Estimating prevalence trends in adult gonorrhoea and syphilis in low- and middle-income countries with the Spectrum-STI model: results for Zimbabwe and Morocco from 1995 to 2016.

OBJECTIVE: To develop a tool for estimating national trends in adult prevalence of sexually transmitted infections by low- and middle-income countries, using standardised, routinely collected programme indicator data. METHODS: The Spectrum-STI model fits time trends in the prevalence of active syphilis through logistic regression on prevalence data from antenatal clinic-based surveys, routine antenatal screening and general population surveys where available, weighting data by their national coverage and representativeness. Gonorrhoea prevalence was fitted as a moving average on population surveys (from the country, neighbouring countries and historic regional estimates), with trends informed additionally by urethral discharge case reports, where these were considered to have reasonably stable completeness. Prevalence data were adjusted for diagnostic test performance, high-risk populations not sampled, urban/rural and male/female prevalence ratios, using WHO's assumptions from latest global and regional-level estimations. Uncertainty intervals were obtained by bootstrap resampling. RESULTS: Estimated syphilis prevalence (in men and women) declined from 1.9% (95% CI 1.1% to 3.4%) in 2000 to 1.5% (1.3% to 1.8%) in 2016 in Zimbabwe, and from 1.5% (0.76% to 1.9%) to 0.55% (0.30% to 0.93%) in Morocco. At these time points, gonorrhoea estimates for women aged 15-49 years were 2.5% (95% CI 1.1% to 4.6%) and 3.8% (1.8% to 6.7%) in Zimbabwe; and 0.6% (0.3% to 1.1%) and 0.36% (0.1% to 1.0%) in Morocco, with male gonorrhoea prevalences 14% lower than female prevalence. CONCLUSIONS: This epidemiological framework facilitates data review, validation and strategic analysis, prioritisation of data collection needs and surveillance strengthening by national experts. We estimated ongoing syphilis declines in both Zimbabwe and Morocco. For gonorrhoea, time trends were less certain, lacking recent population-based surveys.

Trends in Adult Chlamydia and Gonorrhea Prevalence, Incidence and Urethral Discharge Case Reporting in Morocco over 1995-2015-Estimates Using the Spectrum-Sexually Transmitted Infection Model.

BACKGROUND: Evolving health priorities and resource constraints mean that countries require data on sexually transmitted infections (STI) trends to inform program planning and resource allocation. METHODS: The Spectrum modeling tool estimated prevalence and incidence of gonorrhea and chlamydia in Morocco's 15- to 49-year-old population, based on prevalence surveys. Incident cases, broken down between symptomatic and asymptomatic, and treated versus untreated, were compared with urethral discharge (UD) case reports, to estimate reporting completeness among treated UD cases. RESULTS: Gonorrhea prevalence was estimated at 0.37% (95% confidence interval [CI], 0.14-1.0%) in women and 0.32% (0.12-0.87%) in men in 2015; chlamydia prevalences were 3.8% (95% CI, 2.1-6.4%) and 3.0% (95% CI, 1.7-5.1%). Corresponding estimated numbers of new cases in women and men in 2015 were 79,598 (95% CI, 23,918-256,206) and 112,013 (95% CI, 28,700-307,433) for gonorrhea, and 291,908 (95% CI, 161,064-524,270) and 314,032 (95% CI, 186,076-559,133) for chlamydia. Gonorrhea and chlamydia prevalence had declined by an estimated 41% and 27%, respectively, over 1995 to 2015. Prevalence declines probably related to improved STI treatment coverage, and decreasing risk behaviors. Reporting completeness among treated UD cases was estimated at 46% to 77% in 2015. Reported UD cases corresponded to 13% of all estimated (symptomatic and asymptomatic) gonorrhea and chlamydia cases. CONCLUSIONS: STI declines and improvements in treatment coverage are consistent with Morocco's introduction of syndromic management in 2000, scale-up of prevention, and declining human immunodeficiency virus incidence. While gonorrhea is four-fold more common as cause of clinical UD cases than chlamydia, Morocco continues to suffer a large, untreated burden of chlamydia. Reliable monitoring of both STIs requires new periodic surveys and/or novel forms of affordable surveillance beyond high-risk populations.

