232 results found
Wang L, Ma H, Yiu KCY, et al., 2020, Heterogeneity in testing, diagnosis and outcome in SARS-CoV-2 infection across outbreak settings in the Greater Toronto Area, Canada: an observational study., CMAJ Open, Vol: 8, Pages: E627-E636, ISSN: 2291-0026
BACKGROUND: Congregate settings have been disproportionately affected by coronavirus disease 2019 (COVID-19). Our objective was to compare testing for, diagnosis of and death after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection across 3 settings (residents of long-term care homes, people living in shelters and the rest of the population). METHODS: We conducted a population-based prospective cohort study involving individuals tested for SARS-CoV-2 in the Greater Toronto Area between Jan. 23, 2020, and May 20, 2020. We sourced person-level data from COVID-19 surveillance and reporting systems in Ontario. We calculated cumulatively diagnosed cases per capita, proportion tested, proportion tested positive and case-fatality proportion for each setting. We estimated the age- and sex-adjusted rate ratios associated with setting for test positivity and case fatality using quasi-Poisson regression. RESULTS: Over the study period, a total of 173 092 individuals were tested for and 16 490 individuals were diagnosed with SARS-CoV-2 infection. We observed a shift in the proportion of cumulative cases from all cases being related to travel to cases in residents of long-term care homes (20.4% [3368/16 490]), shelters (2.3% [372/16 490]), other congregate settings (20.9% [3446/16 490]) and community settings (35.4% [5834/16 490]), with cumulative travel-related cases at 4.1% (674/16490). Cumulatively, compared with the rest of the population, the diagnosed cases per capita was 64-fold and 19-fold higher among long-term care home and shelter residents, respectively. By May 20, 2020, 76.3% (21 617/28 316) of long-term care home residents and 2.2% (150 077/6 808 890) of the rest of the population had been tested. After adjusting for age and sex, residents of long-term care homes were 2.4 (95% confidence interval [CI] 2.2-2.7) times more likely to test positive, and those who received a diagnosis of COVID-19 were 1.4-fold (95% CI 1.1-1.8) more likely to die than
Moore JR, Donnell DJ, Boily M-C, et al., 2020, Model-based predictions of HIV incidence among African women using HIV risk behaviors and community-level data on male HIV prevalence and viral suppression., J Acquir Immune Defic Syndr
BACKGROUND: Pre-exposure prophylaxis (PrEP) with Tenofovir Disoproxil Fumarate and Emtricitabine (TDF-FTC) has proven highly effective in preventing HIV acquisition and is therefore offered to all participants in the control group as part of the standard of care package in many new HIV prevention studies. We propose a methodology for predicting HIV incidence in a hypothetical "placebo arm" for open-label studies or clinical trials with active control among African women. We apply the method to an open-label PrEP study, HIV Prevention Trials Network (HPTN) 082, which tested strategies to improve PrEP adherence in young African women all of whom were offered PrEP. METHODS: Our model predicted HIV infection risk for female study cohorts in sub-Saharan Africa using baseline behavioral risk factors and contemporary HIV prevalence and viral suppression in the local male population. The model was calibrated to HIV incidence in the Vaginal and Oral Interventions to Control the Epidemic study (VOICE). RESULTS: Our model reproduced the annual HIV incidence of 3.2%-4.8% observed over one year of follow-up in the placebo groups of four completed clinical studies. We predicted an annual HIV incidence of 3.7% (95% CI 3.2-4.2) among HPTN 082 participants in the absence of PrEP and other risk reduction interventions. CONCLUSIONS: We demonstrated the potential of the proposed methodology to provide HIV incidence predictions based on assessment of individual risk behaviors and community and time-specific HIV exposure risk using HIV treatment and viral suppression data. These estimates may serve as comparators in HIV prevention trials without a placebo group.
Dimitrov D, Moore J, Wood D, et al., 2020, Predicted effectiveness of daily and non-daily PrEP for MSM based on sex and pill-taking patterns from HPTN 067/ADAPT, Clinical Infectious Diseases, Vol: 71, Pages: 249-255, ISSN: 1058-4838
Background: HPTN 067/ADAPT evaluated the feasibility of daily and non-daily HIV pre-exposure prophylaxis (PrEP) regimens among high-risk populations, including men who have sex with men (MSM) and transgender women, in Bangkok, Thailand and Harlem, New York, U.S. We used a mathematical model to predict the efficacy and effectiveness of different dosing regimens. Methods: An individual-based mathematical model was used to simulate annual HIV incidence among MSM cohorts. PrEP efficacy for covered sex acts, as defined in the HPTN 067/ADAPT protocol, was estimated using subgroup efficacy estimates from the iPrEx trial. Effectiveness was estimated by comparison of the HIV incidence with and without PrEP use.Results: We estimated that PrEP was highly protective (85%–96% efficacy across regimens and sites) for fully covered acts. PrEP was more protective for partially covered acts in Bangkok (71%–88% efficacy) than in Harlem (62%–81% efficacy). Our model projects 80%, 62%, and 68% effectiveness of daily, time-driven, and event-driven PrEP for MSM in Harlem compared with 90%, 85% and 79% for MSM in Bangkok. Halving the efficacy for partially covered acts decreases effectiveness by 8–9 percentage points in Harlem and by 5–9 percentage points in Bangkok across regimens. Conclusions: Our analysis suggests that PrEP was more effective among MSM in Thailand than in the U.S. as a result of more fully covered sex acts and more pills taken around partially covered acts. Overall, non-daily PrEP was less effective than daily PrEP, especially in the U.S. where the sex act coverage associated with daily use was substantially higher.
