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Edinah Mudimu, Kathryn Peebles, Zindoga Mukandavire, Emily Nightingale, Monisha Sharma, Graham F. Medley, Daniel J. Klein, Katharine Kripke, Anna Bershteyn 

PLOS ONE

Background
Pre-exposure prophylaxis (PrEP) is highly effective in preventing HIV and has the potential to significantly impact the HIV epidemic. Given limited resources for HIV prevention, identifying PrEP provision strategies that maximize impact is critical.

Methods
We used a stochastic individual-based network model to evaluate the direct (infections prevented among PrEP users) and indirect (infections prevented among non-PrEP users as a result of PrEP) benefits of PrEP, the person-years of PrEP required to prevent one HIV infection, and the community-level impact of providing PrEP to populations defined by gender and age in western Kenya and South Africa. We examined sensitivity of results to scale-up of antiretroviral therapy (ART) and voluntary medical male circumcision (VMMC) by comparing two scenarios: maintaining current coverage (“status quo”) and rapid scale-up to meet programmatic targets (“fast-track”).

Results
The community-level impact of PrEP was greatest among women aged 15–24 due to high incidence, while PrEP use among men aged 15–24 yielded the highest proportion of indirect infections prevented in the community. These indirect infections prevented continue to increase over time (western Kenya: 0.4–5.5 (status quo); 0.4–4.9 (fast-track); South Africa: 0.5–1.8 (status quo); 0.5–3.0 (fast-track)) relative to direct infections prevented among PrEP users. The number of person-years of PrEP needed to prevent one HIV infection was lower (59 western Kenya and 69 in South Africa in the status quo scenario; 201 western Kenya and 87 in South Africa in the fast-track scenario) when PrEP was provided only to women compared with only to men over time horizons of up to 5 years, as the indirect benefits of providing PrEP to men accrue in later years.

Conclusions
Providing PrEP to women aged 15–24 prevents the greatest number of HIV infections per person-year of PrEP, but PrEP provision for young men also provides indirect benefits to women and to the community overall. This finding supports existing policies that prioritize PrEP use for young women, while also illuminating the community-level benefits of PrEP availability for men when resources permit.

Monisha Sharma, PhD, Edinah Mudimu, PhD Kate Simeon, MD, Anna Bershteyn, PhD, Jienchi Dorward, MBChB, Lauren R Violette, MPH, Adam Akullian, PhD, Prof Salim S Abdool Karim, MBBCH, Prof Connie Celum, MD, Nigel Garrett, MBBS, Paul K Drain, MD

THE LANCET HIV

Background
The number of people on antiretroviral therapy (ART) requiring treatment monitoring in low-resource settings is rapidly increasing. Point-of-care (POC) testing for ART monitoring might alleviate burden on centralised laboratories and improve clinical outcomes, but its cost-effectiveness is unknown.


Methods
We used cost and effectiveness data from the STREAM trial in South Africa (February, 2017–October, 2018), which evaluated POC testing for viral load, CD4 count, and creatinine, with task shifting from professional to lower-cadre registered nurses compared with laboratory-based testing without task shifting (standard of care). We parameterised an agent-based network model, EMOD-HIV, to project the impact of implementing this intervention in South Africa over 20 years, simulating approximately 175 000 individuals per run. We assumed POC monitoring increased viral suppression by 9 percentage points, enrolment into community-based ART delivery by 25 percentage points, and switching to second-line ART by 1 percentage point compared with standard of care, as reported in the STREAM trial. We evaluated POC implementation in varying clinic sizes (10–50 patient initiating ART per month). We calculated incremental cost-effectiveness ratios (ICERs) and report the mean and 90% model variability of 250 runs, using a cost-effectiveness threshold of US$500 per disability-adjusted life-year (DALY) averted for our main analysis.


