Redefining Disease Severity with Special Area Involvement and Reflecting on Treatment Patterns in a Real-World Psoriasis Population

Abstract Background The International Psoriasis Council (IPC) recommends an approach that considers body surface area (BSA), involvement in special areas, and treatment history for classifying patients as candidates for topical or systemic treatment. This study aimed to quantify the burden of psoriasis by describing BSA distribution, special area involvement, and treatments in a real-world population. Methods This retrospective cohort study included patients with psoriasis from the Optum® deidentified Electronic Health Records database with a BSA value ( 10%) recorded between 1 March 2014 and 1 September 2020. Treatments and special area involvement (face, scalp, palms/soles, nails, genitals) were identified within 90 days of the BSA value and stratified by BSA category. Results Among eligible patients (N = 5120), mean age was 51.4 years and 49.3% were women. The majority of patients (78.9%) were treated with any topical. Proportions of patients with BSA  10% were 23.4%, 41.9%, and 34.6%, respectively; proportions with 0, 1, and 2+ special areas were 21.6%, 31.6%, and 45.7%, respectively; and 44.4%, 45.7%, and 45.9% of patients with BSA  10%, respectively, had 2+ special areas. Conclusion The IPC classification can likely identify many more patients who may benefit from systemic therapy than BSA alone. Graphical Abstrac

Population-level effect of potential HSV2 prophylactic vaccines on HIV incidence in sub-Saharan Africa.

Herpes simplex virus type-2 (HSV2) infection increases HIV transmission. We explore the impact of a potential prophylactic HSV2 vaccination on HIV incidence in Africa using STDSIM an individual-based model. A campaign that achieved 70% coverage over 5 years with a vaccine that reduced susceptibility to HSV2 acquisition and HSV2 reactivation by 75% for 10 years, reduced HIV incidence by 30-40% after 20 years (range 4-66%). Over 20 years, in most scenarios fewer than 100 vaccinations were required to avert one HIV infection. HSV2 vaccines could have a substantial impact on HIV incidence. Intensified efforts are needed to develop an effective HSV2 vaccine

Treating curable sexually transmitted infections to prevent HIV in Africa: still an effective control strategy?

BACKGROUND: Evidence regarding the effectiveness of sexually transmitted infection (STI) treatment for HIV prevention in Africa is equivocal, leading some policy makers to question whether it should continue to be promoted for HIV control. We explore whether treating curable STIs remains a cost-effective HIV control strategy in Africa. METHODS: The model STDSIM was fitted to the characteristics of 4 populations in East and West Africa. Over the simulated HIV epidemics, the population-attributable fractions (PAFs) of incident HIV attributable to STIs, the impact of syndromic STI management on HIV incidence, and the cost per HIV infection averted were evaluated and compared with an estimate of lifetime HIV treatment costs (US $3500). RESULTS: Throughout the HIV epidemics in all cities, the total PAF for. all STIs remained high, with > or = 50$321 and $1665. CONCLUSION: Curable STI interventions may remain cost-saving in populations with generalized HIV epidemics, particularly in populations with high-risk behaviors or low male circumcision rates

Male circumcision for HIV prevention in sub-Saharan Africa: who, what and when?

BACKGROUND AND OBJECTIVE: Male circumcision (circumcision) reduces HIV incidence in men by 50-60%. The United Nations Joint Programme on HIV/AIDS (UNAIDS) recommends the provision of safe circumcision services in countries with high HIV and low circumcision prevalence, prioritizing 12-30 years old HIV-uninfected men. We explore how the population-level impact of circumcision varies by target age group, coverage, time-to-scale-up, level of risk compensation and circumcision of HIV infected men. DESIGN AND METHODS: An individual-based model was fitted to the characteristics of a typical high-HIV-prevalence population in sub-Saharan Africa and three scenarios of individual-level impact corresponding to the central and the 95% confidence level estimates from the Kenyan circumcision trial. The simulated intervention increased the prevalence of circumcision from 25 to 75% over 5 years in targeted age groups. The impact and cost-effectiveness of the intervention were calculated over 2-50 years. Future costs and effects were discounted and compared with the present value of lifetime HIV treatment costs (US$ 4043). RESULTS: Initially, targeting men older than the United Nations Joint Programme on HIV/AIDS recommended age group may be the most cost-effective strategy, but targeting any adult age group will be cost-saving. Substantial risk compensation could negate impact, particularly if already circumcised men compensate. If circumcision prevalence in HIV uninfected men increases less because HIV-infected men are also circumcised, this will reduce impact in men but would have little effect on population-level impact in women. CONCLUSION: Circumcision is a cost-saving intervention in a wide range of scenarios of HIV and initial circumcision prevalence but the United Nations Joint Programme on HIV/AIDS/WHO recommended target age group should be widened to include older HIV-uninfected men and counselling should be targeted at both newly and already circumcised men to minimize risk compensation. To maximize infections-averted, circumcision must be scaled up rapidly while maintaining quality

Empirical observations underestimate the proportion of human immunodeficiency virus infections attributable to sexually transmitted diseases in the Mwanza and Rakai sexually transmitted disease treatment trials: Simulation results.

