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To assess the combined role of anti-viral monoclonal antibodies (mAbs) and vaccines in reducing severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) transmission and mortality in the United States, an agent-based model was developed that accounted for social contacts, movement/travel, disease progression, and viral shedding. The model was calibrated to coronavirus disease 2019 (COVID-19) mortality between October 2020 and April 2021 (aggressive pandemic phase), and projected an extended outlook to estimate mortality during a less aggressive phase (April-August 2021). Simulated scenarios evaluated mAbs for averting infections and deaths in addition to vaccines and aggregated non-pharmaceutical interventions. Scenarios included mAbs as a treatment of COVID-19 and for passive immunity for postexposure prophylaxis (PEP) during a period when variants were susceptible to the mAbs. Rapid diagnostic testing paired with mAbs was evaluated as an early treatment-as-prevention strategy. Sensitivity analyses included increasing mAb supply and vaccine rollout. Allocation of mAbs for use only as PEP averted up to 14% more infections than vaccine alone, and targeting individuals ≥ 65 years averted up to 37% more deaths. Rapid testing for earlier diagnosis and mAb use amplified these benefits. Doubling the mAb supply further reduced infections and mortality. mAbs provided benefits even as proportion of the immunized population increased. Model projections estimated that ~ 42% of expected deaths between April and August 2021 could be averted. Assuming sensitivity to mAbs, their use as early treatment and PEP in addition to vaccines would substantially reduce SARS-CoV-2 transmission and mortality even as vaccination increases and mortality decreases. These results provide a template for informing public health policy for future pandemic preparedness.

Two randomized controlled trials demonstrated no clinical benefit of hydroxychloroquine (HCQ) for either postexposure prophylaxis or early treatment of SARS-CoV-2 infection. Using data from these studies, we calculated the time-weighted average change from baseline SARS-CoV-2 viral load and demonstrated that HCQ did not affect viral clearance.

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.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.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 (incidencelt;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.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.

Adolescent girls and young women (AGYW) are a priority population for pre-exposure prophylaxis (PrEP), a highly effective HIV prevention method. However, effective PrEP use among AGYW has been low. Interventions to support PrEP effective use may improve pill-taking. Affordability of PrEP programs depends on their cost. We, therefore, evaluated the cost of community-based PrEP with effective use counselling.Cost data from a randomized controlled trial were used to evaluate the cost of PrEP provision with effective use counselling offered to AGYW through community-based HIV testing platforms between November 2018 and November 2019. AGYW were randomized to receive (1) group-based community health club effective use counselling, (2) individualized effective use counselling or (3) community-based PrEP dispensary. Task shifting of effective use counselling from nurses to trained lay counsellors was implemented in groups 1 and 2. Personnel costs were estimated from time-and-motion observations and staff interviews. Expenditure and ingredients-based approaches were used to estimate costs for medical and non-medical supplies.In total, 603 AGYW initiated PrEP and accrued a total of 1280 months on PrEP. Average cost per person-month on PrEP with group-based community health club, individualized effective use counselling and community-based PrEP dispensary under the Department of Health scenario were similar and high (USD $55.32, $55.65 and $55.46, respectively) due to low PrEP client volume observed in the clinical trial. Increasing client volume (scaled Department of Health scenario) reduced cost per-person month estimates to USD $15.48, $26.40 and $13.99, respectively.As designed, individualized effective use counselling increased the cost of standard-of-care PrEP delivery by 89%, group-based community health effective use counselling increased the cost of standard-of-care PrEP delivery by 11%. These estimates can inform cost-effectiveness and budget impact analysis for PrEP provision with effective use counselling services.

