Use of Next-Generation Sequencing in a State-Wide Strategy of HIV-1 Surveillance: Impact of the SARS-COV-2 Pandemic on HIV-1 Diagnosis and Transmission.

BACKGROUND: The ongoing severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic posed an unpreceded threat to the management of other pandemics such as human immunodeficiency virus-1 (HIV-1) in the United States. The full impact of the SARS-CoV-2 pandemic on the HIV-1 pandemic needs to be evaluated. METHODS: All individuals with newly reported HIV-1 diagnoses from NC State Laboratory of Public Health were enrolled in this prospective observational study, 2018-2021. We used a sequencing-based recency assay to identify recent HIV-1 infections and to determine the days postinfection (DPI) for each person at the time of diagnosis. RESULTS: Sequencing used diagnostic serum samples from 814 individuals with new HIV-1 diagnoses spanning this 4-year period. Characteristics of individuals diagnosed in 2020 differed from those in other years. People of color diagnosed in 2021 were on average 6 months delayed in their diagnosis compared to those diagnosed in 2020. There was a trend that genetic networks were more known for individuals diagnosed in 2021. We observed no major integrase resistance mutations over the course of the study. CONCLUSIONS: SARS-CoV-2 pandemic may contribute to the spread of HIV-1. Public health resources need to focus on restoring HIV-1 testing and interrupting active, ongoing, transmission.

Preventing tuberculosis with community-based care in an HIV-endemic setting: a modeling analysis.

Introduction: Antiretroviral therapy (ART) and TB preventive treatment (TPT) both prevent tuberculosis (TB) disease and deaths among people living with HIV. Differentiated care models, including community-based care, can increase uptake of ART and TPT to prevent TB in settings with a high burden of HIV-associated TB, particularly among men. Methods: We developed a gender-stratified dynamic model of TB and HIV transmission and disease progression among 100,000 adults ages 15-59 in KwaZulu-Natal, South Africa. We drew model parameters from a community-based ART initiation and resupply trial in sub-Saharan Africa (Delivery Optimization for Antiretroviral Therapy, DO ART) and other scientific literature. We simulated the impacts of community-based ART and TPT care programs during 2018-2027, assuming that community-based ART and TPT care were scaled up to similar levels as in the DO ART trial (i.e., ART coverage increasing from 49% to 82% among men and from 69% to 83% among women) and sustained for ten years. We projected the number of TB cases, deaths, and disability-adjusted life years (DALYs) averted relative to standard, clinic-based care. We calculated program costs and incremental cost-effectiveness ratios from the provider perspective. Results: If community-based ART care could be implemented with similar effectiveness to the DO ART trial, increased ART coverage could reduce TB incidence by 27.0% (range 21.3% - 34.1%) and TB mortality by 36.0% (range 26.9% - 43.8%) after ten years. Increasing both ART and TPT uptake through community-based ART with TPT care could reduce TB incidence by 29.7% (range 23.9% - 36.0%) and TB mortality by 36.0% (range 26.9% - 43.8%). Community-based ART with TPT care reduced gender disparities in TB mortality rates by reducing TB mortality among men by a projected 39.8% (range 32.2% - 46.3%) and by 30.9% (range 25.3% - 36.5%) among women. Over ten years, the mean cost per DALY averted by community-based ART with TPT care was $846 USD (range $709 - $1,012). Conclusions: By substantially increasing coverage of ART and TPT, community-based care for people living with HIV could reduce TB incidence and mortality in settings with high burdens of HIV-associated TB and reduce TB gender disparities.

Population health impact, cost-effectiveness, and affordability of community-based HIV treatment and monitoring in South Africa: A health economics modelling study.