Silhol R, Boily M-C, Dimitrov D, et al., 2020, Understanding the HIV epidemic among MSM in Baltimore: a modelling study estimating the impact of past HIV interventions and who acquired and contributed to infections., JAIDS: Journal of Acquired Immune Deficiency Syndromes, Vol: 84, Pages: 253-262, ISSN: 1525-4135
INTRODUCTION: Men who have sex with men (MSM) in the United States (US) are disproportionately affected by HIV. We estimated the impact of past interventions and contribution of different population groups to incident MSM HIV infections. SETTING: Baltimore, US METHODS:: We used a deterministic model, parameterised and calibrated to demographic and epidemic Baltimore MSM data, to estimate the fraction of HIV infections among MSM averted by condoms and antiretroviral therapy (ART) over 1984-2017 and the fraction of infections acquired and transmission contributed by MSM from different demographic groups and disease and care continuum stages over 10-year periods from 1988 to 2017, using population attributable fractions (PAFs). RESULTS: Condom use and ART averted 19% (95% uncertainty interval: 14-25%) and 23% (15-31%) of HIV infections that would have occurred since 1984 and 1996, respectively. Over 2008-2017, 46% (41-52%) of incident infections were acquired by, and 35% (27-49%) of transmissions contributed by MSM aged 18-24 years old (who constitute 27% of all MSM, 19% of HIV+ MSM). MSM with undiagnosed HIV infection, those with diagnosed infection but not in care, and those on ART contributed to 41% (31-54%), 46% (25-56%), and 14% (7-28%) of transmissions, respectively. CONCLUSION: Condoms and ART have modestly impacted the HIV epidemic among Baltimore MSM to date. Interventions reaching MSM with diagnosed infection who are not in care should be implemented since the largest percentage of HIV transmissions among Baltimore MSM are attributed to this group.
Owen BN, Baggaley R, Maheu-Giroux M, et al., 2020, Patterns and trajectories of anal intercourse practice over the life course among US women at risk of HIV, JIAS (submitted)
Elmes J, Silhol R, Hess KL, et al., 2020, Receptive anal sex contributes substantially to heterosexually‐acquired HIV infections among at‐risk women in Twenty US Cities: results from a modelling analysis, American Journal of Reproductive Immunology, Vol: 84, Pages: 1-14, ISSN: 1046-7408
ProblemReceptive anal intercourse (RAI) is more efficient than receptive vaginal intercourse (RVI) at transmitting HIV, but its contribution to heterosexually‐acquired HIV infections among at‐risk women in the US is unclear.Method of studyWe analysed sexual behaviour data from surveys of 9,152 low‐income heterosexual women living in 20 cities with high rates of HIV conducted in 2010 and 2013 as part of US National HIV Behavioral Surveillance. We estimated RAI prevalence (past‐year RAI) and RAI fraction (fraction of all sex acts (RVI and RAI) at the last sexual episode that were RAI among those reporting past‐year RAI) overall and by key demographic characteristics. These results and HIV incidence were used to calibrate a risk‐equation model to estimate the population attributable fraction of new HIV infections due to RAI (PAFRAI) accounting for uncertainty in parameter assumptions.ResultsRAI prevalence (overall: 32%, city range: 19‐60%) and RAI fraction (overall: 27%, city‐range: 18‐34%) were high overall and across cities, and positively associated with exchange sex. RAI accounted for an estimated 41% (uncertainty range: 18‐55%) of new infections overall (city range: 21‐57%). Variability in PAFRAI estimates was most influenced by uncertainty in the estimate of the per‐act increased risk of RAI relative to RVI and the number of sex acts.ConclusionsRAI may contribute disproportionately to new heterosexually‐acquired HIV infections among at‐risk low‐income women in the US, meaning that tools to prevent HIV transmission during RAI are warranted. Number of RVI and RAI acts should also be collected to monitor heterosexually‐acquired HIV infections.
Owen BN, Maheu-Giroux M, Matse S, et al., 2020, Prevalence and correlates of anal intercourse among female sex workers in eSwatini (vol 15, e0228849, 2020), PLOS ONE, Vol: 15, ISSN: 1932-6203
Nascimento FF, Baral S, Geidelberg L, et al., 2020, Phylodynamic analysis of HIV-1 subtypes B, C and CRF 02_AG in Senegal, EPIDEMICS, Vol: 30, ISSN: 1755-4365
Owen BN, Baggaley RF, Elmes J, et al., 2020, What proportion of female sex workers practise anal intercourse and how frequently? A systematic review and meta-analysis, AIDS and Behavior, Vol: 24, Pages: 697-713, ISSN: 1090-7165
HIV is more efficiently acquired during receptive anal intercourse (AI) compared to vaginal intercourse (VI) and may contribute substantially to female sex workers’ (FSW) high HIV burden. We aim to determine how common and frequent AI is among FSW globally. We searched PubMed, Embase and PsycINFO for studies reporting the proportion of FSW practising AI (prevalence) and/or the number of AI acts (frequency) worldwide from 01/1980 to 10/2018. We assessed the influence of participant and study characteristics on AI prevalence (e.g. continent, study year and interview method) through sub-group analysis. Of 15,830 identified studies, 131 were included. Nearly all (N = 128) reported AI prevalence and few frequency (N = 13), over various recall periods. Most studies used face-to-face interviews (N = 111). Pooled prevalences varied little by recall period (lifetime: 15.7% 95%CI 12.2–19.3%, N = 30, I 2 = 99%; past month: 16.2% 95%CI 10.8–21.6%, N = 18, I 2 = 99%). The pooled proportion of FSW reporting < 100% condom use tended to be non-significantly higher during AI compared to during VI (e.g. any unprotected VI: 19.1% 95%CI 1.7–36.4, N = 5 and any unprotected AI: 46.4% 95%CI 9.1–83.6, N = 5 in the past week). Across all study participants, between 2.4 and 15.9% (N = 6) of all intercourse acts (AI and VI) were anal. Neither AI prevalence nor frequency varied substantially by any participant or study characteristics. Although varied, AI among FSW is generally common, inconsistently protected with condoms and practiced sufficiently frequently to contribute substantially to HIV acquisition in this risk group. Interventions to address barriers to condom use are needed.