Introduction UNAIDS fast track targets for ending the AIDS epidemic by 2030 call for viral suppression in 95% of people using antiretroviral therapy (ART) to treat HIV infection. Difficulties in linking to care following a positive HIV test have impeded progress towards meeting treatment targets. Community‐based HIV services may reduce linkage barriers and have been associated with high retention and favourable clinical outcomes. We use qualitative data from The Delivery Optimization of Antiretroviral Therapy (DO ART) Study, a three‐arm randomized trial of community ART initiation, monitoring and re‐supply conducted in western Uganda and KwaZulu‐Natal South Africa, to identify mechanisms through which community ART delivery may improve treatment outcomes, defined as viral suppression in people living with HIV (PLHIV). Methods We conducted open‐ended interviews with a purposeful sample of 150 DO ART participants across study arms and study sites, from October 2016 to November 2019. Interviews covered experiences of: (1) HIV testing; (2) initiating and refilling ART; and (3) participating in the DO ART Study. A combined inductive content analytic and thematic approach was used to characterize mechanisms through which community delivery of ART may have contributed to viral suppression in the DO ART trial. Results The analysis yielded four potential mechanisms drawn from qualitative data representing the perspectives and priorities of DO ART participants. Empowering participants to schedule, re‐schedule and select the locations of community‐based visits via easy phone contact with clinical staff is characterized as flexibility. Integration refers to combining the components of clinic‐based visits into single interaction with a healthcare provider. Providers” willingness to talk at length with participants during visits, addressing non‐HIV as well as HIV‐related concerns, is termed “a slower pace”. Finally, increased efficiency denotes the time savings and increased income‐generating opportunities for participants brought about by delivering services in the community. Conclusions Understanding the mechanisms through which HIV service delivery innovations produce an effect is key to transferability and potential scale‐up. The perspectives and priorities of PLHIV can indicate actionable changes for HIV care programs that may increase engagement in care and improve treatment outcomes.

Introduction Among people living with HIV in South Africa, viral suppression is lower among men than women. The study aim was to test the impact of lottery incentives, which reward positive health choice (e.g. antiretroviral therapy (ART) linkage) with a chance to win a prize, on strengthening the HIV care continuum including ART initiation and viral suppression for men. Methods We conducted a randomized, prospective trial of lottery incentives in the context of HIV testing and linkage to ART in rural KwaZulu‐Natal, South Africa. Men living with HIV were randomly allocated to: lottery incentives and motivational text messages or motivational text messages only. Lottery prize eligibility was conditional on clinic registration, ART initiation, or viral suppression by one, three and six months respectively. After completing each continuum step, participants in the lottery group were notified whether they had won and were encouraged to continue in care. Lottery prizes were either a mobile phone, data or a gift card (valued at R1000/$100). Kaplan–Meier curves were plotted to determine time to ART initiation by study group. The primary outcome was viral suppression at six months. Results Between November 2017 and December 2018, we tested 740 men for HIV and enrolled 131 HIV‐positive men who reported not being on ART. At baseline, 100 (76%) participants were 30 years and older, 95 (73%) were unemployed and the median CD4 count was 472 cells/μL. At study exit, 84% (110/131) of participants had visited a clinic and 62% (81/131) were virally suppressed. Compared to motivational text messages, lottery incentives decreased the median time to ART initiation from 126 to 66 days (p = 0.0043, age‐adjusted Cox regression) among all participants, and, from 134 days to 20 days (p = 0.0077) among participants who were not virally suppressed at baseline. Lottery incentives had an inconclusive effect on clinic registration (RR = 1.21, 95% CI: 0.83 to 1.76) and on viral suppression at six months (RR = 1.13, 95% CI: 0.73 to 1.75) compared to motivational text messages. Conclusions Conditional lottery incentives shortened the time to ART initiation among South African men. Behavioural economics strategies strengthen linkage to ART, but the study power was limited to see an impact on viral suppression. Clinical Trial Number NCT03808194.