Spectrum-Malaria: a user-friendly projection tool for health impact assessment and strategic planning by malaria control programmes in sub-Saharan Africa.

BACKGROUND: Scale-up of malaria prevention and treatment needs to continue but national strategies and budget allocations are not always evidence-based. This article presents a new modelling tool projecting malaria infection, cases and deaths to support impact evaluation, target setting and strategic planning. METHODS: Nested in the Spectrum suite of programme planning tools, the model includes historic estimates of case incidence and deaths in groups aged up to 4, 5-14, and 15+ years, and prevalence of Plasmodium falciparum infection (PfPR) among children 2-9 years, for 43 sub-Saharan African countries and their 602 provinces, from the WHO and malaria atlas project. Impacts over 2016-2030 are projected for insecticide-treated nets (ITNs), indoor residual spraying (IRS), seasonal malaria chemoprevention (SMC), and effective management of uncomplicated cases (CMU) and severe cases (CMS), using statistical functions fitted to proportional burden reductions simulated in the P. falciparum dynamic transmission model OpenMalaria. RESULTS: In projections for Nigeria, ITNs, IRS, CMU, and CMS scale-up reduced health burdens in all age groups, with largest proportional and especially absolute reductions in children up to 4 years old. Impacts increased from 8 to 10 years following scale-up, reflecting dynamic effects. For scale-up of each intervention to 80% effective coverage, CMU had the largest impacts across all health outcomes, followed by ITNs and IRS; CMS and SMC conferred additional small but rapid mortality impacts. DISCUSSION: Spectrum-Malaria's user-friendly interface and intuitive display of baseline data and scenario projections holds promise to facilitate capacity building and policy dialogue in malaria programme prioritization. The module's linking to the OneHealth Tool for costing will support use of the software for strategic budget allocation. In settings with moderately low coverage levels, such as Nigeria, improving case management and achieving universal coverage with ITNs could achieve considerable burden reductions. Projections remain to be refined and validated with local expert input data and actual policy scenarios.

Impact of malaria interventions on child mortality in endemic African settings: comparison and alignment between LiST and Spectrum-Malaria model.

BACKGROUND: In malaria-endemic countries, malaria prevention and treatment are critical for child health. In the context of intervention scale-up and rapid changes in endemicity, projections of intervention impact and optimized program scale-up strategies need to take into account the consequent dynamics of transmission and immunity. METHODS: The new Spectrum-Malaria program planning tool was used to project health impacts of Insecticide-Treated mosquito Nets (ITNs) and effective management of uncomplicated malaria cases (CMU), among other interventions, on malaria infection prevalence, case incidence and mortality in children 0-4 years, 5-14 years of age and adults. Spectrum-Malaria uses statistical models fitted to simulations of the dynamic effects of increasing intervention coverage on these burdens as a function of baseline malaria endemicity, seasonality in transmission and malaria intervention coverage levels (estimated for years 2000 to 2015 by the World Health Organization and Malaria Atlas Project). Spectrum-Malaria projections of proportional reductions in under-five malaria mortality were compared with those of the Lives Saved Tool (LiST) for the Democratic Republic of the Congo and Zambia, for given (standardized) scenarios of ITN and/or CMU scale-up over 2016-2030. RESULTS: Proportional mortality reductions over the first two years following scale-up of ITNs from near-zero baselines to moderately higher coverages align well between LiST and Spectrum-Malaria -as expected since both models were fitted to cluster-randomized ITN trials in moderate-to-high-endemic settings with 2-year durations. For further scale-up from moderately high ITN coverage to near-universal coverage (as currently relevant for strategic planning for many countries), Spectrum-Malaria predicts smaller additional ITN impacts than LiST, reflecting progressive saturation. For CMU, especially in the longer term (over 2022-2030) and for lower-endemic settings (like Zambia), Spectrum-Malaria projects larger proportional impacts, reflecting onward dynamic effects not fully captured by LiST. CONCLUSIONS: Spectrum-Malaria complements LiST by extending the scope of malaria interventions, program packages and health outcomes that can be evaluated for policy making and strategic planning within and beyond the perspective of child survival.

