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

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 (< 3%, 3-10%, and > 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 < 3%, 3-10%, and > 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 < 3%, 3-10%, and > 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.

Apremilast Adherence and Persistence in Patients with Psoriasis and Psoriatic Arthritis in the Telehealth Setting Versus the In-person Setting During the COVID-19 Pandemic.

INTRODUCTION: Limited access to healthcare during the COVID-19 pandemic prompted patients to seek care using telehealth. In this study, we assessed whether treatment patterns differed for patients with psoriasis (PsO) or psoriatic arthritis (PsA) initiating apremilast by either a telehealth or an in-person visit. METHODS: We estimated adherence and persistence among US patients in the Merative© MarketScan© Commercial and Supplemental Medicare Databases who newly initiated apremilast between April and June 2020, categorized by the type of visit (telehealth or in-person) when apremilast was first prescribed. Adherence was defined as the proportion of days covered (PDC), with PDC ≥ 0.80 considered to indicate high adherence. Persistence was defined as having apremilast available to take without a 60-day gap during follow-up. Factors associated with high adherence and persistence were estimated with logistic and Cox regression. RESULTS: Among apremilast initiators (n = 505), the mean age was 47.6 years, 57.8% were female, and the majority had PsO (79.6%). Telehealth index visits were more likely among patients residing in Northeast USA (odds ratio [OR] 3.31, 95% confidence interval [CI] 1.63-6.71) and Western USA (OR 2.52, 95% CI 1.07-5.93]), those with a prescribing rheumatologist (OR 2.27, 95% CI 1.10-4.68), and those with any baseline telehealth visit (OR 1.91, 85% CI 1.20-3.04). Those initiating apremilast with a telehealth visit (n = 141) had similar mean PDC to those initiating apremilast with an in-person visit (n = 364) (0.695 vs. 0.728; p = 0.272). At the end of the 6-month follow-up, 54.3% of the overall population had high adherence (PDC ≥ 0.80) and 65.1% were persistent. After adjusting for potential confounders, patients initiating apremilast via telehealth had similar full adherence (OR 0.80, 95% CI 0.52-1.21) and persistence as those initiating apremilast in-person. CONCLUSION: Patients with PsO and patients with PsA initiating apremilast via telehealth or in-person during the COVID-19 pandemic had similar medication adherence and persistence during the 6-month follow-up period. These data suggest that patients initiating apremilast can be as effectively managed with telehealth visits as with in-person visits.

The Projected Impact of Population-Wide Achievement of LDL Cholesterol <70 mg/dL on the Number of Recurrent Events Among US Adults with ASCVD.

PURPOSE: Adults with atherosclerotic cardiovascular disease (ASCVD) are recommended high-intensity statins, with those at very high risk for recurrent events recommended adding ezetimibe and/or a proprotein convertase subtilisin/kexin type 9 inhibitor if their low-density lipoprotein cholesterol (LDL-C) is ≥70 mg/dL. We estimated the number of recurrent ASCVD events potentially averted if all adults in the United States (US) ≥45 years of age with ASCVD achieved an LDL-C <70 mg/dL. METHODS: The number of US adults with ASCVD and LDL-C ≥70 mg/dL was estimated from the National Health and Nutrition Examination Survey 2009-2016 (n = 596). The 10-year cumulative incidence of recurrent ASCVD events was estimated from the REasons for Geographic And Racial Differences in Stroke study (n = 5390), weighted to the US population by age, race, and sex. The ASCVD risk reduction by achieving an LDL-C <70 mg/dL was estimated from meta-analyses of lipid-lowering treatment trials. RESULTS: Overall, 14.7 (95% CI, 13.7-15.8) million US adults had ASCVD, of whom 11.6 (95% CI, 10.6-12.5) million had LDL-C ≥70 mg/dL. The 10-year cumulative incidence of ASCVD events was 24.3% (95% CI, 23.2-25.6%). We projected that 2.823 (95% CI, 2.543-3.091) million ASCVD events would occur over 10 years among US adults with ASCVD and LDL-C ≥70 mg/dL. Overall, 0.634 (95% CI, 0.542-0.737) million ASCVD events could potentially be averted if all US adults with ASCVD achieved and maintained LDL-C <70 mg/dL. CONCLUSION: A substantial number of recurrent ASCVD events could be averted over 10 years if all US adults with ASCVD achieved, and maintained, an LDL-C <70 mg/dL.

