Performance analysis of mathematical methods used to forecast the 2022 New York City Mpox outbreak.

In mid-2022, New York City (NYC) became the epicenter of the US mpox outbreak. We provided real-time mpox case forecasts to the NYC Department of Health and Mental Hygiene to aid in outbreak response. Forecasting methodologies evolved as the epidemic progressed. Initially, lacking knowledge of at-risk population size, we used exponential growth models to forecast cases. Once exponential growth slowed, we used a Susceptible-Exposed-Infectious-Recovered (SEIR) model. Retrospectively, we explored if forecasts could have been improved using an SEIR model in place of our early exponential growth model, with or without knowing the case detection rate. Early forecasts from exponential growth models performed poorly, as 2-week mean absolute error (MAE) grew from 53 cases/week (July 1-14) to 457 cases/week (July 15-28). However, when exponential growth slowed, providing insight into susceptible population size, an SEIR model was able to accurately predict the remainder of the outbreak (7-week MAE: 13.4 cases/week). Retrospectively, we found there was not enough known about the epidemiological characteristics of the outbreak to parameterize an SEIR model early on. However, if the at-risk population and case detection rate were known, an SEIR model could have improved accuracy over exponential growth models early in the outbreak.

Large age shifts in HIV-1 incidence patterns in KwaZulu-Natal, South Africa.

Recent declines in adult HIV-1 incidence have followed the large-scale expansion of antiretroviral therapy and primary HIV prevention across high-burden communities of sub-Saharan Africa. Mathematical modeling suggests that HIV risk will decline disproportionately in younger adult age-groups as interventions scale, concentrating new HIV infections in those >age 25 over time. Yet, no empirical data exist to support these projections. We conducted a population-based cohort study over a 16-y period (2004 to 2019), spanning the early scale-up of antiretroviral therapy and voluntary medical male circumcision, to estimate changes in the age distribution of HIV incidence in a hyperepidemic region of KwaZulu-Natal, South Africa, where adult HIV incidence has recently declined. Median age of HIV seroconversion increased by 5.5 y in men and 3.0 y in women, and the age of peak HIV incidence increased by 5.0 y in men and 2.0 y in women. Incidence declined disproportionately among young men (64% in men 15 to 19, 68% in men 20 to 24, and 46% in men 25 to 29) and young women (44% in women 15 to 19, 24% in women 20 to 24) comparing periods pre- versus post-universal test and treat. Incidence was stable (<20% change) in women aged 30 to 39 and men aged 30 to 34. Age shifts in incidence occurred after 2012 and were observed earlier in men than in women. These results provide direct epidemiological evidence of the changing demographics of HIV risk in sub-Saharan Africa in the era of large-scale treatment and prevention. More attention is needed to address lagging incidence decline among older individuals.

How severe would prioritization-induced bottlenecks need to be offset the benefits from prioritizing COVID-19 vaccination to those most at risk in New York City?