Malaria intervention scale-up in Africa: effectiveness predictions for health programme planning tools, based on dynamic transmission modelling.

BACKGROUND: Scale-up of malaria prevention and treatment needs to continue to further important gains made in the past decade, but national strategies and budget allocations are not always evidence-based. Statistical models were developed summarizing dynamically simulated relations between increases in coverage and intervention impact, to inform a malaria module in the Spectrum health programme planning tool. METHODS: The dynamic Plasmodium falciparum transmission model OpenMalaria was used to simulate health effects of scale-up of insecticide-treated net (ITN) usage, indoor residual spraying (IRS), management of uncomplicated malaria cases (CM) and seasonal malaria chemoprophylaxis (SMC) over a 10-year horizon, over a range of settings with stable endemic malaria. Generalized linear regression models (GLMs) were used to summarize determinants of impact across a range of sub-Sahara African settings. RESULTS: Selected (best) GLMs explained 94-97 % of variation in simulated post-intervention parasite infection prevalence, 86-97 % of variation in case incidence (three age groups, three 3-year horizons), and 74-95 % of variation in malaria mortality. For any given effective population coverage, CM and ITNs were predicted to avert most prevalent infections, cases and deaths, with lower impacts for IRS, and impacts of SMC limited to young children reached. Proportional impacts were larger at lower endemicity, and (except for SMC) largest in low-endemic settings with little seasonality. Incremental health impacts for a given coverage increase started to diminish noticeably at above ~40 % coverage, while in high-endemic settings, CM and ITNs acted in synergy by lowering endemicity. Vector control and CM, by reducing endemicity and acquired immunity, entail a partial rebound in malaria mortality among people above 5 years of age from around 5-7 years following scale-up. SMC does not reduce endemicity, but slightly shifts malaria to older ages by reducing immunity in child cohorts reached. CONCLUSION: Health improvements following malaria intervention scale-up vary with endemicity, seasonality, age and time. Statistical models can emulate epidemiological dynamics and inform strategic planning and target setting for malaria control.

Estimating the costs and perceived benefits of oral pre-exposure prophylaxis (PrEP) delivery in ten counties of Kenya: a costing and a contingent valuation study.

