Antiretroviral Therapy Era Research Articles

A retrospective study of distribution of HIV associated malignancies among inpatients from 2007 to 2020 in China

HIV-associated malignancies are responsible for morbidity and mortality increasingly in the era of potent antiretroviral therapy. This study aimed to investigate the distribution of HIV-associated malignancies among inpatients, the immunodeficiency and the effect of antiretroviral therapy (ART) on spectrum of HIV-associated malignancies. A total of 438 cases were enrolled from 2007 to 2020 in Beijing Ditan Hospital. Demographic, clinical and laboratory data, managements, and outcomes were collected and analyzed retrospectively. Of 438 cases, 433 were assigned to non-AIDS-defining cancers (NADCs) (n = 200, 45.7%) and AIDS-defining cancers (ADCs) (n = 233, 53.2%), 5 (1.1%) with lymphoma were not specified further. No significant change was observed in the proportion of NADCs and ADCs as time goes on. Of NADCs, lung cancer (n = 38, 19%) was the most common type, followed by thyroid cancer (n = 17, 8.5%). Patients with ADCs had lower CD4 counts(104.5/μL vs. 314/μL), less suppression of HIVRNA(OR 0.23, 95%CI 0.16–0.35) compared to those with NADCs. ART did not affect spectrum of NADCs, but affect that of ADCs (between patients with detectable and undetectable HIVRNA). ADCs remain frequent in China, and NADCs play an important role in morbidity and mortality of HIV positive population.

A Lower CD4 Count Predicts Most Causes of Death except Cardiovascular Deaths. The Austrian HIV Cohort Study.

(1) Objective: To investigate changes in mortality rates and predictors of all-cause mortality as well as specific causes of death over time among HIV-positive individuals in the combination antiretroviral therapy (cART) era. (2) Methods: We analyzed all-cause as well as cause-specific mortality among the Austrian HIV Cohort Study between 1997 and 2014. Observation time was divided into five periods: Period 1: 1997–2000; period 2: 2001–2004; period 3: 2005–2008; period 4: 2009–2011; and period 5: 2012–2014. Mortality rates are presented as deaths per 100 person-years (d/100py). Potential risk factors associated with all-cause mortality and specific causes of death were identified by using multivariable Cox proportional hazard models. Models were adjusted for time-updated CD4, age and cART, HIV transmission category, population size of residence area and country of birth. To assess potential nonlinear associations, we fitted all CD4 counts per patient using restricted cubic splines with truncation at 1000 cells/mm3. Vital status of patients was cross-checked with death registry data. (3) Results: Of 6848 patients (59,704 person-years of observation), 1192 died: 380 (31.9%) from AIDS-related diseases. All-cause mortality rates decreased continuously from 3.49 d/100py in period 1 to 1.40 d/100py in period 5. Death due to AIDS-related diseases, liver-related diseases and non-AIDS infections declined, whereas cardiovascular diseases as cause of death remained stable (0.27 d/100py in period 1, 0.10 d/100py in period 2, 0.16 d/100py in period 3, 0.09 d/100py in period 4 and 0.14 d/100py in period 5) and deaths due to non-AIDS-defining malignancies increased. Compared to latest CD4 counts of 500 cells/mm3, lower CD4 counts conferred a higher risk of deaths due to AIDS-related diseases, liver-related diseases, non-AIDS infections and non-AIDS-defining malignancies, whereas no significant association was observed for cardiovascular mortality. Results were similar in sensitivity analyses where observation time was divided into two periods: 1997–2004 and 2005–2014. (4) Conclusions: Since the introduction of cART, risk of death decreased and causes of death changed. We do not find evidence that HIV-positive individuals with a low CD4 count are more likely to die from cardiovascular diseases.

Decreasing Incidence and Determinants of Bacterial Pneumonia in People With HIV: The Swiss HIV Cohort Study.

