Introduction
The Spectrum/AIM model is used by national HIV programs and UNAIDS to prepare annual estimates of key HIV indicators. This article describes key updates to paediatric and adult models ...for the 2021 round of HIV estimates.
Methods
Potential updates to Spectrum arise due to newly available data, new analyses of existing data, and the need for new issues to be addressed. Updates are guided by experts through the UNAIDS Reference Group on Estimates, Modelling and Projections. Changes are tested and assessed for impact before being accepted into the final model.
Results
Spectrum tracks children living with HIV by CD4% for ages 0–4 and CD4 count for ages 5–14. Data from IeDEA treatment sites have been used to map the transition from CD4% to CD4 count at age 5. Breastfeeding patterns in sub‐Saharan Africa have been updated with the latest survey data and estimates of continuation on antiretroviral therapy (ART) with breastfeeding have been revised based on recent studies. Model assumptions about the CD4 counts of people who drop out of ART have been revised to account for CD4 count increases while on treatment. If available, monthly data on numbers on ART can now be used to estimate the effects of COVID‐19‐related disruptions during 2020.
Conclusions
These changes are intended to provide more accurate estimates of HIV burden. The effects of these changes on paediatric indicators are small except in countries with new surveys that might have updated patterns of breastfeeding. Changes to the adult model have little effect on total new infections. AIDS‐related deaths will be somewhat lower in countries that have data on ART drop out but might be increased by HIV care disruptions due to COVID‐19. The updated model uses newly available data to improve the estimation of paediatric and adult HIV indicators.
Breastfeeding improves child survival but is a source of mother-to-child HIV transmission among women with unsuppressed HIV infection. Estimated HIV incidence in children is sensitive to ...breastfeeding duration among mothers living with HIV (MLHIV). Breastfeeding duration may vary according to maternal HIV status.
Sub-Saharan Africa.
We analyzed pooled data from nationally representative household surveys conducted during 2003-2019 that included HIV testing and elicited breastfeeding practices. We fitted survival models of breastfeeding duration by country, year, and maternal HIV status for 4 sub-Saharan African regions (Eastern, Central, Southern, and Western).
Data were obtained from 65 surveys in 31 countries. In 2010, breastfeeding in the first month of life ("initial breastfeeding") among MLHIV ranged from 69.1% (95% credible interval: 68-79.9) in Southern Africa to 93.4% (92.7-98.0) in Western Africa. Median breastfeeding duration among MLHIV was the shortest in Southern Africa at 15.6 (14.2-16.3) months and the longest in Eastern Africa at 22.0 (21.7-22.5) months. By comparison, HIV-negative mothers were more likely to breastfeed initially (91.0%-98.7% across regions) and for longer duration (median 18.3-24.6 months across regions). Initial breastfeeding and median breastfeeding duration decreased during 2005-2015 in most regions and did not increase in any region regardless of maternal HIV status.
MLHIV in sub-Saharan Africa are less likely to breastfeed initially and stop breastfeeding sooner than HIV-negative mothers. Since 2020, UNAIDS-supported HIV estimates have accounted for this shorter breastfeeding exposure among HIV-exposed children. MLHIV need support to enable optimal breastfeeding practices and to adhere to antiretroviral therapy for HIV treatment and prevention of postnatal mother-to-child transmission.
Background. The potential impact of antiretroviral therapy (ART) and pre-exposure prophylaxis (PrEP) with overlapping and nonoverlapping antiretrovirals (ARVs) on human immunodeficiency virus (HIV) ...transmission and drug resistance is unknown. Methods. A detailed mathematical model was used to simulate the epidemiological impact of ART alone, PrEP alone, and combined ART + PrEP in South Africa. Results. ART alone initiated at a CD4 lymphocyte cell count <200 cells/μL (80% coverage and 96% effectiveness) prevents 20% of HIV infections over 10 years but increases drug resistance prevalence to 6.6%. PrEP alone (30% coverage and 75% effectiveness) also prevents 21% of infections but with lower resistance prevalence of 0.5%. The ratio of cumulative infections prevented to prevalent drug-resistant cases after 10 years is 7-fold higher for PrEP than for ART. Combined ART + PrEP with overlapping ARVs prevents 35% of infections but increases resistance prevalence to 8.2%, whereas ART + PrEP with nonoverlapping ARVs prevents slightly more infections (37%) and reduces resistance prevalence to 7.2%. Conclusions. Combined ART + PrEP is likely to prevent more HIV infections than either strategy alone, but with higher prevalence of drug resistance. ART is predicted to contribute more to resistance than is PrEP. Optimizing both ART and PrEP effectiveness and delivery are the keys to preventing HIV transmission and drug resistance.
