Pub Date : 2024-10-01Epub Date: 2024-06-20DOI: 10.1097/QAD.0000000000003965
Samuel C Russo, Mollie W Ockene, Allison K Arpante, Julia E Johnson, Hang Lee, Mabel Toribio, Takara L Stanley, Colleen M Hadigan, Steven K Grinspoon, Kristine M Erlandson, Lindsay T Fourman
Objective: Tesamorelin is the only FDA-approved therapy to treat abdominal fat accumulation in people with HIV (PWH). Phase III clinical trials were conducted prior to the introduction of integrase inhibitors (INSTIs), which are now a mainstay of HIV antiretroviral therapy.
Design: We leveraged a randomized double-blind trial of 61 PWH and metabolic dysfunction-associated steatotic liver disease to evaluate the efficacy and safety of tesamorelin 2 mg once daily vs. identical placebo among participants on INSTI-based regimens at baseline.
Methods: In the parent clinical trial, visceral fat cross-sectional area, hepatic fat fraction, and trunk-to-appendicular fat ratio were quantified using magnetic resonance imaging, proton magnetic resonance spectroscopy, and dual-energy x-ray absorptiometry, respectively, at baseline and 12 months. Metabolic and safety outcomes were compared between treatment arms.
Results: Among 38 participants on INSTI-based regimens at baseline, 15 individuals on tesamorelin and 16 individuals on placebo completed the 12-month study. Tesamorelin led to significant declines in visceral fat (median [interquartile range]: -25 [-93, -2] vs. 14 [3, 41] cm 2 , P = 0.001), hepatic fat (-4.2% [-12.3%, -2.7%] vs. -0.5% [-3.9%, 2.7%], P = 0.01), and trunk-to-appendicular fat ratio (-0.1 [-0.3, 0.0] vs. 0.0 [-0.1, 0.1], P = 0.03). Tesamorelin was well tolerated with a similar frequency of adverse events, including hyperglycemia, between groups.
Conclusions: The current analysis provides the first dedicated data on the efficacy and safety of tesamorelin among PWH on INSTI-based regimens. Despite the association of INSTI use with weight gain and adipose tissue dysfunction, tesamorelin had beneficial effects on body composition with no exacerbation of glycemic control.
{"title":"Efficacy and safety of tesamorelin in people with HIV on integrase inhibitors.","authors":"Samuel C Russo, Mollie W Ockene, Allison K Arpante, Julia E Johnson, Hang Lee, Mabel Toribio, Takara L Stanley, Colleen M Hadigan, Steven K Grinspoon, Kristine M Erlandson, Lindsay T Fourman","doi":"10.1097/QAD.0000000000003965","DOIUrl":"10.1097/QAD.0000000000003965","url":null,"abstract":"<p><strong>Objective: </strong>Tesamorelin is the only FDA-approved therapy to treat abdominal fat accumulation in people with HIV (PWH). Phase III clinical trials were conducted prior to the introduction of integrase inhibitors (INSTIs), which are now a mainstay of HIV antiretroviral therapy.</p><p><strong>Design: </strong>We leveraged a randomized double-blind trial of 61 PWH and metabolic dysfunction-associated steatotic liver disease to evaluate the efficacy and safety of tesamorelin 2 mg once daily vs. identical placebo among participants on INSTI-based regimens at baseline.</p><p><strong>Methods: </strong>In the parent clinical trial, visceral fat cross-sectional area, hepatic fat fraction, and trunk-to-appendicular fat ratio were quantified using magnetic resonance imaging, proton magnetic resonance spectroscopy, and dual-energy x-ray absorptiometry, respectively, at baseline and 12 months. Metabolic and safety outcomes were compared between treatment arms.</p><p><strong>Results: </strong>Among 38 participants on INSTI-based regimens at baseline, 15 individuals on tesamorelin and 16 individuals on placebo completed the 12-month study. Tesamorelin led to significant declines in visceral fat (median [interquartile range]: -25 [-93, -2] vs. 14 [3, 41] cm 2 , P = 0.001), hepatic fat (-4.2% [-12.3%, -2.7%] vs. -0.5% [-3.9%, 2.7%], P = 0.01), and trunk-to-appendicular fat ratio (-0.1 [-0.3, 0.0] vs. 0.0 [-0.1, 0.1], P = 0.03). Tesamorelin was well tolerated with a similar frequency of adverse events, including hyperglycemia, between groups.</p><p><strong>Conclusions: </strong>The current analysis provides the first dedicated data on the efficacy and safety of tesamorelin among PWH on INSTI-based regimens. Despite the association of INSTI use with weight gain and adipose tissue dysfunction, tesamorelin had beneficial effects on body composition with no exacerbation of glycemic control.</p>","PeriodicalId":7502,"journal":{"name":"AIDS","volume":" ","pages":"1758-1764"},"PeriodicalIF":3.4,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11365754/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141436523","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-01Epub Date: 2024-07-17DOI: 10.1097/QAD.0000000000003979
Cassandra R Duffy, Julie M Herlihy, Ethan Zulu, Lawrence Mwananyanda, Leah Forman, Tim Heeren, Christopher J Gill, Megan Harper, Roma Chilengi, Roy Chavuma, Barbara Payne-Lohman, Donald M Thea
Objective: To examine the risk of preterm birth (PTB) and small for gestational age (SGA) among women with HIV compared to women without HIV. Secondary objectives were to explore the role of maternal immune activation (IA) and effect of cART timing on these outcomes.