Looker KJ, Johnston C, Welton NJ, et al., 2020, The global and regional burden of genital ulcer disease due to herpes simplex virus: a natural history modelling study, BMJ Global Health, Vol: 5, Pages: 1-15, ISSN: 2059-7908
Introduction Herpes simplex virus (HSV) infection can cause painful, recurrent genital ulcer disease (GUD), which can have a substantial impact on sexual and reproductive health. HSV-related GUD is most often due to HSV type 2 (HSV-2), but may also be due to genital HSV type 1 (HSV-1), which has less frequent recurrent episodes than HSV-2. The global burden of GUD has never been quantified. Here we present the first global and regional estimates of GUD due to HSV-1 and HSV-2 among women and men aged 15–49 years old.Methods We developed a natural history model reflecting the clinical course of GUD following HSV-2 and genital HSV-1 infection, informed by a literature search for data on model parameters. We considered both diagnosed and undiagnosed symptomatic infection. This model was then applied to existing infection estimates and population sizes for 2016. A sensitivity analysis was carried out varying the assumptions made.Results We estimated that 187 million people aged 15–49 years had at least one episode of HSV-related GUD globally in 2016: 5.0% of the world’s population. Of these, 178 million (95% of those with HSV-related GUD) had HSV-2 compared with 9 million (5%) with HSV-1. GUD burden was highest in Africa, and approximately double in women compared with men. Altogether there were an estimated 8 billion person-days spent with HSV-related GUD globally in 2016, with 99% of days due to HSV-2. Taking into account parameter uncertainty, the percentage with at least one episode of HSV-related GUD ranged from 3.2% to 7.9% (120–296 million). However, the estimates were sensitive to the model assumptions.Conclusion Our study represents a first attempt to quantify the global burden of HSV-related GUD, which is large. New interventions such as HSV vaccines, antivirals or microbicides have the potential to improve the quality of life of millions of people worldwide.
Brisson M, Kim JJ, Canfell K, et al., 2020, Impact of HPV vaccination and cervical screening on cervical cancer elimination: a comparative modelling analysis in 78 low-income and lower-middle-income countries, The Lancet, Vol: 395, Pages: 575-590, ISSN: 0140-6736
BackgroundThe WHO Director-General has issued a call for action to eliminate cervical cancer as a public health problem. To help inform global efforts, we modelled potential human papillomavirus (HPV) vaccination and cervical screening scenarios in low-income and lower-middle-income countries (LMICs) to examine the feasibility and timing of elimination at different thresholds, and to estimate the number of cervical cancer cases averted on the path to elimination.MethodsThe WHO Cervical Cancer Elimination Modelling Consortium (CCEMC), which consists of three independent transmission-dynamic models identified by WHO according to predefined criteria, projected reductions in cervical cancer incidence over time in 78 LMICs for three standardised base-case scenarios: girls-only vaccination; girls-only vaccination and once-lifetime screening; and girls-only vaccination and twice-lifetime screening. Girls were vaccinated at age 9 years (with a catch-up to age 14 years), assuming 90% coverage and 100% lifetime protection against HPV types 16, 18, 31, 33, 45, 52, and 58. Cervical screening involved HPV testing once or twice per lifetime at ages 35 years and 45 years, with uptake increasing from 45% (2023) to 90% (2045 onwards). The elimination thresholds examined were an average age-standardised cervical cancer incidence of four or fewer cases per 100 000 women-years and ten or fewer cases per 100 000 women-years, and an 85% or greater reduction in incidence. Sensitivity analyses were done, varying vaccination and screening strategies and assumptions. We summarised results using the median (range) of model predictions.FindingsGirls-only HPV vaccination was predicted to reduce the median age-standardised cervical cancer incidence in LMICs from 19·8 (range 19·4–19·8) to 2·1 (2·0–2·6) cases per 100 000 women-years over the next century (89·4% [86·2–90·1] reduction), and to avert 61·0 million
Owen B, Maheu-Giroux M, Matse S, et al., 2020, Prevalence and correlates of anal intercourse among female sex workers in eSwatini, PLoS One, Vol: 15, ISSN: 1932-6203
IntroductionAs HIV is very effectively acquired during condomless receptive anal intercourse (AI) with serodiscordant and viremic partners, the practice could contribute to the high prevalence among female sex workers (FSW) in eSwatini (formerly known as Swaziland). We aim to estimate the proportion reporting AI (AI prevalence) among Swazi FSW and to identify the correlates of AI practice in order to better inform HIV prevention interventions among this population.MethodsUsing respondent-driven sampling (RDS), 325 Swazi FSW were recruited in 2011. We estimated the prevalence of AI and AI with inconsistent condom use in the past month with any partner type, and inconsistent condom use during AI and vaginal intercourse (VI) by partner type. Univariate and multivariable logistic regression models were used to identify behavioural and structural correlates associated with AI and AI with inconsistent condom use.ResultsRDS-adjusted prevalence of AI and AI with inconsistent condom use was high, at 44%[95% confidence interval (95%CI):35–53%]) and 34%[95%CI:26–42%], respectively and did not vary by partner type. HIV prevalence was high in this sample of FSW (70%), but knowledge that AI increases HIV acquisition risk low, with only 10% identifying AI as the riskiest sex act. Those who reported AI were more likely to be better educated (adjusted odds ratio(aOR) = 1.92[95%CI:1.03–3.57]), to have grown up in rural areas (aOR = 1.90[95%CI:1.09–3.32]), have fewer new clients in the past month (aOR = 0.33[95%CI:0.16–0.68]), and for last sex with clients to be condomless (aOR = 2.09[95%CI:1.07–4.08]). Although FSW reporting AI in past month were more likely to have been raped (aOR = 1.95[95%CI:1.05–3.65]) and harassed because of being a sex worker (aOR = 2.09[95%CI:1.16–3.74]), they were also less likely to have ever been blackmailed (aOR = 0.50[95%CI:0.25–0.98]) or been afraid to walk in public places (aOR = 0.46[95%CI:0.25&ndas
Looker K, Welton N, Sabin K, et al., 2020, Global and regional estimates of the contribution of herpes simplex virus Type 2 infection to HIV incidence: a population attributable fraction analysis using published epidemiological data, Lancet Infectious Diseases, Vol: 20, Pages: 240-249, ISSN: 1473-3099
