Browsing by Subject "antiretroviral therapy"
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Item Antiretroviral therapy, CD4, viral load, and disease stage in HIV patients in Saudi Arabia: a 2001–2013 cross-sectional study(JIDC, 2015-07) Memish, Ziad A.; Al-Tawfiq, Jaffar A.; Filemban, Sanaa M.; Qutb, Sayed; Fodail, Abdullah; Ali, Batol; Darweeish, May; Department of Medicine, IU School of MedicineIntroduction: The incidence of HIV/AIDS is increasing worldwide and in the Middle East. In this study, we analyzed the use of antiretroviral therapy (ART), the patterns of CD4 and viral load (VL), and stage of presentation. Methodology: Laboratory variables, ART use, and CD4 count were obtained and analyzed retrospectively. Results: A total of 997 cases from eight HIV/AIDS care providers were included. Of the total cases, 274 (28.3%) had a CD4 count of < 200 cells/mm3, and 413 (42.3%) had a viral load of > 5 log10. Of the total cases, 50% were on highly active antiretroviral therapy (HAART), and the majority of cases were asymptomatic (70%). Of those patients on ART, 247 (39.5%) took tenofovir/emtricitabine combined with either efavirenz (147; 14.7%) or lopinavir/ritonavir (100; 10%), and 158 (15.8%) were on lamivudine and zidovudine with either efavirenz (32; 3.2%) or lopinavir/ritonavir (126; 12.6%). Other combinations were used in 70 (7%) patients. The mean (± standard deviation) of baseline CD4 and viral load were 401 cells/mm3 (322 cells/mm3) and 4.6 log1010 (1.3 log10), respectively. At diagnosis, 72% of patients were asymptomatic; 50% had AIDS and 20% had CD4 count < 350. Conclusions: ART use was in line with international guidelines, but the number of patients receiving ART was lower than expected. Large proportions of cases presented late with AIDS at diagnosis or had CD4 < 350. Further data is needed to evaluate the medical care of patients with HIV/AIDS in the Kingdom of Saudi Arabia.Item Current strategies for improving access and adherence to antiretroviral therapies in resource-limited settings(2013-03) Scanlon, Michael L; Vreeman, Rachel CThe rollout of antiretroviral therapy (ART) significantly reduced human immunodeficiency virus (HIV)-related morbidity and mortality, but good clinical outcomes depend on access and adherence to treatment. In resource-limited settings, where over 90% of the world’s HIV-infected population resides, data on barriers to treatment are emerging that contribute to low rates of uptake in HIV testing, linkage to and retention in HIV care systems, and suboptimal adherence rates to therapy. A review of the literature reveals limited evidence to inform strategies to improve access and adherence with the majority of studies from sub-Saharan Africa. Data from observational studies and randomized controlled trials support home-based, mobile and antenatal care HIV testing, task-shifting from doctor-based to nurse-based and lower level provider care, and adherence support through education, counseling and mobile phone messaging services. Strategies with more limited evidence include targeted HIV testing for couples and family members of ART patients, decentralization of HIV care, including through home- and community-based ART programs, and adherence promotion through peer health workers, treatment supporters, and directly observed therapy. There is little evidence for improving access and adherence among vulnerable groups such as women, children and adolescents, and other high-risk populations and for addressing major barriers. Overall, studies are few in number and suffer from methodological issues. Recommendations for further research include health information technology, social-level factors like HIV stigma, and new research directions in cost-effectiveness, operations, and implementation. Findings from this review make a compelling case for more data to guide strategies to improve access and adherence to treatment in resource-limited settings.Item Differences between self-reported and electronically monitored adherence among patients receiving antiretroviral therapy in a resource-limited setting(2012-11) Thirumurthy, Harsha; Siripong, Nalyn; Vreeman, Rachel C; Pop-Eleches, Cristian; Habyarimana, James P; Sidle, John E; Siika, Abraham M; Bangsberg, David RBackground Measurement of adherence to antiretroviral therapy (ART) by patient self-report is common in resource-limited settings but widely believed to overstate actual adherence. The extent to which these measures overstate adherence has not been examined among a large patient population. Methods HIV-infected adult patients in Kenya who initiated ART within the past 3 months were followed for 6 months. Adherence was measured by participants’ self-reports of doses missed in the past 7 days during monthly clinic visits and by continuous Medication Event Monitoring System (MEMS) in participants’ pill bottles. Seven-day self-reported adherence was compared to 7-day MEMS adherence, 30-day MEMS adherence, and adherence more than 90% during each of the first 6 months. Results Self-reported and MEMS adherence measures were linked for 669 participants. Mean 7-day self-reported adherence was 98.7% and mean 7-day MEMS adherence was 86.0%, a difference of 12.7% (P <0.01). The difference between the two adherence measures increased over time due to a decline in 7-day MEMS adherence. However, patients with lower MEMS adherence were in fact more likely to self-report missed doses and the difference between self-reported and MEMS adherence was similar for each number of self-reported missed