Design: Prospective observational cohort.
Setting: Urban government-run clinic at Chawama Hospital in Lusaka, Zambia.
Participants: A total of 1481 women with and without HIV with singleton pregnancies enrolled before 26 weeks' gestation by ultrasound dating.
Methods: From August 2019 to November 2022, pregnant women were enrolled in a 1 : 1 ratio of HIV infection. Maternal baseline clinical factors were collected, as well as CD4 + , viral load and CD8 + T-cell IA in women with HIV. Birth outcomes were also collected. The association of HIV-exposure and cART timing on outcomes was assessed by multivariable logistic regression. The independent role of IA was determined by mediation analysis.
Main outcome measures: PTB (<37 weeks) and SGA.
Results: There were 38 fetal deaths and 1230 singleton live births. Maternal HIV infection was associated with PTB [adjusted odds ratio (AOR) 1.60, 95% confidence interval (CI) 1.11-2.32] and to a lesser extent SGA (AOR 1.29, 95% CI 0.98-1.70). Maternal cART timing impacted these associations, with highest risk in women who started cART after conception (PTB AOR 1.77, 95% CI 1.09-2.87, SGA AOR 1.52, 95% CI 1.04-2.22). Maternal IA was not associated with PTB independent of HIV infection.
Conclusions: HIV is associated with PTB. Risk of PTB and SGA was highest in women with HIV who started cART in pregnancy, a modifiable risk factor.
目的与未感染艾滋病病毒的妇女相比,研究感染艾滋病病毒的妇女早产(PTB)和胎龄小(SGA)的风险。次要目标是探讨母体免疫激活(IA)的作用以及 cART 时间对这些结果的影响:设计:前瞻性观察队列:地点:赞比亚卢萨卡 Chawama 医院由政府运营的城市诊所:1481名感染和未感染艾滋病毒的单胎妊娠妇女在妊娠26周前通过超声波测孕登记:方法:2019 年 8 月至 2022 年 11 月,按照 1:1 的 HIV 感染比例招募孕妇。收集了母体基线临床因素,以及感染 HIV 妇女的 CD4、病毒载量和 CD8 T 细胞 IA。此外,还收集了分娩结果。通过多变量逻辑回归评估了 HIV 暴露和 cART 时间与预后的关系。通过中介分析确定IA的独立作用:PTB(结果:38例胎儿死亡,1230例单胎活产。母体艾滋病病毒感染与 PTB 相关(AOR 1.60,95%CI 1.11-2.32),其次与 SGA 相关(AOR 1.29,0.98-1.70)。孕产妇开始 cART 的时间对这些相关性有影响,受孕后开始 cART 的妇女风险最高(PTB AOR 1.77,95%CI 1.09-2.87;SGA AOR 1.52,95%CI 1.04-2.22)。产妇 IA 与 PTB 无关,与 HIV 感染无关:结论:HIV 与 PTB 相关。在妊娠期开始接受 cART 治疗的女性艾滋病毒感染者中,PTB 和 SGA 的风险最高,这是一个可改变的风险因素。
{"title":"Preterm birth among women with HIV: impact of preconception cART initiation.","authors":"Cassandra R Duffy, Julie M Herlihy, Ethan Zulu, Lawrence Mwananyanda, Leah Forman, Tim Heeren, Christopher J Gill, Megan Harper, Roma Chilengi, Roy Chavuma, Barbara Payne-Lohman, Donald M Thea","doi":"10.1097/QAD.0000000000003979","DOIUrl":"10.1097/QAD.0000000000003979","url":null,"abstract":"<p><strong>Objective: </strong>To examine the risk of preterm birth (PTB) and small for gestational age (SGA) among women with HIV compared to women without HIV. Secondary objectives were to explore the role of maternal immune activation (IA) and effect of cART timing on these outcomes.</p><p><strong>Design: </strong>Prospective observational cohort.</p><p><strong>Setting: </strong>Urban government-run clinic at Chawama Hospital in Lusaka, Zambia.</p><p><strong>Participants: </strong>A total of 1481 women with and without HIV with singleton pregnancies enrolled before 26 weeks' gestation by ultrasound dating.</p><p><strong>Methods: </strong>From August 2019 to November 2022, pregnant women were enrolled in a 1 : 1 ratio of HIV infection. Maternal baseline clinical factors were collected, as well as CD4 + , viral load and CD8 + T-cell IA in women with HIV. Birth outcomes were also collected. The association of HIV-exposure and cART timing on outcomes was assessed by multivariable logistic regression. The independent role of IA was determined by mediation analysis.</p><p><strong>Main outcome measures: </strong>PTB (<37 weeks) and SGA.</p><p><strong>Results: </strong>There were 38 fetal deaths and 1230 singleton live births. Maternal HIV infection was associated with PTB [adjusted odds ratio (AOR) 1.60, 95% confidence interval (CI) 1.11-2.32] and to a lesser extent SGA (AOR 1.29, 95% CI 0.98-1.70). Maternal cART timing impacted these associations, with highest risk in women who started cART after conception (PTB AOR 1.77, 95% CI 1.09-2.87, SGA AOR 1.52, 95% CI 1.04-2.22). Maternal IA was not associated with PTB independent of HIV infection.</p><p><strong>Conclusions: </strong>HIV is associated with PTB. Risk of PTB and SGA was highest in women with HIV who started cART in pregnancy, a modifiable risk factor.</p>","PeriodicalId":7502,"journal":{"name":"AIDS","volume":" ","pages":"1749-1757"},"PeriodicalIF":3.4,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11356690/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141625710","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-30DOI: 10.1097/QAD.0000000000004027
Eline Wijstma, Vita W Jongen, Anders Boyd, Henry J C de Vries, Maarten F Schim van der Loeff, Maria Prins, Elske Hoornenborg
Objective: The Dutch HIV pre-exposure prophylaxis (PrEP) pilot provided subsidized PrEP care to maximum 2,900 individuals at a time in Amsterdam. Populations with expected barriers to accessing PrEP elsewhere were prioritized for program inclusion. We evaluated their prior sexual health service engagement and PrEP need.
