Publications
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Silhol R, Anderson R, Stevens O, et al., 2024, Measuring HIV acquisitions among partners of key populations: estimates from HIV transmission dynamic models, JAIDS: Journal of Acquired Immune Deficiency Syndromes, Vol: 95, Pages: e59-e69, ISSN: 1525-4135
Background: Key populations (KPs), including female sex workers (FSW), gay men and other men who have sex with men (MSM), people who inject drugs (PWID), and transgender women (TGW) experience disproportionate risks of HIV acquisition. The UNAIDS Global AIDS 2022 Update reported that one-quarter of all new HIV infections occurred among their non-KP sexual partners. However, this fraction relied on heuristics regarding the ratio of new infections that KPs transmitted to their non-KP partners to the new infections acquired among KPs (herein referred to as “infection ratios”). We recalculated these ratios using dynamic transmission models.Setting: 178 settings (106 countries).Methods: Infection ratios for FSW, MSM, PWID, TGW, and clients of FSW were estimated from 12 models for 2020.Results: Median model estimates of infection ratios were 0.7 (interquartile range: 0.5-1.0; n=172 estimates) and 1.2 (0.8-1.8; n=127) for acquisitions from FSW clients and transmissions from FSW to all their non-KP partners, respectively, which were comparable to previous UNAIDS assumptions (0.2-1.5 across regions). Model estimates for female partners of MSM were 0.5 (0.2-0.8; n=20) and 0.3 (0.2-0.4; n=10) for partners of PWID across settings in Eastern and Southern Africa, lower than corresponding UNAIDS assumptions (0.9 and 0.8, respectively). The few available model estimates for TGW were higher (5.1 (1.2-7.0; n=8)) than UNAIDS assumptions (0.1-0.3). Model estimates for non-FSW partners of FSW clients in Western and Central Africa were high (1.7; 1.0-2.3; n=29). Conclusion: Ratios of new infections among non-KP partners relative to KP were high, confirming the importance of better addressing prevention and treatment needs among KP as central to reducing overall HIV incidence.
Stevens O, Anderson R, Stover J, et al., 2024, Comparison of empirically derived and model-based estimates of key population HIV incidence and the distribution of new infections by population group in sub-Saharan Africa, JAIDS: Journal of Acquired Immune Deficiency Syndromes, Vol: 95, Pages: e46-e58, ISSN: 1525-4135
BACKGROUND: The distribution of new HIV infections among key populations, including female sex workers (FSWs), gay men and other men who have sex with men (MSM), and people who inject drugs (PWID) are essential information to guide an HIV response, but data are limited in sub-Saharan Africa (SSA). We analyzed empirically derived and mathematical model-based estimates of HIV incidence among key populations and compared with the Joint United Nations Programme on HIV/AIDS (UNAIDS) estimates. METHODS: We estimated HIV incidence among FSW and MSM in SSA by combining meta-analyses of empirical key population HIV incidence relative to the total population incidence with key population size estimates (KPSE) and HIV prevalence. Dynamic HIV transmission model estimates of HIV incidence and percentage of new infections among key populations were extracted from 94 country applications of 9 mathematical models. We compared these with UNAIDS-reported distribution of new infections, implied key population HIV incidence and incidence-to-prevalence ratios. RESULTS: Across SSA, empirical FSW HIV incidence was 8.6-fold (95% confidence interval: 5.7 to 12.9) higher than total population female 15-39 year incidence, and MSM HIV incidence was 41.8-fold (95% confidence interval: 21.9 to 79.6) male 15-29 year incidence. Combined with KPSE, these implied 12% of new HIV infections in 2021 were among FSW and MSM (5% and 7% respectively). In sensitivity analysis varying KPSE proportions within 95% uncertainty range, the proportion of new infections among FSW and MSM was between 9% and 19%. Insufficient data were available to estimate PWID incidence rate ratios. Across 94 models, median proportion of new infections among FSW, MSM, and PWID was 6.4% (interquartile range 3.2%-11.7%), both much lower than the 25% reported by UNAIDS. CONCLUSION: Empirically derived and model-based estimates of HIV incidence confirm dramatically higher HIV risk among key populations in SSA. Estimated proportions of
Moore M, Stansfield S, Donnell DJ, et al., 2023, Efficacy estimates of oral pre-exposure prophylaxis for HIV prevention in cisgender women with partial adherence, Nature Medicine, Vol: 29, Pages: 2748-2752, ISSN: 1078-8956
Pre-exposure prophylaxis (PrEP) with tenofovir (TFV) disoproxil fumarate and emtricitabine administered orally daily is effective in preventing human immunodeficiency virus (HIV) acquisition in both men and women with sufficient adherence; however, the adherence-efficacy relationship in cisgender women has not been well established. We calculated the adherence-efficacy curve for cisgender women by using HIV incidence and plasma TFV concentration data from three trials (FEM-PrEP, VOICE and Partners PrEP). We imputed TFV diphosphate (TFV-DP) concentrations, a measure of long-term adherence, from TFV quantification by using data from the HIV Prevention Trials Network 082 study, which measured both TFV-DP and TFV concentrations. Two, four and seven pills per week reduced HIV incidence by 59.3% (95% credible interval (CrI) 29.9-95.8%), 83.8% (95% CI 51.7-99.8%) and 95.9% (95% CI 72.6-100%), respectively. Our adherence-efficacy curve can be validated and updated by HIV prevention studies that directly measure TFV-DP concentrations. The curve suggests that high adherence confers high protection in cisgender women. However, the lower efficacy with partial adherence highlights the need for new PrEP products and interventions to increase adherence.