doses. When analysis was limited to patients who reported rarely or never removing multiple doses at the same time, mean difference was 10.5% (P <0.01). Conclusion There is a sizable and significant difference between self-reported and MEMS adherence. However, a strong relationship between the measures suggests that self-reported adherence is informative for clinical monitoring and program evaluation.Item HIV infection, antiretroviral therapy, and measures of endothelial function, inflammation, metabolism, and oxidative stress(PLOS, 2017-08-17) Dysangco, Andrew; Liu, Ziyue; Stein, James H.; Dubé, Michael P.; Gupta, Samir K.; Medicine, School of MedicineBackground HIV-infected patients have an increased risk of cardiovascular disease (CVD). Impaired endothelial function is an early risk factor for CVD in the general population. It is presumed that HIV infection is associated with impaired endothelial function, but results have been inconsistent. Objectives Our objectives were to determine the relationships between HIV infection, virologic suppression with antiretroviral therapy (ART), in vivo measures of conduit artery and microvascular endothelial function, and circulating biomarkers of pathways associated with CVD. Methods We performed a cross-sectional analysis of three prospectively enrolled groups from a single center: 28 were HIV-infected and virologically-suppressed on a regimen of FTC/TDF/EFV (HIV+ART+), 44 were HIV-infected but not on ART (HIV+ART-), and 39 were HIV-uninfected healthy volunteers (HIV-) matched to the HIV+ART- group for age, sex, smoking status, and height. None had diabetes, uncontrolled hypertension, known CVD, or other pro-inflammatory condition. Flow mediated dilation (FMD), nitroglycerin-mediated dilation (NTGMD), reactive hyperemia velocity time integral (RHVTI), and FMD/RHVTI of the brachial artery were measured, as well as circulating biomarkers of systemic inflammation, metabolism, oxidative stress, and endothelial activation. Results No significant differences were found amongst the three groups in FMD (P = 0.46), NTGMD (P = 0.42), RHVTI (P = 0.17), and FMD/RHVTI (P = 0.22) in unadjusted comparisons. Adjusted ANOVA models which included brachial artery diameter, demographics, and conventional CVD risk factors did not appreciably change these findings. In pairwise comparisons, the HIV+ART- group had significantly higher soluble tumor necrosis factor receptor II, soluble CD163, β-2 microglobulin, interferon-γ- induced protein-10, tissue inhibitor of metalloproteinase-1, and vascular cell adhesion molecule-1 compared to the other two groups (all p<0.05). Correlates of endothelial function differed between study groups. Conclusion Although untreated HIV infection was associated with elevated levels of several biomarkers of inflammation and endothelial activation, we were unable to demonstrate differences in measures of conduit artery and microvascular endothelial function in this study population.Item Improving estimates of children living with HIV from the Spectrum AIDS Impact Model(Lippincott, Williams, and Wilkins, 2016-10) Mahy, Mary; Penazzato, Martina; Ciaranello, Andrea; Mofenson, Lynne; Yiannoutsos, Constantin T.; Davies, Mary-Ann; Stover, John; Department of Biostatistics, Richard M. Fairbanks School of Public HealthObjective: Estimated numbers of children living with HIV determine programmatic and treatment needs. We explain the changes made to the UNAIDS estimates between 2015 and 2016, and describe the challenges around these estimates. Methods: Estimates of children newly infected, living with HIV, and dying of AIDS are developed by country teams using Spectrum software. Spectrum files are available for 160 countries, which represent 98% of the global population. In 2016, the methods were updated to reflect the latest evidence on mother-to-child HIV transmission and improved assumptions on the age children initiate antiretroviral therapy. We report updated results using the 2016 model and validate these estimates against mother-to-child transmission rates and HIV prevalence from population-based surveys for the survey year. Results: The revised 2016 model estimates 27% fewer children living with HIV in 2014 than the 2015 model, primarily due to changes in the probability of mother-to-child transmission among women with incident HIV during pregnancy. The revised estimates were consistent with population-based surveys of HIV transmission and HIV prevalence among children aged 5–9 years, but were lower than surveys among children aged 10–14 years. Conclusions: The revised 2016 model is an improvement on previous models. Paediatric HIV models will continue to evolve as further improvements are made to the assumptions. Commodities forecasting and programme planning rely on these estimates, and increasing accuracy will be critical to enable effective scale-up and optimal use of resources. Efforts are needed to improve empirical measures of HIV prevalence, incidence, and mortality among children.Item In utero exposure to HIV and/or antiretroviral therapy: a systematic review of preclinical and clinical evidence of cognitive outcomes(Wiley, 2019) McHenry, Megan S.; Balogun, Kayode A.; McDonald, Brenna C.; Vreeman, Rachel C.; Whipple, Elizabeth C.; Serghides, Lena; Pediatrics, School of MedicineIntroducion With the increasing number of children exposed to HIV or antiretroviral therapy in utero, there are concerns that this population may have worse neurodevelopmental outcomes compared to those who are unexposed. The objective of this study