Browsing by Author "Althoff, Keri N."
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Item Achieving consistency in measures of HIV-1 viral suppression across countries: derivation of an adjustment based on international antiretroviral treatment cohort data(Wiley, 2021) Johnson, Leigh F.; Kariminia, Azar; Trickey, Adam; Yiannoutsos, Constantin T.; Ekouevi, Didier K.; Minga, Albert K.; Pascom, Ana Roberta Pati; Han, Win Min; Zhang, Lei; Althoff, Keri N.; Rebeiro, Peter F.; Murenzi, Gad; Ross, Jonathan; Hsiao, Nei-Yuan; Marsh, Kimberly; Biostatistics and Health Data Science, Richard M. Fairbanks School of Public HealthIntroduction: The third of the Joint United Nations Programme on HIV/AIDS (UNAIDS) 90-90-90 targets is to achieve a 90% rate of viral suppression (HIV viral load <1000 HIV-1 RNA copies/ml) in patients on antiretroviral treatment (ART) by 2020. However, some countries use different thresholds when reporting viral suppression, and there is thus a need for an adjustment to standardize estimates to the <1000 threshold. We aim to propose such an adjustment, to support consistent monitoring of progress towards the "third 90" target. Methods: We considered three possible distributions for viral loads in ART patients: Weibull, Pareto and reverse Weibull (imposing an upper limit but no lower limit on the log scale). The models were fitted to data on viral load distributions in ART patients in the International epidemiology Databases to Evaluate AIDS (IeDEA) collaboration (representing seven global regions) and the ART Cohort Collaboration (representing Europe), using separate random effects models for adults and children. The models were validated using data from the World Health Organization (WHO) HIV drug resistance report and the Brazilian national ART programme. Results: Models were calibrated using 921,157 adult and 37,431 paediatric viral load measurements, over 2010-2019. The Pareto and reverse Weibull models provided the best fits to the data, but for all models, the "shape" parameters for the viral load distributions differed significantly between regions. The Weibull model performed best in the validation against the WHO drug resistance survey data, while the Pareto model produced uncertainty ranges that were too narrow, relative to the validation data. Based on these analyses, we recommend using the reverse Weibull model. For example, if a country reports an 80% rate of viral suppression at <200 copies/ml, this model estimates the proportion virally suppressed at <1000 copies/ml is 88.3% (0.800.56 ), with uncertainty range 85.5-90.6% (0.800.70 -0.800.44 ). Conclusions: Estimates of viral suppression can change substantially depending on the threshold used in defining viral suppression. It is, therefore, important that viral suppression rates are standardized to the same threshold for the purpose of assessing progress towards UNAIDS targets. We have proposed a simple adjustment that allows this, and this has been incorporated into UNAIDS modelling software.Item Availability of screening and treatment for common mental disorders in HIV clinic settings: data from the global International epidemiology Databases to Evaluate AIDS (IeDEA) Consortium, 2016–2017 and 2020(Wiley, 2023) Parcesepe, Angela M.; Stockton, Melissa; Remch, Molly; Wester, C. William; Bernard, Charlotte; Ross, Jeremy; Haas, Andreas D.; Ajeh, Rogers; Althoff, Keri N.; Enane, Leslie; Pape, William; Minga, Albert; Kwobah, Edith; Tlali, Mpho; Tanuma, Junko; Nsonde, Dominique; Freeman, Aimee; Duda, Stephany N.; Nash, Denis; Lancaster, Kathryn; IeDEA Consortium; Pediatrics, School of MedicineIntroduction: Common mental disorders (CMDs) are highly prevalent among people with HIV. Integrating mental healthcare into HIV care may improve mental health and HIV treatment outcomes. We describe the reported availability of screening and treatment for depression, anxiety and post-traumatic stress disorder (PTSD) at global HIV treatment centres participating in the International epidemiology Databases to Evaluate AIDS (IeDEA) Consortium in 2020 and changes in availability at sites in low- or middle-income countries (LMICs) between 2016/2017 and 2020. Methods: In 2020, 238 sites contributing individual-level data to the IeDEA Consortium and in 2016/2017 a stratified random sample of IeDEA sites in LMICs were eligible to participate in site surveys on the availability of screening and treatment for CMDs. We assessed trends over time for 68 sites across 27 LMICs that participated in both surveys. Results: Among the 238 sites eligible to participate in the 2020 site survey, 227 (95%) participated, and mental health screening and treatment data were available for 223 (98%) sites across 41 countries. A total of 95 sites across 29 LMICs completed the 2016/2017 survey. In 2020, 68% of sites were in urban settings, and 77% were in LMICs. Overall, 50%, 14% and 12% of sites reported screening with a validated instrument for depression, anxiety and PTSD, respectively. Screening plus treatment in the form of counselling was available for depression, anxiety and PTSD at 46%, 13% and 11% of sites, respectively. Screening plus treatment in the form of medication was available for depression, anxiety and PTSD at 36%, 11% and 8% of sites, respectively. Among sites that participated in both surveys, screening for depression was more commonly available in 2020 than 2016/2017 (75% vs. 59%, respectively, p = 0.048). Conclusions: Reported availability of screening for depression increased among this group of IeDEA sites in LMICs between 2016/2017 and 2020. However, substantial gaps persist in the availability of mental healthcare at HIV treatment sites across global settings, particularly in resource-constrained settings. Implementation of sustainable strategies to integrate mental health services into HIV care is needed.Item Delayed presentation of HIV among older individuals: a growing problem(Elsevier, 2022) Justice, Amy C.; Goetz, Matthew B.; Stewart, Cameron N.; Hogan, Brenna C.; Humes, Elizabeth; Luz, Paula M.; Castilho, Jessica L.; Nash, Denis; Brazier, Ellen; Musick, Beverly; Yiannoutsos, Constantin; Malateste, Karen; Jaquet, Antoine; Cornell, Morna; Shamu, Tinei; Rajasuriar, Reena; Jiamsakul, Awachana; Althoff, Keri N.; Biostatistics and Health Data Science, Richard M. Fairbanks School of Public HealthLate presentation for care is a major impediment to the prevention and effective treatment of HIV infection. Older individuals are at increased risk of late presentation, represent a growing proportion of people with late presentation, and might require interventions tailored to their age group. We provide a summary of the literature published globally between 2016-21 (reporting data from 1984-2018) and quantify the association of age with delayed presentation. Using the most common definitions of late presentation and older age from these earlier studies, we update this work with data from the International Epidemiology Databases to Evaluate AIDS (IeDEA) consortium, focusing on data from 2000-19, encompassing four continents. Finally, we consider how late presentation among older individuals might be more effectively addressed as electronic medical records become widely adopted.Item Effects of National Adoption of Treat-All Guidelines on Pre-Antiretroviral Therapy (ART) CD4 Testing and Viral Load Monitoring After ART initiation: A Regression Discontinuity Analysis(Oxford University Press, 2021) Brazier, Ellen; Tymejczyk, Olga; Zaniewski, Elizabeth; Egger, Matthias; Wools-Kaloustian, Kara; Yiannoutsos, Constantin T.; Jaquet, Antoine; Althoff, Keri N.; Lee, Jennifer S.; Caro-Vega, Yanink; Luz, Paula M.; Tanuma, Junko; Niyongabo, Théodore; Nash, Denis; Medicine, School of MedicineBackground: The World Health Organization's Treat-All guidance recommends CD4 testing before initiating antiretroviral therapy (ART), and routine viral load (VL) monitoring (over CD4 monitoring) for patients on ART. Methods: We used regression discontinuity analyses to estimate changes in CD4 testing and VL monitoring among 547 837 ART-naive patients enrolling in human immunodeficiency virus (HIV) care during 2006-2018 at 225 clinics in 26 countries where Treat-All policies were adopted. We examined CD4 testing within 12 months before and VL monitoring 6 months after ART initiation among adults (≥20 years), adolescents (10-19 years), and children (0-9 years) in low/lower-middle-income countries (L/LMICs) and high/upper-middle-income countries (H/UMICs). Results: Treat-All adoption led to an immediate decrease in pre-ART CD4 testing among adults in L/LMICs, from 57.0% to 48.1% (-8.9 percentage points [pp]; 95% CI: -11.0, -6.8), and a small increase in H/UMICs, from 90.1% to 91.7% (+1.6pp; 95% CI: 0.2, 3.0), with no changes among adolescents or children; decreases in pre-ART CD4 testing accelerated after Treat-All adoption in L/LMICs. In L/LMICs, VL monitoring after ART initiation was low among all patients in L/LMICs before Treat-All; while there was no immediate change at Treat-All adoption, VL monitoring trends significantly increased afterwards. VL monitoring increased among adults immediately after Treat-All adoption, from 58.2% to 61.1% (+2.9pp; 95% CI: 0.5, 5.4), with no significant changes among adolescents/children. Conclusions: While on-ART VL monitoring has improved in L/LMICs, Treat-All adoption has accelerated and disparately worsened suboptimal pre-ART CD4 monitoring, which may compromise care outcomes for individuals with advanced HIV.Item Global estimates of viral suppression in children and adolescents and adults on antiretroviral therapy adjusted for missing viral load measurements: a multiregional, retrospective cohort study in 31 countries(Elsevier, 2021) Han, Win Min; Law, Matthew G.; Egger, Matthias; Wools-Kaloustian, Kara; Moore, Richard; McGowan, Catherine; Kumarasamy, Nagalingesawaran; Desmonde, Sophie; Edmonds, Andrew; Davies, Mary-Ann; Yiannoutsos, Constantin; Althoff, Keri N.; Cortes, Claudia P.; Mohamed, Thahira Jamal; Jaquet, Antoine; Anastos, Kathryn; Euvrard, Jonathan; Castelnuovo, Barbara; Salters, Kate; Esteves Coelho, Lara; Ekouevi, Didier K.; Eley, Brian; Diero, Lameck; Zaniewski, Elizabeth; Ford, Nathan; Sohn, Annette H.; Kariminia, Azar; IeDEA collaboration; Medicine, School of MedicineBackground: As countries move towards the UNAIDS's 95-95-95 targets and with strong evidence that undetectable equals untransmittable, it is increasingly important to assess whether those with HIV who are receiving antiretroviral therapy (ART) achieve viral suppression. We estimated the proportions of children and adolescents and adults with viral suppression at 1, 2, and 3 years after initiating ART. Methods: In this retrospective cohort study, seven regional cohorts from the International epidemiology Databases to Evaluate AIDS (IeDEA) consortium contributed data from individuals initiating ART between Jan 1, 2010, and Dec 31, 2019, at 148 sites in 31 countries with annual viral load monitoring. Only people with HIV who started ART after the time a site started routine viral load monitoring were included. Data up to March 31, 2020, were analysed. We estimated the proportions of children and adolescents (aged <18 years at ART initiation) and adults (aged ≥18 years at ART initiation) with viral suppression (viral load <1000 copies per mL) at 1, 2, and 3 years after ART initiation using an intention-to-treat approach and an adjusted approach that accounted for missing viral load measurements. Findings: 21 594 children and adolescents (11 812 [55%] female, 9782 [45%] male) from 106 sites in 22 countries and 255 662 adults (163 831 [64%] female, 91 831 [36%] male) from 143 sites in 30 countries were included. Using the intention-to-treat approach, the proportion of children and adolescents with viral suppression was 7303 (36%) of 20 478 at 1 year, 5709 (30%) of 19 135 at 2 years, and 4287 (24%) of 17 589 at 3 years after ART initiation; the proportion of adults with viral suppression was 106 541 (44%) of 240 600 at 1 year, 79 141 (36%) of 220 925 at 2 years, and 57 970 (29%) of 201 124 at 3 years after ART initiation. After adjusting for missing viral load measurements among those who transferred, were lost to follow-up, or who were in follow-up without viral load testing, the proportion of children and adolescents with viral suppression was 12 048 (64% [plausible range 43-81]) of 18 835 at 1 year, 10 796 (62% [41-77]) of 17 553 at 2 years, and 9177 (59% [38-91]) of 15 667 at 3 years after ART initiation; the proportion