Design: Cross-sectional analysis using enrolment data.
Methods: We included individuals ever enrolled in the PrEP program at the Center for Sexual Health (CSH) Amsterdam between 2019-2023. We calculated the proportion belonging to higher-priority groups (i.e.,<25 years old, transgender, sex worker, uninsured or migrant). We defined classes of sexual health service engagement in the 12 months preceding enrolment using latent class analysis (LCA). We compared engagement classes, sexual behavior and positivity of HIV and sexually transmitted infections (STI) between higher- and lower-priority groups.
Results: 2,004/4,075 (49%) individuals enrolled belonged to higher-priority groups. LCA showed three classes of prior engagement: "Newly engaged" (14%,n = 551) were new to the CSH-Amsterdam; "PrEP initiators" (40%,n = 1,642) previously visited the CSH-Amsterdam but had not used PrEP; "PrEP experienced" individuals (46%,n = 1,882) previously accessed PrEP. Higher-priority groups were more often "newly engaged" or "PrEP-initiators" than "PrEP-experienced". Higher-priority groups less often had condomless anal sex with casual partners or chemsex in the prior six months. Positivity of bacterial STI was similar between higher-priority (n = 300/2,004, 15.0%) and lower-priority (n = 315/2,071, 15.2%) groups. 13/14 HIV diagnoses at enrolment were in higher-priority groups.
Conclusion: Higher-priority populations had less often previously used sexual health services and accounted for most new HIV diagnoses at enrolment. Engaging these populations in sexual healthcare, including PrEP, should be stressed.
{"title":"Outcomes of a policy to prioritize populations with expected healthcare barriers for subsidized PrEP care in Amsterdam, the Netherlands: a cross-sectional study.","authors":"Eline Wijstma, Vita W Jongen, Anders Boyd, Henry J C de Vries, Maarten F Schim van der Loeff, Maria Prins, Elske Hoornenborg","doi":"10.1097/QAD.0000000000004027","DOIUrl":"https://doi.org/10.1097/QAD.0000000000004027","url":null,"abstract":"<p><strong>Objective: </strong>The Dutch HIV pre-exposure prophylaxis (PrEP) pilot provided subsidized PrEP care to maximum 2,900 individuals at a time in Amsterdam. Populations with expected barriers to accessing PrEP elsewhere were prioritized for program inclusion. We evaluated their prior sexual health service engagement and PrEP need.</p><p><strong>Design: </strong>Cross-sectional analysis using enrolment data.</p><p><strong>Methods: </strong>We included individuals ever enrolled in the PrEP program at the Center for Sexual Health (CSH) Amsterdam between 2019-2023. We calculated the proportion belonging to higher-priority groups (i.e.,<25 years old, transgender, sex worker, uninsured or migrant). We defined classes of sexual health service engagement in the 12 months preceding enrolment using latent class analysis (LCA). We compared engagement classes, sexual behavior and positivity of HIV and sexually transmitted infections (STI) between higher- and lower-priority groups.</p><p><strong>Results: </strong>2,004/4,075 (49%) individuals enrolled belonged to higher-priority groups. LCA showed three classes of prior engagement: \"Newly engaged\" (14%,n = 551) were new to the CSH-Amsterdam; \"PrEP initiators\" (40%,n = 1,642) previously visited the CSH-Amsterdam but had not used PrEP; \"PrEP experienced\" individuals (46%,n = 1,882) previously accessed PrEP. Higher-priority groups were more often \"newly engaged\" or \"PrEP-initiators\" than \"PrEP-experienced\". Higher-priority groups less often had condomless anal sex with casual partners or chemsex in the prior six months. Positivity of bacterial STI was similar between higher-priority (n = 300/2,004, 15.0%) and lower-priority (n = 315/2,071, 15.2%) groups. 13/14 HIV diagnoses at enrolment were in higher-priority groups.</p><p><strong>Conclusion: </strong>Higher-priority populations had less often previously used sexual health services and accounted for most new HIV diagnoses at enrolment. Engaging these populations in sexual healthcare, including PrEP, should be stressed.</p>","PeriodicalId":7502,"journal":{"name":"AIDS","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2024-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142339225","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-30DOI: 10.1097/QAD.0000000000004028
Daniele Pastori, Francesco Del Sole, Tommaso Brogi, Maria Del Ben, Caterina Fimiani, Claudio Maria Mastroianni, Ivano Mezzaroma
Objective: To evaluate the association between increased epicardial fat thickness (EFT) and liver stiffness measurement (LSM), as assessed by elastography in people living with Human Immunodeficiency Virus type 1 (HIV-1) infection (PWH).