BACKGROUND: Prioritization of higher-risk people for COVID-19 vaccination could prevent more deaths, but could slow vaccination speed. We used mathematical modeling to examine the trade-off between vaccination speed and prioritization for individuals age 65+ and essential workers. METHODS: We used a stochastic, discrete-time susceptible-exposed-infected-recovered (SEIR) model with age- and comorbidity-adjusted COVID-19 outcomes (infections, hospitalizations, and deaths). The model was calibrated to COVID-19 hospitalizations, ICU census, and deaths in NYC. We assumed 10,000 vaccinations per day, initially restricted to healthcare workers and nursing home populations, and subsequently expanded to other populations at alternative times (4, 5, or 6 weeks after vaccine launch) and speeds (20,000, 50,000, 100,000, or 150,000 vaccinations per day), as well as prioritization options (+/- prioritization of people age 65+ and essential workers). In sensitivity analyses, we examined the effect of a SARS-COV-2 variant with greater transmissibility. RESULTS: To be beneficial, prioritization must not create a bottleneck that decreases vaccination speed by > 50% without a more transmissible variant, or by > 33% with the emergence of the more transmissible variant. More specifically, prioritizing people age 65+ and essential workers increased the number of lives saved per vaccine dose delivered: 3000 deaths could be averted by delivering 83,000 vaccinations per day without prioritization or 50,000 vaccinations per day with prioritization. Other tradeoffs involve vaccination speed and timing. Compared to the slowest-examined vaccination speed of 20,000 vaccinations per day, achieving the fastest-examined vaccination speed of 150,000 vaccinations per day would avert additional 313,700 (28.6%) infections and 1693 (24.1%) deaths. Emergence of a more transmissible variant would double COVID-19 infections, hospitalizations, and deaths over the first 6 months of vaccination. The fastest-examined vaccination speed could only offset the harm of the more transmissible variant if achieved within 5 weeks of vaccine launch. CONCLUSIONS: Faster vaccination speed with sooner vaccination expansion would save more lives. Prioritization of COVID-19 vaccines to higher-risk populations would be more beneficial only if it does not create an excessive vaccine delivery bottleneck.

A quantitative assessment of the consistency of projections from five mathematical models of the HIV epidemic in South Africa: a model comparison study.

BACKGROUND: Mathematical models are increasingly used to inform HIV policy and planning. Comparing estimates obtained using different mathematical models can test the robustness of estimates and highlight research gaps. As part of a larger project aiming to determine the optimal allocation of funding for HIV services, in this study we compare projections from five mathematical models of the HIV epidemic in South Africa: EMOD-HIV, Goals, HIV-Synthesis, Optima, and Thembisa. METHODS: The five modelling groups produced estimates of the total population, HIV incidence, HIV prevalence, proportion of people living with HIV who are diagnosed, ART coverage, proportion of those on ART who are virally suppressed, AIDS-related deaths, total deaths, and the proportion of adult males who are circumcised. Estimates were made under a "status quo" scenario for the period 1990 to 2040. For each output variable we assessed the consistency of model estimates by calculating the coefficient of variation and examining the trend over time. RESULTS: For most outputs there was significant inter-model variability between 1990 and 2005, when limited data was available for calibration, good consistency from 2005 to 2025, and increasing variability towards the end of the projection period. Estimates of HIV incidence, deaths in people living with HIV, and total deaths displayed the largest long-term variability, with standard deviations between 35 and 65% of the cross-model means. Despite this variability, all models predicted a gradual decline in HIV incidence in the long-term. Projections related to the UNAIDS 95-95-95 targets were more consistent, with the coefficients of variation below 0.1 for all groups except children. CONCLUSIONS: While models produced consistent estimates for several outputs, there are areas of variability that should be investigated. This is important if projections are to be used in subsequent cost-effectiveness studies.

Detection and Kinetics of Subgenomic Severe Acute Respiratory Syndrome Coronavirus 2 RNA Viral Load in Longitudinal Diagnostic RNA-Positive Samples.

While detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) by diagnostic reverse-transcription polymerase chain reaction (RT-PCR) is highly sensitive for viral RNA, the nucleic acid amplification of subgenomic RNAs (sgRNAs) that are the product of viral replication may more accurately identify replication. We characterized the diagnostic RNA and sgRNA detection by RT-PCR from nasal swab samples collected daily by participants in postexposure prophylaxis or treatment studies for SARS-CoV-2. Among 1932 RT-PCR-positive swab samples with sgRNA tests, 40% (767) had detectable sgRNA. Above a diagnostic RNA viral load (VL) threshold of 5.1 log10 copies/mL, 96% of samples had detectable sgRNA with VLs that followed a linear trend. The trajectories of diagnostic RNA and sgRNA VLs differed, with 80% peaking on the same day but duration of sgRNA detection being shorter (8 vs 14 days). With a large sample of daily swab samples we provide comparative sgRNA kinetics and a diagnostic RNA threshold that correlates with replicating virus independent of symptoms or duration of illness.