Findings
POC testing at 70% coverage of patients on ART was projected to reduce HIV infections by 4·5% (90% model variability 1·6 to 7·6) and HIV-related deaths by 3·9% (2·0 to 6·0). In clinics with 30 ART initiations per month, the intervention had an ICER of $197 (90% model variability –27 to 863) per DALY averted; results remained cost-effective when varying background viral suppression, ART dropout, intervention effectiveness, and reduction in HIV transmissibility. At higher clinic volumes (≥40 ART initiations per month), POC testing was cost-saving and at lower clinic volumes (20 ART initiations per month) the ICER was $734 (93 to 2569). A scenario that assumed POC testing did not increase enrolment into community ART delivery produced ICERs that exceeded the cost-effectiveness threshold for all clinic volumes.


Interpretation
POC testing is a promising strategy to cost-effectively improve patient outcomes in moderately sized clinics in South Africa. Results are most sensitive to changes in intervention impact on enrolment into community-based ART delivery.


Funding
National Institutes of Health.

Anna Bershteyn, Monisha Sharma, Adam Akullian, Kathryn Peebles, Supriya Sarkar, R Scott Braithwaite, Edinah Mudimu

JOURNAL OF THE INTERNATIONAL AIDS SOCIETY

Introduction

Over one hundred implementation studies of HIV pre‐exposure prophylaxis (PrEP) are completed, underway or planned. We synthesized evidence from these studies to inform mathematical modelling of the prevention cascade for oral and long‐acting PrEP in the setting of western Kenya, one of the world’s most heavily HIV‐affected regions.

Methods

We incorporated steps of the PrEP prevention cascade – uptake, adherence, retention and re‐engagement after discontinuation – into EMOD‐HIV, an open‐source transmission model calibrated to the demography and HIV epidemic patterns of western Kenya. Early PrEP implementation research from East Africa was used to parameterize prevention cascades for oral PrEP as currently implemented, delivery innovations for oral PrEP, and future long‐acting PrEP. We compared infections averted by PrEP at the population level for different cascade assumptions and sub‐populations on PrEP. Analyses were conducted over the 2020 to 2040 time horizon, with additional sensitivity analyses for the time horizon of analysis and the time when long‐acting PrEP becomes available.

Results

The maximum impact of oral PrEP diminished by over 98% across all prevention cascades, with the exception of long‐acting PrEP under optimistic assumptions about uptake and re‐engagement after discontinuation. Long‐acting PrEP had the highest population‐level impact, even after accounting for possible delays in product availability, primarily because its effectiveness does not depend on drug adherence. Retention was the most significant cascade step reducing the potential impact of long‐acting PrEP. These results were robust to assumptions about the sub‐populations receiving PrEP, but were highly influenced by assumptions about re‐initiation of PrEP after discontinuation, about which evidence was sparse.

Conclusions

Implementation challenges along the prevention cascade compound to diminish the population‐level impact of oral PrEP. Long‐acting PrEP is expected to be less impacted by user uptake and adherence, but it is instead dependent on product availability in the short term and retention in the long term. To maximize the impact of long‐acting PrEP, ensuring timely product approval and rollout is critical. Research is needed on strategies to improve retention and patterns of PrEP re‐initiation.

Adam Akullian , Michelle Morrison, Geoffrey P Garnett, Zandile Mnisi, Nomthandazo Lukhele, Daniel Bridenbecker, Anna Bershteyn

THE LANCET HIV

Background

The rapid scale-up of antiretroviral therapy (ART) towards the UNAIDS 90-90-90 goals over the last decade has sparked considerable debate as to whether universal test and treat can end the HIV-1 epidemic in sub-Saharan Africa. We aimed to develop a network transmission model, calibrated to capture age-specific and sex-specific gaps in the scale-up of ART, to estimate the historical and future effect of attaining and surpassing the UNAIDS 90-90-90 treatment targets on HIV-1 incidence and mortality, and to assess whether these interventions will be enough to achieve epidemic control (incidence of 1 infection per 1000 person-years) by 2030.