Introduction Promising HIV vaccine candidates are steadily progressing through the clinical trial pipeline. Once available, HIV vaccines will be an important complement but also potential competitor to other biomedical prevention tools such as pre‐exposure prophylaxis (PrEP). Accordingly, the value of HIV vaccines and the policies for rollout may depend on that interplay and tradeoffs with utilization of existing products. In this economic modelling analysis, we estimate the cost‐effectiveness of HIV vaccines considering their potential interaction with PrEP and condom use. Methods We developed a dynamic model of HIV transmission among the men who have sex with men population (MSM), aged 15‐64 years, in Seattle, WA offered PrEP and HIV vaccine over a time horizon of 2025‐2045. A healthcare sector perspective with annual discount rate of 3% for costs (2017 USD) and quality‐adjusted life years (QALYs) was used. The primary economic endpoint is the incremental cost‐effectiveness ratio (ICER) when compared to no HIV vaccine availability. Results HIV vaccines improved population health and increased healthcare costs. Vaccination campaigns achieving 90% coverage of high‐risk men and 60% coverage of other men within five years of introduction are projected to avoid 40% of new HIV infections between 2025 and 2045. This increased total healthcare costs by $30 million, with some PrEP costs shifted to HIV vaccine spending. HIV vaccines are estimated to have an ICER of $42,473/QALY, considered cost‐effective using a threshold of $150,000/QALY. Results were most sensitive to HIV vaccine efficacy and future changes in the cost of PrEP drugs. Sensitivity analysis found ranges of 30‐70% HIV vaccine efficacy remained cost‐effective. Results were also sensitive to reductions in condom use among PrEP and vaccine users. Conclusions Access to an HIV vaccine is desirable as it could increase the overall effectiveness of combination HIV prevention efforts and improve population health. Planning for the rollout and scale‐up of HIV vaccines should carefully consider the design of policies that guide interactions between vaccine and PrEP utilization and potential competition.

Introduction Understanding the cost of strategies to reach and deliver pre‐exposure prophylaxis (PrEP) to priority populations is essential to assess the cost‐effectiveness and budget impact of HIV prevention programmes. Providing PrEP through maternal and child health and family planning clinics offers a promising strategy to reach women in high HIV burden settings. We estimated incremental costs and explored the cost drivers of integrating PrEP delivery into routine maternal and child health and family planning services in Kenya. Methods We conducted a costing study from the provider perspective within the PrEP Implementation for Young Women and Adolescents programme in western Kenya. We identified all within‐ and above‐facility activities supporting PrEP delivery and measured clinical service time using time‐and‐motion studies. We obtained input costs from programme budgets, expenditure records and staff interviews. We estimated changes in costs if creatinine testing were postponed from initiation to first follow‐up visit and if PrEP were prioritized to clients at high HIV risk using a behavioural risk assessment tool. We also projected costs under Ministry of Health (MOH) implementation assuming MOH salaries and programme supervision. We estimated annual numbers of PrEP visits from programme data abstracted from 16 facilities between November 2017 and June 2018. We report the cost per client‐month of PrEP dispensed in 2017 USD. Results For an annual programme output of 24,005 screenings, 4198 PrEP initiations and 4427 follow‐up visits, the average cost per client‐month of PrEP dispensed in the study was $26.52. Personnel, drugs and laboratory tests comprised 43%, 25% and 14% of programme costs respectively. Postponing creatinine testing and prioritizing PrEP delivery to clients at high HIV risk reduced total programme costs by 8% and 14% respectively. In the MOH scenario assuming no changes in outputs, the projected cost per client‐month of PrEP dispensed decreased to $16.54 and total programme costs decreased by 38%. Conclusions Incremental PrEP costs are sensitive to the service delivery strategy used to engage priority populations. Postponing creatinine testing and prioritizing PrEP delivery to clients at high HIV risk may reduce costs. Context‐specific cost data are crucial to assess the cost‐effectiveness and affordability of PrEP delivery models.

Introduction Adolescent girls and young women (AGYW) in Africa have high HIV incidence despite scale‐up of HIV testing and HIV treatment. Placebo‐controlled trials of tenofovir‐based pre‐exposure prophylaxi (PrEP) in diverse populations demonstrated that PrEP works with close to 100% effectiveness if taken with high, but not perfect, adherence. Divergent efficacy estimates among African AGYW led to demonstration and implementation projects to better understand motivations for HIV prevention, uptake, adherence and persistence to PrEP. To inform PrEP programmes, the design and initial findings from PrEP demonstration projects for AGYW are reviewed. Discussion Early lessons from PrEP implementation projects among young African women include: (1) awareness and demand creation with positive messaging about the benefits of PrEP are critical to motivate AGYW to consider this novel prevention technology and to foster awareness among peers, partners, parents and guardians to support AGYW's effective PrEP use; (2) PrEP initiation is high in projects that are integrating PrEP into youth‐friendly clinics, family planning clinics and mobile clinics; (3) young African women at risk are initiating PrEP, based on behavioural characteristics, history of intimate partner violence, depression and 30% prevalence of chlamydia and/or gonorrhoea; (4) provision of youth‐friendly PrEP delivery programmes that integrate reproductive health services, including contraception and the diagnosis and treatment of sexually transmitted infections, increase health impact; (5) messages that emphasize the necessity for high adherence while at potential risk of HIV exposure and support strategies that addresses AGYW's adherence challenges are essential; and, (6) a substantial proportion of AGYW do not persist with PrEP, and strategies are needed to help AGYW assess their ongoing need, motivation and challenges with persisting with PrEP. Conclusions PrEP is feasible to implement in integrated reproductive health service delivery models to reach African AGYW. While PrEP demonstration projects indicate that women with behavioural risks and high rates of sexually transmitted diseases are initiating PrEP; effective strategies to support AGYW's adherence and persistence with PrEP are needed. Lessons learned from oral PrEP delivery, a novel first generation HIV prevention product, are relevant to longer‐acting and less adherence‐dependent strategies which are currently in clinical trials.