Self-Assessed Severity as a Determinant of Coronavirus Disease 2019 Symptom Specificity: A Longitudinal Cohort Study.

Coronavirus disease 2019 symptom definitions rarely include symptom severity. We collected daily nasal swab samples and symptom diaries from contacts of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) case patients. Requiring ≥1 moderate or severe symptom reduced sensitivity to predict SARS-CoV-2 shedding from 60.0% (95% confidence interval [CI], 52.9%-66.7%) to 31.5% (95% CI, 25.7%- 38.0%) but increased specificity from 77.5% (95% CI, 75.3%-79.5%) to 93.8% (95% CI, 92.7%-94.8%).

Real-Time Infectious Disease Modeling to Inform Emergency Public Health Decision Making.

Infectious disease transmission is a nonlinear process with complex, sometimes unintuitive dynamics. Modeling can transform information about a disease process and its parameters into quantitative projections that help decision makers compare public health response options. However, modelers face methodologic challenges, data challenges, and communication challenges, which are exacerbated under the time constraints of a public health emergency. We review methods, applications, challenges and opportunities for real-time infectious disease modeling during public health emergencies, with examples drawn from the two deadliest pandemics in recent history: HIV/AIDS and coronavirus disease 2019 (COVID-19).

Using time-weighted average change from baseline of SARS-CoV-2 viral load to assess impact of hydroxychloroquine as postexposure prophylaxis and early treatment for COVID-19.

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.

Understanding the Evolving Role of Voluntary Medical Male Circumcision as a Public Health Strategy in Eastern and Southern Africa: Opportunities and Challenges.

PURPOSE OF REVIEW: Voluntary male medical circumcision (VMMC) has been a cornerstone of HIV prevention in Eastern and Southern Africa (ESA) and is credited in part for declines in HIV incidence seen in recent years. However, these HIV incidence declines change VMMC cost-effectiveness and how it varies across populations. RECENT FINDINGS: Mathematical models project continued cost-effectiveness of VMMC in much of ESA despite HIV incidence declines. A key data gap is how demand generation cost differs across age groups and over time as VMMC coverage increases. Additionally, VMMC models usually neglect non-HIV effects of VMMC, such as prevention of other sexually transmitted infections and medical adverse events. While small compared to HIV effects in the short term, these could become important as HIV incidence declines. Evidence to date supports prioritizing VMMC in ESA despite falling HIV incidence. Updated modeling methodologies will become necessary if HIV incidence reaches low levels.

Hydroxychloroquine as Postexposure Prophylaxis to Prevent Severe Acute Respiratory Syndrome Coronavirus 2 Infection : A Randomized Trial.

BACKGROUND: Effective prevention against coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is currently limited to nonpharmaceutical strategies. Laboratory and observational data suggested that hydroxychloroquine had biological activity against SARS-CoV-2, potentially permitting its use for prevention. OBJECTIVE: To test hydroxychloroquine as postexposure prophylaxis for SARS-CoV-2 infection. DESIGN: Household-randomized, double-blind, controlled trial of hydroxychloroquine postexposure prophylaxis. (ClinicalTrials.gov: NCT04328961). SETTING: National U.S. multicenter study. PARTICIPANTS: Close contacts recently exposed (<96 hours) to persons with diagnosed SARS-CoV-2 infection. INTERVENTION: Hydroxychloroquine (400 mg/d for 3 days followed by 200 mg/d for 11 days) or ascorbic acid (500 mg/d followed by 250 mg/d) as a placebo-equivalent control. MEASUREMENTS: Participants self-collected mid-turbinate swabs daily (days 1 to 14) for SARS-CoV-2 polymerase chain reaction (PCR) testing. The primary outcome was PCR-confirmed incident SARS-CoV-2 infection among persons who were SARS-CoV-2 negative at enrollment. RESULTS: Between March and August 2020, 671 households were randomly assigned: 337 (407 participants) to the hydroxychloroquine group and 334 (422 participants) to the control group. Retention at day 14 was 91%, and 10 724 of 11 606 (92%) expected swabs were tested. Among the 689 (89%) participants who were SARS-CoV-2 negative at baseline, there was no difference between the hydroxychloroquine and control groups in SARS-CoV-2 acquisition by day 14 (53 versus 45 events; adjusted hazard ratio, 1.10 [95% CI, 0.73 to 1.66]; P > 0.20). The frequency of participants experiencing adverse events was higher in the hydroxychloroquine group than the control group (66 [16.2%] versus 46 [10.9%], respectively; P = 0.026). LIMITATION: The delay between exposure, and then baseline testing and the first dose of hydroxychloroquine or ascorbic acid, was a median of 2 days. CONCLUSION: This rigorous randomized controlled trial among persons with recent exposure excluded a clinically meaningful effect of hydroxychloroquine as postexposure prophylaxis to prevent SARS-CoV-2 infection. PRIMARY FUNDING SOURCE: Bill & Melinda Gates Foundation.