BackgroundA 2017 systematic review and meta-analysis of 55 prospective studies found the adjusted risk of HIV acquisition to be at least tripled in individuals with herpes simplex virus type 2 (HSV-2) infection. We aimed to assess the potential contribution of HSV-2 infection to HIV incidence, given an effect of HSV-2 on HIV acquisition.MethodsWe used a classic epidemiological formula to estimate the global and regional (WHO regional) population attributable fraction (PAF) and number of incident HIV infections attributable to HSV-2 infection by age (15–24 years, 25–49 years, and 15–49 years), sex, and timing of HSV-2 infection (established vs recently acquired). Estimates were calculated by incorporating HSV-2 and HIV infection data with pooled relative risk (RR) estimates for the effect of HSV-2 infection on HIV acquisition from a systematic review and meta-analysis. Because HSV-2 and HIV have shared sexual and other risk factors, in addition to HSV-related biological factors that increase HIV risk, we only used RR estimates that were adjusted for potential confounders.FindingsAn estimated 420 000 (95% uncertainty interval 317 000–546 000; PAF 29·6% [22·9–37·1]) of 1·4 million sexually acquired incident HIV infections in individuals aged 15–49 years in 2016 were attributable to HSV-2 infection. The contribution of HSV-2 to HIV was largest for the WHO African region (PAF 37·1% [28·7–46·3]), women (34·8% [23·5–45·0]), individuals aged 25–49 years (32·4% [25·4–40·2]), and established HSV-2 infection (26·8% [19·7–34·5]).InterpretationA large burden of HIV is likely to be attributable to HSV-2 infection, even if the effect of HSV-2 infection on HIV had been imperfectly measured in studies providing adjusted RR estimates, potentially because of residual confounding. The contribution is likely to
Brisson M, Kim J, Canfell K, et al., Cervical cancer elimination in 78 Low and Lower-Middle Income Countries: Comparative modelling of the impact of HPV vaccination and cervical screening, The Lancet, ISSN: 0140-6736
Background The World Health Organization Director-General has issued a call for action to eliminate cervical cancer as a public health problem. To help inform global efforts, we modeled potential human papillomavirus (HPV) vaccination and cervical screening scenarios in low and lower-middle income countries (LMIC) to examine feasibility and timing of elimination at different thresholds, and to estimate the number of cancers averted on the path to elimination. Methods The WHO Cervical Cancer Elimination Modelling Consortium (CCEMC), which consists of three independent transmission-dynamic models identified by the WHO using predefined criteria, projected reductions in cervical cancer incidence over time in 78 LMIC for three standardized base-case scenarios: 1) Girls-only vaccination, 2) Girls-only vaccination & once lifetime screening, and 3) Girls-only vaccination & twice lifetime screening. Girls were vaccinated at 9 years old (with a catch-up to age 14 years) assuming 90% coverage and 100% lifetime protection against HPV types 16, 18, 31, 33, 45, 52 and 58. Cervical screening involved HPV testing once or twice per lifetime at ages 35 and 45 years with increasing uptake from 45% (2023) to 90% (2045+). The elimination thresholds examined were the average age-standardized cervical cancer incidence ≤4 and ≤10 per 100,000 women-years, and ≥85% reduction in incidence. Sensitivity analyses were performed, varying vaccination and screening strategies and assumptions. We summarised results using the median (minimum-maximum) of model predictions. Findings Girls-only HPV vaccination was predicted to reduce the average age-standardized cervical cancer incidence in LMIC from 19·8 (19·4-19·8) to 2·1 (2·0-2·6) per 100,000 women-years over the next century (89% (86-90) reduction), and to avert 61·2 (60·6-63·7) million cases. Adding twice lifetime screening reduced the incidence to 0·7 (0·
Maheu-Giroux M, Marsh K, Doyle C, et al., 2019, National HIV testing and diagnosis coverage in sub-Saharan Africa: a new modeling tool for estimating the "first 90" from program and survey data, AIDS, Vol: 33, Pages: S255-S269, ISSN: 0269-9370
OBJECTIVE: HIV testing services (HTS) are a crucial component of national HIV responses. Learning one's HIV diagnosis is the entry point to accessing life-saving antiretroviral treatment and care. Recognizing the critical role of HTS, the Joint United Nations Programme on HIV/AIDS (UNAIDS) launched the 90-90-90 targets stipulating that by 2020, 90% of people living with HIV know their status, 90% of those who know their status receive antiretroviral therapy, and 90% of those on treatment have a suppressed viral load. Countries will need to regularly monitor progress on these three indicators. Estimating the proportion of people living with HIV who know their status (i.e., the "first 90"), however, is difficult. METHODS: We developed a mathematical model (henceforth referred to as "F90") that formally synthesizes population-based survey and HTS program data to estimate HIV status awareness over time. The proposed model uses country-specific HIV epidemic parameters from the standard UNAIDS Spectrum model to produce outputs that are consistent with other national HIV estimates. The F90 model provides estimates of HIV testing history, diagnosis rates, and knowledge of HIV status by age and sex. We validate the F90 model using both in-sample comparisons and out-of-sample predictions using data from three countries: Côte d'Ivoire, Malawi, and Mozambique. RESULTS: In-sample comparisons suggest that the F90 model can accurately reproduce longitudinal sex-specific trends in HIV testing. Out-of-sample predictions of the fraction of PLHIV ever tested over a 4-to-6-year time horizon are also in good agreement with empirical survey estimates. Importantly, out-of-sample predictions of HIV knowledge are consistent (i.e., within 4% points) with those of the fully calibrated model in the three countries when HTS program data are included. The F90 model's predictions of knowledge of status are higher than available self-reported HIV awareness estimates, howe
Spicknall I, Looker K, Gottlieb S, et al., 2019, Review of mathematical models of HSV-2 vaccination: Implications for vaccine development, Vaccine, Vol: 37, Pages: 7396-7407, ISSN: 0264-410X
Development of a vaccine against herpes simplex virus type 2 (HSV-2), a life-long sexually-transmitted infection (STI), would be a major step forward in improving global sexual and reproductive health. In this review, we identified published literature of dynamic mathematical models assessing the impact of either prophylactic or therapeutic HSV-2 vaccination at the population level. We compared each study’s model structure and assumptions as well as predicted vaccination impact. We examined possible causes of heterogeneity across model predictions, key gaps, and the implications of these findings for future modelling efforts. Only eight modelling studies have assessed the potential public health impact of HSV-2 vaccination, with the majority focusing on impact of prophylactic vaccines. The studies showed that even an imperfect prophylactic HSV-2 vaccine could have an important public health impact on HSV-2 incidence, and could also impact HIV indirectly in high HIV prevalence settings. Therapeutic vaccines also may provide public health benefits, though they have been explored less extensively. However, there was substantial variation in predicted population-level impact for both types of vaccine, reflecting differences in assumptions between model scenarios. Importantly, many models did not account for heterogeneity in infection rates such as by age, sex and sexual activity. Future modelling work to inform decisions on HSV vaccine development and implementation should consider cost-effectiveness, account for additional HSV-2 sequelae such as neonatal transmission, and model greater heterogeneity in infection rates between individuals, more realistic vaccine deployment, and more thorough sensitivity and uncertainty analyses.