Community-based delivery and monitoring of antiretroviral therapy (ART) for HIV has the potential to increase viral suppression for individual- and population-level health benefits. However, the cost-effectiveness and budget impact are needed for public health policy. We used a mathematical model of HIV transmission in KwaZulu-Natal, South Africa, to estimate population prevalence, incidence, mortality, and disability-adjusted life-years (DALYs) from 2020 to 2060 for two scenarios: 1) standard clinic-based HIV care and 2) five-yearly home testing campaigns with community ART for people not reached by clinic-based care. We parameterised model scenarios using observed community-based ART efficacy. Using a health system perspective, we evaluated incremental cost-effectiveness and net health benefits using a threshold of $750/DALY averted. In a sensitivity analysis, we varied the discount rate; time horizon; costs for clinic and community ART, hospitalisation, and testing; and the proportion of the population receiving community ART. Uncertainty ranges (URs) were estimated across 25 best-fitting parameter sets. By 2060, community ART following home testing averted 27.9% (UR: 24.3-31.5) of incident HIV infections, 27.8% (26.8-28.8) of HIV-related deaths, and 18.7% (17.9-19.7) of DALYs compared to standard of care. Adolescent girls and young women aged 15-24 years experienced the greatest reduction in incident HIV (30.7%, 27.1-34.7). In the first five years (2020-2024), community ART required an additional $44.9 million (35.8-50.1) annually, representing 14.3% (11.4-16.0) of the annual HIV budget. The cost per DALY averted was $102 (85-117) for community ART compared with standard of care. Providing six-monthly refills instead of quarterly refills further increased cost-effectiveness to $78.5 per DALY averted (62.9-92.8). Cost-effectiveness was robust to sensitivity analyses. In a high-prevalence setting, scale-up of decentralised ART dispensing and monitoring can provide large population health benefits and is cost-effective in preventing death and disability due to HIV.

Modelling cervical cancer elimination using single-visit screening and treatment strategies in the context of high HIV prevalence: estimates for KwaZulu-Natal, South Africa.

INTRODUCTION: In settings with high HIV prevalence, cervical cancer incidence rates are up to six-fold higher than the global average of 13.1 cases per 100,000 women-years. To inform strategies for global cervical cancer elimination, we used a dynamic transmission model to evaluate scalable screening and treatment strategies, accounting for HIV-associated cancer risks and weighing prevention gains against overtreatment. METHODS: We developed a dynamic model of HIV-HPV co-infection and disease progression, which we calibrated to KwaZulu-Natal, South Africa. Our baseline scenario reflects the current practice of HPV vaccination with a multi-visit screening and treatment strategy involving cytology and colposcopy triage. We evaluated 13 comparator scenarios with increased vaccination coverage and one-time, two-time or repeat HIV-targeted cervical cancer screening with the following single-visit strategies: HPV DNA testing, HPV genotyping, automated visual evaluation (AVE) and HPV DNA with AVE triage. In all scenarios, HIV antiretroviral therapy, condom use and voluntary male medical circumcision continue at baseline levels. We simulated cancer incidence under each scenario from 2020 to 2120 using the 25 best-fitting parameter sets. We present the median and range of model output from these simulations to account for parameter uncertainty. RESULTS: We estimate that cervical cancer incidence will decrease by 87% with the continuation of current cervical cancer and HIV prevention strategies, from an age-standardized rate per 100,000 women of 80.4 (range 58.2, 112.1) in 2020 to 10.7 (4.2, 29.9) in 2120. Scenarios scaling up vaccination and single-visit strategies resulted in near- and long-term gains. With repeat HIV-targeted screening, incidence rates were projected to be 29-34% lower in 2030 relative to the baseline scenario, and elimination (incidence <4/100,000) was achieved with HPV DNA testing in 2095 and with AVE in 2114. A strategy of HPV DNA with AVE triage optimized the tradeoff between cancer cases averted and overtreatment. CONCLUSIONS: Single-visit screening strategies could avert a substantial burden of cervical cancer and accelerate progress towards elimination in settings with a high burden of HIV. Increasing the screening frequency among women with HIV and reducing loss-to-follow-up for treatment will be key components of a successful elimination strategy.