Evaluating a Simple Approach to Identify Adults Meeting the 2018 AHA/ACC Cholesterol Guideline Definition of Very High Risk for Atherosclerotic Cardiovascular Disease.

PURPOSE: The 2018 American Heart Association/American College of Cardiology (AHA/ACC) cholesterol guideline defines very high atherosclerotic cardiovascular disease (ASCVD) risk as a history of ≥ 2 major ASCVD events or 1 major ASCVD event and multiple high-risk conditions. We tested if a simplified approach, having a history of a major ASCVD event, would identify a high proportion of patients that meet the 2018 AHA/ACC cholesterol guideline criteria for very high risk. METHODS: We analyzed data from US adults with health insurance in the MarketScan database who had experienced an acute coronary syndrome in the past year (recent ACS, n = 3626), a myocardial infarction (MI) other than a recent ACS (n = 7572), an ischemic stroke (n = 3551), or symptomatic peripheral artery disease (PAD, n = 5919). Patients were followed from January 1, 2016, through December 31, 2017, for recurrent ASCVD events. RESULTS: Among 16,344 patients with a history of a major ASCVD event, 94.0% met the 2018 AHA/ACC cholesterol guideline definition for very high risk including 92.9%, 96.5%, 93.1%, and 96.2% with a recent ACS, history of MI, history of stroke, and symptomatic PAD, respectively. The incidence of ASCVD events per 1000 person-years was 50.4 (95% CI: 47.6-53.3) among all patients with a history of a major ASCVD event versus 53.1 (95% CI: 50.1-56.1) among patients who met the 2018 AHA/ACC cholesterol guideline definition of very high risk. CONCLUSION: The vast majority of patients with a recent ACS, history of MI, ischemic stroke, or symptomatic PAD meet the 2018 AHA/ACC cholesterol guideline definition of very high risk.

Use of negative control outcomes to assess the comparability of patients initiating lipid-lowering therapies.

PURPOSE: Clinical trials have demonstrated efficacy of proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9i) in reducing risk of cardiovascular disease events, but effectiveness in routine clinical care has not been well-studied. We used negative control outcomes to assess potential confounding in an observational study of PCSK9i versus ezetimibe or high-intensity statin. METHODS: Using commercial claims, we identified U.S. adults initiating PCSK9i, ezetimibe, or high-intensity statin in 2015-2018, with other lipid-lowering therapy (LLT) use in the year prior (LLT cohort) or atherosclerotic cardiovascular disease (ASCVD) in the past 90 days (ASCVD cohort). We compared initiators of PCSK9i to ezetimibe and high-intensity statin by estimating one-year risks of negative control outcomes influenced by frailty or health-seeking behaviors. Inverse probability of treatment and censoring weighted estimators of risk differences (RDs) were used to evaluate residual confounding after controlling for covariates. RESULTS: PCSK9i initiators had lower one-year risks of negative control outcomes associated with frailty, such as decubitus ulcer in the ASCVD cohort (PCSK9i vs. high-intensity statin RD = -3.5%, 95% confidence interval (CI): -4.6%, -2.5%; PCSK9i vs. ezetimibe RD = -1.3%, 95% CI: -2.1%, -0.6%), with similar but attenuated associations in the LLT cohort. Lower risks of accidents and fractures were also observed for PCSK9i, varying by cohort. Risks were similar for outcomes associated with health-seeking behaviors, although trended higher for PCSK9i in the ASCVD cohort. CONCLUSIONS: Observed associations suggest lower frailty and potentially greater health-seeking behaviors among PCSK9i initiators, particularly those with a recent ASCVD diagnosis, with the potential to bias real-world analyses of treatment effectiveness.

Characteristics of patients with diabetes and a history of myocardial infarction initiating PCSK9 and SGLT2 inhibitors.