Stannah J, Soni N, Lam JKS, et al., 2023, Trends in HIV testing, the treatment cascade, and HIV incidence among men who have sex with men in Africa: A systematic review and meta-analysis, The Lancet HIV, Vol: 10, Pages: e528-e542, ISSN: 2352-3018
Background:Gay, bisexual, and other men who have sex with men (MSM) are disproportionately affected by HIV. In Africa, MSM face structural barriers to HIV prevention and treatment that increase their vulnerability to HIV acquisition and transmission, and undermine the HIV response. In this systematic review, we aimed to explore progress towards increases in HIV testing, improving engagement in the HIV treatment cascade, and HIV incidence reductions among MSM in Africa.Methods:We searched Embase, MEDLINE, Global Health, Scopus, and Web of Science for cross-sectional and longitudinal studies reporting HIV testing, knowledge of status, care, antiretroviral therapy (ART) use, viral suppression, and HIV incidence among MSM in Africa published between Jan 1, 1980, and March 3, 2023. We pooled surveys using Bayesian generalised linear mixed-effects models, used meta-regression to assess time trends, and compared HIV incidence estimates among MSM with those of all men.Findings:Of 9278 articles identified, we included 152 unique studies published in 2005–23. In 2020, we estimate that 73% (95% credible interval [CrI] 62–87) of MSM had ever tested for HIV. HIV testing in the past 12 months increased over time in central, western, eastern, and southern Africa (odds ratio per year [ORyear] 1·23, 95% CrI 1·01–1·51, n=46) and in 2020 an estimated 82% (70–91) had tested in the past 12 months, but only 51% (30–72) of MSM living with HIV knew their HIV status. Current ART use increased over time in central and western (ORyear 1·41, 1·08–1·93, n=9) and eastern and southern Africa (ORyear 1·37, 1·04–1·84, n=17). We estimated that, in 2020, 73% (47–88) of all MSM living with HIV in Africa were currently on ART. Nevertheless, we did not find strong evidence to suggest that viral suppression increased, with only 69% (38–89) of MSM living with HIV estimated to be virally sup
Stansfield SE, Heitner J, Mitchell KM, et al., 2023, Population-level impact of expanding PrEP coverage by offering long-acting injectable PrEP to MSM in three high-resource settings: a model comparison analysis, Journal of the International AIDS Society, Vol: 26, Pages: 139-149, ISSN: 1758-2652
INTRODUCTION: Long-acting injectable cabotegravir (CAB-LA) demonstrated superiority to daily tenofovir disoproxil fumarate/emtricitabine (TDF/FTC) for HIV pre-exposure prophylaxis (PrEP) in the HPTN 083/084 trials. We compared the potential impact of expanding PrEP coverage by offering CAB-LA to men who have sex with men (MSM) in Atlanta (US), Montreal (Canada) and the Netherlands, settings with different HIV epidemics. METHODS: Three risk-stratified HIV transmission models were independently parameterized and calibrated to local data. In Atlanta, Montreal and the Netherlands, the models, respectively, estimated mean TDF/FTC coverage starting at 29%, 7% and 4% in 2022, and projected HIV incidence per 100 person-years (PY), respectively, decreasing from 2.06 to 1.62, 0.08 to 0.03 and 0.07 to 0.001 by 2042. Expansion of PrEP coverage was simulated by recruiting new CAB-LA users and by switching different proportions of TDF/FTC users to CAB-LA. Population effectiveness and efficiency of PrEP expansions were evaluated over 20 years in comparison to baseline scenarios with TDF/FTC only. RESULTS: Increasing PrEP coverage by 11 percentage points (pp) from 29% to 40% by 2032 was expected to avert a median 36% of new HIV acquisitions in Atlanta. Substantially larger increases (by 33 or 26 pp) in PrEP coverage (to 40% or 30%) were needed to achieve comparable reductions in Montreal and the Netherlands, respectively. A median 17 additional PYs on PrEP were needed to prevent one acquisition in Atlanta with 40% PrEP coverage, compared to 1000+ in Montreal and 4000+ in the Netherlands. Reaching 50% PrEP coverage by 2032 by recruiting CAB-LA users among PrEP-eligible MSM could avert >45% of new HIV acquisitions in all settings. Achieving targeted coverage 5 years earlier increased the impact by 5-10 pp. In the Atlanta model, PrEP expansions achieving 40% and 50% coverage reduced differences in PrEP access between PrEP-indicated White and Black MSM from 23 to 9 pp and 4 pp, resp
Ong JJ, Booton RD, Tucker JD, et al., 2023, Economic evaluation of improving HIV self-testing among men who have sex with men in China using a crowdsourced intervention: a cost-effectiveness analysis, AIDS, Vol: 37, Pages: 671-678, ISSN: 0269-9370
Objectives: Crowdsourcing, which taps into the wisdom of crowds, has been successful in generating strategies to enhance HIV self-testing (HIVST) uptake. We determined the cost-effectiveness of a crowdsourced intervention (one-off or annual) compared with a control scenario (no crowdsourcing) among MSM living in China.Design: Economic evaluation.Methods: We used data from our cluster randomized controlled trial of MSM (NCT02796963). We used a micro-costing approach to measure direct health costs ($USD2017) from a health provider perspective. Using outputs from a dynamic transmission model over a 20-year time horizon, we estimated the incremental cost-effectiveness ratios using cost per disability-adjusted life years (DALYs) averted with 3% discounting. An intervention was considered highly cost-effective if it was less than one gross domestic product (GDP, $8823) per DALY averted.Results: Across all cities, the crowdsourced intervention was highly cost-effective compared with the control scenario (incremental cost-effectiveness ratios ranged from $2263 to 6152 per DALY averted for annual crowdsourcing; $171 to 204 per DALY averted for one-off crowdsourcing). The one-off intervention was cost-saving in Guangzhou and Qingdao. Sensitivity analyses confirmed the robustness of the findings; specifically, changes in discounting, costs of the crowdsourced intervention, costs of HIV testing and cost of antiretroviral therapy did not alter our conclusions.Conclusion: Scaling up a one-off or annual crowdsourced HIV prevention intervention in four cities in China was very likely to be cost-effective. Further research is warranted to evaluate the feasibility of scaling up crowdsourced HIV prevention interventions in other settings and populations.