Background: Kenya included oral PrEP in the national guidelines as part of combination HIV prevention, and subsequently began providing PrEP to individuals who are at elevated risk of HIV infection in 2017. However, as scale-up continued, there was a recognized gap in knowledge on the cost of delivering oral PrEP. This gap limited the ability of the Government of Kenya to budget for its PrEP scale-up and to evaluate PrEP relative to other HIV prevention strategies. The following study calculated the actual costs of oral PrEP scale-up as it was being delivered in ten counties in Kenya. This costing also allowed for a comparison of various models of service delivery in different geographic regions from the perspective of service providers in Kenya. In addition, the analysis was also conducted to understand factors that indicate why some individuals place a greater value on PrEP than others, using a contingent valuation technique. Methods: Data collection was completed between November 2017 and September 2018. Costing data was collected from 44 Kenyan health facilities, consisting of 23 public facilities, 5 private facilities and 16 drop-in centers (DICEs) through a cross-sectional survey in ten counties. Financial and programmatic data were collected from financial and asset records and through interviewer administered questionnaires. The costs associated with PrEP provision were calculated using an ingredients-based costing approach which involved identification and costing of all the economic inputs (both direct and indirect) used in PrEP service delivery. In addition, a contingent valuation study was conducted at the same 44 facilities to understand factors that reveal why some individuals place a greater value on PrEP than others. Interviews were conducted with 2,258 individuals (1,940 current PrEP clients and 318 non-PrEP clients). A contingent valuation method using a "payment card approach" was used to determine the maximum willingness to pay (WTP) of respondents regarding obtaining access to oral PrEP services. Results: The weighted cost of providing PrEP was $253 per person year, ranging from $217 at health centers to $283 at dispensaries. Drop-in centers (DICEs), which served about two-thirds of the client volume at surveyed facilities, had a unit cost of $276. The unit cost was highest for facilities targeting MSM ($355), while it was lowest for those targeting FSW ($248). The unit cost for facilities targeting AGYW was $323 per person year. The largest percentage of costs were attributable to personnel (58.5%), followed by the cost of drugs, which represented 25% of all costs. The median WTP for PrEP was $2 per month (mean was $4.07 per month). This covers only one-third of the monthly cost of the medication (approximately $6 per month) and less than 10% of the full cost of delivering PrEP ($21 per month). A sizable proportion of current clients (27%) were unwilling to pay anything for PrEP. Certain populations put a higher value on PrEP services, including: FSW and MSM, Muslims, individuals with higher education, persons between the ages of 20 and 35, and households with a higher income and expenditures. Discussion: This is the most recent and comprehensive study on the cost of PrEP delivery in Kenya. These results will be used in determining resource requirements and for resource mobilization to facilitate sustainable PrEP scale-up in Kenya and beyond. This contingent valuation study does have important implications for Kenya's PrEP program. First, it indicates that some populations are more motivated to adopt oral PrEP, as indicated by their higher WTP for the service. MSM and FSW, for example, placed a higher value on PrEP than AGYW. Higher educated individuals, in turn, put a much higher value on PrEP than those with less education (which may also reflect the higher "ability to pay" among those with more education). This suggests that any attempt to increase demand or improve PrEP continuation should consider these differences in client populations. Cost recovery from existing PrEP clients would have potentially negative consequences for uptake and continuation.

Prevalence of syphilis, gonorrhoea and chlamydia in women in Fiji, the Federated States of Micronesia, Papua New Guinea and Samoa, 1995-2017: Spectrum-STI model estimates.

OBJECTIVE: To estimate prevalence levels of and time trends for active syphilis, gonorrhoea and chlamydia in women aged 15-49 years in four countries in the Pacific (Fiji, the Federated States of Micronesia [FSM], Papua New Guinea [PNG] and Samoa) to inform surveillance and control strategies for sexually transmitted infections (STIs). METHODS: The Spectrum-STI model was fitted to data from prevalence surveys and screenings of adult female populations collected during 1995-2017 and adjusted for diagnostic test performance and to account for undersampled high-risk populations. For chlamydia and gonorrhoea, data were further adjusted for age and differences between urban and rural areas. RESULTS: Prevalence levels were estimated as a percentage (95% confidence interval). In 2017, active syphilis prevalence was estimated in Fiji at 3.89% (2.82 to 5.06), in FSM at 1.48% (0.93 to 2.16), in PNG at 3.91% (1.67 to 7.24) and in Samoa at 0.16% (0.07 to 0.37). For gonorrhoea, the prevalence in Fiji was 1.63% (0.50 to 3.87); in FSM it was 1.59% (0.49 to 3.58); in PNG it was 11.0% (7.25 to 16.1); and in Samoa it was 1.61% (1.17 to 2.19). The prevalence of chlamydia in Fiji was 24.1% (16.5 to 32.7); in FSM it was 23.9% (18.5 to 30.6); in PNG it was 14.8% (7.39 to 24.7); and in Samoa it was 30.6% (26.8 to 35.0). For each specific disease within each country, the 95% confidence intervals overlapped for 2000 and 2017, although in PNG the 2017 estimates for all three STIs were below the 2000 estimates. These patterns were robust in the sensitivity analyses. DISCUSSION: This study demonstrated a persistently high prevalence of three major bacterial STIs across four countries in WHO's Western Pacific Region during nearly two decades. Further strengthening of strategies to control and prevent STIs is warranted.