Study objective: Proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9i) and sodium-glucose cotransporter-2 inhibitors (SGLT2i) reduce the risk for atherosclerotic cardiovascular disease (ASCVD) events in patients with diabetes and ASCVD. We assessed factors associated with initiating either medication among patients with diabetes and a prior myocardial infarction (MI). Setting/participants: US adults ≥19 years old with private health insurance (MarketScan) or government health insurance (Medicare) who had diabetes and a prior MI and initiated a PCSK9i or an SGLT2i in 2017 or 2018. Main outcome measures: PCSK9i or SGLT2i initiation was identified using pharmacy claims. Results: Overall, 8102 patients initiated a PCSK9i (n = 1501; 18.5%) or an SGLT2i (n = 6601; 81.5%). Patients with 2 and ≥3 versus 1 prior MI (risk ratio [RR]: 1.32 [95%CI: 1.17-1.48] and 1.68 [1.41-2.01], respectively), prior coronary revascularization (1.47 [1.31-1.64]), prior stroke (1.28 [1.06-1.56]), history of peripheral artery disease (1.27 [1.14-1.41]), receiving cardiologist care (1.51 [1.36-1.67]) or taking ezetimibe (2.57 [2.35-2.82]) were more likely to initiate a PCSK9i versus an SGLT2i. Patients with a history of short-term (RR 1.07 [95%CI 1.05-1.09]) or long-term (1.07 [1.04-1.09]) diabetes complications, and taking a low/moderate- and high-intensity statin dosage (1.61 [1.51-1.70] and 1.68 [1.58-1.77], respectively) were more likely to initiate an SGLT2i versus a PCSK9i. Among patients who initiated a PCSK9i, 2.9% subsequently initiated an SGLT2i; 0.8% who initiated an SGLT2i subsequently initiated a PCSK9i. Conclusion: The decision to initiate PCSK9i or SGLT2i is explained by having very high cardiovascular disease risk for those initiating PCSK9i and diabetes complications for those initiating SGLT2i.

Effectiveness of Blood Lipid Management in Patients With Peripheral Artery Disease.

BACKGROUND: Low-density lipoprotein cholesterol (LDL-C) is associated with heightened risk of major adverse cardiovascular events (MACE) and major adverse limb events (MALE) in peripheral artery disease (PAD). Lipid-lowering therapies (LLT) that reduce LDL-C decrease this risk. OBJECTIVES: The authors examined LLT use and actual achieved LDL-C in PAD. METHODS: PAD patients in MarketScan from 2014 to 2018 were identified. Outcomes included LLT use, defined as high-intensity (HI) (high-intensity statin, statin plus ezetimibe, or PCSK9 inhibitor), low-intensity (any other lipid regimen), or no therapy, and follow-up LDL-C. Factors associated with LDL-C <70 mg/dl were identified with multivariable logistic regression. RESULTS: Among 250,103 PAD patients, 20.5% and 39.5% were treated at baseline with HI and low-intensity LLT, respectively; 40.0% were on no LLT. Over a 15-month median follow-up period, HI LLT use increased by 1.5%. Among 18,747 patients with LDL-C data, at baseline, 25.1% were on HI LLT, median LDL-C was 91 mg/dl, and 24.5% had LDL-C <70 mg/dl. Within the HI LLT subgroup, median LDL-C was 81 mg/dl, and 64% had LDL-C ≥70 mg/dl. At follow-up, HI LLT use increased by 3.7%, median LDL-C decreased by 4.0 mg/dl, and an additional 4.1% of patients had LDL-C <70 mg/dl. HI LLT use was greater after follow-up MACE (55.0%) or MALE (41.0%) versus no ischemic event (26.1%). After MACE or MALE, LDL-C was <70 mg/dl in 41.5% and 36.1% of patients, respectively, versus 27.1% in those without an event. Factors associated with follow-up LDL-C <70 mg/dl included smoking, hypertension, diabetes, prior lower extremity revascularization, and prior myocardial infarction but not prior acute or critical limb ischemia. CONCLUSIONS: In PAD, LLT use is suboptimal, LDL-C remains elevated, and LLT intensity is a poor surrogate for achieved LDL-C. Less aggressive lipid management was observed in PAD versus cardiovascular disease, highlighting missed opportunities for implementation of proven therapies in PAD.

Risk for recurrent cardiovascular disease events among patients with diabetes and chronic kidney disease.