BACKGROUND AND OBJECTIVES: Population attributable fractions (PAF) from observational studies may under- or overestimate the contribution of cofactor sexually transmitted disease (STD) to human immunodeficiency virus (HIV) spread. Empirical PAF estimates from the Mwanza and Rakai trials indicated the proportion of HIV infections attributable to STDs was higher in Mwanza than Rakai. GOAL OF THIS STUDY: Estimate the "true" proportion (PAFM) of HIV infections attributable to STDs in the Mwanza and Rakai STD trial populations and explore how the evaluated interventions prevented HIV infections. STUDY DESIGN: The STDSIM model was used to simulate the 2 populations at the baseline of the trials (with no STD treatment interventions) and counterfactual scenarios in which STD cofactor effects on HIV spread were removed either at the start of the trials or 2, 10, and 20 years into the HIV epidemics. Similar methods were used to quantify the contribution of the cure of each STD to overall HIV impact in each site. RESULTS: : In Mwanza, the highest PAFM for the effect of any single STD over the 2 years of the trial was due to chancroid (40%). The PAFM for all curable STD was 65%. In Rakai, herpes simplex virus type 2 (HSV-2) was the most important STD (PAFM = 23%); the PAFM for curable STD was 20%. In both sites, the proportion of new infections due to treatable STD decreased over time. The decrease was greater for Rakai, where a behavioral risk reduction that preceded the trial reduced STD prevalence. In both sites, the importance of HSV-2 increased later in the HIV epidemics and STD increased transmission of HIV more than acquisition of HIV. In the Mwanza trial, treatment of chancroid contributed most to preventing new HIV infections. CONCLUSIONS: PAFs calculated from empirical data underestimated the contribution of STD to HIV spread in the Mwanza and Rakai trial populations because STD effects on HIV transmission (as opposed to acquisition) were not captured in the observationally based studies

Proportion of new HIV infections attributable to herpes simplex 2 increases over time: simulations of the changing role of sexually transmitted infections in sub-Saharan African HIV epidemics.

OBJECTIVE: To understand the changing impact of herpes simplex 2 (HSV-2) and other sexually transmitted infections (STIs) on HIV incidence over time in four sub-Saharan African cities, using simulation models. METHODS: An individual-based stochastic model was fitted to demographic, behavioural and epidemiological data from cross-sectional population-based surveys in four African cities (Kisumu, Kenya; Ndola, Zambia; Yaoundé, Cameroon; and Cotonou, Benin) in 1997. To estimate the proportion of new HIV infections attributable to HSV-2 and other STIs over time, HIV incidence in the fitted model was compared with that in model scenarios in which the cofactor effect of the STIs on HIV susceptibility and infectivity were removed 5, 10, 15, 20 and 25 years into the simulated HIV epidemics. RESULTS: The proportion of incident HIV attributable to HSV-2 infection (the model estimated population attributable fraction (PAF(M))) increased with maturity of the HIV epidemic. In the different cities, the PAF(M) was 8-31% 5 years into the epidemic, but rose to 35-48% 15 years after the introduction of HIV. In contrast, the proportion of incident HIV attributable to chancroid decreased over time with strongest effects five years after HIV introduction, falling to no effect 15 years after. Sensitivity analyses showed that, in the model, recurrent HSV-2 ulcers had more of an impact on HIV incidence than did primary HSV-2 ulcers, and that the effect of HSV-2 on HIV infectivity may be more important for HIV spread than the effect on HIV susceptibility, assuming that HSV-2 has similar cofactor effects on HIV susceptibility and infectivity. The overall impact of other curable STIs on HIV spread (syphilis, gonorrhoea and chlamydia) remained relatively constant over time. CONCLUSIONS: Although HSV-2 appears to have a limited impact on HIV incidence in the early stages of sub-Saharan African HIV epidemics when the epidemic is concentrated in core groups, it has an increasingly large impact as the epidemic progresses. In generalised HIV epidemics where control programmes for curable STIs are already in place, interventions against HSV-2 may have a key role in HIV prevention

Understanding the differences between contrasting HIV epidemics in east and west Africa: results from a simulation model of the Four Cities Study.