Methods: 91 PWH on effective antiretroviral treatment (ART) were enrolled. EFT was measured by transthoracic echocardiography. Liver steatosis was evaluated by ultrasound Hamaguchi criteria and LSM by elastography with Acoustic Radiation Force Impulse (ARFI) Tecnique. LSM ≥8 Kpa was suggestive of clinically relevant fibrosis.
Results: Mean age was 54.3 years and 27.5% were women. EFT correlated with HIV-1 infection duration (rS 0.252, p = 0.016), age at study entry (rS 0.527, p < 0.001), BMI (rS 0.363, p < 0.001), waist circumference (rS 0.549, p < 0.001), HDL (rS -0.391, p < 0.001), triglycerides (rS 0.375, p < 0.001), Hamaguchi score (rS 0.279, p = 0.007), right lobe of the liver (rS 0.259, p = 0.014), Left ventricular mass/Body surface area (rS 0.220, p = 0.036).A LSM ≥8 Kpa was found in 20.9% of PWH, more commonly in those with EFT above the median >5.6 mm (30.4% vs 11.1%, p = 0.038). LSM significantly correlated with EFT (rS 0.274, p = 0.009), CD4+ cells (rS -0.320, p = 0.003) and nadir of CD4+ cells (rS -0.292, p = 0.007).In a subgroup (n = 53), an HOMA-IR index >2.33 identified increased EFT, (AUC 0.73, 95%CI 0.59-0.84, p = 0.001) while an HOMA-IR >3.27 predicted increased LSM (AUC 0.76, 95%CI 0.62-0.87, p = 0.005).
Conclusions: PWH with increased EFT have worse metabolic profile and a high proportion of clinically relevant fibrosis at ARFI elastography, despite normal liver function tests. The HOMA-IR index might be used to identify PWH with increased EFT and liver fibrosis.
{"title":"Epicardial fat and liver stiffness by ARFI elastography in people living with Human Immunodeficiency Virus type 1 (HIV-1) infection without liver disease.","authors":"Daniele Pastori, Francesco Del Sole, Tommaso Brogi, Maria Del Ben, Caterina Fimiani, Claudio Maria Mastroianni, Ivano Mezzaroma","doi":"10.1097/QAD.0000000000004028","DOIUrl":"https://doi.org/10.1097/QAD.0000000000004028","url":null,"abstract":"<p><strong>Objective: </strong>To evaluate the association between increased epicardial fat thickness (EFT) and liver stiffness measurement (LSM), as assessed by elastography in people living with Human Immunodeficiency Virus type 1 (HIV-1) infection (PWH).</p><p><strong>Methods: </strong>91 PWH on effective antiretroviral treatment (ART) were enrolled. EFT was measured by transthoracic echocardiography. Liver steatosis was evaluated by ultrasound Hamaguchi criteria and LSM by elastography with Acoustic Radiation Force Impulse (ARFI) Tecnique. LSM ≥8 Kpa was suggestive of clinically relevant fibrosis.</p><p><strong>Results: </strong>Mean age was 54.3 years and 27.5% were women. EFT correlated with HIV-1 infection duration (rS 0.252, p = 0.016), age at study entry (rS 0.527, p < 0.001), BMI (rS 0.363, p < 0.001), waist circumference (rS 0.549, p < 0.001), HDL (rS -0.391, p < 0.001), triglycerides (rS 0.375, p < 0.001), Hamaguchi score (rS 0.279, p = 0.007), right lobe of the liver (rS 0.259, p = 0.014), Left ventricular mass/Body surface area (rS 0.220, p = 0.036).A LSM ≥8 Kpa was found in 20.9% of PWH, more commonly in those with EFT above the median >5.6 mm (30.4% vs 11.1%, p = 0.038). LSM significantly correlated with EFT (rS 0.274, p = 0.009), CD4+ cells (rS -0.320, p = 0.003) and nadir of CD4+ cells (rS -0.292, p = 0.007).In a subgroup (n = 53), an HOMA-IR index >2.33 identified increased EFT, (AUC 0.73, 95%CI 0.59-0.84, p = 0.001) while an HOMA-IR >3.27 predicted increased LSM (AUC 0.76, 95%CI 0.62-0.87, p = 0.005).</p><p><strong>Conclusions: </strong>PWH with increased EFT have worse metabolic profile and a high proportion of clinically relevant fibrosis at ARFI elastography, despite normal liver function tests. The HOMA-IR index might be used to identify PWH with increased EFT and liver fibrosis.</p>","PeriodicalId":7502,"journal":{"name":"AIDS","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2024-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142339223","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-27DOI: 10.1097/QAD.0000000000004025
Jeanne Brochon, Thierry Ducruet, Suzanne Taillefer, Valérie Lamarre, Christian Renaud, Marie-Elaine Metras, Christos Karatzios, Joseph H Puyat, Joel Singer, Silvie Valois, Hugo Soudeyns, Isabelle Boucoiran, Fatima Kakkar
Objectives: While studies have demonstrated increased morbidity and mortality risk in infancy among children who are HIV-exposed and uninfected (CHEU), longitudinal data are limited. The objective of this study was to assess long-term risk of hospitalization among CHEU compared to children who are HIV-unexposed and uninfected (CHUU), and determine risk factors for hospitalization among CHEU.