BACKGROUND: Adults who have experienced multiple cardiovascular disease (CVD) events have a very high risk for additional events. Diabetes and chronic kidney disease (CKD) are each associated with an increased risk for recurrent CVD events following a myocardial infarction (MI). METHODS: We compared the risk for recurrent CVD events among US adults with health insurance who were hospitalized for an MI between 2014 and 2017 and had (1) CVD prior to their MI but were free from diabetes or CKD (prior CVD), and those without CVD prior to their MI who had (2) diabetes only, (3) CKD only and (4) both diabetes and CKD. We followed patients from hospital discharge through December 31, 2018 for recurrent CVD events including coronary, stroke, and peripheral artery events. RESULTS: Among 162,730 patients, 55.2% had prior CVD, and 28.3%, 8.3%, and 8.2% had diabetes only, CKD only, and both diabetes and CKD, respectively. The rate for recurrent CVD events per 1000 person-years was 135 among patients with prior CVD and 110, 124 and 171 among those with diabetes only, CKD only and both diabetes and CKD, respectively. Compared to patients with prior CVD, the multivariable-adjusted hazard ratio for recurrent CVD events was 0.92 (95%CI 0.90-0.95), 0.89 (95%CI: 0.85-0.93), and 1.18 (95%CI: 1.14-1.22) among those with diabetes only, CKD only, and both diabetes and CKD, respectively. CONCLUSION: Following MI, adults with both diabetes and CKD had a higher risk for recurrent CVD events compared to those with prior CVD without diabetes or CKD.

Ischemic Event Rates in Very-High-Risk Adults.

BACKGROUND: The 2018 American Heart Association/American College of Cardiology (AHA/ACC) cholesterol guideline includes recommendations for intensive lipid-lowering therapy in patients at very high risk for atherosclerotic cardiovascular disease (ASCVD) events. OBJECTIVES: This study sought to estimate event rates among adults with a history of ASCVD who met and did not meet the definition of very high risk in the 2018 AHA/ACC cholesterol guideline. METHODS: Data from U.S. adults with health insurance in the MarketScan database who had a history of ASCVD on January 1, 2016 (n = 27,775) were analyzed. Very high risk for ASCVD events was defined as a history of ≥2 major ASCVD events or 1 event and ≥2 high-risk conditions. Patients were followed through December 31, 2017, for ASCVD events, including myocardial infarction, ischemic stroke, and major adverse limb events. RESULTS: Overall, 15,366 patients (55.3%) with ASCVD met the definition of very high risk. Among patients with and without very high risk, the ASCVD event rate per 1,000 person-years was 53.1 (95% confidence interval [CI]: 50.1 to 56.1) and 17.0 (95% CI: 15.2 to 18.9), respectively. Among patients with ≥2 major ASCVD events and with 1 event and ≥2 high-risk conditions, the ASCVD event rate per 1,000 person-years was 89.8 (95% CI: 82.2 to 98.0) and 41.3 (95% CI: 38.3 to 44.4), respectively. The age- and sex-adjusted hazard ratios for ASCVD events among patients with very high risk, overall, with ≥2 major ASCVD events and with 1 event and ≥2 high-risk conditions versus those without very high risk were 2.98 (95% CI: 2.63 to 3.37), 4.89 (95% CI: 4.22 to 5.66), and 2.33 (95% CI: 2.04 to 2.66), respectively. CONCLUSIONS: The 2018 AHA/ACC cholesterol guideline directs intensive lipid-lowering therapy to adults with a very high ASCVD event rate.

Trends in Public and Global Health Education among Nationally Recognized Undergraduate Liberal Arts Colleges in the United States.

The prevalence of public health and global health (PH/GH) curricular offerings appear to be increasing in terms of undergraduate curricula and in the context of liberal arts education in the United States. Liberal arts colleges (LACs) represent stand-alone institutions, which exclusively focus on undergraduate education. The objective of this study was to assess the prevalence of PH/GH study pathways and PH/GH course offerings among LACs. All LACs identified through the US News and World Report (USNWR) college rankings were contacted with a survey about the following: formal majors, minors, or concentrations in PH/GH; independent study (IS) pathways for PH/GH; specific PH/GH courses offered; and the number of students graduating in 2016, 2017, and 2018 with formal and IS degrees in PH/GH. Demographic characteristics of the colleges came from the USNWR database. Almost half (43%) of all LACs in our sample offer a PH/GH major, minor, concentration, or IS pathway. Almost all (90%) colleges offer at least one course in PH/GH. Approximately 2,000 students attending these LACs pursued or are pursuing graduation with majors, minors, or concentrations in PH/GH for the years 2016-2018. The number of students pursuing formal PH/GH programs has increased by 25% from 2016 to 2018. Student interest in public health is rising in U.S. LACs, with more students seeking formal curricular or IS PH degree pathways. Public health messages are prevalent even among institutions without formal programs. Colleges without programs should consider integrating public health into their curriculum.