Impact of catch-up human papillomavirus vaccination on cervical cancer incidence in Kenya: A mathematical modeling evaluation of HPV vaccination strategies in the context of moderate HIV prevalence.

BACKGROUND: Cervical cancer incidence is high in Kenya due to HIV and limited access to cancer prevention services. Human papillomavirus (HPV) has been shown to increase HIV acquisition; however, the potential impact of HPV vaccination on HIV is unknown. We modeled the health impact of HPV vaccination in the context of the HIV epidemiology in Kenya. METHODS: Using a validated compartmental transmission model of HIV and HPV set in Kenya, we evaluated five scenarios of nonavalent HPV vaccination: single-age-vaccination of 10-year-old girls at 90% coverage; multi-age-cohort (MAC) vaccination of 10-14-year-old girls at 90% coverage; MAC plus moderate-coverage (50%) catch-up vaccination of 15-24-year-old women; MAC plus high-coverage (80%) catch-up of 15-24-year-old women; and MAC plus catch-up of 15-44-year-old women at 80% coverage (HPV-FASTER). We compared cervical cancer incidence, HIV prevalence, and cumulative cervical cancer and HIV cases averted after 50 years to a baseline scenario without vaccination. In all scenarios, we assumed the UNAIDS 90-90-90 goal for HIV treatment is attained by 2030. FINDINGS: In 2021, model-estimated cervical cancer incidence is 44/100,000 and HIV prevalence among women is 6·5%. In 2070, projected cancer incidence declines to 27/100,000 and HIV prevalence reaches 0·3% without vaccination. With single-age-vaccination, cancer incidence in 2070 is reduced by 68%, averting 64,529 cumulative cancer cases. MAC vaccination reduces cancer incidence by 75%, averting 206,115 cancer cases. Moderate and high-coverage catch-up and HPV-FASTER reduce cancer incidence by 80%, 82%, and 84%, averting 254,930, 278,690, and 326,968 cancer cases, respectively. In all scenarios, HIV prevalence in 2070 is reduced by a relative 8-11%, with 15,609-34,981 HIV cases averted after 50 years. INTERPRETATION: HPV vaccination can substantially reduce cervical cancer incidence in Kenya in the next 50 years, particularly if women up to age 24 are vaccinated. HIV treatment scale-up can also alleviate cervical cancer burden. However, HPV vaccination has modest additional impact on HIV when antiretroviral therapy coverage is high. FUNDING: National Institutes of Health, Bill and Melinda Gates Foundation.

Estimating the effect of HIV on cervical cancer elimination in South Africa: Comparative modelling of the impact of vaccination and screening.