Mitchell KM, Boily MC, Hanscom B, et al., 2023, Estimating the impact of HIV PrEP regimens containing long-acting injectable cabotegravir or daily oral tenofovir disoproxil fumarate/emtricitabine among men who have sex with men in the United States: a mathematical modelling study for HPTN 083, The Lancet Regional Health - Americas, Vol: 18, ISSN: 2667-193X
Background:The HPTN 083 trial demonstrated superiority of HIV pre-exposure prophylaxis (PrEP) containing long-acting injectable cabotegravir (CAB) to daily oral tenofovir disoproxil fumarate/emtricitabine (TDF/FTC) among men who have sex with men (MSM). We compared the potential population-level impact of TDF/FTC and CAB among MSM in Atlanta, Georgia.Methods:An MSM HIV transmission model was calibrated to Atlanta-specific data on HIV prevalence and PrEP usage (percentage of uninfected MSM on PrEP), assuming only PrEP-indicated MSM used PrEP. CAB effectiveness (efficacy × adherence) of 91% was estimated using data from HPTN 083 and previous TDF/FTC trials. We estimated HIV infections averted over 5/10 years if TDF/FTC use were maintained, or if all TDF/FTC users switched to CAB in January 2022 (vs. no PrEP or continued TDF/FTC use). CAB scenarios with 10%/20% more users were also considered. Progress towards Ending the HIV Epidemic (EHE) goals (75%/90% fewer HIV infections in 2025/2030 vs. 2017) was estimated.Findings:We predicted TDF/FTC at current usage (∼28%) would avert 36.3% of new HIV infections (95% credible interval 25.6–48.7%) among all Atlanta MSM over 2022–2026 vs. no PrEP. Switching to CAB with similar usage may prevent 44.6% (33.2–56.6%) infections vs. no PrEP and 11.9% (5.2–20.2%) infections vs. continued TDF/FTC. Increasing CAB usage 20% could increase the incremental impact over TDF/FTC to 30.0% over 2022–2026, getting ∼60% towards reaching EHE goals (47%/54% fewer infections in 2025/2030). Reaching the 2030 EHE goal would require 93% CAB usage.Interpretation:If CAB effectiveness were like HPTN 083, CAB could prevent more infections than TDF/FTC at similar usage. Increased CAB usage could contribute substantially towards reaching EHE goals, but the usage required to meet EHE goals is unrealistic.
Remien RH, Dacus J-D, Farley JE, et al., 2023, HTPN 078: an enhanced case management study to achieve viral suppression among viremic HIV-positive men who have sex with men in the United States., AIDS, Vol: 37, Pages: 217-231, ISSN: 0269-9370
OBJECTIVES: After identifying and recruiting men who have sex with men living with HIV and virally unsuppressed, this study attempted to enhance treatment and care via case management to increase the proportion who achieved viral suppression. DESIGN: Participants were randomized into one of two study arms: standard of care (SOC) or enhanced case management (CM) intervention. Participants were followed for 12 months with quarterly study assessments, with blood collected for CD4+ cell count testing, HIV viral load testing (primary prespecified outcome), and plasma storage. METHODS: Participants identified via respondent-driven sampling and direct recruitment and were invited to participate in the randomized controlled trial. The CM intervention provided a wide range of support services including, health education, clinical care coordination, medication adherence support, and social service assistance. The month-12 assessment included questions about healthcare utilization, stigma, substance use, and mental health. RESULTS: Among the 144 participants virally unsuppressed at baseline, most had had a previous positive HIV test result; were Black, non-Hispanic, gay and bisexual men, aged 22-50. Among the 128 participants at the last study visit, 68 were virally suppressed, with no statistically significant difference between the CM and SOC arms (viral suppression 42% and 53%, respectively; adjusted odds ratio = 0.62 [P = 0.15; 95% confidence interval: 0.32, 1.2]). CONCLUSIONS: Reaching targets of at least 90% sustained viral suppression among all people with HIV will likely require more than an individual-level CM approach that addresses barriers to optimal care and treatment at multiple levels.
