Impact and cost-effectiveness of the national scale-up of HIV pre-exposure prophylaxis among female sex workers in South Africa: a modelling analysis.

INTRODUCTION: In 2016, South Africa (SA) initiated a national programme to scale-up pre-exposure prophylaxis (PrEP) among female sex workers (FSWs), with ∼20,000 PrEP initiations among FSWs (∼14% of FSW) by 2020. We evaluated the impact and cost-effectiveness of this programme, including future scale-up scenarios and the potential detrimental impact of the COVID-19 pandemic. METHODS: A compartmental HIV transmission model for SA was adapted to include PrEP. Using estimates on self-reported PrEP adherence from a national study of FSW (67.7%) and the Treatment and Prevention for FSWs (TAPS) PrEP demonstration study in SA (80.8%), we down-adjusted TAPS estimates for the proportion of FSWs with detectable drug levels (adjusted range: 38.0-70.4%). The model stratified FSW by low (undetectable drug; 0% efficacy) and high adherence (detectable drug; 79.9%; 95% CI: 67.2-87.6% efficacy). FSWs can transition between adherence levels, with lower loss-to-follow-up among highly adherent FSWs (aHR: 0.58; 95% CI: 0.40-0.85; TAPS data). The model was calibrated to monthly data on the national scale-up of PrEP among FSWs over 2016-2020, including reductions in PrEP initiations during 2020. The model projected the impact of the current programme (2016-2020) and the future impact (2021-2040) at current coverage or if initiation and/or retention are doubled. Using published cost data, we assessed the cost-effectiveness (healthcare provider perspective; 3% discount rate; time horizon 2016-2040) of the current PrEP provision. RESULTS: Calibrated to national data, model projections suggest that 2.1% of HIV-negative FSWs were currently on PrEP in 2020, with PrEP preventing 0.45% (95% credibility interval, 0.35-0.57%) of HIV infections among FSWs over 2016-2020 or 605 (444-840) infections overall. Reductions in PrEP initiations in 2020 possibly reduced infections averted by 18.57% (13.99-23.29). PrEP is cost-saving, with $1.42 (1.03-1.99) of ART costs saved per dollar spent on PrEP. Going forward, existing coverage of PrEP will avert 5,635 (3,572-9,036) infections by 2040. However, if PrEP initiation and retention doubles, then PrEP coverage increases to 9.9% (8.7-11.6%) and impact increases 4.3 times with 24,114 (15,308-38,107) infections averted by 2040. CONCLUSIONS: Our findings advocate for the expansion of PrEP to FSWs throughout SA to maximize its impact. This should include strategies to optimize retention and should target women in contact with FSW services.

Potential benefit of extended dose schedules of human papillomavirus vaccination in the context of scarce resources and COVID-19 disruptions in low-income and middle-income countries: a mathematical modelling analysis.

BACKGROUND: The WHO Strategic Advisory Group of Experts recommended that an extended interval of 3-5 years between the two doses of the human papillomavirus (HPV) vaccine could be considered to alleviate vaccine supply shortages. However, three concerns have limited the introduction of extended schedules: girls could be infected between the two doses, the vaccination coverage for the second dose could be lower at ages 13-14 years than at ages 9-10 years, and identifying girls vaccinated with a first dose to give them the second dose could be difficult. Using mathematical modelling, we examined the potential effect of these concerns on the population-level impact and efficiency of extended dose HPV vaccination schedules. METHODS: We used HPV-ADVISE, an individual-based, transmission-dynamic model of multitype HPV infection and disease, calibrated to country-specific data for four low-income and middle-income countries (India, Viet Nam, Uganda, and Nigeria). For the extended dose scenarios, we varied the vaccination coverage of the second dose among girls previously vaccinated, the one-dose vaccine efficacy, and the one-dose vaccine duration of protection. We also examined a strategy in which girls aged 14 years were vaccinated irrespective of their previous vaccination status. We used a scenario of girls-only two-dose vaccination at age 9 years (vaccine=9 valent, vaccine-type efficacy=100%, duration of protection=lifetime, and coverage=80%) as our comparator. We estimated two outcomes: the relative reduction in the age-standardised cervical cancer incidence (population-level impact) and the number of cervical cancers averted per 100 000 doses (efficiency). FINDINGS: Our model projected substantial reductions in cervical cancer incidence over 100 years with the two-dose schedule (79-86% depending on the country), compared with no vaccination. Projections for the 5-year extended schedule, in which the second dose is given only to girls previously vaccinated at age 9 years, were similar to the current two-dose schedule, unless vaccination coverage of the second dose is very low (reductions in cervical cancer incidence of 71-78% assuming 30% coverage at age 14 years among girls vaccinated at age 9 years). However, when the dose at age 14 years is given to girls irrespective of vaccination status and assuming high vaccination coverage, the model projected a substantially greater reduction in cervical cancer incidence compared with the current two-dose schedule (reductions in cervical cancer incidence of 86-93% assuming 70% coverage at age 14 years, irrespective of vaccination status). Efficiency of the extended schedule was greater than the two-dose schedule, even with a drop in vaccination coverage. INTERPRETATION: The three concerns are unlikely to have a substantial effect on the population-level impact of extended dose schedules. Hence, extended dose schedules will likely provide similar cervical cancer reductions as two-dose schedules, while reducing the number of doses required in the short-term, providing a more efficient use of scarce resources, and offering a 5-year time window to reassess the necessity of the second dose. FUNDING: WHO, Canadian Institute of Health Research Foundation, Fonds de recherche du Québec-Santé, Digital Research Alliance of Canada, and Bill & Melinda Gates Foundation.

Time trends in social contacts before and during the COVID-19 pandemic: the CONNECT study.