Bacterial pneumonia is a leading reason for hospitalization among people with HIV (PWH); however, evidence regarding its drivers in the era of potent antiretroviral therapy is limited. We assessed risk factors for bacterial pneumonia in the Swiss HIV Cohort Study using marginal models. We further assessed the relationship between risk factors and changes in bacterial pneumonia incidence using mediation analysis. We included 12927 PWH with follow-ups between 2008 and 2018. These patients had 985 bacterial pneumonia events during a follow-up of 100779 person-years. Bacterial pneumonia incidence significantly decreased from 13.2 cases/1000 person-years in 2008 to 6.8 cases/1000 person-years in 2018. Older age, lower education level, intravenous drug use, smoking, lower CD4-cell count, higher HIV load, and prior pneumonia were significantly associated with higher bacterial pneumonia incidence. Notably, CD4 cell counts 350-499 cells/μL were significantly associated with an increased risk compared to CD4 ≥ 500 cells/µL (adjusted hazard ratio, 1.39; 95% confidence interval, 1.01-1.89). Decreasing incidence over the last decade can be explained by increased CD4-cell counts and viral suppression and decreased smoking frequency. Improvements in cascade of care of HIV and decrease in smoking may have mediated a substantial decrease in bacterial pneumonia incidence.

Soluble Biomarkers of Cognition and Depression in Adults with HIV Infection in the Combination Therapy Era.

Cognitive impairment and depression continue to be common among people with HIV (PWH) in the combination antiretroviral therapy (ART) era. A better understanding of the biological mechanisms that may underpin these disorders is needed. The purpose of this review is to describe published findings on soluble biomarkers from blood and cerebrospinal fluid (CSF) that have been associated with either cognition or depression among PWH in the setting of ART. Several biomarkers, including those that reflect viral persistence, monocyte/macrophage activation, and other processes, are associated with cognition and depressive symptoms. Some but not all results have been consistent across multiple studies. More research has been published on biomarkers of cognition relative to biomarkers of depression (particularly from CSF). More studies are needed that investigate multiple biomarkers to understand the role of distinct but additive pathways in these disorders and to guide the development of new therapies.

A Meta-Analytic Review of the Effect of Antiretroviral Therapy on Neurocognitive Outcomes in Adults Living with HIV-1 in Low-and Middle-Income Countries.

HIV-associated neurocognitive impairment remains a challenge even in the era of antiretroviral therapy (ART). Over 90% of people living with HIV are in low- and middle-income countries. Hence, it is not surprising that such countries bear a considerable burden of comorbidities like HIV-associated neurocognitive impairment despite an overall increase in life expectancy. The literature suggests differences in patient characteristics, clinical profile, prevalent HIV subtypes, treatment choices, pharmacogenetics, and socioeconomic factors between low- and middle-income countries compared with high-income countries. Therefore, we aimed to evaluate the effect of ART on neurocognitive outcomes in low- and middle-income countries. A comprehensive search of five databases (PubMed, CINAHL, CENTRAL, PsychInfo, Google scholar) for studies published between 1996 to 2020 was performed to identify studies that reported neurocognitive outcomes in ART-treated and ART naïve HIV positive individuals. Two independent reviewers conducted study screening, data extraction, and evaluation of the risk of bias. Pooled effect size estimates (Hedges' g) and 95% CI were computed using random-effects models. Sensitivity analysis, subgroup analysis, meta-regression, and evaluation of publication bias were also conducted. Forty studies (24 cross-sectional, 13 longitudinal studies, and two randomized controlled trials) contributed to a series of meta-analyses. We found significant small to moderate effects of antiretroviral therapy for global cognition (Hedges' g observed = 0.30; 95% CI: 0.15, 0.44; k = 25; p = 0.0003; I2 = 92.1%; tau = 0.32; Q = 305.1), executive function (Hedges' g = 0.24, 95%CI: 0.02,0.46; p-0.04; k = 8; I2 = 37.5%; tau = 0.23; Q = 11.2), and speed of information processing (Hedges' g = 0.25, 95% CI: 0.05, 0.45; k = 9; p = 0.02; I2 = 86.4%; tau = 0.21; Q = 58.9). We found no significant ART effect on attention-working memory, learning and memory, motor function, and verbal fluency. No significant effect was seen with the duration of therapy, efavirenz use, and Central Penetrating Effectiveness (CPE) of antiretroviral therapy. Subgroup analyses identified study design (between-group and within-group; cross-sectional and longitudinal) and normative scores as significant sources of heterogeneity. Meta-regression analysis indicated that nadir CD4 modified the magnitude of ART's effect on cognitive outcomes. Age, gender, and country income-group were not significant moderators. Our findings provide systematic evidence that antiretroviral therapy improves neurocognitive outcomes in the domains of global cognition, executive function and speed of information processing, of people living with HIV in low- and middle-income countries, especially those with advanced immunosuppression. However, these findings are not definitive as they are limited by the probability of publication bias, high heterogeneity, and exclusion of significant confounders. Prospero registration number: CRD42020203791.