Methods

We used eSwatini (formerly Swaziland) as a case study to develop our model. We used data on HIV prevalence by 5-year age bins, sex, and year from the 2007 Swaziland Demographic Health Survey (SDHS), the 2011 Swaziland HIV Incidence Measurement Survey, and the 2016 Swaziland Population Health Impact Assessment (PHIA) survey. We estimated the point prevalence of ART coverage among all HIV-infected individuals by age, sex, and year. Age-specific data on the prevalence of male circumcision from the SDHS and PHIA surveys were used as model inputs for traditional male circumcision and scale-up of voluntary medical male circumcision (VMMC). We calibrated our model using publicly available data on demographics; HIV prevalence by 5-year age bins, sex, and year; and ART coverage by age, sex, and year. We modelled the effects of five scenarios (historical scale-up of ART and VMMC [status quo], no ART or VMMC, no ART, age-targeted 90-90-90, and 100% ART initiation) to quantify the contribution of ART scale-up to declines in HIV incidence and mortality in individuals aged 15–49 by 2016, 2030, and 2050.

Findings

Between 2010 and 2016, status-quo ART scale-up among adults (aged 15–49 years) in eSwatini (from 34·0% in 2010 to 74·1% in 2016) reduced HIV incidence by 43·57% (95% credible interval 39·71 to 46·36) and HIV mortality by 56·17% (54·06 to 58·92) among individuals aged 15–49 years, with larger reductions in incidence among men and mortality among women. Holding 2016 ART coverage levels by age and sex into the future, by 2030 adult HIV incidence would fall to 1·09 (0·87 to 1·29) per 100 person-years, 1·42 (1·13 to 1·71) per 100 person-years among women and 0·79 (0·63 to 0·94) per 100 person-years among men. Achieving the 90-90-90 targets evenly by age and sex would further reduce incidence beyond status-quo ART, primarily among individuals aged 15–24 years (an additional 17·37% [7·33 to 26·12] reduction between 2016 and 2030), with only modest additional incidence reductions in adults aged 35–49 years (1·99% [–5·09 to 7·74]). Achieving 100% ART initiation among all people living with HIV within an average of 6 months from infection—an upper bound of plausible treatment effect—would reduce adult HIV incidence to 0·73 infections (0·55 to 0·92) per 100 person-years by 2030 and 0·46 (0·33 to 0·59) per 100 person-years by 2050.

Interpretation

Scale-up of ART over the last decade has already contributed to substantial reductions in HIV-1 incidence and mortality in eSwatini. Focused ART targeting would further reduce incidence, especially in younger individuals, but even the most aggressive treatment campaigns would be insufficient to end the epidemic in high-burden settings without a renewed focus on expanding preventive measures.

Funding

Global Good Fund and the Bill & Melinda Gates Foundation.

Alain Vandormael, Adam Akullian, Mark Siedner, Tulio de Oliveira, Till Bärnighausen and Frank Tanser

NATURE COMMUNICATIONS

Over the past decade, there has been a massive scale-up of primary and secondary prevention services to reduce the population-wide incidence of HIV. However, the impact of these services on HIV incidence has not been demonstrated using a prospectively followed, population-based cohort from South Africa—the country with the world’s highest rate of new infections. To quantify HIV incidence trends in a hyperendemic population, we tested a cohort of 22,239 uninfected participants over 92,877 person-years of observation. We report a 43% decline in the overall incidence rate between 2012 and 2017, from 4.0 to 2.3 seroconversion events per 100 person-years. Men experienced an earlier and larger incidence decline than women (59% vs. 37% reduction), which is consistent with male circumcision scale-up and higher levels of female antiretroviral therapy coverage. Additional efforts are needed to get more men onto consistent, suppressive treatment so that new HIV infections can be reduced among women.

Carol Camlin, Adam Akullian, Torsten Neilands, Monica Getahun, Anna Bershteyn, Sarah Ssali, ElvinGeng, Monica Gandhi, Craig Cohen, Irene Maeri,  Patrick Eyul, Maya L.Petersen, Diane Havlir, Moses Kamya, Elizabeth Bukusi, Edwin Charlebois

HEALTH & PLACE

Mobility in sub-Saharan Africa links geographically-separate HIV epidemics, intensifies transmission by enabling higher-risk sexual behavior, and disrupts care. This population-based observational cohort study measured complex dimensions of mobility in rural Uganda and Kenya. Survey data were collected every 6 months beginning in 2016 from a random sample of 2308 adults in 12 communities across three regions, stratified by intervention arm, baseline residential stability and HIV status. Analyses were survey-weighted and stratified by sex, region, and HIV status. In this study, there were large differences in the forms and magnitude of mobility across regions, between men and women, and by HIV status.