To evaluate prospectively the association between serological markers of selected infections, including HPV, and risk of developing cervical cancer (CC) and pre-cancer, we performed a nested case-c ...

A total of 308,036 women were selected from the European Prospective Investigation into Cancer and Nutrition (EPIC) to evaluate the association between tobacco smoking and the risk of cervical intr ...

Introduction Tuberculosis (TB) is the leading cause of HIV‐associated mortality in Africa. As HIV testing, linkage to care and antiretroviral treatment initiation intensify to meet UNAIDS targets, it is not known what effect these efforts will have on TB detection and prevention. We aimed to characterize the TB care cascade of screening, diagnostic testing, treatment and provision of isoniazid preventive therapy (IPT) in a study of community‐based HIV screening and linkage to care and determine whether symptom screening results affected progress along the cascade. Methods Between June 2013 and March 2015, HIV‐infected adults enrolled in the Linkages study, a multi‐site, community‐based, randomized HIV screening and linkage‐to‐care study in South Africa and Uganda. All participants were screened for TB symptoms at entry after testing positive for HIV and referred to local clinics for care. During the 9 month follow‐up, participants were periodically surveyed about clinic linkage and initiation of HIV care as well as subsequent TB testing, treatment, or IPT. We compared outcomes between persons with and without a positive symptom screen at baseline using descriptive statistics and Poisson regression to calculate relative risks of outcomes along the care cascade. Results and discussion Of the 1,325 HIV‐infected adults enrolled, 26% reported at least one TB symptom at the time of HIV diagnosis. Loss of appetite and fever were the most commonly reported symptoms on a TB symptom screen. Despite 92% HIV linkage success, corresponding TB linkage was incomplete. Baseline TB symptoms were associated with an increased risk of a TB diagnosis (relative risk 3.23, 95% CI 1.51 to 6.91), but only 34% of symptomatic persons had sputum TB testing. Fifty‐five percent of participants diagnosed with TB started TB treatment. In South Africa, only 18% of asymptomatic participants initiated IPT after linkage to HIV care, and presence of symptoms was not associated with IPT initiation (relative risk 0.86 95% CI 0.6 to 1.23). Conclusions HIV linkage to care interventions provide an opportunity to improve completion of the TB care cascade, but will require additional support to realize full benefits.

Vaccines based on human papillomavirus (HPV) 16 and 18 virus-like particles have the potential to prevent approximately 70% of cervical cancers. In Australia, public vaccination against HPV commenced in April 2007, and includes routine vaccination of females aged 12-13 years, and a 2-year school and GP-based catch-up in females aged 12-26 years. The objectives of this study were to estimate initial vaccination coverage rates, to describe current patterns of sexual behavior in young females, and to predict the impact of vaccination on HPV16 infections. We reviewed early coverage data, estimating that coverage in 2007/2008 will reach 86% (feasible range 67-90%) for 12- to 13-year-old girls, with lower rates attained in older females. A review of survey data found that the median age of first intercourse in Australian females is 16 years, with approximately 90% of women sexually active at 22 years. Using these data, we performed an analysis of HPV transmission to predict the impact of vaccination on HPV infection rates. The public program is predicted to result in a reduction in the age-standardized incidence of HPV16 infections of 56% by 2010 (feasible range 48-61%), and 92% by 2050 (feasible range 76-95%). Elective vaccination of older women and vaccination of males may provide some incremental gains, but the benefits to women of vaccinating males will be less if coverage of females remains high. In conclusion, the current vaccination program is expected to result in a substantial and rapid reduction in the incidence of HPV16 in Australia.