Design: Longitudinal cohort study (1988-2015) linking the Centre maternel et infantile sur le SIDA cohort (Montreal, Quebec) to administrative data from the Régie de l'assurance maladie du Québec (RAMQ), a universal health insurance provider in the province of Quebec.
Methods: CHEU from the CMIS cohort were matched 1:3 by age, sex and postal code with CHUU controls from the RAMQ database. Incidence and causes of hospitalization between CHEU and CHUU were compared using Poisson regression.
Results: 726 CHEU were matched to 2178 CHUU. Risk of first hospitalization was significantly higher among CHEU at 1 year (IRR 2.22, [1.86-2.66]), 5 years (IRR 1.62, [1.39-1.90]) and over the lifespan (IRR 1.55, [1.33-1.81]). Among CHEU, significant risk factors for hospitalization on univariate regression analysis included birth year before 2005, prematurity, small for gestational age (SGA), detectable maternal viral load (dVL) at delivery, and maternal hepatitis C co-infection. In the adjusted analysis, small for gestational age and dVL remained significant risk factors.
Conclusions: CHEU had a higher rate of hospitalization than CHUU controls across their lifespan. Significant risk factors included SGA and detectable maternal dVL, suggesting a need enhanced pediatric care for these children.
{"title":"Increased risk of hospitalization among children who were HIV-exposed and uninfected compared to population controls.","authors":"Jeanne Brochon, Thierry Ducruet, Suzanne Taillefer, Valérie Lamarre, Christian Renaud, Marie-Elaine Metras, Christos Karatzios, Joseph H Puyat, Joel Singer, Silvie Valois, Hugo Soudeyns, Isabelle Boucoiran, Fatima Kakkar","doi":"10.1097/QAD.0000000000004025","DOIUrl":"https://doi.org/10.1097/QAD.0000000000004025","url":null,"abstract":"<p><strong>Objectives: </strong>While studies have demonstrated increased morbidity and mortality risk in infancy among children who are HIV-exposed and uninfected (CHEU), longitudinal data are limited. The objective of this study was to assess long-term risk of hospitalization among CHEU compared to children who are HIV-unexposed and uninfected (CHUU), and determine risk factors for hospitalization among CHEU.</p><p><strong>Design: </strong>Longitudinal cohort study (1988-2015) linking the Centre maternel et infantile sur le SIDA cohort (Montreal, Quebec) to administrative data from the Régie de l'assurance maladie du Québec (RAMQ), a universal health insurance provider in the province of Quebec.</p><p><strong>Methods: </strong>CHEU from the CMIS cohort were matched 1:3 by age, sex and postal code with CHUU controls from the RAMQ database. Incidence and causes of hospitalization between CHEU and CHUU were compared using Poisson regression.</p><p><strong>Results: </strong>726 CHEU were matched to 2178 CHUU. Risk of first hospitalization was significantly higher among CHEU at 1 year (IRR 2.22, [1.86-2.66]), 5 years (IRR 1.62, [1.39-1.90]) and over the lifespan (IRR 1.55, [1.33-1.81]). Among CHEU, significant risk factors for hospitalization on univariate regression analysis included birth year before 2005, prematurity, small for gestational age (SGA), detectable maternal viral load (dVL) at delivery, and maternal hepatitis C co-infection. In the adjusted analysis, small for gestational age and dVL remained significant risk factors.</p><p><strong>Conclusions: </strong>CHEU had a higher rate of hospitalization than CHUU controls across their lifespan. Significant risk factors included SGA and detectable maternal dVL, suggesting a need enhanced pediatric care for these children.</p>","PeriodicalId":7502,"journal":{"name":"AIDS","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2024-09-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142339224","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-23DOI: 10.1097/QAD.0000000000004023
Michael J A Reid, Rebecca Bunnell, Marie Davis, Hillary Carter, Maureen Bartee, Tatiana Marrufo, John Nkengasong
{"title":"Sustaining two decades of PEPFAR's response to global HIV/AIDS: mitigating the impact of climate threats.","authors":"Michael J A Reid, Rebecca Bunnell, Marie Davis, Hillary Carter, Maureen Bartee, Tatiana Marrufo, John Nkengasong","doi":"10.1097/QAD.0000000000004023","DOIUrl":"10.1097/QAD.0000000000004023","url":null,"abstract":"","PeriodicalId":7502,"journal":{"name":"AIDS","volume":" ","pages":""},"PeriodicalIF":4.3,"publicationDate":"2024-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11562490/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142278969","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-18DOI: 10.1097/qad.0000000000004017
Jennifer O Lam,Craig E Hou,Catherine Lee,Zahra Samiezade-Yazd,Tory Levine,Michael A Horberg,Derek D Satre,Michael J Silverberg
OBJECTIVEHypertension is a major risk factor for dementia, but sustained blood pressure control is difficult to achieve. We evaluated whether inadequately controlled hypertension may contribute to excess dementia risk among people with HIV.DESIGNRetrospective cohort study.METHODSWe studied demographically matched people with and without HIV between 7/1/2013 and 12/31/2021 who were ≥50 years old and had a hypertension diagnosis but no dementia diagnosis. Hypertension control was calculated using a disease management index (DMI) which captured degree and duration above the hypertension treatment goals of systolic blood pressure (SBP) <140 mmHg and diastolic blood pressure (DBP) <90 mmHg. DMI values ranged from 0% to 100% (perfect control); hypertension was considered "inadequately controlled" if DMI<80% (i.e., in control for <80% of the time). Annual, time-updated DMI was calculated for SBP and DBP. Associations of SPB and DPB control with incident dementia were evaluated using extended Cox regression models.RESULTSThe study included 3,099 hypertensive people with HIV (mean age: 58.3 years, 90.2% men) and 66,016 people without HIV. Each year of inadequate SBP control was associated with greater dementia risk in both people with HIV (adjusted hazard ratio [aHR] = 1.26, 0.92-1.64) and people without HIV (aHR = 1.27 (1.21-1.33); p-interaction = 0.85). Similarly, inadequate DBP control was associated with greater dementia risk in both people with HIV (aHR = 1.43, 0.90-1.95) and people without HIV (aHR = 1.71, 1.50-1.93; p-interaction = 0.57).CONCLUSIONSFindings suggest the association of inadequate hypertension control with greater dementia risk is similar by HIV status. Stronger associations of DBP control with dementia merits further investigation.