Attempting to explain heterogeneous HIV epidemics in sub-Saharan Africa: potential role of historical changes in risk behaviour and male circumcision.

BACKGROUND: A key conclusion of the Four Cities Study, carried out to explore reasons for heterogeneity in the HIV epidemic between two cities in sub-Saharan Africa with relatively low prevalence (Cotonou and Yaoundé) and two with high prevalence (Kisumu and Ndola), was that differences in biological cofactors outweighed differences in sexual risk behaviours. The authors explore an alternative hypothesis, that risk behaviours were historically higher in the high-prevalence cities. They also investigate the effects of different prevalence of male circumcision on the HIV epidemics in the four cities. METHODS: A transmission model was fitted to data from the Four Cities Study. Default scenarios included biological cofactor effects on HIV transmission. Counter-factual scenarios were simulated without biological cofactors, with and without higher historical sexual behaviours, and with various rates of male circumcision. RESULTS: Simulated adult HIV prevalence in 1997 for the default scenarios was 3.1%, 7.8%, 28.9% and 27.1% in Cotonou, Yaoundé, Kisumu and Ndola, respectively, in line with data. Without biological cofactors, even implausibly high historical levels of risk behaviour in East Africa could not reproduce the observed heterogeneity in the late 1990s. Increasing the proportion of men circumcised in Ndola from 10% to 100% reduced HIV prevalence in 1997 to 7%. Decreasing the proportion circumcised in Yaoundé from 100% to 10% increased HIV prevalence to 26%. CONCLUSIONS: Differences in male circumcision rates are likely to have played a key role in the heterogeneous spread of HIV across Africa. The effect of circumcision interventions can vary depending on the epidemic setting, with a larger effect in more generalised epidemics.

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.

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.

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% of HIV transmission attributed to STIs. The PAF for herpes simplex virus type 2 increased during the epidemics, whereas the PAF for curable STIs and the relative impact of syndromic management decreased. The models showed that the absolute impact of syndromic management remains high in generalized epidemics, and it remained cost-saving in 3 of the 4 populations in which the cost per HIV infection averted ranged between US $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.

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.

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.

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.

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.

Can population differences explain the contrasting results of the Mwanza, Rakai, and Masaka HIV/sexually transmitted disease intervention trials?: A modeling study.

OBJECTIVE: To determine whether population differences can explain the contrasting impacts on HIV observed in the Mwanza trial of sexually transmitted disease (STD) syndromic treatment (ST), the Rakai trial of STD mass treatment (MT), and the Masaka trial of information, education, and communication (IEC) with and without ST as well as to predict the effectiveness of each intervention strategy in each population. METHODS: Stochastic modeling of the transmission of HIV and 6 STDs was used with parameters fitted to demographic, sexual behavior, and epidemiological data from the trials and general review of STD/HIV biology. RESULTS: The baseline trial populations could be simulated by assuming higher risk behavior in Uganda compared with Mwanza in the 1980s, followed by reductions in risk behavior in Uganda preceding the trials. In line with trial observations, the projected HIV impacts were larger for the ST intervention in Mwanza than for the MT intervention in Rakai or the IEC and IEC + ST interventions in Masaka. All 4 simulated intervention strategies were more effective in reducing incidence of HIV infection in Mwanza than in either Rakai or Masaka. CONCLUSIONS: Population differences in sexual behavior, curable STD rates, and HIV epidemic stage can explain most of the contrast in HIV impact observed between the 3 trials. This study supports the hypothesis that STD management is an effective HIV prevention strategy in populations with a high prevalence of curable STDs, particularly in an early HIV epidemic.