Stannah J, Anato JLF, Mitchell KM, et al., 2022, PESUD36 Improving our understanding of how structural determinants impact HIV epidemics: a scoping review of dynamic models to guide future research, AIDS 2022 - the 24th International AIDS Conference, Publisher: Wiley, Pages: 142-143, ISSN: 1758-2652
Mitchell KM, Maheu-Giroux M, Dimitrov D, et al., 2022, How can progress towards Ending the HIV Epidemic in the United States be monitored?, Clinical Infectious Diseases, Vol: 75, Pages: 163-169, ISSN: 1058-4838
The plan for Ending the HIV Epidemic (EHE) in the United States aims to reduce new infections by 75% by 2025 and by 90% by 2030. For EHE to be successful, it is important to accurately measure changes in numbers of new HIV infections after 5 and 10 years (to determine whether the EHE goals have been achieved) but also over shorter time-scales (to monitor progress and intensify prevention efforts if required). In this viewpoint, we aim to demonstrate why the method used to monitor progress towards the EHE goals needs to be carefully considered. We briefly describe and discuss different methods to estimate numbers of new HIV infections, based on longitudinal cohort studies, cross-sectional incidence surveys and routine surveillance data. We particularly focus on identifying conditions under which unadjusted and adjusted estimates based on routine surveillance data can be used to estimate changes in new HIV infections.
Wong NS, Lee SS, Mitchell KM, et al., 2022, Impact of pre-event testing and quarantine on reducing the risk of COVID-19 epidemic rebound: a modelling study, BMC Infectious Diseases, Vol: 22, ISSN: 1471-2334
BACKGROUND: With the evolving growth of the COVID-19 epidemic, travel restriction policies would need to be adjusted accordingly. Prohibition of mass event may be relaxed for social and economic benefits when virus transmission stops but could bear the risk of epidemic rebound. Against the background of the varied SARS-CoV-2 prevalence internationally, we modelled the potential impacts of pre-event interventions on epidemic risk of holding a mass event when COVID-19 is under control. METHODS: We developed a mathematical model of SARS-CoV-2 transmission in Guangdong Province, China, where local virus transmission ceased to occur. A large-scale international trade fair was assumed to be held, with influx of people from overseas and rest of China over a short period of time, who participated for 2-week. Scenarios of pre-event intervention (none, quarantine arrangement and polymerase chain reaction (PCR) testing for participants) were compared. The influence of contact pattern, SARS-CoV-2 prevalence outside the province and China, and testing coverage were examined in sensitivity analyses. RESULTS: In basecase scenario (no event), the epidemic has been under control since March 2020. The event would lead to the detection of 1% more confirmed cases by 31 July when community contact rate increases to pre-epidemic level. In event scenario without additional interventions, there would be 599 (93%) more new infections comparing with basecase scenario. To avert new infections, quarantining all participants before the event would be the most effective strategy, followed by quarantining all overseas participants and testing all other participants, and testing all participants before the event and on day 7. However, testing strategy is likely to be affected by the SARS-CoV-2 prevalence outside the event province. CONCLUSIONS: Pre-event interventions are effective for reducing the risk of epidemic rebound caused by an international large-scale event. Universal testing for partici
Silhol R, Geidelberg L, Mitchell K, et al., 2021, Assessing the potential impact of disruptions due to COVID-19 on HIV among key and lower-risk populations in the largest cities of Cameroon and Benin, JAIDS: Journal of Acquired Immune Deficiency Syndromes, Vol: 87, Pages: 899-911, ISSN: 1525-4135
Background: The COVID-19 pandemic indirectly impacts HIV epidemiology in Central/West Africa. We estimated the potential impact of COVID-19-related disruptions to HIV prevention/treatment services and sexual partnerships on HIV incidence and HIV-related deaths among key populations including female sex workers (FSW), their clients, men who have sex with men (MSM), and overall.Setting: Yaoundé (Cameroon) and Cotonou (Benin).Methods: We used mathematical models of HIV calibrated to city- and risk-population-specific demographic/behavioural/epidemic data. We estimated the relative change in 1-year HIV incidence and HIV-related deaths for various disruption scenarios of HIV prevention/treatment services and decreased casual/commercial partnerships, compared to a scenario without COVID-19.Results: A 50% reduction in condom use in all partnerships over 6 months would increase 1-year HIV incidence by 39%, 42%, 31% and 23% among MSM, FSW, clients, and overall in Yaoundé respectively, and 69%, 49% and 23% among FSW, clients and overall respectively in Cotonou. Combining a 6-month interruption of ART initiation and 50% reduction in HIV prevention/treatment use would increase HIV incidence by 50% and HIV-related deaths by 20%. This increase in HIV infections would be halved by a simultaneous 50% reduction in casual and commercial partnerships.Conclusions: Reductions in condom use following COVID-19 would increase infections among key populations disproportionately, particularly FSW in Cotonou, who need uninterrupted condom provision. Disruptions in HIV prevention/treatment services have the biggest impacts on HIV infections and deaths overall, only partially mitigated by equal reductions in casual/commercial sexual partnerships. Maintaining ART provision must be prioritised to minimise short-term excess HIV-related deaths.