of adults with viral suppression was 176 964 (79% [53-80]) of 225 418 at 1 year, 145 552 (72% [48-79]) of 201 238 at 2 years, and 115 260 (65% [43-69]) of 178 458 at 3 years after ART initiation. Interpretation: Although adults with HIV are approaching the global target of 95% viral suppression, progress among children and adolescents is much slower. Substantial efforts are still needed to reach the viral suppression target for children and adolescents.Item Global variations in mortality in adults after initiating antiretroviral treatment: an updated analysis of the International epidemiology Databases to Evaluate AIDS cohort collaboration(Wolters Kluwer, 2019-12-15) Johnson, Leigh F.; Anderegg, Nanina; Zaniewski, Elizabeth; Eaton, Jeffrey W.; Rebeiro, Peter F.; Carriquiry, Gabriela; Nash, Denis; Yotebieng, Marcel; Ekouevi, Didier K.; Holmes, Charles B.; Choi, Jun Y.; Jiamsakul, Awachana; Bakoyannis, Giorgos; Althoff, Keri N.; Sohn, Annette H.; Yiannoutsos, Constantin; Egger, Matthias; Biostatistics, School of Public HealthBackground: UNAIDS models use data from the International epidemiology Databases to Evaluate AIDS (IeDEA) collaboration in setting assumptions about mortality rates after antiretroviral treatment (ART) initiation. This study aims to update these assumptions with new data, to quantify the extent of regional variation in ART mortality and to assess trends in ART mortality. Methods: Adult ART patients from Africa, Asia and the Americas were included if they had a known date of ART initiation during 2001-2017 and a baseline CD4 cell count. In cohorts that relied only on passive follow-up (no patient tracing or linkage to vital registration systems), mortality outcomes were imputed in patients lost to follow-up based on a meta-analysis of tracing study data. Poisson regression models were fitted to the mortality data. Results: 464 048 ART patients were included. In multivariable analysis, mortality rates were lowest in Asia and highest in Africa, with no significant differences between African regions. Adjusted mortality rates varied significantly between programmes within regions. Mortality rates in the first 12 months after ART initiation were significantly higher during 2001-2006 than during 2010-2014, although the difference was more substantial in Asia and the Americas [adjusted incidence rate ratio (aIRR) 1.43, 95% CI: 1.22-1.66] than in Africa (aIRR 1.07, 95% CI: 1.04-1.11). Conclusion: There is substantial variation in ART mortality between and within regions, even after controlling for differences in mortality by age, sex, baseline CD4 category and calendar period. ART mortality rates have declined substantially over time, although declines have been slower in Africa.Item Implications of COVID-19 for HIV Research: data sources, indicators, and longitudinal analyses(Wiley, 2020-10) Rebeiro, Peter F.; Duda, Stephany N.; Wools-Kaloustian, Kara K.; Nash, Denis; Althoff, Keri N.; Medicine, School of MedicineItem Long-term HIV care outcomes under universal HIV treatment guidelines: A retrospective cohort study in 25 countries(Public Library of Science, 2024-03-18) Brazier, Ellen; Tymejczyk, Olga; Wools-Kaloustian, Kara; Jiamsakul, Awachana; Torres, Marco Tulio Luque; Lee, Jennifer S.; Abuogi, Lisa; Khol, Vohith; Cordero, Fernando Mejía; Althoff, Keri N.; Law, Matthew G.; Nash, Denis; International epidemiology Databases to Evaluate AIDS (IeDEA); Medicine, School of MedicineBackground: While national adoption of universal HIV treatment guidelines has led to improved, timely uptake of antiretroviral therapy (ART), longer-term care outcomes are understudied. There is little data from real-world service delivery settings on patient attrition, viral load (VL) monitoring, and viral suppression (VS) at 24 and 36 months after HIV treatment initiation. Methods and findings: For this retrospective cohort analysis, we used observational data from 25 countries in the International epidemiology Databases to Evaluate AIDS (IeDEA) consortium's Asia-Pacific, Central Africa, East Africa, Central/South America, and North America regions for patients who were ART naïve and aged ≥15 years at care enrollment between 24 