Policy Review and Modeling Analysis of Mitigation Measures for Coronavirus Disease Epidemic Control, Health System, and Disease Burden, South Korea.

We reviewed the timeline of key policies for control of the coronavirus disease epidemic and determined their impact on the epidemic and hospital burden in South Korea. Using a discrete stochastic transmission model, we estimated that multilevel policies, including extensive testing, contact tracing, and quarantine, reduced contact rates by 90% and rapidly decreased the epidemic in Daegu and nationwide during February‒March 2020. Absence of these prompt responses could have resulted in a >10-fold increase in infections, hospitalizations, and deaths by May 15, 2020, relative to the status quo. The model suggests that reallocation of persons who have mild or asymptomatic cases to community treatment centers helped avoid overwhelming hospital capacity and enabled healthcare workers to provide care for more severely and critically ill patients in hospital beds and negative-pressure intensive care units. As small outbreaks continue to occur, contact tracing and maintenance of hospital capacity are needed.

Sustainable HIV treatment in Africa through viral-load-informed differentiated care.

There are inefficiencies in current approaches to monitoring patients on antiretroviral therapy in sub-Saharan Africa. Patients typically attend clinics every 1 to 3 months for clinical assessment. The clinic costs are comparable with the costs of the drugs themselves and CD4 counts are measured every 6 months, but patients are rarely switched to second-line therapies. To ensure sustainability of treatment programmes, a transition to more cost-effective delivery of antiretroviral therapy is needed. In contrast to the CD4 count, measurement of the level of HIV RNA in plasma (the viral load) provides a direct measure of the current treatment effect. Viral-load-informed differentiated care is a means of tailoring care so that those with suppressed viral load visit the clinic less frequently and attention is focussed on those with unsuppressed viral load to promote adherence and timely switching to a second-line regimen. The most feasible approach to measuring viral load in many countries is to collect dried blood spot samples for testing in regional laboratories; however, there have been concerns over the sensitivity and specificity of this approach to define treatment failure and the delay in returning results to the clinic. We use modelling to synthesize evidence and evaluate the cost-effectiveness of viral-load-informed differentiated care, accounting for limitations of dried blood sample testing. We find that viral-load-informed differentiated care using dried blood sample testing is cost-effective and is a recommended strategy for patient monitoring, although further empirical evidence as the approach is rolled out would be of value. We also explore the potential benefits of point-of-care viral load tests that may become available in the future.

Point-of-Care HIV Viral Load Testing: an Essential Tool for a Sustainable Global HIV/AIDS Response.