Routine health system data are central to monitoring HIV trends. In Mozambique, the reported number of women receiving antenatal care (ANC) and antiretroviral therapy for prevention of ...mother-to-child transmission (PMTCT) has exceeded the Spectrum-estimated number of pregnant women since 2017. In some provinces, reported HIV prevalence in pregnant women has declined faster than epidemiologically plausible. We hypothesized that these issues are linked and caused by programmatic overenumeration of HIV-negative pregnant women at ANC.
We triangulated program-reported ANC client numbers with survey-based fertility estimates and facility birth data adjusted for the proportion of facility births. We used survey-reported ANC attendance to produce adjusted time series of HIV prevalence in pregnant women, adjusted for hypothesized program double counting. We calibrated the Spectrum HIV estimation models to adjusted HIV prevalence data to produce adjusted adult and pediatric HIV estimates.
ANC client numbers were not consistent with facility birth data or modeled population estimates indicating ANC data quality issues in all provinces. Adjusted provincial ANC HIV prevalence in 2021 was median 45% interquartile range 35%-52% or 2.3 percentage points (interquartile range 2.5-3.5) higher than reported HIV prevalence. In 2021, calibrating to adjusted antenatal HIV prevalence lowered PMTCT coverage to less than 100% in most provinces and increased the modeled number of new child infections by 35%. The adjusted results better reconciled adult and pediatric antiretroviral treatment coverage and antenatal HIV prevalence with regional fertility estimates.
Adjusting HIV prevalence in pregnant women using nationally representative household survey data on ANC attendance produced estimates more consistent with surveillance data. The number of children living with HIV in Mozambique has been substantially underestimated because of biased routine ANC prevalence. Renewed focus on HIV surveillance among pregnant women would improve PMTCT coverage and pediatric HIV estimates.
UNAIDS has established new program targets for 2025 to achieve the goal of eliminating AIDS as a public health threat by 2030. This study reports on efforts to use mathematical models to estimate the ...impact of achieving those targets.
We simulated the impact of achieving the targets at country level using the Goals model, a mathematical simulation model of HIV epidemic dynamics that includes the impact of prevention and treatment interventions. For 77 high-burden countries, we fit the model to surveillance and survey data for 1970 to 2020 and then projected the impact of achieving the targets for the period 2019 to 2030. Results from these 77 countries were extrapolated to produce estimates for 96 others. Goals model results were checked by comparing against projections done with the Optima HIV model and the AIDS Epidemic Model (AEM) for selected countries. We included estimates of the impact of societal enablers (access to justice and law reform, stigma and discrimination elimination, and gender equality) and the impact of Coronavirus Disease 2019 (COVID-19). Results show that achieving the 2025 targets would reduce new annual infections by 83% (71% to 86% across regions) and AIDS-related deaths by 78% (67% to 81% across regions) by 2025 compared to 2010. Lack of progress on societal enablers could endanger these achievements and result in as many as 2.6 million (44%) cumulative additional new HIV infections and 440,000 (54%) more AIDS-related deaths between 2020 and 2030 compared to full achievement of all targets. COVID-19-related disruptions could increase new HIV infections and AIDS-related deaths by 10% in the next 2 years, but targets could still be achieved by 2025. Study limitations include the reliance on self-reports for most data on behaviors, the use of intervention effect sizes from published studies that may overstate intervention impacts outside of controlled study settings, and the use of proxy countries to estimate the impact in countries with fewer than 4,000 annual HIV infections.