Serious adverse drug reactions in sub-Saharan Africa in the era of antiretroviral treatment: A systematic review.

We aimed to summarize and describe the burden of serious adverse drug reactions (ADRs) in sub‐Saharan Africa (SSA) in the era of antiretroviral therapy. We searched Medline, CINAHL, Africa‐Wide Information, Scopus, and Web of Science, without language restriction up to March 2021. We hand‐searched reference lists, conference abstracts, and dissertation databases. We included studies reporting proportions of admissions attributed to ADRs, admissions prolonged by ADRs, or in‐hospital deaths attributed to ADRs. Two reviewers independently screened the studies, reviewed the study quality using a previously published tool, and extracted the data. We tested for heterogeneity using I2‐statistics and summarized the study results using medians and interquartile ranges. Subgroup analyses summarized the results by study quality, setting, methodology, and population. From 1005 unique references identified, we included 15 studies. Median study quality was 7/10; heterogeneity was very high. Median [IQR] proportion of admissions attributed to ADRs was 4.8% [1.5% to 7.0%] (14 studies) and 6.4% [4.0% to 8.4%] in nine active surveillance studies in adults. Two pediatric studies reported the proportion of admissions prolonged by ADRs (0.29% and 0.99%). Three studies reported the proportion of in‐hospital deaths attributed to ADRs (2.5%, 13%, and 16%). Antiretroviral and antituberculosis drugs were often implicated in serious ADRs. Evidence of the burden of serious ADRs in SSA is patchy and heterogeneous. A few high‐quality studies suggest that the burden is considerable, and that it reflects the regional impact of the HIV pandemic. Further characterization of this burden is required, ideally in studies of standardized methodology.

Impact of Direct-Acting Antivirals on the Outcome of HIV/HCV Coinfected Patients with Non-Hodgkin Lymphomas in the Modern Anti-Retroviral Therapy Era: A Retrospective Multicenter Study of 74 Cases

Impact of Direct-Acting Antivirals on the Outcome of HIV/HCV Coinfected Patients with Non-Hodgkin Lymphomas in the Modern Anti-Retroviral Therapy Era: A Retrospective Multicenter Study of 74 Cases

Comparative Analysis of Mature T-Cell and NK/T-Cell Lymphomas in Patients with and without HIV: Results from the NA-Accord and Complete Cohorts