was to systematically review the clinical and preclinical literature on the effects of in utero exposure to HIV and/or antiretroviral therapy (ART) on neurodevelopment. Methods We systematically searched OVID Medline, PsycINFO and Embase, as well as the Cochrane Collaborative Database, Google Scholar and bibliographies of pertinent articles. Titles, abstracts, and full texts were assessed independently by two reviewers. Data from included studies were extracted. Results are summarized qualitatively. Results The search yielded 3027 unique titles. Of the 255 critically reviewed full-text articles, 25 met inclusion criteria for the systematic review. Five articles studied human subjects and looked at brain structure and function. The remaining 20 articles were preclinical studies that mostly focused on behavioural assessments in animal models. The few clinical studies had mixed results. Some clinical studies found no difference in white matter while others noted higher fractional anisotropy and lower mean diffusivity in the brains of HIV-exposed uninfected children compared to HIV-unexposed uninfected children, correlating with abnormal neurobehavioral scores. Preclinical studies focused primarily on neurobehavioral changes resulting from monotherapy with either zidovudine or lamivudine. Various developmental and behavioural changes were noted in preclinical studies with ART exposure, including decreased grooming, decreased attention, memory deficits and fewer behaviours associated with appropriate social interaction. Conclusions While the existing literature suggests that there may be some neurobehavioral differences associated with HIV and ART exposure, limited data are available to substantially support these claims. More research is needed comparing neurobiological factors between HIV-exposed uninfected and HIV-unexposed uninfected children and using exposures consistent with current clinical care.Item Trends Over Time for Adolescents Enrolling in HIV Care in Kenya, Tanzania, and Uganda From 2001–2014(Wolters Kluwer, 2018-10) Apondi, Edith; Humphrey, John M.; Sang, Edwin; Mwangi, Ann; Keter, Alfred; Musick, Beverly S.; Nalugoda, Fred K.; Ssali, John; Bukusi, Elizabeth; Yiannoutsos, Constantin T.; Wools-Kaloustian, Kara; Ayaya, Samuel; Medicine, School of MedicineBackground: The data needed to understand the characteristics and outcomes, over time, of adolescents enrolling in HIV care in East Africa are limited. Setting: Six HIV care programs in Kenya, Tanzania, and Uganda. Methods: This retrospective cohort study included individuals enrolling in HIV care as younger adolescents (10–14 years) and older adolescents (15–19 years) from 2001–2014. Descriptive statistics were used to compare groups at enrollment and antiretroviral therapy (ART) initiation over time. The proportion of adolescents was compared with the total number of individuals aged 10 years and older enrolling over time. Competing-risk analysis was used to estimate 12-month attrition after enrollment/pre-ART initiation; post-ART attrition was estimated by Kaplan–Meier method. Results: A total of 6344 adolescents enrolled between 2001 and 2014. The proportion of adolescents enrolling among all individuals increased from 2.5% (2001–2004) to 3.9% (2013–2014, P < 0.0001). At enrollment, median CD4 counts in 2001–2004 compared with 2013–2014 increased for younger (188 vs. 379 cells/mm3, P < 0.0001) and older (225 vs. 427 cells/mm3, P < 0.0001) adolescents. At ART initiation, CD4 counts increased for younger (140 vs. 233 cells/mm3, P < 0.0001) and older (64 vs. 323 cells/mm3, P < 0.0001) adolescents. Twelve-month attrition also increased for all adolescents both after enrollment/pre-ART initiation (4.7% vs. 12.0%, P < 0.001) and post-ART initiation (18.7% vs. 31.2%, P < 0.001). Conclusions: Expanding HIV services and ART coverage was likely associated with earlier adolescent enrollment and ART initiation but also with higher attrition rates before and after ART initiation. Interventions are needed to promote retention in care among adolescents.Item Viral Bad News Sent by EVAIL(MDPI, 2021-06-18) Clauss, Matthias; Chelvanambi, Sarvesh; Cook, Christine; ElMergawy, Rabab; Dhillon, Navneet; Medicine, School of MedicineThis article reviews the current knowledge on how viruses may utilize Extracellular Vesicle Assisted Inflammatory Load (EVAIL) to exert pathologic activities. Viruses are classically considered to exert their pathologic actions through acute or chronic infection followed by the host response. This host response causes the release of cytokines leading to vascular endothelial cell dysfunction and cardiovascular complications. However, viruses may employ an alternative pathway to soluble cytokine-induced pathologies—by initiating the release of extracellular vesicles (EVs), including exosomes. The best-understood example of this alternative pathway is human immunodeficiency virus (HIV)-elicited EVs and their propensity to harm vascular endothelial cells. Specifically, an HIV-encoded accessory protein called the “negative factor” (Nef) was demonstrated in EVs from the body fluids of HIV patients on successful combined antiretroviral therapy (ART); it was also demonstrated to be sufficient in inducing endothelial and cardiovascular dysfunction. This review will highlight HIV-Nef as an example of how HIV can produce EVs loaded with proinflammatory cargo to disseminate cardiovascular pathologies. It will further discuss whether EV production can explain SARS-CoV-2-mediated pulmonary and cardiovascular pathologies.