OBJECTIVE: To determine if the differences in risk behaviours, the proportions of males circumcised and prevalences of sexually transmitted infections (STIs) observed in two African cities with low prevalence of HIV (Cotonou, Benin, and Yaoundé, Cameroon) and two cities with high prevalence (Kisumu, Kenya, and Ndola, Zambia) could explain the contrasting HIV epidemics in the four cities. METHODS: An individual-based stochastic model, STDSIM, was fitted to the demographic, behavioural and epidemiological characteristics of the four urban study populations based on data from the Four Cities Study and other relevant sources. Model parameters pertaining to STI and HIV natural history and transmission were held constant across the four populations. The probabilities of HIV, syphilis and chancroid acquisition were assumed to be doubled among uncircumcised males. A priori plausible ranges for model inputs and outputs were defined and sexual behaviour characteristics, including those pertaining to commercial sex workers (CSWs) and their clients, which were allowed to vary across the sites, were identified based on comparisons of the empirical data from the four sites. The proportions of males circumcised in the model, 100% in Cotonou and Yaoundé, 25% in Kisumu and 10% in Ndola, were similar to those observed. A sensitivity analysis was conducted to assess how changes in critical parameters may affect the model fit. RESULTS: Population characteristics observed from the study that were replicated in the model included younger ages at sexual debut and marriage in east Africa compared with west Africa and higher numbers of casual partners in the past 12 months in Yaoundé than in the other three sites. The patterns in prevalence of STIs in females in the general population and CSWs were well fitted. HIV prevalence by age and sex and time trends in prevalence in the model were consistent with study data with the highest simulated prevalences in Kisumu and Ndola, intermediate in Yaoundé and lowest in Cotonou. The sensitivity analysis suggested that the effect of circumcision on the development of the HIV epidemics may have been mediated indirectly by its effect on ulcerative STI. CONCLUSIONS: The contrasting HIV epidemics in east and west Africa could be replicated in our model by assuming that male circumcision reduced susceptibility to HIV, syphilis and chancroid. Varying rates of male circumcision may have played an important role in explaining the strikingly different HIV epidemics observed in different parts of sub-Saharan Africa

Higher risk behaviour and rates of sexually transmitted diseases in Mwanza compared to Uganda may help explain HIV prevention trial outcomes.

OBJECTIVE: To determine to what extent the higher impact of treatment for sexually transmitted diseases (STD) on HIV incidence in Mwanza, Tanzania than in Rakai and Masaka, Uganda might be explained by baseline differences between the trial populations. DESIGN: A re-analysis of baseline data from the three trial populations comparing demography, sexual risk behaviour and HIV/STD epidemiology. METHODS: Data were compared after age-standardization and adjustments for sample selection where necessary. STD rates were also adjusted for the sensitivities and specificities of the diagnostic techniques used. RESULTS: Demographic patterns were similar across populations, apart from effects of AIDS on fertility and mortality (including widowhood) in Uganda. Higher sexual risk behaviours, including younger age of sexual debut, higher numbers of recent partners and lower frequency of condom use, were apparent in Mwanza compared to Masaka and Rakai. High-titre serological syphilis, gonorrhoea, chlamydia infection and trichomoniasis were all more prevalent in Mwanza, except for chlamydia infection in males. There was little difference between sites in the seroprevalence of Herpes simplex virus type-2. Age patterns in the prevalence of short-duration STD and current risk behaviours were similar across sites but all-titre serological syphilis was more prevalent among older participants in Rakai and Masaka than Mwanza. CONCLUSIONS: Differences between trial populations included higher reported risk behaviour and higher rates of curable STD in Mwanza compared to Rakai and Masaka. These differences probably relate to previous reductions in risk behaviour in Uganda and may explain, at least in part, the contrasting results of these trials

Quantifying HIV-1 transmission due to contaminated injections

Assessments of the importance of different routes of HIV-1 (HIV) transmission are vital for prioritization of control efforts. Lack of consistent direct data and large uncertainty in the risk of HIV transmission from HIV-contaminated injections has made quantifying the proportion of transmission caused by contaminated injections in sub-Saharan Africa difficult and unavoidably subjective. Depending on the risk assumed, estimates have ranged from 2.5% to 30% or more. We present a method based on an age-structured transmission model that allows the relative contribution of HIV-contaminated injections, and other routes of HIV transmission, to be robustly estimated, both fully quantifying and substantially reducing the associated uncertainty. To do this, we adopt a Bayesian perspective, and show how prior beliefs regarding the safety of injections and the proportion of HIV incidence due to contaminated injections should, in many cases, be substantially modified in light of age-stratified incidence and injection data, resulting in improved (posterior) estimates. Applying the method to data from rural southwest Uganda, we show that the highest estimates of the proportion of incidence due to injections are reduced from 15.5% (95% credible interval) (0.7%, 44.9%) to 5.2% (0.5%, 17.0%) if random mixing is assumed, and from 14.6% (0.7%, 42.5%) to 11.8% (1.2%, 32.5%) under assortative mixing. Lower, and more widely accepted, estimates remain largely unchanged, between 1% and 3% (0.1–6.3%). Although important uncertainty remains, our analysis shows that in rural Uganda, contaminated injections are unlikely to account for a large proportion of HIV incidence. This result is likely to be generalizable to many other populations in sub-Saharan Africa