Background: Clinicopathological characteristics and prognosis for patients with HIV (PWH) and T-cell lymphomas (TCLs) in the current antiretroviral therapy (ART) era remains unknown. The primary objective of this study was to determine outcomes of patients with mature T and NK/T-cell lymphomas with and without HIV (PWoH) in North America. A secondary objective was to define variations in the survival of patients with TCLs and AIDS-defining B-cell lymphomas (A-BCLs) in the presence of ART.Methods: The study population included patients from two source populations, the NA-ACCORD (The North American AIDS Cohort Collaboration on Research and Design) and COMPLETE (Comprehensive Oncology Measures for Peripheral T-cell Lymphoma), both of which have been previously described. The NA-ACCORD collaborates with >20 longitudinal cohorts of adults (aged ≥ 18 years) with HIV in the United States and Canada. Within the NA-ACCORD cohort, we included patients with a validated incidental diagnosis of mature T and NK/TCL (n=52) or the most common A-BCLs including Burkitt's lymphoma (n=101), diffuse large B-cell lymphoma (DLBCL, n=500) and primary CNS lymphoma (PCNSL, n=64) between 1996 and 2016. COMPLETE is a prospective, multicenter cohort study of patients with newly diagnosed incidental mature TCLs in the United States between 2010 and 2014. Of the 452 eligible patients, 450 were included for analysis after exclusion of two patients with HIV infection. Patients were followed from diagnosis to the first of death, loss to follow-up or administrative censoring at 5 years. Kaplan-Meier and log-rank tests were used to estimate and compare survival.Results: At the time of TCL diagnosis, PWH were significantly younger than patients without HIV (PWoH) (49 years vs. 60 years respectively; p<0.001). PWH were predominantly men (96% vs. 63%; p<0.001), of white race (64% vs. 77%; p<0.006), with chronic kidney disease (19% vs. 2.2%; p<0.001) and with co-infections such as hepatitis B virus (13% vs. 0.9%; p<0.001) and hepatitis C virus (19% vs. 1.1%; p<0.001). Anaplastic large-cell lymphoma (ALCL, n=26) was the most common histological subtype within PWH relative to peripheral T-cell lymphoma-not otherwise specified (PTCL-NOS, n=143) among PWoH. More than 92% of the patients within the NA-ACCORD cohort were on at least one class of ART during their cohort enrollment period. Median duration of ART prior to lymphoma diagnosis was 2.9 years (0.7-9.4) and comparable for patients with TCLs and A-BCLs. The median time from NA-ACCORD cohort enrollment to lymphoma diagnosis was 2.3 years (IQR: 0.3-5.9 years) for TCLs and comparable for patients with the A-BCL subgroups (2.8 years, IQR: 0.6-7.2 years; p=0.21).At the end of the 5-year follow-up period, the survival probability since TCL diagnosis was markedly lower at 0.32 (95% confidence interval [CI]: 0.21-0.49) among PWH in contrast to 0.45 (95% CI: 0.41-0.51) for PWoH. Specifically, survival probability since ALCL diagnosis was distinctively lower at 0.23 (95% CI: 0.11-0.47) among PWH in contrast to 0.76 (95% CI: 0.66-0.87) for PWoH. Mortality following lymphoma diagnosis was elevated for PWH vs. PWoH even after adjusting for statistically significant baseline clinical characteristics such as age, race, and ALCL status in multivariate analysis (adjusted HR: 1.92; 95% CI: 1.27, 2.91). Among PWH with TCL, CD4 <200 and viral load (VL) >500 (n=10) was associated with a lower survival relative to those with counts >200 and/or VL <500 (n=12, p=0.031). Upon stratification of PWH into different calendar periods based on year of diagnosis (1996-1999 vs. 2000-2009 vs. 2010-2016), we observed an improvement in survival for all subgroups over time. Overall, among PWH, PCNSL had the worst median overall survival (3.8 months, 95% Cl: 2.0-7.2 months) followed by ALCL (10.6 months, 95% Cl: 2.1-33.4 months), DLBCL (15.6 months, 95% CI: 12.7-22.2 months) and Burkitt's lymphoma.Conclusions: Our report based on two large observational cohorts in North America highlights poor outcomes for TCLs among PWH compared to PWoH. In addition, within the PWH group, our study is the first to delineate inferior survival for patients with ALCLs relative to DLBCL and Burkitt's lymphoma accentuating the need for novel therapies. However, the overall prognosis for these lymphomas among PWH has improved in the last two decades, particularly among those with CD4>200, underscoring the impact of early and sustained ART. DisclosuresAlonso: Merck: Research Funding. Foss: Kyowa: Honoraria; Acrotech: Honoraria, Speakers Bureau; Seattle Genetics: Honoraria, Speakers Bureau; Mallinckrodt: Honoraria; Daiichi Sankyo: Honoraria; Kura: Honoraria. Jain: Trillium Therapeutics, Inc: Research Funding; Acro Biotech, Inc: Research Funding; Abcuro, Inc: Research Funding.