The global public health community has set ambitious treatment targets to end the HIV/AIDS pandemic. With the notable absence of a cure, the goal of HIV treatment is to achieve sustained suppression of an HIV viral load, which allows for immunological recovery and reduces the risk of onward HIV transmission. Monitoring HIV viral load in people living with HIV is therefore central to maintaining effective individual antiretroviral therapy as well as monitoring progress toward achieving population targets for viral suppression. The capacity for laboratory-based HIV viral load testing has increased rapidly in low- and middle-income countries, but implementation of universal viral load monitoring is still hindered by several barriers and delays. New devices for point-of-care HIV viral load testing may be used near patients to improve HIV management by reducing the turnaround time for clinical test results. The implementation of near-patient testing using these new and emerging technologies may be an essential tool for ensuring a sustainable response that will ultimately enable an end to the HIV/AIDS pandemic. In this report, we review the current and emerging technology, the evidence for decentralized viral load monitoring by non-laboratory health care workers, and the additional considerations for expanding point-of-care HIV viral load testing.

Immunogenicity of membrane-bound HIV-1 gp41 membrane-proximal external region (MPER) segments is dominated by residue accessibility and modulated by stereochemistry.

Structural characterization of epitope-paratope pairs has contributed to the understanding of antigenicity. By contrast, few structural studies relate to immunogenicity, the process of antigen-induced immune responses in vivo. Using a lipid-arrayed membrane-proximal external region (MPER) of HIV-1 glycoprotein 41 as a model antigen, we investigated the influence of physicochemical properties on immunogenicity in relation to structural modifications of MPER/liposome vaccines. Anchoring the MPER to the membrane via an alkyl tail or transmembrane domain retained the MPER on liposomes in vivo, while preserving MPER secondary structure. However, structural modifications that affected MPER membrane orientation and antigenic residue accessibility strongly impacted induced antibody responses. The solvent-exposed MPER tryptophan residue (Trp-680) was immunodominant, focusing immune responses, despite sequence variability elsewhere. Nonetheless, immunogenicity could be readily manipulated using site-directed mutagenesis or structural constraints to modulate amino acid surface display. These studies provide fundamental insights for immunogen design aimed at targeting B cell antibody responses.

Antigen delivery by lipid-enveloped PLGA microparticle vaccines mediated by in situ vesicle shedding.

Lipid-coated poly(lactide-co-glycolide) microparticles (LCMPs) consist of a solid polymer core wrapped by a surface lipid bilayer. Previous studies demonstrated that immunization with LCMPs surface-decorated with nanograms of antigen elicit potent humoral immune responses in mice. However, the mechanism of action for these vaccines remained unclear, as LCMPs are too large to drain efficiently to lymph nodes from the vaccination site. Here, we characterized the stability of the lipid envelope of LCMPs and discovered that in the presence of serum the lipid coating of the particles spontaneously delaminates, shedding antigen-displaying vesicles. Lipid delamination generated 180 nm liposomes in a temperature- and lipid/serum-dependent manner. Vesicle shedding was restricted by inclusion of high-TM lipids or cholesterol in the LCMP coating. Administration of LCMPs bearing stabilized lipid envelopes generated weaker antibody responses than those of shedding-competent LCMPs, suggesting that in situ release of antigen-loaded vesicles plays a key role in the remarkable potency of LCMPs as vaccine adjuvants.

Moving beyond hotspots of HIV prevalence to geospatial hotspots of UNAIDS 95-95-95 targets in sub-Saharan Africa.

The HIV epidemic in sub-Saharan Africa displays a varied geographical distribution, with particular regions termed as HIV hotspots due to a higher prevalence of infection. Addressing these hotspots is essential for controlling the epidemic. However, these regions, influenced by historical factors, challenge standard interventions. Legacy effects-the lasting impact of past events-play a substantial role in the persistence of these hotspots. To address this challenge of the standard interventions, we propose a shift towards the UNAIDS 95-95-95 targets. Spatial analysis of HIV viral load and antiretroviral therapy coverage can provide a more comprehensive perspective on the epidemic's dynamics. Studies in Zambia and Zimbabwe, using this approach, have revealed disparities in HIV care metrics across regions. By focusing on the UNAIDS 95-95-95 targets, more effective control strategies can be designed, with consideration of both historical and current factors. This approach would offer a solution-oriented strategy, emphasising tailored interventions based on specific regional needs.