Gottlieb SL, Giersing BK, Hickling J, et al., 2019, Meeting report: initial World Health Organization consultation on herpes simplex virus (HSV) vaccine preferred product characteristics, March 2017, Vaccine, Vol: 37, Pages: 7408-7418, ISSN: 0264-410X
The development of vaccines against herpes simplex virus (HSV) is an important global goal for sexual and reproductive health. A key priority to advance development of HSV vaccines is the definition of preferred product characteristics (PPCs), which provide strategic guidance on World Health Organization (WHO) preferences for new vaccines, specifically from a low- and middle-income country (LMIC) perspective. To start the PPC process for HSV vaccines, the WHO convened a global stakeholder consultation in March 2017, to define the priority public health needs that should be addressed by HSV vaccines and discuss the key considerations for HSV vaccine PPCs, particularly for LMICs. Meeting participants outlined an initial set of overarching public health goals for HSV vaccines in LMICs, which are: to reduce the acquisition of HIV associated with HSV-2 infection in high HIV-prevalence populations and to reduce the burden of HSV-associated disease, including mortality and morbidity due to neonatal herpes and impacts on sexual and reproductive health. Participants also considered the role of prophylactic versus therapeutic vaccines, whether both HSV-2 and HSV-1 should be targeted, important target populations, and infection and disease endpoints for clinical trials. This article summarizes the main discussions from the consultation.
Gottlieb SL, Giersing B, Boily M-C, et al., 2019, Modelling efforts needed to advance herpes simplex virus (HSV) vaccine development: Key findings from the World Health Organization Consultation on HSV Vaccine Impact Modelling., Vaccine, Vol: 37, Pages: 7336-7345, ISSN: 0264-410X
Development of a vaccine against herpes simplex virus (HSV) is an important goal for global sexual and reproductive health. In order to more precisely define the health and economic burden of HSV infection and the theoretical impact and cost-effectiveness of an HSV vaccine, in 2015 the World Health Organization convened an expert consultation meeting on HSV vaccine impact modelling. The experts reviewed existing model-based estimates and dynamic models of HSV infection to outline critical future modelling needs to inform development of a comprehensive business case and preferred product characteristics for an HSV vaccine. This article summarizes key findings and discussions from the meeting on modelling needs related to HSV burden, costs, and vaccine impact, essential data needs to carry out those models, and important model components and parameters.
Stannah J, Dale E, Elmes J, et al., 2019, HIV testing and engagement with the HIV treatment cascade among men who have sex with men in Africa: A systematic review and meta-analysis, Lancet HIV, Vol: 6, Pages: e769-e787, ISSN: 2405-4704
BackgroundHIV disproportionately affects gay, bisexual, and other men who have sex with men (MSM) in Africa, where many countries criminalise same-sex behaviour. We assessed changes in the engagement of African MSM with HIV testing and treatment cascade stages over time, and the influence of anti-LGBT legislation and stigma.MethodsWe systematically searched the peer-reviewed literature to October 10th , 2018 for studies and extracted or derived estimates of HIV testing and/or engagement with the HIV treatment cascade among African MSM from published reports. We derived pooled estimates using inverse-variance random-effects models. We used subgroup and meta-regression analysis to assess associations between testing and status awareness outcomes and study and participant characteristics including the severity of country-level anti-LGBT legislation.FindingsOur searches identified 75 independent eligible studies that provided estimates for 44,993 MSM across one or more of five testing and treatment cascade outcomes. HIV testing increased significantly over time overall, with pooled overall proportions of MSM ever tested of 67·3% (95%Confidence interval 62·1-72·3%,N=44) and tested in the past 12 months of 50·1% (42·4-57·8%,N=31) post-2011 – 14% and 18% points higher than pre-2011, respectively. Post-2011, ever testing was highest in Southern(80·0%) and lowest in Northern(34·4%) and Central(56·1%) Africa, with the greatest increase in Western Africa(from 42·4 to 70·9%). Levels of both testing outcomes and status awareness were statistically significantly lower in countries with the most severe anti-LGBT legislation.Few estimates were available for later stages of the treatment cascade. Available data post61 2011 suggest that the pooled proportion of MSM HIV-positive aware has remained low (18·5%, 12·5-25·3%,N=28) whereas proportions of current ART use were 23·7%
Stannah J, Silhol R, Elmes J, et al., 2019, Increases in HIV incidence following receptive anal intercourse among women: A systematic review and meta-analysis., AIDS and Behavior, Vol: 24, Pages: 667-681, ISSN: 1090-7165
Receptive anal intercourse (RAI) carries a greater per-act risk of HIV acquisition than receptive vaginal intercourse (RVI) and may influence HIV epidemics driven by heterosexual sex. This systematic review explores the association between RAI and incident HIV among women, globally. We searched Embase and Medline through September 2018 for longitudinal studies reporting crude (cRR) or adjusted (aRR) relative risks of HIV acquisition by RAI practice among women. Of 27,563 articles identified, 17 eligible studies were included. We pooled independent study estimates using random-effects models. Women reporting RAI were more likely to acquire HIV than women not reporting RAI (pooled cRR = 1.56 95% CI 1.03-2.38, N = 18, I2 = 72%; pooled aRR = 2.23, 1.01-4.92, N = 5, I2 = 70%). In subgroup analyses the association was lower for women in Africa (pooled cRR = 1.16, N = 13, I2 = 21%) than outside Africa (pooled cRR = 4.10, N = 5, I2 = 79%) and for high-risk (pooled aRR = 1.69, N = 4, I2 = 63%) than general-risk women (pooled aRR = 8.50, N = 1). Interview method slightly influenced cRR estimates (p value = 0.04). In leave-one-out sensitivity analyses pooled estimates were generally robust to removing individual study estimates. Main limitations included poor exposure definition, incomplete adjustment for confounders, particularly condom use, and use of non-confidential interview methods. More and better data are needed to explain differences in risk by world region and risk population. Women require better counselling and greater choice in prevention modalities that are effective during RVI and RAI.