{"title":"Hypertension control and risk of age-associated dementia in people with hiv infection.","authors":"Jennifer O Lam,Craig E Hou,Catherine Lee,Zahra Samiezade-Yazd,Tory Levine,Michael A Horberg,Derek D Satre,Michael J Silverberg","doi":"10.1097/qad.0000000000004017","DOIUrl":"https://doi.org/10.1097/qad.0000000000004017","url":null,"abstract":"OBJECTIVEHypertension is a major risk factor for dementia, but sustained blood pressure control is difficult to achieve. We evaluated whether inadequately controlled hypertension may contribute to excess dementia risk among people with HIV.DESIGNRetrospective cohort study.METHODSWe studied demographically matched people with and without HIV between 7/1/2013 and 12/31/2021 who were ≥50 years old and had a hypertension diagnosis but no dementia diagnosis. Hypertension control was calculated using a disease management index (DMI) which captured degree and duration above the hypertension treatment goals of systolic blood pressure (SBP) <140 mmHg and diastolic blood pressure (DBP) <90 mmHg. DMI values ranged from 0% to 100% (perfect control); hypertension was considered \"inadequately controlled\" if DMI<80% (i.e., in control for <80% of the time). Annual, time-updated DMI was calculated for SBP and DBP. Associations of SPB and DPB control with incident dementia were evaluated using extended Cox regression models.RESULTSThe study included 3,099 hypertensive people with HIV (mean age: 58.3 years, 90.2% men) and 66,016 people without HIV. Each year of inadequate SBP control was associated with greater dementia risk in both people with HIV (adjusted hazard ratio [aHR] = 1.26, 0.92-1.64) and people without HIV (aHR = 1.27 (1.21-1.33); p-interaction = 0.85). Similarly, inadequate DBP control was associated with greater dementia risk in both people with HIV (aHR = 1.43, 0.90-1.95) and people without HIV (aHR = 1.71, 1.50-1.93; p-interaction = 0.57).CONCLUSIONSFindings suggest the association of inadequate hypertension control with greater dementia risk is similar by HIV status. Stronger associations of DBP control with dementia merits further investigation.","PeriodicalId":7502,"journal":{"name":"AIDS","volume":"44 1","pages":""},"PeriodicalIF":3.8,"publicationDate":"2024-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142261358","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-16DOI: 10.1097/QAD.0000000000004016
Edgar T Overton, Amy Kantor, Kathleen V Fitch, Mosepele Mosepele, Judith A Aberg, Carl J Fichtenbaum, Grace A McComsey, Carlos Malvestutto, Michael T Lu, Eugenia Negredo, Jose Bernardino, Aubri B Hickman, Pamela S Douglas, Steven K Grinspoon, Markella Zanni, Heather Ribaudo, Christina Wyatt
Objectives: To determine baseline prevalence of proteinuria and albuminuria among REPRIEVE participants and evaluate associated risk factors.
Design: Cross sectional analysis of a baseline sample of participants from the REPRIEVE Trial.
Methods: REPRIEVE is an international primary cardiovascular prevention RCT of pitavastatin calcium vs. placebo among PWH on antiretroviral therapy. A representative subset (2791 participants) had urine collected at study entry. Urine protein to creatinine ratios (uPCR) and albumin to creatinine ratios (uACR) were classified as normal, moderately increased and severely increased. These were dichotomized to Normal or Abnormal for log-binomial regression analysis. Demographic, cardiometabolic, and HIV-specific data were compared among those with normal versus abnormal results.
Results: Overall, median age 49 years, 41% female sex, 47% black or African American race, 36% had eGFR <90 mL/min/1.73 mm2. For uPCR, 27% had moderately or severely increased values. For uACR, 9% had moderately or severely increased values. In the fully adjusted model for proteinuria, female sex, older age, residence in sub-Saharan Africa or East Asia, lower BMI, lower CD4 cell count, and use of TDF were associated with abnormal values. In the fully adjusted model for albuminuria, a diagnosis of HTN was associated with abnormal values.
Conclusions: Abnormal proteinuria and albuminuria remain common (27% and 9%) despite controlled HIV. Lower current CD4 count and TDF use were strongly associated with proteinuria. Certain modifiable comorbidities, including HTN and smoking, were associated with abnormal values. In PWH with preserved eGFR, urine measures identify subclinical kidney disease and afford the opportunity for intervention.