Booton RD, Ong JJ, Lee A, et al., 2021, Modelling the impact of an HIV testing intervention on HIV transmission among men who have sex with men in China, HIV Medicine, Vol: 22, Pages: 467-477, ISSN: 1464-2662
ObjectivesAn intervention developed through participatory crowdsourcing methods increased HIV self‐testing among men who have sex with men [MSM; relative risk (RR) = 1.89]. We estimated the long‐term impact of this intervention on HIV transmission among MSM in four cities (Guangzhou, Shenzhen, Jinan and Qingdao).MethodsA mathematical model of HIV transmission, testing and treatment among MSM in China was parameterized using city‐level demographic and sexual behaviour data and calibrated to HIV prevalence, diagnosis and antiretroviral therapy (ART) coverage data. The model was used to project the HIV infections averted over 20 years (2016–2036) from the intervention to increase self‐testing, compared with current testing rates.ResultsRunning the intervention once would avert < 2.2% infections over 20 years. Repeating the intervention (RR = 1.89) annually would avert 6.4–10.7% of new infections, while further increases in the self‐testing rate (hypothetical RR = 3) would avert 11.7–20.7% of new infections.ConclusionsRepeated annual interventions would give a three‐ to seven‐fold increase in long‐term impact compared with a one‐off intervention. Other interventions will be needed to more effectively reduce the HIV burden in this population.
Moore M, Donnell DJ, Boily M-C, et al., 2021, Estimated long-acting PrEP effectiveness in the HPTN 084 cohort using a model-based HIV incidence in the absence of PrEP, Publisher: JOHN WILEY & SONS LTD, Pages: 34-34
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Soni N, Giguère K, Boily M-C, et al., 2021, Under-reporting of known HIV-positive status among people living with HIV: a systematic review and meta-analysis, AIDS and Behavior, Vol: 25, Pages: 3858-3870, ISSN: 1090-7165
Monitoring progress towards the UNAIDS ‘first 90’ target requires accurate estimates of levels of diagnosis among people living with HIV (PLHIV), which is often estimated using self-report. We conducted a systematic review and meta-analysis quantifying under-reporting of known HIV-positive status using objective knowledge proxies. Databases were searched for studies providing self-reported and biological/clinical markers of prior knowledge of HIV-positive status among PLHIV. Random-effects models were used to derive pooled estimates of levels of under-reporting. Thirty-two estimates from 26 studies were included (41,465 PLHIV). The pooled proportion under-reporting known HIV-positive status was 20% (95% confidence interval 13–26%, I2 = 99%). In sub-group analysis, under-reporting was higher among men who have sex with men (32%, number of estimates [Ne] = 10) compared to the general population (9%, Ne = 10) and among Black (18%, Ne = 5) than non-Black (3%, Ne = 3) individuals. Supplementing self-reported data with biological/clinical proxies may improve the validity of the ‘first 90’ estimates.
Mitchell KM, Dimitrov D, Silhol R, et al., 2021, The potential effect of COVID-19-related disruptions on HIV incidence and HIV-related mortality among men who have sex with men in the USA: a modelling study, The Lancet HIV, Vol: 8, Pages: e206-e215, ISSN: 2405-4704
BACKGROUND: During the COVID-19 pandemic, men who have sex with men (MSM) in the USA have reported similar or fewer sexual partners and reduced HIV testing and care access compared with before the pandemic. Pre-exposure prophylaxis (PrEP) use has also declined. We aimed to quantify the potential effect of COVID-19 on HIV incidence and HIV-related mortality among US MSM. METHODS: We used a calibrated, deterministic, compartmental HIV transmission model for MSM in Baltimore (MD, USA) and available data on COVID-19-related disruptions to HIV services to predict effects of reductions in sexual partners (0%, 25%, 50%), condom use (5%), HIV testing (20%), viral suppression (10%), PrEP initiations (72%), PrEP adherence (9%), and antiretroviral therapy (ART) initiations (50%). In our main analysis, we modelled disruptions due to COVID-19 starting Jan 1, 2020, and lasting 6 months. We estimated the median change in cumulative new HIV infections and HIV-related deaths among MSM over 1 and 5 years, compared with a base case scenario without COVID-19-related disruptions. FINDINGS: A 25% reduction in sexual partners for 6 months among MSM in Baltimore, without HIV service changes, could reduce new HIV infections by median 12·2% (95% credible interval 11·7 to 12·8) over 1 year and median 3·0% (2·6 to 3·4) over 5 years. In the absence of changes in sexual behaviour, the 6-month estimated reductions in condom use, HIV testing, viral suppression, PrEP initiations, PrEP adherence, and ART initiations combined are predicted to increase new HIV infections by median 10·5% (5·8 to 16·5) over 1 year, and by median 3·5% (2·1 to 5·4) over 5 years. Disruptions to ART initiations and viral suppression are estimated to substantially increase HIV-related deaths (ART initiations by median 1·7% [0·8 to 3·2], viral suppression by median 9·5% [5·2 to 15·9]) over 1 year, with
Booton RD, Fu G, MacGregor L, et al., 2021, The impact of disruptions due to COVID-19 on HIV transmission and control among men who have sex with men in China, Journal of the International AIDS Society, Vol: 24, ISSN: 1758-2652