BACKGROUND: Since the beginning of the COVID-19 pandemic, many countries, including Canada, have adopted unprecedented physical distancing measures such as closure of schools and non-essential businesses, and restrictions on gatherings and household visits. We described time trends in social contacts for the pre-pandemic and pandemic periods in Quebec, Canada. METHODS: CONNECT is a population-based study of social contacts conducted shortly before (2018/2019) and during the COVID-19 pandemic (April 2020 - February 2021), using the same methodology for both periods. We recruited participants by random digit dialing and collected data by self-administered web-based questionnaires. Questionnaires documented socio-demographic characteristics and social contacts for two assigned days. A contact was defined as a two-way conversation at a distance ≤ 2 m or as a physical contact, irrespective of masking. We used weighted generalized linear models with a Poisson distribution and robust variance (taking possible overdispersion into account) to compare the mean number of social contacts over time and by socio-demographic characteristics. RESULTS: A total of 1291 and 5516 Quebecers completed the study before and during the pandemic, respectively. Contacts significantly decreased from a mean of 8 contacts/day prior to the pandemic to 3 contacts/day during the spring 2020 lockdown. Contacts remained lower than the pre-COVID period thereafter (lowest = 3 contacts/day during the Christmas 2020/2021 holidays, highest = 5 in September 2020). Contacts at work, during leisure activities/in other locations, and at home with visitors showed the greatest decreases since the beginning of the pandemic. All sociodemographic subgroups showed significant decreases of contacts since the beginning of the pandemic. The mixing matrices illustrated the impact of public health measures (e.g. school closure, gathering restrictions) with fewer contacts between children/teenagers and fewer contacts outside of the three main diagonals of contacts between same-age partners/siblings and between children and their parents. CONCLUSION: Physical distancing measures in Quebec significantly decreased social contacts, which most likely mitigated the spread of COVID-19.

Costs and Scale-Up Costs of Integrating HIV Self-Testing Into Civil Society Organisation-Led Programmes for Key Populations in Côte d'Ivoire, Senegal, and Mali.

Despite significant progress on the proportion of individuals who know their HIV status in 2020, Côte d'Ivoire (76%), Senegal (78%), and Mali (48%) remain far below, and key populations (KP) including female sex workers (FSW), men who have sex with men (MSM), and people who use drugs (PWUD) are the most vulnerable groups with a HIV prevalence at 5-30%. HIV self-testing (HIVST), a process where a person collects his/her own specimen, performs a test, and interprets the result, was introduced in 2019 as a new testing modality through the ATLAS project coordinated by the international partner organisation Solthis (IPO). We estimate the costs of implementing HIVST through 23 civil society organisations (CSO)-led models for KP in Côte d'Ivoire (N = 7), Senegal (N = 11), and Mali (N = 5). We modelled costs for programme transition (2021) and early scale-up (2022-2023). Between July 2019 and September 2020, a total of 51,028, 14,472, and 34,353 HIVST kits were distributed in Côte d'Ivoire, Senegal, and Mali, respectively. Across countries, 64-80% of HIVST kits were distributed to FSW, 20-31% to MSM, and 5-8% to PWUD. Average costs per HIVST kit distributed were $15 for FSW (Côte d'Ivoire: $13, Senegal: $17, Mali: $16), $23 for MSM (Côte d'Ivoire: $15, Senegal: $27, Mali: $28), and $80 for PWUD (Côte d'Ivoire: $16, Senegal: $144), driven by personnel costs (47-78% of total costs), and HIVST kits costs (2-20%). Average costs at scale-up were $11 for FSW (Côte d'Ivoire: $9, Senegal: $13, Mali: $10), $16 for MSM (Côte d'Ivoire: $9, Senegal: $23, Mali: $17), and $32 for PWUD (Côte d'Ivoire: $14, Senegal: $50). Cost reductions were mainly explained by the spreading of IPO costs over higher HIVST distribution volumes and progressive IPO withdrawal at scale-up. In all countries, CSO-led HIVST kit provision to KP showed relatively high costs during the study period related to the progressive integration of the programme to CSO activities and contextual challenges (COVID-19 pandemic, country safety concerns). In transition to scale-up and integration of the HIVST programme into CSO activities, this model shows large potential for substantial economies of scale. Further research will assess the overall cost-effectiveness of this model.

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

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

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.

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 smaller proportional increases over 5 years. The other individual disruptions (to HIV testing, PrEP and condom use, PrEP initiation, and partner numbers) were estimated to have little effect on HIV-related deaths (<1% change over 1 or 5 years). A 25% reduction in sexual partnerships is estimated to offset the effect of the combined service disruptions on new HIV infections (change over 1 year: median -3·9% [-7·4 to 1·0]; over 5 years: median 0·0% [-0·9 to 1·4]), but not on HIV deaths (change over 1 year: 11·0% [6·2 to 17·7]; over 5 years: 2·6% [1·5 to 4·3]). INTERPRETATION: Maintaining access to ART and adherence support is of the utmost importance to maintain viral suppression and minimise excess HIV-related mortality due to COVID-19 restrictions in the USA, even if disruptions to services are accompanied by reductions in sexual partnerships. FUNDING: National Institutes of Health.

Heterogeneity in testing, diagnosis and outcome in SARS-CoV-2 infection across outbreak settings in the Greater Toronto Area, Canada: an observational study.

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 the rest of the population. INTERPRETATION: Long-term care homes and shelters had disproportionate diagnosed cases per capita, and residents of long-term care homes diagnosed with COVID-19 had higher case fatality than the rest of the population. Heterogeneity across micro-epidemics among specific populations and settings may reflect underlying heterogeneity in transmission risks, necessitating setting-specific COVID-19 prevention and mitigation strategies.