{"title":"Proteinuria and albuminuria among a global primary CVD prevention cohort of PWH: prevalence and associated factors.","authors":"Edgar T Overton, Amy Kantor, Kathleen V Fitch, Mosepele Mosepele, Judith A Aberg, Carl J Fichtenbaum, Grace A McComsey, Carlos Malvestutto, Michael T Lu, Eugenia Negredo, Jose Bernardino, Aubri B Hickman, Pamela S Douglas, Steven K Grinspoon, Markella Zanni, Heather Ribaudo, Christina Wyatt","doi":"10.1097/QAD.0000000000004016","DOIUrl":"10.1097/QAD.0000000000004016","url":null,"abstract":"<p><strong>Objectives: </strong>To determine baseline prevalence of proteinuria and albuminuria among REPRIEVE participants and evaluate associated risk factors.</p><p><strong>Design: </strong>Cross sectional analysis of a baseline sample of participants from the REPRIEVE Trial.</p><p><strong>Methods: </strong>REPRIEVE is an international primary cardiovascular prevention RCT of pitavastatin calcium vs. placebo among PWH on antiretroviral therapy. A representative subset (2791 participants) had urine collected at study entry. Urine protein to creatinine ratios (uPCR) and albumin to creatinine ratios (uACR) were classified as normal, moderately increased and severely increased. These were dichotomized to Normal or Abnormal for log-binomial regression analysis. Demographic, cardiometabolic, and HIV-specific data were compared among those with normal versus abnormal results.</p><p><strong>Results: </strong>Overall, median age 49 years, 41% female sex, 47% black or African American race, 36% had eGFR <90 mL/min/1.73 mm2. For uPCR, 27% had moderately or severely increased values. For uACR, 9% had moderately or severely increased values. In the fully adjusted model for proteinuria, female sex, older age, residence in sub-Saharan Africa or East Asia, lower BMI, lower CD4 cell count, and use of TDF were associated with abnormal values. In the fully adjusted model for albuminuria, a diagnosis of HTN was associated with abnormal values.</p><p><strong>Conclusions: </strong>Abnormal proteinuria and albuminuria remain common (27% and 9%) despite controlled HIV. Lower current CD4 count and TDF use were strongly associated with proteinuria. Certain modifiable comorbidities, including HTN and smoking, were associated with abnormal values. In PWH with preserved eGFR, urine measures identify subclinical kidney disease and afford the opportunity for intervention.</p>","PeriodicalId":7502,"journal":{"name":"AIDS","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2024-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142278968","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-16DOI: 10.1097/QAD.0000000000004015
Anjana Yadav, Gabrielle Gionet, Antoneta Karaj, Andrew V Kossenkov, Toshitha Kannan, Mary E Putt, Alisa J Stephens Shields, Rebecca L Ashare, Ronald G Collman
Objective: People with HIV (PWH) experience excess comorbidities, including neurocognitive disorders, which are linked to inflammation, particularly monocyte-macrophage activation. Smoking contributes to morbidity and mortality in well-treated PWH. We investigated associations between smoking, neurocognitive function, and inflammation in PWH on ART.
Design: We used baseline data on cognition and inflammation from a longitudinal study of virologically-suppressed PWH who do and do not smoke.
Methods: Participants completed 4 neurocognitive tests (7 measures), with a composite score as the primary measure. Inflammatory markers were plasma sCD14, sCD163, and CCL2/MCP-1; %CD14+ monocytes expressing CD16, CD163, and CCR2; and %CD8+ T cells co-expressing CD38/HLA-DR. Exploratory analyses included a plasma cytokine/chemokine panel, neurofilament light chain (NFL), hsCRP and monocyte transcriptomes by RNAseq.
Results: We recruited 58 PWH (26 current smoking [PWH/S], 32 no current smoking [PWH/NS]). Mean composite and individual neurocognitive scores did not differ significantly by smoking status except for the color shape task; PWH/S exhibited worse cognitive flexibility, with adjusted mean times 317.2 (95%CI 1.4, 632.9) msec longer than PWH/NS. PWH/S had higher plasma sCD14 than PWH/NS (median(IQR) 1820(1678, 2105) versus 1551(1284, 1760) ng/ml, p=0.009). Other inflammatory markers were not significantly different between PWH/S and PWH/NS. Monocyte transcriptomes showed several functions, regulators and gene sets that differed by smoking status.
Conclusions: sCD14, a marker of monocyte activation, is elevated in PWH who smoke. While neurocognitive measures and other inflammatory markers did not generally differ, these data implicate smoking-related myeloid activation and monocyte gene dysregulation in the HIV/smoking synergy driving HIV-associated comorbidities.