INTRODUCTION: The COVID-19 pandemic is impacting HIV care globally, with gaps in HIV treatment expected to increase HIV transmission and HIV-related mortality. We estimated how COVID-19-related disruptions could impact HIV transmission and mortality among men who have sex with men (MSM) in four cities in China, over a one- and five-year time horizon. METHODS: Regional data from China indicated that the number of MSM undergoing facility-based HIV testing reduced by 59% during the COVID-19 pandemic, alongside reductions in ART initiation (34%), numbers of all sexual partners (62%) and consistency of condom use (25%), but initial data indicated no change in viral suppression. A mathematical model of HIV transmission/treatment among MSM was used to estimate the impact of disruptions on HIV infections/HIV-related deaths. Disruption scenarios were assessed for their individual and combined impact over one and five years for 3/4/6-month disruption periods, starting from 1 January 2020. RESULTS: Our model predicted new HIV infections and HIV-related deaths would be increased most by disruptions to viral suppression, with 25% reductions (25% virally suppressed MSM stop taking ART) for a three-month period increasing HIV infections by 5% to 14% over one year and deaths by 7% to 12%. Observed reductions in condom use increased HIV infections by 5% to 14% but had minimal impact (<1%) on deaths. Smaller impacts on infections and deaths (<3%) were seen for disruptions to facility HIV testing and ART initiation, but reduced partner numbers resulted in 11% to 23% fewer infections and 0.4% to 1.0% fewer deaths. Longer disruption periods (4/6 months) amplified the impact of disruption scenarios. When realistic disruptions were modelled simultaneously, an overall decrease in new HIV infections occurred over one year (3% to 17%), but not for five years (1% increase to 4% decrease), whereas deaths mostly increased over one year (1% to 2%) and five years (1.2 increase to 0.3 d
Geidelberg L, Mitchell KM, Alary M, et al., 2021, A mathematical model impact analysis of a real-life pre-exposure prophylaxis and treatment-as-prevention study among female sex workers in Cotonou, Benin, JAIDS: Journal of Acquired Immune Deficiency Syndromes, Vol: 86, Pages: e28-e42, ISSN: 1525-4135
BACKGROUND: Daily pre-exposure prophylaxis (PrEP) and treatment-as-prevention (TasP) reduce HIV acquisition and transmission risk, respectively. A demonstration study (2015-2017) assessed TasP and PrEP feasibility among female sex workers (FSW) in Cotonou, Benin. SETTING: Cotonou, Benin METHODS:: We developed a compartmental HIV transmission model, featuring PrEP, and ART among the high-risk (FSW, clients) and low-risk populations, calibrated to historical epidemiological and demonstration study data, reflecting observed lower PrEP uptake, adherence and retention compared to TasP. We estimated the population-level impact of the two-year study and several twenty-year intervention scenarios, varying coverage and adherence independently and together. We report the percentage (median, 2.5th-97.5th percentile uncertainty interval (95%UI)) of HIV infections prevented comparing the intervention and counterfactual (2017 coverages: 0% PrEP, 49% ART) scenarios. RESULTS: The two-year study (2017 coverages: 9% PrEP, 83% ART) prevented an estimated 8% (95%UI 6-12) and 6% (3-10) infections among FSW over two and twenty years, respectively, compared to 7% (3-11) and 5% (2-9) overall. The PrEP and TasP arms prevented 0.4% (0.2-0.8) and 4.6% (2.2-8.7) infections overall over 20 years, respectively. Twenty-year PrEP and TasP scale-ups (2035 coverages: 47% PrEP, 88% ART) prevented 21% (17-26) and 17% (10-27) infections among FSW respectively, and 5% (3-10) and 17% (10-27) overall. Compared to TasP scale-up alone, PrEP and TasP combined scale-up prevented 1.9x and 1.2x more infections among FSW and overall, respectively. CONCLUSIONS: The modest demonstration study impact was modest, and mostly from TasP. Increasing PrEP adherence and coverage improves impact substantially among FSW, but little overall. We recommend TasP in prevention packages.
Wong NS, Powers KA, Tucker JD, et al., 2021, Modelling the impact of a sex work crackdown on syphilis transmission among female sex workers and their clients in South China, SEXUALLY TRANSMITTED INFECTIONS, Vol: 97, Pages: 45-50, ISSN: 1368-4973
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Silhol R, Geidelberg L, Mitchell K, et al., 2021, COVID-19 and associated disruptions may indirectly affect HIV outcomes in two capital cities in Western/Central Africa: a modelling study, Publisher: JOHN WILEY & SONS LTD
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, JAIDS: Journal of Acquired Immune Deficiency Syndromes, Vol: 85, Pages: 423-429, ISSN: 1525-4135
Background: Pre-exposure prophylaxis (PrEP) with tenofovir disoproxil fumarate and emtricitabine 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 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.Results: Our model reproduced the annual HIV incidence of 3.2%–4.8% observed over 1 year of follow-up in the placebo groups of 4 completed clinical studies. We predicted an annual HIV incidence of 3.7% (95% confidence interval: 3.2 to 4.2) among HIV Prevention Trials Network 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.