Impact of Decarceration Plus Alcohol, Substance Use, and Mental Health Screening on Life Expectancies of Black Sexual Minority Men and Black Transgender Women Living With HIV in the United States: A Simulation Study Based on HPTN 061.

BACKGROUND: Given the disproportionate rates of incarceration and lower life expectancy (LE) among Black sexual minority men (BSMM) and Black transgender women (BTW) with HIV, we modeled the impact of decarceration and screening for psychiatric conditions and substance use on LE of US BSMM/BTW with HIV. METHODS: We augmented a microsimulation model previously validated to predict LE and leading causes of death in the US with estimates from the HPTN 061 cohort and the Veteran's Aging Cohort Studies. We estimated independent associations among psychiatric and substance use disorders, to simulate the influence of treatment of one condition on improvement on others. We used this augmented simulation to estimate LE for BSMM/BTW with HIV with a history of incarceration under alternative policies of decarceration (ie, reducing the fraction exposed to incarceration), screening for psychiatric conditions and substance use, or both. RESULTS: Baseline LE was 61.3 years. Reducing incarceration by 25%, 33%, 50%, and 100% increased LE by 0.29, 0.31, 0.53, and 1.08 years, respectively, versus no reductions in incarceration. When reducing incarceration by 33% and implementing screening for alcohol, tobacco, substance use, and depression, in which a positive screen triggers diagnostic assessment for all psychiatric and substance use conditions and linkage to treatment, LE increased by 1.52 years compared with no screening or decarceration. DISCUSSION: LE among BSMM/BTW with HIV is short compared with other people with HIV. Reducing incarceration and improving screening and treatment of psychiatric conditions and substance use could substantially increase LE in this population.

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.

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 new infections among key populations in 2021 were sensitive to population size assumptions and were substantially lower than estimates reported by UNAIDS.

Measuring HIV Acquisitions Among Partners of Key Populations: Estimates From HIV Transmission Dynamic Models.

BACKGROUND: Key populations (KPs), including female sex workers (FSWs), 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: One hundred seventy-eight 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 with the 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 the 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 the 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). CONCLUSIONS: 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.

Optimizing the pipeline of multipurpose prevention technologies: opportunities across women's reproductive lifespans.

HIV/AIDS and maternal mortality are the two leading causes of death among women of reproductive age in sub-Saharan Africa. A growing body of research investigates opportunities for multipurpose prevention technologies (MPTs) that prevent unintended pregnancy, HIV, and/or other sexually transmitted infections (STIs) with a single product. More than two dozen MPTs are currently in development, most of them combining contraception with HIV pre-exposure prophylaxis, with or without protection from other STIs. If successful, such MPTs could offer women benefits at multiple levels: greater motivation for effective use; lower product administration burden; accelerated integration of HIV, STI, and reproductive health services; and opportunities to circumvent stigma by using contraception as a "fig leaf" for HIV and/or STI prevention. However, even if women find respite from product burden, lack of motivation, and/or stigma in contraceptive-containing MPTs, their use of MPTs will be interrupted, often multiple times, over the reproductive lifecourse due to desire for pregnancy, pregnancy and breastfeeding, menopause, and changes in risk. Interruptions to the benefits of MPTs could be avoided by combining HIV/STI prevention with other life-stage-appropriate reproductive health products. New product concepts could include combining prenatal supplements with HIV and STI prevention, emergency contraception with HIV post-exposure prophylaxis, or hormone replacement therapies for menopause with HIV and STI prevention. Research is needed to optimize the MPT pipeline based on the populations underserved by available options and the capacity of resource-constrained health systems to deliver novel preventative healthcare products.