Drolet M, Benard E, Perez N, et al., 2019, Population-level impact and herd effects following the introduction of human papillomavirus vaccination programs: updated systematic review and meta-analysis, Lancet, Vol: 394, Pages: 497-509, ISSN: 0140-6736
BackgroundMore than ten years have elapsed since human papillomavirus (HPV) vaccination was implemented. We performed a systematic review and meta-analysis of the population-level impact of female-only HPV vaccination on HPV infections, anogenital wart diagnoses (AGW) and cervical intraepithelial neoplasia grade 2+ (CIN2+) to summarise the most recent evidence about the effectiveness of HPV vaccines in real-world settings and to quantify the impact of multiple age-cohort vaccination.MethodsWe updated our prior review (01/01/2007–28/02/2014), by searching Medline and Embase (01/02/2014–11/10/2018) for studies that examined changes, between pre- and post-vaccination periods, in HPV infections, AGW, or CIN2+. We stratified all analyses by sex, age, and years since HPV vaccination introduction. We used random-effects models to estimate pooled relative risks and performed subgroup analysis to identify the main sources of heterogeneity. FindingsWe identified 65 eligible articles conducted in 14 high-income countries. After 5-8 years of vaccination, HPV-16/18, AGW, and CIN2+ decreased significantly by about 80%, 70%, and 50% among girls aged 15-19 years and by 65%, 55%, and 30% among women aged 20-24 years. Significant cross-protection and herd effects were also observed. HPV-31/33/45 decreased significantly by 50% among girls aged 15-19 years and AGW decreased significantly by 30-50% among boys/men aged 15-24 years. After 5-8 years of vaccination, countries with multi-cohort vaccination and high coverage (≥50%) had greater reductions in AGW, 44 and 85 percentage points among girls and boys aged 15-19 years, respectively, than countries with single-cohort vaccination and/or low vaccination coverage. InterpretationOur meta-analysis, including data from >60 million individuals from 14 high-income countries, shows a substantial impact of female-only HPV vaccination programs on AGW among girls/women and boys/men, and HPV infections and CIN2+ among girls/women
Maheu-Giroux M, Diabate S, Boily M-C, et al., 2019, Cost-effectiveness of accelerated HIV response scenarios in Côte d’Ivoire, JAIDS-Journal of Acquired Immune Deficiency Syndromes, Vol: 80, Pages: 503-512, ISSN: 1525-4135
Background: Despite Côte d’Ivoire epidemic being labelled as ‘generalized’, key populations (KP) are important to overall transmission. Using a dynamic model of HIV transmission, we previously estimated the impact of several treatment-as-prevention strategies that reached –or missed– the UNAIDS 90-90-90 targets in different populations groups, including KP and clients of female sex workers (CFSW). To inform program planning and resources allocation, we assessed the cost-effectiveness of these scenarios.Methods: Costing was performed from the provider’s perspective. Unit costs were obtained from the Ivorian Programme national de lutte contre le Sida (USD 2015) and discounted at 3%. Net incremental cost-effectiveness ratios (ICER) per adult HIV infection prevented and per disability-adjusted life years (DALY) averted were estimated over 2015-2030.Results: The three most cost-effective and affordable scenarios were the ones that projected current programmatic trends (ICER=$210; 90% uncertainty interval [90UI%]: $150-$300), attaining the 90-90-90 objectives among KP and CFSW (ICER=$220; 90%UI: $80-$510), and among KP only (ICER=$290; 90%UI: $90-$660). The least cost-effective scenario was the one that reached the UNAIDS 90-90-90 target accompanied by a 25% point drop in condom use in KP (ICER=$710; 90%UI: $450-$1,270). In comparison, the UNAIDS scenario had a net ICER of $570 (90%UI: $390-$900) per DALY averted.Conclusions: According to commonly used thresholds, accelerating the HIV response can be considered very cost-effective for all scenarios. However, when balancing epidemiological impact, cost-effectiveness, and affordability, scenarios that sustain both high condom use and rates of viral suppression among KP and CFSW appear most promising in Côte d’Ivoire.