Changing Patterns of Lymphoma in the Antiretroviral Therapy Era in Johannesburg, South Africa.

South Africa has a high HIV prevalence, which associates with an increased risk of lymphoma. Antiretroviral therapy (ART) became accessible in 2004, but the program has substantially expanded. Changes in lymphoma patterns are documented in high-income countries after wide-scale ART including declining high-grade B-cell non-Hodgkin lymphomas (HG B-NHLs), particularly diffuse large B-cell lymphoma, and increased Hodgkin lymphoma (HL). There are limited data from Africa. This study aimed to compare HG B-NHL characteristics in the early (2007) and later (2017) ART era. All incident lymphomas at the National Health Laboratory Service, Johannesburg, were identified using the laboratory information system, and data were collected for each patient. The total number of lymphoma cases increased from 397 (2007) to 582 (2017). This was associated with improved lymphoma classification and patient referral for oncological care. HG B-NHL remained the most diagnosed lymphoma subtype in 2017 comprising 70% of HIV-associated lymphomas, followed by HL (24%). Diffuse large B-cell lymphoma comprised 65% of all HG B-NHLs and 45% of all lymphomas in people with HIV in 2017. Significantly more patients were on ART in 2017, with improvements in virological control documented. Despite this, 47.6% of patients were not virologically suppressed, and 37.5% of patients were ART-naive at time of diagnosis in 2017. Immunological reconstitution was suboptimal, which may reflect late initiation of ART. Public health initiatives to initiate ART as early as possible and to retain patients in ART programs may assist in decreasing the number of HIV-associated lymphomas in our setting.

Cause of hospitalization and death in the antiretroviral era in Sub-Saharan Africa published 2008-2018: A systematic review.

Background:Worldwide despite the availability of antiretroviral therapy, human immunodeficiency virus/acquired immunodeficiency syndrome still causes morbidity and mortality among patients. In Sub-Saharan Africa, human immunodeficiency virus/acquired immunodeficiency syndrome remains a major public health concern. The aim of this study was to identify the causes of morbidity and mortality in the modern antiretroviral therapy era in Sub-Saharan Africa.Methods:We conducted a systematic review according to the Preferred Reporting Items for Systematic Review and Meta-Analysis guidelines. We searched relevant studies from 3 databases which are Google Scholar, PubMed, and CINAHL. Two review authors independently screened titles, abstracts, and full-text articles in duplicate, extracted data, and assessed bias. Discrepancies were resolved by discussion or arbitration of a third review author. R software version 3.6.2 was used to analyze the data. Maximum values were used in order to show which disease was mostly spread out by looking at the highest prevalence reported. This systematic review protocol was registered with the International Prospective Register of Systematic Reviews (PROSPERO).Results:A total of 409 articles were obtained from the database search, finally 12 articles met the inclusion criteria and were eligible for data extraction. Among them, 3 were conducted in Nigeria, 2 were conducted in Uganda, 3 were conducted in South Africa, 1 in Gabon, 1 in Ethiopia, 1 in Ghana, and 1 in Burkina Faso. In most of the included studies, tuberculosis was the leading cause of hospitalization which accounted for between 18% and 40.7% and it was also the leading cause of death and accounted for between 16% and 44.3%, except in 1 which reported anemia as the leading cause of hospitalization and in 2 which reported wasting syndrome and meningitis respectively as the leading causes of death. Opportunistic malignancies accounted between for 1.8% to 5% of hospitalization and 1.2% to 9.8% of deaths.Conclusions:Tuberculosis is the commonest cause of hospitalization and death in Sub-Saharan Africa, but it is always followed by other infectious disease and other non-AIDS related causes.

Allopregnanolone and neuroHIV: Potential benefits of neuroendocrine modulation in the era of antiretroviral therapy.