Modelling impact and cost-effectiveness of oral pre-exposure prophylaxis in 13 low-resource countries.

INTRODUCTION: Oral pre-exposure prophylaxis (PrEP) provision is a priority intervention for high HIV prevalence settings and populations at substantial risk of HIV acquisition. This mathematical modelling analysis estimated the impact, cost and cost-effectiveness of scaling up oral PrEP in 13 countries. METHODS: We projected the impact and cost-effectiveness of oral PrEP between 2018 and 2030 using a combination of the Incidence Patterns Model and the Goals model. We created four PrEP rollout scenarios involving three priority populations-female sex workers (FSWs), serodiscordant couples (SDCs) and adolescent girls and young women (AGYW)-both with and without geographic prioritization. We applied the model to 13 countries (Eswatini, Ethiopia, Haiti, Kenya, Lesotho, Mozambique, Namibia, Nigeria, Tanzania, Uganda, Zambia and Zimbabwe). The base case assumed achievement of the Joint United Nations Programme on HIV/AIDS 90-90-90 antiretroviral therapy targets, 90% male circumcision coverage by 2020 and 90% efficacy and adherence levels for oral PrEP. RESULTS: In the scenarios we examined, oral PrEP averted 3% to 8% of HIV infections across the 13 countries between 2018 and 2030. For all but three countries, more than 50% of the HIV infections averted by oral PrEP in the scenarios we examined could be obtained by rollout to FSWs and SDCs alone. For several countries, expanding oral PrEP to include medium-risk AGYW in all regions greatly increased the impact. The efficiency and impact benefits of geographic prioritization of rollout to AGYW varied across countries. Variations in cost-effectiveness across countries reflected differences in HIV incidence and expected variations in unit cost. For most countries, rolling out oral PrEP to FSWs, SDCs and geographically prioritized AGYW was not projected to have a substantial impact on the supply chain for antiretroviral drugs. CONCLUSIONS: These modelling results can inform prioritization, target-setting and other decisions related to oral PrEP scale-up within combination prevention programmes. We caution against extensive use given limitations in cost data and implementation approaches. This analysis highlights some of the immediate challenges facing countries-for example, trade-offs between overall impact and cost-effectiveness-and emphasizes the need to improve data availability and risk assessment tools to help countries make informed decisions.

The Spectrum-STI Groups model: syphilis prevalence trends across high-risk and lower-risk populations in Yunnan, China.

The Spectrum-STI model, structured by sub-groups within a population, was used in a workshop in Yunnan, China, to estimate provincial trends in active syphilis in 15 to 49-year-old adults. Syphilis prevalence data from female sex workers (FSW), men who have sex with men (MSM), and lower-risk women and men in Yunnan were identified through literature searches and local experts. Sources included antenatal care clinic screening, blood donor screening, HIV/STI bio-behavioural surveys, sentinel surveillance, and epidemiology studies. The 2017 provincial syphilis prevalence estimates were 0.26% (95% confidence interval 0.17-0.34%) in women and 0.28% (0.20-0.36%) in men. Estimated prevalence was 6.8-fold higher in FSW (1.69% (0.68-3.97%) than in lower-risk women (0.25% (0.18-0.35%)), and 22.7-fold higher in MSM (5.35% (2.74-12.47%) than in lower-risk men (0.24% (0.17-0.31%). For all populations, the 2017 estimates were below the 2005 estimates, but differences were not significant. In 2017 FSW and MSM together accounted for 9.3% of prevalent cases. These estimates suggest Yunnan's STI programs have kept the overall prevalence of syphilis low, but prevalence remains high in FSW and MSM. Strengthening efforts targeting FSW and MSM, and identification of other risk populations e.g. among heterosexual men, are critical to reduce syphilis.