Moore M, Boily M-C, Mitchell KM, et al., 2020, Identifying regions of greatest need for ending the HIV epidemic: a plan for America, JAIDS: Journal of Acquired Immune Deficiency Syndromes, Vol: 85, Pages: 395-398, ISSN: 1525-4135
BACKGROUND: In the 2019 State of the Union Address, President Trump announced a plan for "Ending the HIV Epidemic" in the United States, with a goal to reduce new HIV infections by 90% by 2030. Phase I of the plan set an intermediate goal of a 75% reduction within 5 years, focusing on select states and counties. METHODS: We assessed the feasibility of the first phase of the plan by estimating the fraction of HIV diagnoses that occur within the targeted region, using a statistical model to predict new HIV cases in each county. We suggested new areas that should be added to the current plan, prioritizing by both a "Density Metric" of new HIV cases and a "Gap Metric" quantifying shortcomings in antiretroviral therapy and pre-exposure prophylaxis uptake. RESULTS: We found the current plan targets less than 60% of new diagnoses. The plan should be expanded to Puerto Rico, Florida, Georgia, Louisiana, and Maryland as well as parts of New York, North Carolina, Texas, and Virginia, areas which were prioritized by both metrics. CONCLUSION: Many of the highest priority areas, both by density of HIV cases and by lack of viral suppression and pre-exposure prophylaxis use, were not covered by the original plan, particularly in the South. The current plan to end the HIV epidemic must be expanded to these areas to feasibly allow for a 75% reduction in new HIV cases within 5 years.
Mitchell KM, Dimitrov D, Hughes JP, et al., 2020, Assessing the use of surveillance data to estimate the impact of prevention interventions on HIV incidence in cluster-randomized controlled trials, Epidemics, Vol: 33, Pages: 1-8, ISSN: 1755-4365
BackgroundIn cluster-randomized controlled trials (C-RCTs) of HIV prevention strategies, HIV incidence is expensive to measure directly. Surveillance data on HIV diagnoses or viral suppression could provide cheaper incidence estimates. We used mathematical modelling to evaluate whether these measures can replace HIV incidence measurement in C-RCTs.MethodsWe used a US HIV transmission model to simulate C-RCTs of expanded antiretroviral therapy(ART), pre-exposure prophylaxis(PrEP) and HIV testing, together or alone. We tested whether modelled reductions in total new HIV diagnoses, diagnoses with acute infection, diagnoses with early infection(CD4 > 500 cells/μl), diagnoses adjusted for testing volume, or the proportion virally non-suppressed, reflected HIV incidence reductions.ResultsOver a two-year trial expanding PrEP alone, modelled reductions in total diagnoses underestimated incidence reductions by a median six percentage points(pp), with acceptable variability(95 % credible interval -14,-2pp). For trials expanding HIV testing alone or alongside ART + PrEP, greater, highly variable bias was seen[-20pp(-128,-1) and -30pp(-134,-16), respectively]. Acceptable levels of bias were only seen over longer trial durations when levels of awareness of HIV-positive status were already high. Expanding ART alone, only acute and early diagnoses reductions reflected incidence reduction well, with some bias[-3pp(-6,-1) and -8pp(-16,-3), respectively]. Early and adjusted diagnoses also reliably reflected incidence when scaling up PrEP alone[bias -5pp(-11,1) and 10pp(3,18), respectively]. For trials expanding testing (alone or with ART + PrEP), bias for all measures explored was too variable for them to replace direct incidence measures, unless using diagnoses when HIV status awareness was already high.ConclusionsSurveillance measures based on HIV diagnoses may sometimes be adequate surrogates for HIV incidence reduction in C-RCTs expanding ART or PrEP only, if adjusted for b
Mitchell KM, Dimitrov D, Silhol R, et al., 2020, Estimating the potential impact of COVID-19-related disruptions on HIV incidence and mortality among men who have sex with men in the United States: a modelling study., Publisher: Cold Spring Harbor Laboratory
Background: During the COVID-19 pandemic, gay and other men who have sex with men (MSM) in the United States (US) report similar or fewer sexual partners and reduced HIV testing and care access. Pre-exposure prophylaxis (PrEP) use has declined. We estimated the potential impact of COVID-19 on HIV incidence and mortality among US MSM. Methods: We used a calibrated HIV transmission model for MSM in Baltimore, Maryland, and available data on COVID-19-related disruptions to predict impacts of data-driven reductions in sexual partners(0%,25%,50%), condom use(5%), HIV testing(20%), viral suppression(10%), PrEP initiations(72%), PrEP use(9%) and ART initiations(50%), exploring different disruption durations and magnitudes. We estimated the median (95% credible interval) change in cumulative new HIV infections and deaths among MSM over one and five years, compared with a scenario without COVID-19-related disruptions. Findings: A six-month 25% reduction in sexual partners among Baltimore MSM, without HIV service changes, could reduce new HIV infections by 12·2%(11·7,12·8%) and 3·0%(2·6,3·4%) over one and five years, respectively. In the absence of changes in sexual behaviour, the six-month data-driven disruptions to condom use, testing, viral suppression, PrEP initiations, PrEP use and ART initiations combined were predicted to increase new HIV infections by 10·5%(5·8,16·5%) over one year, and by 3·5%(2·1,5·4%) over five years. A 25% reduction in partnerships offsets the negative impact of these combined service disruptions on new HIV infections (overall reduction 3·9%(-1·0,7·4%), 0·0%(-1·4,0·9%) over one, five years, respectively), but not on HIV deaths (corresponding increases 11·0%(6·2,17·7%), 2·6%(1·5,4·3%)). The predicted impacts of reductions in partnerships or viral suppression doubled if they lasted 12
Booton RD, Fu G, MacGregor L, et al., 2020, Estimating the impact of disruptions due to COVID-19 on HIV transmission and control among men who have sex with men in China, Publisher: medRxiv