Mitchell KM, Hoots B, German D, et al., 2019, Improvements in the HIV care continuum needed to meaningfully reduce HIV incidence among men who have sex with men in Baltimore, US: a modelling study for HPTN 078, Journal of the International AIDS Society, Vol: 22, ISSN: 1758-2652
Introduction HIV prevalence is high among men who have sex with men (MSM) in Baltimore, Maryland, United States, and levels of viral suppression among HIV-positive MSM are relatively low. The HIV Prevention Trials Network (HPTN) 078 trial seeks to increase levels of viral suppression among US MSM by increasing rates of diagnosis and linkage to care and treatment. We estimated the increases in viral suppression needed to reach different HIV incidence reduction targets, and the impact of meeting diagnosis and treatment targets.Methods: We used a mathematical model of HIV transmission among MSM from Baltimore, US, parameterised with behavioural data and fitted to HIV prevalence and care continuum data for Baltimore wherever possible, to project increases in viral suppression needed to reduce the HIV incidence rate among Baltimore MSM by 10, 20, 30, or 50% after 2, 5, and 10 years. We also projected HIV incidence reductions achieved if US national targets – 90% of people living with HIV (PLHIV) know their HIV serostatus, 90% of those diagnosed are retained in HIV medical care and 80% of those diagnosed are virally suppressed - or UNAIDS 90-90-90 targets (90% of PLHIV know their status, 90% of those diagnosed receive antiretroviral therapy (ART), 90% of those receiving ART are virally suppressed) are each met by 2020.Results: To reduce the HIV incidence rate by 20% and 50% after 5 years (compared with the base-case at the same time point), the proportion of all HIV-positive MSM who are virally suppressed must increase above 2015 levels by a median 13 percentage points (95% uncertainty interval 9-16 percentage points) from median 49% to 60%, and 27 percentage points (22-35) from 49% to 75%, respectively. Meeting all three US or 90-90-90 UNAIDS targets results in a 48% (31-63%) and 51% (38-65%) HIV incidence rate reduction in 2020, respectively. Conclusions: Substantial improvements in levels of viral suppression will be needed to achieve significant incidence reduct
Baggaley R, Owen B, Silhol R, et al., 2018, Does per-act HIV-1 transmission risk through anal sex vary by gender? An updated systematic review and meta-analysis, American Journal of Reproductive Immunology, Vol: 80, ISSN: 1046-7408
Quantifying HIV‐1 transmission risk per‐act of anal intercourse (AI) is important for HIV‐1 prevention. We updated previous reviews by searching Medline and Embase to 02/2018. We derived pooled estimates of receptive AI (URAI) and insertive AI (UIAI) risk unprotected by condoms using random‐effects models. Subgroup analyses were conducted by gender, study design, and whether antiretroviral treatment (ART) had been introduced by the time of the study. Two new relevant studies were identified, one of which met inclusion criteria, adding three new cohorts and increasing number of individuals/partnerships included from 1869 to 14 277. Four studies, all from high‐income countries, were included. Pooled HIV‐1 risk was higher for URAI (1.25%, 95% CI 0.55%‐2.23%, N = 5, I2 = 87%) than UIAI (0.17%, 95 % CI 0.09%‐0.26%, N = 3, I2 = 0%). The sole heterosexual URAI estimate (3.38%, 95% CI 1.85%‐4.91%), from a study of 72 women published in a peer‐reviewed journal, was significantly higher than the men‐who‐have‐sex‐with‐men (MSM) pooled estimate (0.75%, 95% CI 0.56%‐0.98%, N = 4, P < 0.0001) and higher than the only other heterosexual estimate identified (0.4%, 95% CI 0.08%‐2.0%, based on 59 women, excluded for being a pre‐2013 abstract). Pooled per‐act URAI risk varied by study design (retrospective‐partner studies: 2.56%, 95% CI 1.20%‐4.42%, N = 2 (one MSM, one heterosexual); prospective studies: 0.71%, 95% CI 0.51%‐0.93%, N = 3 MSM, P < 0.0001). URAI risk was lower for studies conducted in the ART era (0.75%, 95% CI 0.52%‐1.03%) than pre‐ART (1.67%, 95% CI 0.44%‐3.67%) but not significantly so (P = 0.537). Prevention messages must emphasize that HIV‐1 infectiousness through AI remains high, even in the ART era. Further studies, particularly among heterosexual populations and in resource‐limited settings, are required to elucidate whether AI risk differs by gender, region and following population‐level ART scale‐up.
Mboup A, Behanzin L, Guedou FA, et al., 2018, Early antiretroviral therapy and daily pre-exposure prophylaxis for HIV prevention among female sex workers in Cotonou, Benin: a prospective observational demonstration study, Journal of the International AIDS Society, Vol: 21, ISSN: 1758-2652
IntroductionIn sub‐Saharan Africa, HIV prevalence remains high, especially among key populations. In such situations, combination prevention including clinical, behavioural, structural and biological components, as well as adequate treatment are important. We conducted a demonstration project at the Dispensaire IST, a clinic dedicated to female sex workers (FSWs) in Cotonou, on early antiretroviral therapy (E‐ART, or immediate “test‐and‐treat”) and pre‐exposure prophylaxis (PrEP). We present key indicators such as uptake, retention and adherence.MethodsIn this prospective observational study, we recruited FSWs from October 4th 2014 to December 31st 2015 and followed them until December 31st 2016. FSWs were provided with daily tenofovir disoproxil fumarate/emtricitabine (Truvada®) for PrEP or received a first‐line antiretroviral regimen as per Benin guidelines. We used generalized estimating equations to assess trends in adherence and sexual behaviour.ResultsAmong FSWs in the catchment area, HIV testing coverage within the study framework was 95.5% (422/442). At baseline, HIV prevalence was 26.3% (111/422). Among eligible FSWs, 95.5% (105/110) were recruited for E‐ART and 88.3% (256/290) for PrEP. Overall retention at the end of the study was 59.0% (62/105) for E‐ART and 47.3% (121/256) for PrEP. Mean (±SD) duration of follow‐up was 13.4 (±7.9) months for E‐ART and 11.8 (±7.9) months for PrEP. Self‐reported adherence was over 90% among most E‐ART participants. For PrEP, adherence was lower and the proportion with 100% adherence decreased over time from 78.4% to 56.7% (p‐trend < 0.0001). During the 250.1 person‐years of follow‐up among PrEP initiators, two seroconversions occurred (incidence 0.8/100 person‐years (95% confidence interval: 0.3 to 1.9/100 person‐years)). The two seroconverters had stopped using PrEP for at least six months before being found HIV‐infected. In both groups, there was no evidence of reduced condom use.