{"title":"Association of smoking with neurocognition, inflammatory and myeloid cell activation profiles in people with HIV on ART.","authors":"Anjana Yadav, Gabrielle Gionet, Antoneta Karaj, Andrew V Kossenkov, Toshitha Kannan, Mary E Putt, Alisa J Stephens Shields, Rebecca L Ashare, Ronald G Collman","doi":"10.1097/QAD.0000000000004015","DOIUrl":"https://doi.org/10.1097/QAD.0000000000004015","url":null,"abstract":"<p><strong>Objective: </strong>People with HIV (PWH) experience excess comorbidities, including neurocognitive disorders, which are linked to inflammation, particularly monocyte-macrophage activation. Smoking contributes to morbidity and mortality in well-treated PWH. We investigated associations between smoking, neurocognitive function, and inflammation in PWH on ART.</p><p><strong>Design: </strong>We used baseline data on cognition and inflammation from a longitudinal study of virologically-suppressed PWH who do and do not smoke.</p><p><strong>Methods: </strong>Participants completed 4 neurocognitive tests (7 measures), with a composite score as the primary measure. Inflammatory markers were plasma sCD14, sCD163, and CCL2/MCP-1; %CD14+ monocytes expressing CD16, CD163, and CCR2; and %CD8+ T cells co-expressing CD38/HLA-DR. Exploratory analyses included a plasma cytokine/chemokine panel, neurofilament light chain (NFL), hsCRP and monocyte transcriptomes by RNAseq.</p><p><strong>Results: </strong>We recruited 58 PWH (26 current smoking [PWH/S], 32 no current smoking [PWH/NS]). Mean composite and individual neurocognitive scores did not differ significantly by smoking status except for the color shape task; PWH/S exhibited worse cognitive flexibility, with adjusted mean times 317.2 (95%CI 1.4, 632.9) msec longer than PWH/NS. PWH/S had higher plasma sCD14 than PWH/NS (median(IQR) 1820(1678, 2105) versus 1551(1284, 1760) ng/ml, p=0.009). Other inflammatory markers were not significantly different between PWH/S and PWH/NS. Monocyte transcriptomes showed several functions, regulators and gene sets that differed by smoking status.</p><p><strong>Conclusions: </strong>sCD14, a marker of monocyte activation, is elevated in PWH who smoke. While neurocognitive measures and other inflammatory markers did not generally differ, these data implicate smoking-related myeloid activation and monocyte gene dysregulation in the HIV/smoking synergy driving HIV-associated comorbidities.</p>","PeriodicalId":7502,"journal":{"name":"AIDS","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2024-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142278966","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-16DOI: 10.1097/QAD.0000000000004014
Thor Ueland, Isaac Nkele, Hedda Hoel, Shahin Lockman, Annika E Michelsen, Thato Moshomo, Pål Aukrust, Terence Mohammed, Marius Trøseid, Mosepele Mosepele
Background: HIV is associated with increased risk of cardiovascular disease. We investigated soluble markers of extracellular matrix (ECM) remodeling and inflammation in relation to presence of carotid plaques in a well-characterized adult cross-sectional study of people with HIV (PWH) and matched people without HIV in Botswana.
Methods: Using enzyme immunoassays we analyzed plasma ECM remodeling mediators including Galectin-3 (GAL-3), Cystatin B (CysB) and Growth/differentiation factor 15 (GDF-15) and the inflammatory marker IL-18 in 196 without HIV and 197 PWH of which 36 were ART-naïve.
Results: We found i) PWH had higher plasma levels of the ECM markers GAL-3 and CysB and the NLRP3 inflammasome activation marker IL-18, mainly in ART naïve participants, ii) PWH on ART had markedly higher GDF-15, associated with use of first generation nucleoside analogs; iii) high levels of CysB and IL-18 correlated with presence of carotid plaques.
Conclusion: In PWH, high levels of CysB and IL-18 were associated with the presence of carotid plaques. For IL-18 this was observed in the study population as a whole, while the association for CysB was restricted to PWH.
{"title":"Markers of extracellular matrix degradation and inflammasome activation are associated with carotid plaques in virally suppressed people with HIV in Botswana.","authors":"Thor Ueland, Isaac Nkele, Hedda Hoel, Shahin Lockman, Annika E Michelsen, Thato Moshomo, Pål Aukrust, Terence Mohammed, Marius Trøseid, Mosepele Mosepele","doi":"10.1097/QAD.0000000000004014","DOIUrl":"https://doi.org/10.1097/QAD.0000000000004014","url":null,"abstract":"<p><strong>Background: </strong>HIV is associated with increased risk of cardiovascular disease. We investigated soluble markers of extracellular matrix (ECM) remodeling and inflammation in relation to presence of carotid plaques in a well-characterized adult cross-sectional study of people with HIV (PWH) and matched people without HIV in Botswana.</p><p><strong>Methods: </strong>Using enzyme immunoassays we analyzed plasma ECM remodeling mediators including Galectin-3 (GAL-3), Cystatin B (CysB) and Growth/differentiation factor 15 (GDF-15) and the inflammatory marker IL-18 in 196 without HIV and 197 PWH of which 36 were ART-naïve.</p><p><strong>Results: </strong>We found i) PWH had higher plasma levels of the ECM markers GAL-3 and CysB and the NLRP3 inflammasome activation marker IL-18, mainly in ART naïve participants, ii) PWH on ART had markedly higher GDF-15, associated with use of first generation nucleoside analogs; iii) high levels of CysB and IL-18 correlated with presence of carotid plaques.</p><p><strong>Conclusion: </strong>In PWH, high levels of CysB and IL-18 were associated with the presence of carotid plaques. For IL-18 this was observed in the study population as a whole, while the association for CysB was restricted to PWH.</p>","PeriodicalId":7502,"journal":{"name":"AIDS","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2024-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142278967","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}