increased dysbiosis risk. The CIN2+ risk associated with progestin-only injectable use requires further evaluation.
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January 2020