The new targets for 2025 build on the progress made since 2010 and represent ambitious short-term goals. Achieving these targets would bring us close to the goals of reducing new HIV infections and AIDS-related deaths by 90% between 2010 and 2030. By 2025, global new infections and AIDS deaths would drop to 4.4 and 3.9 per 100,000 population, and the number of people living with HIV (PLHIV) would be declining. There would be 32 million people on treatment, and they would need continuing support for their lifetime. Incidence for the total global population would be below 0.15% everywhere. The number of PLHIV would start declining by 2023.
Previously, The Joint United Nations Programme on HIV/AIDS estimated proportions of adult new HIV infections among key populations (KPs) in the last calendar year, globally and in 8 regions. We ...refined and updated these, for 2010 and 2022, using country-level trend models informed by national data.
Infections among 15-49 year olds were estimated for sex workers (SWs), male clients of female SW, men who have sex with men (MSM), people who inject drugs (PWID), transgender women (TGW), and non-KP sex partners of these groups. Transmission models used were Goals (71 countries), AIDS Epidemic Model (13 Asian countries), Optima (9 European and Central Asian countries), and Thembisa (South Africa). Statistical Estimation and Projection Package fits were used for 15 countries. For 40 countries, new infections in 1 or more KPs were approximated from first-time diagnoses by the mode of transmission. Infection proportions among nonclient partners came from Goals, Optima, AIDS Epidemic Model, and Thembisa. For remaining countries and groups not represented in models, median proportions by KP were extrapolated from countries modeled within the same region.
Across 172 countries, estimated proportions of new adult infections in 2010 and 2022 were both 7.7% for SW, 11% and 20% for MSM, 0.72% and 1.1% for TGW, 6.8% and 8.0% for PWID, 12% and 10% for clients, and 5.3% and 8.2% for nonclient partners. In sub-Saharan Africa, proportions of new HIV infections decreased among SW, clients, and non-KP partners but increased for PWID; elsewhere these groups' 2010-to-2022 differences were opposite. For MSM and TGW, the proportions increased across all regions.
KPs continue to have disproportionately high HIV incidence.
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.
Mortality rates for people living with HIV (PLHIV) on antiretroviral therapy (ART) in high-income countries continue to decline. We compared mortality rates among PLHIV on ART in Europe for 2016-2020 ...with Spectrum's estimates.
The AIDS Impact Module in Spectrum is a compartmental HIV epidemic model coupled with a demographic population projection model. We used national Spectrum projections developed for the 2022 HIV estimates round to calculate mortality rates among PLHIV on ART, adjusting to the age/country distribution of PLHIV starting ART from 1996 to 2020 in the Antiretroviral Therapy Cohort Collaboration (ART-CC)'s European cohorts.
In the ART-CC, 11,504 of 162,835 PLHIV died. Between 1996-1999 and 2016-2020, AIDS-related mortality in the ART-CC decreased from 8.8 (95% CI: 7.6 to 10.1) to 1.0 (0.9-1.2) and from 5.9 (4.4-8.1) to 1.1 (0.9-1.4) deaths per 1000 person-years among men and women, respectively. Non-AIDS-related mortality decreased from 9.1 (7.9-10.5) to 6.1 (5.8-6.5) and from 7.0 (5.2-9.3) to 4.8 (4.3-5.2) deaths per 1000 person-years among men and women, respectively. Adjusted all-cause mortality rates in Spectrum among men were near ART-CC estimates for 2016-2020 (Spectrum: 7.02-7.47 deaths per 1000 person-years) but approximately 20% lower in women (Spectrum: 4.66-4.70). Adjusted excess mortality rates in Spectrum were 2.5-fold higher in women and 3.1-3.4-fold higher in men in comparison to the ART-CC's AIDS-specific mortality rates.
Spectrum's all-cause mortality estimates among PLHIV are consistent with age/country-controlled mortality observed in ART-CC, with some underestimation of mortality among women. Comparing results suggest that 60%-70% of excess deaths among PLHIV on ART in Spectrum are from non-AIDS causes.