We found that adult migration varied widely by region, higher proportions of men than women migrated within the past one and five years, and men predominated across all but the most localized scales of migration: a higher proportion of women than men migrated within county of origin. Labor-related mobility was more common among men than women, while women were more likely to travel for non-labor reasons. Labor-related mobility was associated with HIV positive status for both men and women, adjusting for age and region, but the association was especially pronounced in women. The forms, drivers, and correlates of mobility in eastern Africa are complex and highly gendered. An in-depth understanding of mobility may help improve implementation and address gaps in the HIV prevention and care continua.

Dylan Green, Brenda Kharono, Diana M. Tordoff, Adam Akullian, Anna Bershteyn, Michelle Morrison, Geoff Garnett, Ann Duerr, Paul Drain

BMC

Background

Despite policies for universal HIV testing and treatment (UTT) regardless of CD4 count, there are still 1.8 million new HIV infections and 1 million AIDS-related deaths annually. The UNAIDS 90-90-90 goals target suppression of HIV viral load in 73% of all HIV-infected people worldwide by 2030. However, achieving these targets may not lead to expected reductions in HIV incidence if the remaining 27% (persons with unsuppressed viral load) are the drivers of HIV transmission through high-risk behaviors. We aim to conduct a systematic review and meta-analysis to understand the demographics, mobility, geographic distribution, and risk profile of adults who are not virologically suppressed in sub-Saharan Africa in the era of UTT.

Methods

We will review the published and grey literature for study sources that contain data on demographic and behavioral strata of virologically suppressed and unsuppressed populations since 2014. We will search PubMed and Embase using four sets of search terms tailored to identify characteristics associated with virological suppression (or lack thereof) and each of the individual 90-90-90 goals. Record screening and data abstraction will be done independently and in duplicate. We will use random effects meta-regression analyses to estimate the distribution of demographic and risk features among groups not virologically suppressed and for each individual 90-90-90 goal.

Discussion

The results of our review will help elucidate factors associated with failure to achieve virological suppression in sub-Saharan Africa, as well as factors associated with failure to achieve each of the 90-90-90 goals. These data will help quantify the population-level effects of current HIV treatment interventions to improve strategies for maximizing virological suppression and ending the HIV epidemic.

 

INTERNATIONAL JOURNAL OF HEALTH GEOGRAPHICS

Background

Large geographical variations in the intensity of the HIV epidemic in sub-Saharan Africa call for geographically targeted resource allocation where burdens are greatest. However, data available for mapping the geographic variability of HIV prevalence and detecting HIV ‘hotspots’ is scarce, and population-based surveillance data are not always available. Here, we evaluated the viability of using clinic-based HIV prevalence data to measure the spatial variability of HIV in South Africa and Tanzania.

Methods

Population-based and clinic-based HIV data from a small HIV hyper-endemic rural community in South Africa as well as for the country of Tanzania were used to map smoothed HIV prevalence using kernel interpolation techniques. Spatial variables were included in clinic-based models using co-kriging methods to assess whether cofactors improve clinic-based spatial HIV prevalence predictions. Clinic- and population-based smoothed prevalence maps were compared using partial rank correlation coefficients and residual local indicators of spatial autocorrelation.

Results

Routinely-collected clinic-based data captured most of the geographical heterogeneity described by population-based data but failed to detect some pockets of high prevalence. Analyses indicated that clinic-based data could accurately predict the spatial location of so-called HIV ‘hotspots’ in > 50% of the high HIV burden areas.

Conclusion

Clinic-based data can be used to accurately map the broad spatial structure of HIV prevalence and to identify most of the areas where the burden of the infection is concentrated (HIV ‘hotspots’). Where population-based data are not available, HIV data collected from health facilities may provide a second-best option to generate valid spatial prevalence estimates for geographical targeting and resource allocation.