Silhol R, Boily M-C, Dimitrov D, et al., 2018, Understanding HIV Transmission Dynamics and the Impact of Past HIV Interventions Among MSM in Baltimore: A Modelling Study for HPTN 078, HIV Research for Prevention Meeting (HIVR4P) - AIDS Vaccine, Microbicide and ARV-Based Prevention Science, Publisher: MARY ANN LIEBERT, INC, Pages: 283-283, ISSN: 0889-2229
Borquez A, Beletsky L, Nosyk B, et al., 2018, The effect of public health-oriented drug law reform on HIV incidence in people who inject drugs in Tijuana, Mexico: an epidemic modelling study, Lancet Public Health, Vol: 3, Pages: e429-e437, ISSN: 2468-2667
BackgroundAs countries embark on public health-oriented drug law reform, health impact evaluations are needed. In 2012, Mexico mandated the narcomenudeo reform, which depenalised the possession of small amounts of drugs and instituted drug treatment instead of incarceration. We investigated the past and future effect of this drug law reform on HIV incidence in people who inject drugs in Tijuana, Mexico.MethodsIn this epidemic modelling study, we used data from the El Cuete IV cohort study to develop a deterministic model of injecting and sexual HIV transmission in people who inject drugs in Tijuana between 2012 and 2030. The population was stratified by sex, incarceration status, syringe confiscation by the police, HIV stage, and exposure to drug treatment or rehabilitation (either opioid agonist treatment or compulsory drug abstinence programmes). We modelled the effect of these exposures on HIV risk in people who inject drugs, estimating the effect of observed and potential future reform enforcement levels.FindingsIn 2011, prior to the narcomenudeo reform, 547 (75%) of 733 people who inject drugs in the El Cuete cohort reported having ever been incarcerated, on average five times since starting injecting. Modelling estimated the limited reform implementation averted 2% (95% CI 0·2–3·0) of new HIV infections in people who inject drugs between 2012 and 2017. If implementation reduced incarceration in people who inject drugs by 80% from 2018 onward, 9% (95% CI 4–16) of new HIV infections between 2018 and 2030 could be averted, with 21% (10–33) averted if people who inject drugs were referred to opioid agonist treatment instead of being incarcerated. Referral to compulsory drug abstinence programmes instead of prison could have a lower or potentially negative impact with −2% (95% CI −23 to 9) infections averted.InterpretationMexican drug law reform has had a negligible effect on the HIV epidemic among people who inject drugs
Shannon K, Crago A-L, Baral S, et al., 2018, The global response and unmet actions for HIV and sex workers, Lancet, Vol: 392, Pages: 698-710, ISSN: 0140-6736
Female, male, and transgender sex workers continue to have disproportionately high burdens of HIV infection in low-income, middle-income, and high-income countries in 2018. 4 years since our Lancet Series on HIV and sex work, our updated analysis of the global HIV burden among female sex workers shows that HIV prevalence is unacceptably high at 10·4% (95% CI 9·5–11·5) and is largely unchanged. Comprehensive epidemiological data on HIV and antiretroviral therapy (ART) coverage are scarce, particularly among transgender women. Sustained coverage of treatment is markedly uneven and challenged by lack of progress on stigma and criminalisation, and sustained human rights violations. Although important progress has been made in biomedical interventions with pre-exposure prophylaxis and early ART feasibility and demonstration projects, limited coverage and retention suggest that sustained investment in community and structural interventions is required for sex workers to benefit from the preventive interventions and treatments that other key populations have. Evidence-based progress on full decriminalisation grounded in health and human rights—a key recommendation in our Lancet Series—has stalled, with South Africa a notable exception. Additionally, several countries have rolled back rights to sex workers further. Removal of legal barriers through the decriminalisation of sex work, alongside political and funding investments to support community and structural interventions, is urgently needed to reverse the HIV trajectory and ensure health and human rights for all sex workers.
Mukandavire C, Walker J, Schwartz S, et al., 2018, Estimating the contribution of key populations towards spread of HIV in Dakar, Senegal, Journal of the International AIDS Society, Vol: 21, ISSN: 1758-2652
IntroductionKey populations including female sex workers (FSW) and men who have sex with men (MSM) bear a disproportionate burden of HIV. However, the role of focusing prevention efforts on these groups for reducing a country’s HIV epidemic is debated. We estimate the extent to which HIV transmission amongst FSW and MSM contributes to overall HIV transmission in Dakar, Senegal, using a dynamic assessment of the population attributable fraction (PAF).MethodsA dynamic transmission model of HIV among FSW, their clients, MSM and the lower-risk adult population was parameterized and calibrated within a Bayesian framework using setting-specific demographic, behavioural, HIV epidemiological, and antiretroviral treatment (ART) coverage data for 1985-2015. We used the model to estimate the 10-year PAF of commercial sex between FSW and their clients, and sex between men, to overall HIV transmission (defined as the percentage of new infections prevented when these modes of transmission are removed). Additionally, we estimated the prevention benefits associated with historical increases in condom use and ART uptake, and impact of further increases in prevention and treatment.ResultsThe model projections suggest that unprotected sex between men contributed to 42% (2.5 to 97.5th percentile range 24-59%) of transmissions between 1995-2005, increasing to 64% (37-79%) from 2015-2025. The 10-year PAF of commercial sex is smaller, diminishing from 21% (7-39%) in 1995 to 14% (5-35%) in 2015. Without ART, 49% (32-71%) more HIV infections would have occurred since 2000, when ART was initiated, whereas without condom use since 1985, 67% (27-179%) more HIV infections would have occurred, and the overall HIV prevalence would have been 60% (29-211%) greater than what it is now. Further large decreases in HIV incidence (68%) can be achieved by scaling up ART in MSM to 74% coverage and reducing their susceptibility to HIV by a two-thirds through any prevention modality.ConclusionsUnprote
Borquez A, Beletsky L, Nosyk B, et al., Evaluating the impact of public health oriented drug law reform on HIV incidence among people who inject drugs in Tijuana, Mexico: an epidemic modelling analysis, Lancet, ISSN: 0140-6736
Background: As countries embark on public health-oriented drug law reform, health impact evaluations are needed. In 2012, Mexico mandated the ‘Narcomenudeo reform’, depenalising possession of small amounts of drugs and instituting drug treatment instead of incarceration. We investigated its impact on HIV incidence among people who iinject drugs (PWID) in Tijuana, Mexico.Methods: We developed a deterministic model of injecting and sexual HIV transmission among PWID in Tijuana disaggregated by sex, incarceration status, syringe confiscation by the police, and exposure to drug treatment/”rehabilitation” (either opioid agonist therapy (OAT) or compulsory drug abstinence programmes (CAP)). We modelled the effect of these exposures on HIV risk among PWID, estimating the impact of observed and potential future reform enforcement levels. Findings: Modelling estimated the limited reform implementation averted 2% [95% Confidence Interval (CI): 0.2-15 3%] of new HIV infections among PWID between 2012-2017. If implementation reduced incarceration among PWID by 80% from 2018 onward, 9% [95% CI: 4-16%] of new HIV infections between 2018-2030 could be averted, with 21% [95% CI: 10‐33%] averted if PWID were referred to OAT instead of incarcerated. However, referral to CAP instead of prison could have a lower or potentially negative impact with -2% [95% CI: 23‐9%] infections averted. Interpretation Mexican drug law reform has had negligible impact on the HIV epidemic among PWID in Tijuana.
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