Introduction
Model‐based estimates of key HIV indicators depend on past epidemic trends that are derived based on assumptions about HIV disease progression and mortality in the absence of ...antiretroviral treatment (ART). Population‐based HIV Impact Assessment (PHIA) household surveys conducted between 2015 and 2018 found substantial numbers of respondents living with untreated HIV infection. CD4 cell counts measured in these individuals provide novel information to estimate HIV disease progression and mortality rates off ART.
Methods
We used Bayesian multi‐parameter evidence synthesis to combine data on (1) cross‐sectional CD4 cell counts among untreated adults living with HIV from 10 PHIA surveys, (2) survival after HIV seroconversion in East African seroconverter cohorts, (3) post‐seroconversion CD4 counts and (4) mortality rates by CD4 count predominantly from European, North American and Australian seroconverter cohorts. We used incremental mixture importance sampling to estimate HIV natural history and ART uptake parameters used in the Spectrum software. We validated modelled trends in CD4 count at ART initiation against ART initiator cohorts in sub‐Saharan Africa.
Results
Median untreated HIV survival decreased with increasing age at seroconversion, from 12.5 years 95% credible interval (CrI): 12.1–12.7 at ages 15–24 to 7.2 years (95% CrI: 7.1–7.7) at ages 45–54. Older age was associated with lower initial CD4 counts, faster CD4 count decline and higher HIV‐related mortality rates. Our estimates suggested a weaker association between ART uptake and HIV‐related mortality rates than previously assumed in Spectrum. Modelled CD4 counts in untreated people living with HIV matched recent household survey data well, though some intercountry variation in frequencies of CD4 counts above 500 cells/mm3 was not explained. Trends in CD4 counts at ART initiation were comparable to data from ART initiator cohorts. An alternate model that stratified progression and mortality rates by sex did not improve model fit appreciably.
Conclusions
Synthesis of multiple data sources results in similar overall survival as previous Spectrum parameter assumptions but implies more rapid progression and longer survival in lower CD4 categories. New natural history parameter values improve consistency of model estimates with recent cross‐sectional CD4 data and trends in CD4 counts at ART initiation.
Abstract
Background
Antiretroviral therapy (ART) is critical for ending the HIV epidemic. Tenofovir-containing ART is the first-line regimen in many countries including South Africa, with limited ...access to second-line ART. High levels of drug resistance have been reported among patients after virologic failure on tenofovir-containing first-line regimens (TenoRes Study, Lancet Infect Dis 2016). We assessed drug resistance at the population level using mathematical modeling.
Methods
We developed a stochastic individual-based model of the heterosexual HIV epidemic in KwaZulu-Natal South Africa, and compared drug resistance from scenarios of tenofovir-containing ART scale-up, either CD4-based (threshold < 500 cells/mL) or Fast-track (80% coverage by 2020). The model represents details of HIV transmission and disease progression, demography, sexual behavior, condom use, circumcision, treatment interventions and drug resistance dynamics including key mutations (M184V, K65R and non-nucleoside reverse transcriptase inhibitor (NNRTI)). Using an initial population of 2.5 million, we performed 100 simulations from 1978 to 2030. We examined the prevalence of (majority) transmitted and acquired resistance by 2030.
Results
The total resistance (proportion of HIV-infected persons with drug resistance) reached 34% from CD4-based ART by 2030, with 30% relative contribution from transmitted resistance and 70% from acquired resistance. In contrast, Fast-track ART reduced the total resistance to 22%; though, there was an increased relative contribution from transmitted resistance (~ 50%). In both scenarios, NNRTI mutations were the most prevalent, followed by M184V and K65R mutations. About 48% of persons with acquired drug- resistance harbored dual drug mutations, 44.7% had triple mutations and 7.3% just single mutations, from CD4-based ART. The respective estimates from Fast-track ART were similar; 49% for dual, 44.1% for triple and 6.9% for single mutations. In both scenarios, NNRTI mutations comprised about 80% of prevalent transmitted resistance.
Conclusion
Current WHO-recommended first-line ART could lead to substantial drug resistance. Effective surveillance for resistance transmission and access to second-line regimens would be crucial.
Disclosures
All authors: No reported disclosures.
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