Carol S Camlin, Adam Akullian, Torsten B Neilands,  Monica Getahun,  Patrick Eyul,  Irene Maeri, Sarah Ssali,  Elvin Geng,  Monica Gandhi,  Craig R Cohen,  Moses R Kamya,  Thomas Odeny, Elizabeth A Bukusi,  Edwin D Charlebois

JOURNAL OF THE INTERNATIONAL AIDS SOCIETY

Introduction

There are significant knowledge gaps concerning complex forms of mobility emergent in sub‐Saharan Africa, their relationship to sexual behaviours, HIV transmission, and how sex modifies these associations. This study, within an ongoing test‐and‐treat trial (SEARCH, NCT01864603), sought to measure effects of diverse metrics of mobility on behaviours, with attention to gender.

Methods

Cross‐sectional data were collected in 2016 from 1919 adults in 12 communities in Kenya and Uganda, to examine mobility (labour/non‐labour‐related travel), migration (changes of residence over geopolitical boundaries) and their associations with sexual behaviours (concurrent/higher risk partnerships), by region and sex. Multilevel mixed‐effects logistic regression models, stratified by sex and adjusted for clustering by community, were fitted to examine associations of mobility with higher‐risk behaviours, in past 2 years/past 6 months, controlling for key covariates.

Results

The population was 45.8% male and 52.4% female, with mean age 38.7 (median 37, IQR: 17); 11.2% had migrated in the past 2 years. Migration varied by region (14.4% in Kenya, 11.5% in southwestern and 1.7% in eastern and Uganda) and sex (13.6% of men and 9.2% of women). Ten per cent reported labour‐related travel and 45.9% non‐labour‐related travel in past 6 months—and varied by region and sex: labour‐related mobility was more common in men (18.5%) than women (2.9%); non‐labour‐related mobility was more common in women (57.1%) than men (32.6%). In 2015 to 2016, 24.6% of men and 6.6% of women had concurrent sexual partnerships; in past 6 months, 21.6% of men and 5.4% of women had concurrent partnerships. Concurrency in 2015 to 2016 was more strongly associated with migration in women [aRR = 2.0, 95% CI(1.1 to 3.7)] than men [aRR = 1.5, 95% CI(1.0 to 2.2)]. Concurrency in past 6 months was more strongly associated with labour‐related mobility in women [aRR = 2.9, 95% CI(1.0 to 8.0)] than men [aRR = 1.8, 95% CI(1.2 to 2.5)], but with non‐labour‐related mobility in men [aRR = 2.2, 95% CI(1.5 to 3.4)].

Conclusions

In rural eastern Africa, both longer‐distance/permanent, and localized/shorter‐term forms of mobility are associated with higher‐risk behaviours, and are highly gendered: the HIV risks associated with mobility are more pronounced for women. Gender‐specific interventions among mobile populations are needed to combat HIV in the region.

SCIENCE DIRECT

Western Kenya suffers a highly endemic and also very heterogeneous epidemic of human immunodeficiency virus (HIV). Although female sex workers (FSW) and their male clients are known to be at high risk for HIV, HIV prevalence across regions in Western Kenya is not strongly correlated with the fraction of women engaged in commercial sex. An agent-based network model of HIV transmission, geographically stratified at the county level, was fit to the HIV epidemic, scale-up of interventions, and populations of FSW in Western Kenya under two assumptions about the potential mobility of FSW clients. In the first, all clients were assumed to be resident in the same geographies as their interactions with FSW. In the second, some clients were considered non-resident and engaged only in interactions with FSW, but not in longer-term non-FSW partnerships in these geographies. Under both assumptions, the model successfully reconciled disparate geographic patterns of FSW and HIV prevalence. Transmission patterns in the model suggest a greater role for FSW in local transmission when clients were resident to the counties, with 30.0% of local HIV transmissions attributable to current and former FSW and clients, compared to 21.9% when mobility of clients was included. Nonetheless, the overall epidemic drivers remained similar, with risky behavior in the general population dominating transmission in high-prevalence counties. Our modeling suggests that co-location of high-risk populations and generalized epidemics can further amplify the spread of HIV, but that large numbers of formal FSW and clients are not required to observe or mechanistically explain high HIV prevalence in the general population.