Browsing by Subject "Antiretroviral therapy"
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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 Adjusting Mortality for Loss to Follow-Up: Analysis of Five ART Programmes in Sub-Saharan Africa(Public Library of Science, 2010-11-30) Brinkhof, Martin W. G.; Spycher, Ben D.; Yiannoutsos, Constantin; Weigel, Ralf; Wood, Robin; Messou, Eugène; Boulle, Andrew; Egger, Matthias; Sterne, Jonathan A. C.; Biostatistics, School of Public HealthEvaluation of antiretroviral treatment (ART) programmes in sub-Saharan Africa is difficult because many patients are lost to follow-up. Outcomes in these patients are generally unknown but studies tracing patients have shown mortality to be high. We adjusted programme-level mortality in the first year of antiretroviral treatment (ART) for excess mortality in patients lost to follow-up. Methods and Findings Treatment-naïve patients starting combination ART in five programmes in Côte d'Ivoire, Kenya, Malawi and South Africa were eligible. Patients whose last visit was at least nine months before the closure of the database were considered lost to follow-up. We filled missing survival times in these patients by multiple imputation, using estimates of mortality from studies that traced patients lost to follow-up. Data were analyzed using Weibull models, adjusting for age, sex, ART regimen, CD4 cell count, clinical stage and treatment programme. A total of 15,915 HIV-infected patients (median CD4 cell count 110 cells/µL, median age 35 years, 68% female) were included; 1,001 (6.3%) were known to have died and 1,285 (14.3%) were lost to follow-up in the first year of ART. Crude estimates of mortality at one year ranged from 5.7% (95% CI 4.9–6.5%) to 10.9% (9.6–12.4%) across the five programmes. Estimated mortality hazard ratios comparing patients lost to follow-up with those remaining in care ranged from 6 to 23. Adjusted estimates based on these hazard ratios ranged from 10.2% (8.9–11.6%) to 16.9% (15.0–19.1%), with relative increases in mortality ranging from 27% to 73% across programmes. Conclusions Naïve survival analysis ignoring excess mortality in patients lost to follow-up may greatly underestimate overall mortality, and bias ART programme evaluations. Adjusted mortality estimates can be obtained based on excess mortality rates in patients lost to follow-up.Item Cerebrospinal fluid neopterin decay characteristics after initiation of antiretroviral therapy(Springer Nature, 2013-05-10) Yilmaz, Aylin; Yiannoutsos, Constantin T.; Fuchs, Dietmar; Price, Richard W.; Crozier, Kathryn; Hagberg, Lars; Spudich, Serena; Gisslén, Magnus; Biostatistics and Health Data Science, Richard M. Fairbanks School of Public HealthBackground: Neopterin, a biomarker of macrophage activation, is elevated in the cerebrospinal fluid (CSF) of most HIV-infected individuals and decreases after initiation of antiretroviral therapy (ART). We studied decay characteristics of neopterin in CSF and blood after commencement of ART in HIV-infected subjects and estimated the set-point levels of CSF neopterin after ART-mediated viral suppression. Methods: CSF and blood neopterin were longitudinally measured in 102 neurologically asymptomatic HIV-infected subjects who were treatment-naïve or had been off ART for ≥ 6 months. We used a non-linear model to estimate neopterin decay in response to ART and a stable neopterin set-point attained after prolonged ART. Seven subjects with HIV-associated dementia (HAD) who initiated ART were studied for comparison. Results: Non-HAD patients were followed for a median 84.7 months. Though CSF neopterin concentrations decreased rapidly after ART initiation, it was estimated that set-point levels would be below normal CSF neopterin levels (<5.8 nmol/L) in only 60/102 (59%) of these patients. Pre-ART CSF neopterin was the primary predictor of set-point (P <0.001). HAD subjects had higher baseline median CSF neopterin levels than non-HAD subjects (P <0.0001). Based on the non-HAD model, only 14% of HAD patients were predicted to reach normal levels. Conclusions: After virologically suppressive ART, abnormal CSF neopterin levels persisted in 41% of non-HAD and the majority of HAD patients. ART is not fully effective in ameliorating macrophage activation in CNS as well as blood, especially in subjects with higher pre-ART levels of immune activation.Item Delivery of HIV care during the 2007 post-election crisis in Kenya: a case study analyzing the response of the Academic Model Providing Access to Healthcare (AMPATH) program(Springer Nature, 2013-12-01) Goodrich, Suzanne; Ndege, Samson; Kimaiyo, Sylvester; Some, Hosea; Wachira, Juddy; Braitstein, Paula; Sidle, John