Introduction The COVID-19 pandemic is impacting HIV care globally, with gaps in HIV treatment expected to increase HIV transmission and HIV-related mortality. We estimated how COVID-19-related disruptions could impact HIV transmission and mortality among men who have sex with men (MSM) in four cities in China. Methods Regional data from China indicated that the number of MSM undergoing facility-based HIV testing reduced by 59% during the COVID-19 pandemic, alongside reductions in ART initiation (34%), numbers of sexual partners (62%) and consistency of condom use (25%). A deterministic mathematical model of HIV transmission and treatment among MSM in China was used to estimate the impact of these disruptions on the number of new HIV infections and HIV-related deaths. Disruption scenarios were assessed for their individual and combined impact over 1 and 5 years for a 3-, 4- or 6-month disruption period. Results Our China model predicted that new HIV infections and HIV-related deaths would be increased most by disruptions to viral suppression, with 25% reductions for a 3-month period increasing HIV infections by 5-14% over 1 year and deaths by 7-12%. Observed reductions in condom use increased HIV infections by 5-14% but had minimal impact (<1%) on deaths. Smaller impacts on infections and deaths (<3%) were seen for disruptions to facility testing and ART initiation, but reduced partner numbers resulted in 11-23% fewer infections and 0.4-1.0% fewer deaths. Longer disruption periods of 4 and 6 months amplified the impact of combined disruption scenarios. When all realistic disruptions were modelled simultaneously, an overall decrease in new HIV infections was always predicted over one year (3-17%), but not over 5 years (1% increase - 4% decrease), while deaths mostly increased over one year (1-2%) and 5 years (1.2 increase - 0.3 decrease). Conclusions The overall impact of COVID-19 on new HIV infections and HIV-related deaths is dependent on the nature, scale and
Foss AM, Prudden HJ, Mitchell KM, et al., 2020, Using data from 'visible' populations to estimate the size and importance of 'hidden' populations in an epidemic: A modelling technique., Infectious Disease Modelling, Vol: 5, Pages: 798-813, ISSN: 2468-2152
We used reported behavioural data from cisgender men who have sex with men and transgender women (MSM/TGW) in Bangalore, mainly collected from 'hot-spot' locations that attract MSM/TGW, to illustrate a technique to deal with potential issues with the representativeness of this sample. A deterministic dynamic model of HIV transmission was developed, incorporating three subgroups of MSM/TGW, grouped according to their reported predominant sexual role (insertive, receptive or versatile). Using mathematical modelling and data triangulation for 'balancing' numbers of partners and role preferences, we compared three different approaches to determine if our technique could be useful for inferring characteristics of a more 'hidden' insertive MSM subpopulation, and explored their potential importance for the HIV epidemic. Projections for 2009 across all three approaches suggest that HIV prevalence among insertive MSM was likely to be less than half that recorded in the surveys (4.5-6.5% versus 13.1%), but that the relative size of this subgroup was over four times larger (61-69% of all MSM/TGW versus 15%). We infer that the insertive MSM accounted for 10-20% of all prevalent HIV infections among urban males aged 15-49. Mathematical modelling can be used with data on 'visible' MSM/TGW to provide insights into the characteristics of 'hidden' MSM. A greater understanding of the sexual behaviour of all MSM/TGW is important for effective HIV programming. More broadly, a hidden subgroup with a lower infectious disease prevalence than more visible subgroups, has the potential to contain more infections, if the hidden subgroup is considerably larger in size.
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.
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%
Brown P, Tan A-C, El-Esawi MA, et al., 2019, Large expert-curated database for benchmarking document similarity detection in biomedical literature search, Database: the journal of biological databases and curation, Vol: 2019, Pages: 1-66, ISSN: 1758-0463
Document recommendation systems for locating relevant literature have mostly relied on methods developed a decade ago. This is largely due to the lack of a large offline gold-standard benchmark of relevant documents that cover a variety of research fields such that newly developed literature search techniques can be compared, improved and translated into practice. To overcome this bottleneck, we have established the RElevant LIterature SearcH consortium consisting of more than 1500 scientists from 84 countries, who have collectively annotated the relevance of over 180 000 PubMed-listed articles with regard to their respective seed (input) article/s. The majority of annotations were contributed by highly experienced, original authors of the seed articles. The collected data cover 76% of all unique PubMed Medical Subject Headings descriptors. No systematic biases were observed across different experience levels, research fields or time spent on annotations. More importantly, annotations of the same document pairs contributed by different scientists were highly concordant. We further show that the three representative baseline methods used to generate recommended articles for evaluation (Okapi Best Matching 25, Term Frequency–Inverse Document Frequency and PubMed Related Articles) had similar overall performances. Additionally, we found that these methods each tend to produce distinct collections of recommended articles, suggesting that a hybrid method may be required to completely capture all relevant articles. The established database server located at https://relishdb.ict.griffith.edu.au is freely available for the downloading of annotation data and the blind testing of new methods. We expect that this benchmark will be useful for stimulating the development of new powerful techniques for title and title/abstract-based search engines for relevant articles in biomedical research.
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