Adult female syphilis prevalence, congenital syphilis case incidence and adverse birth outcomes, Mongolia 2000-2016: Estimates using the Spectrum STI tool.

INTRODUCTION: Mongolia's health ministry prioritizes control of Sexually Transmitted Infections, including syphilis screening and treatment in antenatal care (ANC). METHODS: Adult syphilis prevalence trends were fitted using the Spectrum-STI estimation tool, using data from ANC surveys and routine screening over 1997-2016. Estimates were combined with programmatic data to estimate numbers of treated and untreated pregnant women with syphilis and associated incidence congenital syphilis (CS) and CS-attributable adverse birth outcomes (ABO), which we compared with CS case reports. RESULTS: Syphilis prevalence in pregnant women was estimated at 1.7% in 2000 and 3.0% in 2016. We estimated 652 CS cases, of which 410 ABO, in 2016. Far larger, annually increasing numbers of CS cases and ABO were estimated to have been prevented: 1654 cases, of which 789 ABO in 2016 - thanks to increasing coverages of ANC (99% in 2016), ANC-based screening (97% in 2016) and treatment of women diagnosed (81% in 2016). The 42 CS cases reported nationally over 2016 (liveborn infants only) represented 27% of liveborn infants with clinical CS, but only 7% of estimated CS cases among women found syphilis-infected in ANC, and 6% of all estimated CS cases including those born to women with undiagnosed syphilis. DISCUSSION/CONCLUSION: Mongolia's ANC-based syphilis screening program is reducing CS, but maternal prevalence remains high. To eliminate CS (target: <50 cases per 100,000 live births), Mongolia should strengthen ANC services, limiting losses during referral for treatment, and under-diagnosis of CS including still-births and neonatal deaths, and expand syphilis screening and prevention programs.

Trends in adult chlamydia and gonorrhoea prevalence, incidence and urethral discharge case reporting in Mongolia from 1995 to 2016 - estimates using the Spectrum-STI model.

OBJECTIVE: To estimate Mongolia's prevalence and incidence trends of gonorrhoea and chlamydia in women and men 15-49 years old to inform control of STIs and HIV, a national health sector priority. METHODS: We applied the Spectrum-STI estimation model, fitting data from two national population surveys (2001 and 2008) and from routine gonorrhoea screening of pregnant women in antenatal care (1997 to 2016) adjusted for diagnostic test performance, male/female differences and missing high-risk populations. Prevalence and incidence estimates were then used to assess completeness of national case reporting. RESULTS: Gonorrhoea prevalence was estimated at 3.3% (95% confidence interval, 1.6-3.9%) in women and 2.9% (1.6-4.1%) in men in 2016; chlamydia prevalence levels were 19.5% (17.3-21.9%) and 15.6% (10.0-21.2%), respectively. Corresponding new incident cases in women and men in 2016 totalled 60 334 (36 147 to 121 933) and 76 893 (35 639 to 254 913) for gonorrhoea and 131 306 (84 232 to 254 316) and 148 162 (71 885 to 462 588) for chlamydia. Gonorrhoea and chlamydia prevalence declined by an estimated 33% and 11%, respectively from 2001 to 2016.Comparing numbers of symptomatic and treated cases estimated by Spectrum with gonorrhoea case reports suggests that 15% of symptomatic treated gonorrhoea cases were reported in 2016; only a minority of chlamydia episodes were reported as male urethral discharge cases. DISCUSSION: Gonorrhoea and chlamydia prevalence are estimated to have declined in Mongolia during the early 2000s, possibly associated with syndromic management in primary care facilities and improving treatment coverage since 2001 and scale up of HIV/STI prevention interventions since 2003. However, prevalence remains high with most gonorrhoea and chlamydia cases not treated or recorded in the public health system.

The prevalence and incidence of active syphilis in women in Morocco, 1995-2016: Model-based estimation and implications for STI surveillance.