E.; Sitienei, Jackline; Owino, Regina; Chesoli, Cleophas; Gichunge, Catherine; Komen, Fanice; Ojwang, Claris; Sang, Edwin; Siika, Abraham; Wools-Kaloustian, Kara; Medicine, School of MedicineBackground: Widespread violence followed the 2007 presidential elections in Kenya resulting in the deaths of a reported 1,133 people and the displacement of approximately 660,000 others. At the time of the crisis the United States Agency for International Development-Academic Model Providing Access to Healthcare (USAID-AMPATH) Partnership was operating 17 primary HIV clinics in western Kenya and treating 59,437 HIV positive patients (23,437 on antiretroviral therapy (ART)). Methods: This case study examines AMPATH's provision of care and maintenance of patients on ART throughout the period of disruption. This was accomplished by implementing immediate interventions including rapid information dissemination through the media, emergency hotlines and community liaisons; organization of a Crisis Response leadership team; the prompt assembly of multidisciplinary teams to address patient care, including psychological support staff (in clinics and in camps for internally displaced persons (IDP)); and the use of the AMPATH Medical Records System to identify patients on ART who had missed clinic appointments. Results: These interventions resulted in the opening of all AMPATH clinics within five days of their scheduled post-holiday opening dates, 23,949 patient visits in January 2008 (23,259 previously scheduled), uninterrupted availability of antiretrovirals at all clinics, treatment of 1,420 HIV patients in IDP camps, distribution of basic provisions, mobilization of outreach services to locate missing AMPATH patients and delivery of psychosocial support to 300 staff members and 632 patients in IDP camps. Conclusion: Key lessons learned in maintaining the delivery of HIV care in a crisis situation include the importance of advance planning to develop programs that can function during a crisis, an emphasis on a rapid programmatic response, the ability of clinics to function autonomously, patient knowledge of their disease, the use of community and patient networks, addressing staff needs and developing effective patient tracking systems.Item Distribution of hepatitis C virus (HCV) genotypes in a Saudi Arabian hospital during the 2015–2020 period(Dipartimento di Medicina e Chirurgia, Università degli studi di Salerno, 2021-09-10) Almosa, Fadel Ali M.; Alnasser, Ali Hassan A.; Al-Tawfiq, Jaffar A.; Medicine, School of MedicineHepatitis C virus (HCV) is the leading cause of chronic liver disease. HCV genotypes and subtypes are important predictors of disease progression and antiviral treatment response. To our knowledge, there had been limited studies of HCV genotypes in Qatif, Saudi Arabia. This study aims to assess the distribution of HCV genotypes in Qatif Central Hospital, Qatif, Saudi Arabia. This is a retrospective study of adult patients with HCV infection between January 2015 and December 2020. Only patients with documented HCV genotyping were included. A total of 356 HCVinfected patients fulfilled the inclusion criteria and were included in further analysis. Of those patients, 179 (50.3%) were males, and most were Saudi (N=347, 97.5%). The median age was 60 years, and 191 (53.7%) were 50-69 years of age. Genotype 2 was present in 118 (33.1%) of the patients, followed by genotype 4 in 92 (25.8%), genotype 1B in 62 (17.4%), and genotype 1A in 37 (10.4%). The study showed that HCV genotype 2 is the predominant variant among chronic HCV patients in the study population. Monitoring the epidemiology of HCV genotypes may provide guidance in treatment decisions.Item Global HIV mortality trends among children on antiretroviral treatment corrected for under‐reported deaths: an updated analysis of the International epidemiology Databases to Evaluate AIDS collaboration(Wiley, 2021-09) Kassanjee, Reshma; Johnson, Leigh F.; Zaniewski, Elizabeth; Ballif, Marie; Christ, Benedikt; Yiannoutsos, Constantin T.; Nyakato, Patience; Desmonde, Sophie; Edmonds, Andrew; Sudjaritruk, Tavitiya; Pinto, Jorge; Vreeman, Rachel; Dahourou, Désiré Lucien; Twizere, Christelle; Kariminia, Azar; Carlucci, James G.; Kasozi, Charles; Davies, Mary-Ann; Biostatistics, School of Public HealthIntroduction: The Joint United Nations Programme on HIV/AIDS (UNAIDS) projections of paediatric HIV prevalence and deaths rely on the International epidemiology Databases to Evaluate AIDS (IeDEA) consortium for mortality estimates among children living with HIV (CHIV) receiving antiretroviral therapy (ART). Previous estimates, based on data through 2014, may no longer be accurate due to expanded paediatric