months before and 12 months after national adoption of universal treatment guidelines, occurring 2012 to 2018. We estimated crude cumulative incidence of loss-to-clinic (CI-LTC) at 12, 24, and 36 months after enrollment among patients enrolling in care before and after guideline adoption using competing risks regression. Guideline change-associated hazard ratios of LTC at each time point after enrollment were estimated via cause-specific Cox proportional hazards regression models. Modified Poisson regression was used to estimate relative risks of retention, VL monitoring, and VS at 12, 24, and 36 months after ART initiation. There were 66,963 patients enrolling in HIV care at 109 clinics with ≥12 months of follow-up time after enrollment (46,484 [69.4%] enrolling before guideline adoption and 20,479 [30.6%] enrolling afterwards). More than half (54.9%) were females, and median age was 34 years (interquartile range [IQR]: 27 to 43). Mean follow-up time was 51 months (standard deviation: 17 months; range: 12, 110 months). Among patients enrolling before guideline adoption, crude CI-LTC was 23.8% (95% confidence interval [95% CI] 23.4, 24.2) at 12 months, 31.0% (95% CI [30.6, 31.5]) at 24 months, and 37.2% (95% [CI 36.8, 37.7]) at 36 months after enrollment. Adjusting for sex, age group, enrollment CD4, clinic location and type, and country income level, enrolling in care and initiating ART after guideline adoption was associated with increased hazard of LTC at 12 months (adjusted hazard ratio [aHR] 1.25 [95% CI 1.08, 1.44]; p = 0.003); 24 months (aHR 1.38 [95% CI 1.19, 1.59]; p < .001); and 36 months (aHR 1.34 [95% CI 1.18, 1.53], p < .001) compared with enrollment before guideline adoption, with no before-after differences among patients with no record of ART initiation by end of follow-up. Among patients retained after ART initiation, VL monitoring was low, with marginal improvements associated with guideline adoption only at 12 months after ART initiation. Among those with VL monitoring, VS was high at each time point among patients enrolling before guideline adoption (86.0% to 88.8%) and afterwards (86.2% to 90.3%), with no substantive difference associated with guideline adoption. Study limitations include lags in and potential underascertainment of care outcomes in real-world service delivery data and potential lack of generalizability beyond IeDEA sites and regions included in this analysis. Conclusions: In this study, adoption of universal HIV treatment guidelines was associated with lower retention after ART initiation out to 36 months of follow-up, with little change in VL monitoring or VS among retained patients. Monitoring long-term HIV care outcomes remains critical to identify and address causes of attrition and gaps in HIV care quality.Item Risk of Incident Diabetes Mellitus, Weight Gain, and Their Relationships With Integrase Inhibitor-Based Initial Antiretroviral Therapy Among Persons With Human Immunodeficiency Virus in the United States and Canada(Oxford University Press, 2021) Rebeiro, Peter F.; Jenkins, Cathy A.; Bian, Aihua; Lake, Jordan E.; Bourgi, Kassem; Moore, Richard D.; Horberg, Michael A.; Matthews, W. Christopher; Silverberg, Michael J.; Thorne, Jennifer; Mayor, Angel M.; Lima, Viviane D.; Palella, Frank J., Jr.; Saag, Michael S.; Althoff, Keri N.; Gill, M. John; Wong, Cherise; Klein, Marina B.; Crane, Heidi M.; Marconi, Vincent C.; Shepherd, Bryan E.; Sterling, Timothy R.; Koethe, John R.; Medicine, School of MedicineBackground: Integrase strand transfer inhibitor (INSTI)-based combination antiretroviral therapy (cART) is associated with greater weight gain among persons with human immunodeficiency virus (HIV), though metabolic consequences, such as diabetes mellitus (DM), are unclear. We examined the impact of initial cART regimen and weight on incident DM in a large North American HIV cohort (NA-ACCORD). Methods: cART-naive adults (≥18 years) initiating INSTI-, protease inhibitor (PI)-, or nonnucleoside reverse transcriptase inhibitor (NNRTI)-based regimens from January 2007 through December 2017 who had weight measured 12 (±6) months after treatment initiation contributed time until clinical