BACKGROUND: Evolving health priorities and resource constraints mean that countries require data on trends in sexually transmitted infections (STI) burden, to inform program planning and resource allocation. We applied the Spectrum STI estimation tool to estimate the prevalence and incidence of active syphilis in adult women in Morocco over 1995 to 2016. The results from the analysis are being used to inform Morocco's national HIV/STI strategy, target setting and program evaluation. METHODS: Syphilis prevalence levels and trends were fitted through logistic regression to data from surveys in antenatal clinics, women attending family planning clinics and other general adult populations, as available post-1995. Prevalence data were adjusted for diagnostic test performance, and for the contribution of higher-risk populations not sampled in surveys. Incidence was inferred from prevalence by adjusting for the average duration of infection with active syphilis. RESULTS: In 2016, active syphilis prevalence was estimated to be 0.56% in women 15 to 49 years of age (95% confidence interval, CI: 0.3%-1.0%), and around 21,675 (10,612-37,198) new syphilis infections have occurred. The analysis shows a steady decline in prevalence from 1995, when the prevalence was estimated to be 1.8% (1.0-3.5%). The decline was consistent with decreasing prevalences observed in TB patients, fishermen and prisoners followed over 2000-2012 through sentinel surveillance, and with a decline since 2003 in national HIV incidence estimated earlier through independent modelling. CONCLUSIONS: Periodic population-based surveys allowed Morocco to estimate syphilis prevalence and incidence trends. This first-ever undertaking engaged and focused national stakeholders, and confirmed the still considerable syphilis burden. The latest survey was done in 2012 and so the trends are relatively uncertain after 2012. From 2017 Morocco plans to implement a system to record data from routine antenatal programmatic screening, which should help update and re-calibrate next trend estimations.

Comparing longitudinal CD4 responses to cART among non-perinatally HIV-infected youth versus adults: Results from the HIVRN Cohort.

BACKGROUND: Youth have residual thymic tissue and potentially greater capacity for immune reconstitution than adults after initiation of combination antiretroviral therapy (cART). However, youth face behavioral and psychosocial challenges that may make them more likely than adults to delay ART initiation and less likely to attain similar CD4 outcomes after initiating cART. This study compared CD4 outcomes over time following cART initiation between ART-naïve non-perinatally HIV-infected (nPHIV) youth (13-24 years-old) and adults (≥25-44 years-old). METHODS: Retrospective analysis of ART-naïve nPHIV individuals 13-44 years-old, who initiated their first cART between 2008 and 2011 at clinical sites in the HIV Research Network. A linear mixed model was used to assess the association between CD4 levels after cART initiation and age (13-24, 25-34, 35-44 years), accounting for random variation within participants and between sites, and adjusting for key variables including gender, race/ethnicity, viral load, gaps in care (defined as > 365 days between CD4 tests), and CD4 levels prior to cART initiation (baseline CD4). RESULTS: Among 2,595 individuals (435 youth; 2,160 adults), the median follow-up after cART initiation was 179 weeks (IQR 92-249). Baseline CD4 was higher for youth (320 cells/mm3) than for ages 25-34 (293) or 35-44 (258). At 239 weeks after cART initiation, median unadjusted CD4 was higher for youth than adults (576 vs. 539 and 476 cells/mm3, respectively), but this difference was not significant when baseline CD4 was controlled. Compared to those with baseline CD4 ≤200 cells/mm3, individuals with baseline CD4 of 201-500 and >500 cells/mm3 had greater predicted CD4 levels: 390, 607, and 831, respectively. Additionally, having no gaps in care and higher viral load were associated with better CD4 outcomes. CONCLUSIONS: Despite having residual thymic tissue, youth attain similar, not superior, CD4 gains as adults. Early ART initiation with minimal delay is as essential to optimizing outcomes for youth as it is for their adult counterparts.

How should we best estimate the mean recency duration for the BED method?