HIV care and treatment eligibility, and the possibility of unreported deaths in CHIV considered lost to follow-up (LTFU). We therefore estimated all-cause mortality and its trends in CHIV (<15 years old) on ART using extended and new IeDEA data. Methods: We analysed (i) IeDEA observational data from CHIV in routine care globally, and (ii) novel data from an IeDEA tracing study that determined outcomes in a sample of CHIV after being LTFU in southern Africa. We included 45,711 CHIV on ART during 2004 to 2017 at 72 programmes in Africa, Asia-Pacific and Latin America. We used mixed effects Poisson regression to estimate mortality by age, sex, CD4 at ART start, time on ART, region and calendar year. For Africa, in an adjusted analysis that accounts for unreported deaths among those LTFU, we first modified the routine data by simulating mortality outcomes within six months after LTFU, based on a Gompertz survival model fitted to the tracing data (n = 221). Results: Observed mortality rates were 1.8 (95% CI: 1.7 to 1.9) and 9.4 (6.3 to 13.4) deaths per 100 person-years in the routine and tracing data, respectively. We found strong evidence of higher mortality at shorter ART durations, lower CD4 values, and in infancy. Averaging over covariate patterns, the adjusted mortality rate was 54% higher than the unadjusted rate. In unadjusted analyses, mortality reduced by an average 60% and 73% from 2005 to 2017, within and outside of Africa, respectively. In the adjusted analysis for Africa, this temporal reduction was 42%. Conclusions: Mortality rates among CHIV have decreased substantially over time. However, when accounting for worse outcomes among those LTFU, mortality estimates increased and temporal improvements were slightly reduced, suggesting caution in interpreting analyses based only on programme data. The improved and updated IeDEA estimates on mortality among CHIV on ART support UNAIDS efforts to accurately model global HIV statistics.Item High Unreported Mortality in Children and Youth (<25 Years) Living With HIV Who Were Lost to Care From Antiretroviral Therapy Programs in Southern Africa: Results From a Multicountry Tracing Study(Wolters Kluwer, 2022-12-15) Nyakato, Patience; Christ, Benedikt; Anderegg, Nanina; Muhairwe, Josephine; Jefferys, Laura; van Dijk, Janneke; Vinikoor, Michael J.; van Lettow, Monique; Chimbetete, Cleophas; Phiri, Sam J.; Egger, Matthias; Ballif, Marie; Yiannoutsos, Constantin T.; Schomaker, Michael; Kassanjee, Reshma; Davies, Mary-Ann; Cornell, Morna; International epidemiology Databases to Evaluate AIDS Southern Africa (IeDEA-SA); Biostatistics and Health Data Science, Richard M. Fairbanks School of Public HealthBackground: Antiretroviral therapy program mortality maybe underestimated if deceased patients are misclassified as lost. Methods: We used two-stage inverse probability weighting to account for probability of being: sampled for tracing and found by the tracer. Results: Among 680 children and youth aged <25 years on antiretroviral therapy who were lost and traced in Southern Africa between October 2017 and November 2019, estimated mortality was high at 9.1% (62/680). After adjusting for measured covariates and within-site clustering, mortality remained lower for young adults aged 20–24 years compared with infants aged <2 years [adjusted hazard ratio: 0.40 (95% confidence interval: 0.31 to 0.51)]. Conclusions: Our study confirms high unreported mortality in children and youth who are lost and the need for tracing to assess vital status among those who are lost to accurately report on program mortality.Item Impact of the COVID-19 pandemic on TB services at ART programmes in low- and middle-income countries: a multi-cohort survey(Wiley, 2022) Marti, Mariana; Zürcher, Kathrin; Enane, Leslie A.; Diero, Lameck; Marcy, Olivier; Tiendrebeogo, Thierry; Yotebieng, Marcel; Twizere, Christelle; Khusuwan, Suwimon; Yunihastuti, Evy; Reubenson, Gary; Shah, N. Sarita; Egger, Matthias; Ballif, Marie; Fenner, Lukas; IeDEA global consortium; Pediatrics, School of MedicineIntroduction: COVID-19 stretched healthcare systems to their limits, particularly in settings with a pre-existing high burden of infectious diseases, including HIV and tuberculosis (TB). We studied the impact of COVID-19 on TB services at antiretroviral therapy (ART) clinics in low- and middle-income countries. Methods: We surveyed ART clinics providing TB services in the International Epidemiology Databases to Evaluate AIDS (IeDEA) consortium in Africa and the Asia-Pacific until July 2021 (TB diagnoses until the end of 2021). We collected site-level data using standardized questionnaires. Results: Of 46 participating ART clinics, 32 (70%) were in