Background: In 2020, the World Health Organization (WHO) launched its initiative to eliminate cervical cancer as a public health problem. To inform global efforts for countries with high HIV and cervical cancer burden, we assessed the impact of human papillomavirus (HPV) vaccination and cervical cancer screening and treatment in South Africa, on cervical cancer and the potential for achieving elimination before 2120, considering faster HPV disease progression and higher cervical cancer risk among women living with HIV(WLHIV) and HIV interventions. Methods: Three independent transmission-dynamic models simulating HIV and HPV infections and disease progression were used to predict the impact on cervical cancer incidence of three scenarios for all women: 1) girls' vaccination (9-14 years old), 2) girls' vaccination plus 1 lifetime cervical screen (at 35 years), and 3) girls' vaccination plus 2 lifetime cervical screens (at 35 and 45 years) and three enhanced scenarios for WLHIV: 4) vaccination of young WLHIV aged 15-24 years, 5) three-yearly cervical screening of WLHIV aged 15-49 years, or 6) both. Vaccination assumed 90% coverage and 100% lifetime protection with the nonavalent vaccine (against HPV-16/18/31/33/45/52/58). Cervical cancer screening assumed HPV testing with uptake increasing from 45% (2023), 70% (2030) to 90% (2045+). We also assumed that UNAIDS 90-90-90 HIV treatment and 70% male circumcision targets are reached by 2030. We examined three elimination thresholds: age-standardised cervical cancer incidence rates below 4 or 10 per 100,000 women-years, and >85% reduction in cervical cancer incidence rate. We conducted sensitivity analyses and presented the median age-standardised predictions of outcomes of the three models (minimum-maximum across models). Findings: Girls' vaccination could reduce age-standardised cervical cancer incidence from a median of 47.6 (40.9-79.2) in 2020 to 4.5 (3.2-6.3) per 100,000 women-years by 2120, averting on average ∼4% and ∼46% of age-standardised cumulative cervical cancer cases over 25 and 100 years, respectively, compared to the basecase. Adding 2 lifetime screens helped achieve elimination over the century among all women (2120 cervical cancer incidence: 3.6 (1.9-3.6) per 100,000 women-years), but not among WLHIV (10.8 (5.3-11.6)), and averted more cumulative cancer cases overall (∼45% over 25 years and ∼61% over 100 years compared to basecase) than girls' vaccination alone. Adding three-yearly cervical screening among WLHIV (to girls' vaccination and 2 lifetime cervical screens) further reduced age-standardised cervical cancer incidence to 3.3 (1.8-3.6) per 100,000 women-years overall and to 5.2 (3.9-8.5) among WLHIV by 2120 and averted on average 12-13% additional cumulative cancer cases among all women and 21-24% among WLHIV than girls' vaccination and 2 lifetime cervical screens over 25 years or longer. Long-term vaccine protection and using the nonavalent vaccine was required for elimination. Interpretation: High HPV vaccination coverage of girls and 2 lifetime cervical screens could eliminate cervical cancer among women overall in South Africa by the end of the century and substantially decrease cases among all women and WLHIV over the short and medium term. Cervical cancer elimination in WLHIV would likely require enhanced prevention strategies for WLHIV. Screening of WLHIV remains an important strategy to reduce incidence and alleviate disparities in cervical cancer burden between women with and without HIV, despite HIV interventions scale-up. Funding: World Health Organization. National Cancer Institute, National Institutes of Health. MRC Centre for Global Infectious Disease Analysis, UK Medical Research Council. National Institute of Child Health and Human Development research. Cancer Association of South Africa. Canadian Institutes of Health Research and the Fonds de recherche du Québec - Santé research.

A Framework for Cervical Cancer Elimination in Low-and-Middle-Income Countries: A Scoping Review and Roadmap for Interventions and Research Priorities.

The World Health Organization announced an ambitious call for cervical cancer elimination worldwide. With existing prevention and treatment modalities, cervical cancer elimination is now within reach for high-income countries. Despite limited financing and capacity constraints in low-and-middle-income countries (LMICs), prevention and control efforts can be supported through integrated services and new technologies. We conducted this scoping review to outline a roadmap toward cervical cancer elimination in LMICs and highlight evidence-based interventions and research priorities to accelerate cervical cancer elimination. We reviewed and synthesized literature from 2010 to 2020 on primary and secondary cervical cancer prevention strategies. In addition, we conducted expert interviews with gynecologic and infectious disease providers, researchers, and LMIC health officials. Using these data, we developed a logic model to summarize the current state of science and identified evidence gaps and priority research questions for each prevention strategy. The logic model for cervical cancer elimination maps the needs for improved collaboration between policy makers, production and supply, healthcare systems, providers, health workers, and communities. The model articulates responsibilities for stakeholders and visualizes processes to increase access to and coverage of prevention methods. We discuss the challenges of contextual factors and highlight innovation needs. Effective prevention methods include HPV vaccination, screening using visual inspection and HPV testing, and thermocoagulation. However, vaccine coverage remains low in LMICs. New strategies, including single-dose vaccination could enhance impact. Loss to follow-up and treatment delays could be addressed by improved same-day screen-and-treat technologies. We provide a practical framework to guide cervical cancer elimination in LMICs. The scoping review highlights existing and innovative strategies, unmet needs, and collaborations required to achieve elimination across implementation contexts.