BED estimates of HIV incidence from cross-sectional surveys are obtained by restricting, to fixed time T, the period over which incidence is estimated. The appropriate mean recency duration (Ω(T)) then refers to the time where BED optical density (OD) is less than a pre-set cut-off C, given the patient has been HIV positive for at most time T. Five methods, tested using data for postpartum women in Zimbabwe, provided similar estimates of Ω(T) for C = 0.8: i) The ratio (r/s) of the number of BED-recent infections to all seroconversions over T = 365 days: 192 days [95% CI 168-216]. ii) Linear mixed modeling (LMM): 191 days [95% CI 174-208]. iii) Non-linear mixed modeling (NLMM): 196 days [95% CrI 188-204]. iv) Survival analysis (SA): 192 days [95% CI 168-216]. Graphical analysis: 193 days. NLMM estimates of Ω(T)--based on a biologically more appropriate functional relationship than LMM--resulted in best fits to OD data, the smallest variance in estimates of VT, and best correspondence between BED and follow-up estimates of HIV incidence, for the same subjects over the same time period. SA and NLMM produced very similar estimates of Ω(T) but the coefficient of variation of the former was .3 times as high. The r/s method requires uniformly distributed seroconversion events but is useful if data are available only from a single follow-up. The graphical method produces the most variable results, involves unsound methodology and should not be used to provide estimates of Ω(T). False-recent rates increased as a quadratic function of C: for incidence estimation C should thus be chosen as small as possible, consistent with an adequate resultant number of recent cases, and accurate estimation of Ω(T). Inaccuracies in the estimation of Ω(T) should not now provide an impediment to incidence estimation.

A general HIV incidence inference scheme based on likelihood of individual level data and a population renewal equation.

We derive a new method to estimate the age specific incidence of an infection with a differential mortality, using individual level infection status data from successive surveys. The method consists of a) an SI-type model to express the incidence rate in terms of the prevalence and its derivatives as well as the difference in mortality rate, and b) a maximum likelihood approach to estimate the prevalence and its derivatives. Estimates can in principle be obtained for any chosen age and time, and no particular assumptions are made about the epidemiological or demographic context. This is in contrast with earlier methods for estimating incidence from prevalence data, which work with aggregated data, and the aggregated effect of demographic and epidemiological rates over the time interval between prevalence surveys. Numerical simulation of HIV epidemics, under the presumption of known excess mortality due to infection, shows improved control of bias and variance, compared to previous methods. Our analysis motivates for a) effort to be applied to obtain accurate estimates of excess mortality rates as a function of age and time among HIV infected individuals and b) use of individual level rather than aggregated data in order to estimate HIV incidence rates at times between two prevalence surveys.

Statistical power and estimation of incidence rate ratios obtained from BED incidence testing for evaluating HIV interventions among young people.

BACKGROUND: The objectives of this study were to determine the capacity of BED incidence testing to a) estimate the effect of a HIV prevention intervention and b) provide adequate statistical power, when used among young people from sub-Saharan African settings with high HIV incidence rates. METHODS: Firstly, after having elaborated plausible scenarios based on empirical data and the characteristics of the BED HIV-1 Capture EIA (BED) assay, we conducted statistical calculations to determine the BED theoretical power and HIV incidence rate ratio (IRR) associated with an intervention when using BED incidence testing. Secondly, we simulated a cross-sectional study conducted in a population among whom an HIV intervention was rolled out. Simulated data were analyzed using a log-linear Poisson model to recalculate the IRR and its confidence interval, and estimate the BED practical power. Calculations were conducted with and without corrections for misclassifications. RESULTS: Calculations showed that BED incidence testing can yield a BED theoretical power of 75% or more of the power that can be obtained in a classical cohort study conducted over a duration equal to the BED window period. Statistical analyses using simulated populations showed that the effect of a prevention intervention can be estimated with precision using classical statistical analysis of BED incidence testing data, even with an imprecise knowledge of the characteristics of the BED assay. The BED practical power was lower but of the same magnitude as the BED theoretical power. CONCLUSIONS: BED incidence testing can be applied to reasonably small samples to achieve good statistical power when used among young people to estimate IRR.