Africa and 14 (30%) in the Asia-Pacific; 52% provided tertiary care. Most clinics (85%) reported disrupted routine HIV care services during the pandemic, both in Africa (84%) and the Asia-Pacific (86%). The most frequently reported impacts were on staff (52%) and resource shortages (37%; protective clothing, face masks and disinfectants). Restrictions in TB health services were observed in 12 clinics (26%), mainly reduced access to TB diagnosis and postponed follow-up visits (6/12, 50% each), and restrictions in TB laboratory services (22%). Restrictions of TB services were addressed by dispensing TB drugs for longer periods than usual (7/12, 58%), providing telehealth services (3/12, 25%) and with changes in directly observed therapy (DOT) (e.g. virtual DOT, 3/12). The number of TB diagnoses at participating clinics decreased by 21% in 2020 compared to 2019; the decline was more pronounced in tertiary than primary/secondary clinics (24% vs. 12%) and in sites from the Asia-Pacific compared to Africa (46% vs. 14%). In 2021, TB diagnoses continued to decline in Africa (-8%) but not in the Asia-Pacific (+62%) compared to 2020. During the pandemic, new infection control measures were introduced or intensified at the clinics, including wearing face masks, hand sanitation and patient triage. Conclusions: The COVID-19 pandemic led to staff shortages, reduced access to TB care and delays in follow-up visits for people with TB across IeDEA sites in Africa and the Asia-Pacific. Increased efforts are needed to restore and secure ongoing access to essential TB services in these contexts.Item Lipodystrophy in HIV infected patients on long term Antiretroviral therapy in western Kenya(Association of Kenya Physicians, 2007) Diero, L. O.; Fife, K. H.; Kaloustian, K. W.; Sidle, J.; Dube, M. P.; Fife, R. S.; Mureithi, J.; Mwangi, A.; Association of Kenya Physicians Scientific Conference (11th : Mar. 2007 : Eldoret, Kenya)Changes in fat distribution has been observed in patients on highly active antiretroviral therapy. The frequently reported drugs that cause fat redistribution are stavudine and protease inhibitors. Stavudine also causes a high incidence of metabolic complications and peripheral neuropathy.Item Patient-reported factors associated with reengagement among HIV-infected patients disengaged from care in East Africa(Wolters Kluwer, 2016-01-28) Camlin, Carol S.; Neilands, Torsten B.; Odeny, Thomas A.; Lyamuya, Rita; Nakiwogga-Muwanga, Alice; Diero, Lameck; Bwana, Mwebesa; Braitstein, Paula; Somi, Geoffrey; Kambugu, Andrew; Bukusi, Elizabeth A.; Glidden, David V.; Wools-Kaloustian, Kara K.; Wenger, Megan; Department of Medicine, IU School of MedicineOBJECTIVE: Engagement in care is key to successful HIV treatment in resource-limited settings; yet little is known about the magnitude and determinants of reengagement among patients out of care. We assessed patient-reported reasons for not returning to clinic, identified latent variables underlying these reasons, and examined their influence on subsequent care reengagement. DESIGN: We used data from the East Africa International Epidemiologic Databases to Evaluate AIDS to identify a cohort of patients disengaged from care (>3 months late for last appointment, reporting no HIV care in preceding 3 months) (n = 430) who were interviewed about reasons why they stopped care. Among the 399 patients for whom follow-up data were available, 104 returned to clinic within a median observation time of 273 days (interquartile range: 165-325). METHODS: We conducted exploratory and confirmatory factor analyses (EFA, CFA) to identify latent variables underlying patient-reported reasons, then used these factors as predictors of time to clinic return in adjusted Cox regression models. RESULTS: EFA and CFA findings suggested a six-factor structure that lent coherence to the range of barriers and motivations underlying care disengagement, including poverty, transport costs, and interference with work responsibilities; health system 'failures,' including poor treatment by providers; fearing disclosure of HIV status; feeling healthy; and treatment fatigue/seeking spiritual alternatives to medicine. Factors related to poverty and poor treatment predicted higher rate of return to clinic, whereas the treatment fatigue factor was suggestive of a reduced rate of return. CONCLUSION: Certain barriers to reengagement appear easier to overcome than factors such as treatment fatigue. Further research will be needed to identify the easiest, least expensive interventions to reengage patients lost to HIV care systems. Interpersonal interventions may continue to play an important role in addressing psychological barriers to retention.