DM, virologic failure, cART regimen switch, administrative close, death, or loss to follow-up. Multivariable Cox regression yielded adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) for incident DM by cART class. Mediation analyses, with 12-month weight as mediator, similarly adjusted for all covariates. Results: Among 22 884 eligible individuals, 47% started NNRTI-, 30% PI-, and 23% INSTI-based cART with median follow-up of 3.0, 2.3, and 1.6 years, respectively. Overall, 722 (3%) developed DM. Persons starting INSTIs vs NNRTIs had incident DM risk (HR, 1.17 [95% CI, .92-1.48]), similar to PI vs NNRTI initiators (HR, 1.27 [95% CI, 1.07-1.51]). This effect was most pronounced for raltegravir (HR, 1.42 [95% CI, 1.06-1.91]) vs NNRTI initiators. The INSTI-DM association was attenuated (HR, 1.03 [95% CI, .71-1.49] vs NNRTIs) when accounting for 12-month weight. Conclusions: Initiating first cART regimens with INSTIs or PIs vs NNRTIs may confer greater risk of DM, likely mediated through weight gain.Item Service delivery challenges in HIV care during the first year of the COVID-19 pandemic: results from a site assessment survey across the global IeDEA consortium(Wiley, 2022) Brazier, Ellen; Ajeh, Rogers; Maruri, Fernanda; Musick, Beverly; Freeman, Aimee; Wester, C. William; Lee, Man-Po; Shamu, Tinei; Crabtree Ramírez, Brenda; d’Almeida, Marcelline; Wools-Kaloustian, Kara; Kumarasamy, N.; Althoff, Keri N.; Twizere, Christella; Grinsztejn, Beatriz; Tanser, Frank; Messou, Eugène; Byakwaga, Helen; Duda, Stephany N.; Nash, Denis; International epidemiology Databases to Evaluate AIDS; Biostatistics, School of Public HealthIntroduction: Interruptions in treatment pose risks for people with HIV (PWH) and threaten progress in ending the HIV epidemic; however, the COVID-19 pandemic's impact on HIV service delivery across diverse settings is not broadly documented. Methods: From September 2020 to March 2021, the International epidemiology Databases to Evaluate AIDS (IeDEA) research consortium surveyed 238 HIV care sites across seven geographic regions to document constraints in HIV service delivery during the first year of the pandemic and strategies for ensuring care continuity for PWH. Descriptive statistics were stratified by national HIV prevalence (<1%, 1-4.9% and ≥5%) and country income levels. Results: Questions about pandemic-related consequences for HIV care were completed by 225 (95%) sites in 42 countries with low (n = 82), medium (n = 86) and high (n = 57) HIV prevalence, including low- (n = 57), lower-middle (n = 79), upper-middle (n = 39) and high- (n = 50) income countries. Most sites reported being subject to pandemic-related restrictions on travel, service provision or other operations (75%), and experiencing negative impacts (76%) on clinic operations, including decreased hours/days, reduced provider availability, clinic reconfiguration for COVID-19 services, record-keeping interruptions and suspension of partner support. Almost all sites in low-prevalence and high-income countries reported increased use of telemedicine (85% and 100%, respectively), compared with less than half of sites in high-prevalence and lower-income settings. Few sites in high-prevalence settings (2%) reported suspending antiretroviral therapy (ART) clinic services, and many reported adopting mitigation strategies to support adherence, including multi-month dispensing of ART (95%) and designating community ART pick-up points (44%). While few sites (5%) reported stockouts of first-line ART regimens, 10-11% reported stockouts of second- and third-line regimens, respectively, primarily in high-prevalence and lower-income settings. Interruptions in HIV viral load (VL) testing included suspension of testing (22%), longer turnaround times (41%) and supply/reagent stockouts (22%), but did not differ across settings. Conclusions: While many sites in high HIV prevalence settings and lower-income countries reported introducing or expanding measures to support treatment adherence and continuity of care, the COVID-19 pandemic resulted in disruptions to VL testing and ART supply chains that may negatively affect the quality of HIV care in these settings.