Introduction South Africa faces epidemics of HIV and non-communicable diseases (NCDs). The aim of this study was to characterize the prevalence of non-communicable disease risk factors and depression, stratified by HIV status, in a community with a high burden of HIV. Methods We conducted a home-based HIV counselling and testing study in KwaZulu-Natal, South Africa between November 2011 and June 2012. Contiguous households were approached and all adults ≥18 years old were offered an HIV test. During follow-up visits in January 2015, screening for HIV, depression, obesity, blood glucose, cholesterol and blood pressure were conducted using point-of-care tests. Results Of the 570 participants located and screened; 69% were female and 33% were HIV-positive. NCD risk factor prevalence was high in this sample; 71% were overweight (body mass index (BMI) 25 to 29.9 kg/m2) or obese (BMI≥30 kg/m2), 4% had hyperglycaemia (plasma glucose >11.0 mmol/l/200 mg/dl), 33% had hypertension (HTN, >140/90 mmHg), 20% had hyperlipidaemia (low density cholesterol >5.2 mmol/l/193.6 mg/dl) and 12% had major depressive symptoms (nine item Patient Health Questionnaire ≥10). Of the 570 participants, 87% had one or more of HIV, hyperglycaemia, HTN, hyperlipidaemia and/or depression. Over half (56%) had two or more. Older age and female gender were significantly associated with the prevalence of both HIV infection and NCD risk factors. Around 80% of both HIV-positive and negative persons had one of the measured risk factors (i.e. obesity, hyperglycaemia, hyperlipidaemia, HTN), or depression. Conclusions In a community-based sample of adults in KwaZulu-Natal, South Africa, the prevalence of both HIV infection and NCD risk factors were high. This study is among the first to quantify the substantial burden of NCD risk factors and depression in this non-clinic based population.

Introduction : Achieving the UNAIDS goals of 90–90-90 will require more than doubling the number of people accessing HIV care in Uganda. Community-based programmes for entry into HIV care are effective strategies to expand access to HIV care, but few programmes have been evaluated with a particular focus on scale-up. Methods : Integrated Community Based Initiatives, a Uganda-based non-governmental organization, designed and implemented a programme of community-based HIV counselling and testing and facilitated linkage to care utilizing community health extension workers (CHEWs) in rural Sheema District, Uganda. CHEWs performed programme activities during 1 October 2015 through 31 March 2016. Outcomes for this evaluation were (1) the number of people tested for HIV, and (2) the proportion of those testing positive who were seen at an ART clinic within three months of their positive test, and (3) the cost of the programme per person newly diagnosed with HIV. Microcosting methods were used to calculate the programme costs. Program scalability factors were evaluated using a published framework. Results : Sixty-two CHEWs attended a five-day training that introduced the biology of HIV, the conduct of confidential HIV testing, HIV prevention messages, and linkage, referral, and reporting requirements. CHEWs received a $30 monthly stipend and a field testing kit that included a bicycle, field bag, umbrella, gumboots, reporting booklet, pens, and HIV testing materials. Trained CHEWs tested 43,696 persons for HIV infection during the six-month programme period. Nine-hundred seventy-four participants (2.2%) were identified as HIV positive, and 623 participants (64%) were linked to HIV care. An estimated 69% of adult residents received testing as part of this campaign. The programme cost $3.02 per person test, $135.70 per positive person identified, and $212.15 per HIV-positive person linked to care. Conclusions : Lay community health extension workers (CHEWs) can be rapidly trained to scale-up home-based HIV testing and counselling (HTC) and linkage to care in a high-quality and low-cost manner to large numbers of people in a rural, high burden setting. A combination HIV testing approach, such as adding partner testing to community-based testing, could increase the proportion of HIV-positive persons identified. Keywords HIV; community health workers; Uganda; task shifting; linkage to care; scalability To access the supplementary material to this article please see Supplementary Files under Article Tools online . (Published: 21 July 2017) Asiimwe S et al. Journal of the International AIDS Society 2017, 20 :21633 http://www.jiasociety.org/index.php/jias/article/view/21633 | http://dx.doi.org/10.7448/IAS.20.5.21633