Forty years into the HIV pandemic, approximately 50% of infected individuals still suffer from a constellation of neurological disorders collectively known as ‘neuroHIV.’ Although combination antiretroviral therapy (cART) has been a tremendous success, in its present form, it cannot eradicate HIV. Reservoirs of virus reside within the central nervous system, serving as sources of HIV virotoxins that damage mitochondria and promote neurotoxicity. Although understudied, there is evidence that HIV or the HIV regulatory protein, trans‐activator of transcription (Tat), can dysregulate neurosteroid formation potentially contributing to endocrine dysfunction. People living with HIV commonly suffer from endocrine disorders, including hypercortisolemia accompanied by paradoxical adrenal insufficiency upon stress. Age‐related comorbidities often onset sooner and with greater magnitude among people living with HIV and are commonly accompanied by hypogonadism. In the post‐cART era, these derangements of the hypothalamic‐pituitary‐adrenal and ‐gonadal axes are secondary (i.e., relegated to the brain) and indicative of neuroendocrine dysfunction. We review the clinical and preclinical evidence for neuroendocrine dysfunction in HIV, the capacity for hormone therapeutics to play an ameliorative role and the future steroid‐based therapeutics that may have efficacy as novel adjunctives to cART.

A Cross-Sectional Study of Human Immunodeficiency Virus-Associated Neurocognitive Deficit in Central India.

BackgroundWith the advent of modern era of combination antiretroviral therapy (cART) and increased longevity of people living with human immunodeficiency virus (PLHIV), human immunodeficiency virus-associated neurocognitive disorder (HAND) is commonly observed. This study explores the prevalence of HAND and the demographic and treatment variables in people with HAND, in Central India.Research methodologyPLHIV on cART visiting HIV clinic underwent screening for substance abuse using CAGE-AID, and depression using PHQ-2 followed by PHQ-9. The screening rules out overt conditions which might interfere with cognitive abilities of the individual and thereby act as confounding factor. Thus, a sample population of 96 was obtained, on whom International HIV Dementia Scale (IHDS) was applied to screen for dementia. Out of 96, 16 individuals detected to suffer from HAND. Quality of Life was assessed by Patient’s Assessment of Own Functioning Inventory (PAOFI).ResultsPrevalence of HAND was estimated to be 16/96 (16.66%). It was more common amongst unmarried individuals (p < 0.001) and lower educational status (p < 0.01) among social variables; while shorter duration of ART (<3 years) (p < 0.01) and lower CD4 nadir (≤200 cell/mm3; p<0.01) showed significant correlation among clinical variables. PAOFI revealed significant association between HAND and quality of life (p-value < 0.01, CI = 95%). Modified Mental State Examination (3MS), which determines cognitive ability in various domains based on tasks, was mostly affected for - similarities and read and obey (for 43.75% population).ConclusionSocial and clinical variables play a significant role in development of HAND. Routine screening for HAND in PLHIV will help in early identification and management of the disease. The quality of life for those suffering from the burden of HIV and HAND can be significantly improved if approached and treated early in the course of the disease.

HIV-associated wasting prevalence in the era of modern antiretroviral therapy.

Objective:To understand the prevalence of HIV-associated wasting (HIVAW) in the United States.Design:Medical and pharmacy claims study using IBM MarketScan Commercial, Medicare Supplemental and Medicaid Databases.Methods:Study period: July 2012–September 2018 (first HIV diagnosis claim = HIV index date). People with HIV (PWH) were excluded if they were aged less than 18 years, had any malignancy claim or had less than 6 months of enrollment data pre or post-HIV index date. HIVAW was defined by proxy using claims for weight loss–related diagnoses, appetite stimulant/nontestosterone anabolic agents or enteral/parenteral nutrition. Prevalence was reported cumulatively, by insurance type and antiretroviral therapy (ART) pharmacy claims (defined as ≥1 pharmacy claim of any ART within 12 months post-HIV index date). Statistical analysis assessed factors potentially associated with HIVAW.Results:The study population comprised 42 587 PWH (64.6% male, mean age 44 years, 67.5% on Medicaid, 63.9% on ART). Cumulative HIVAW prevalence (2012–2018) was 18.3% (n = 7804) for all PWH (17.9% on ART, 19.1% not on ART). HIVAW prevalence by payer was 7.5% for Commercial and Medicare Supplemental and 23.5% for Medicaid. The strongest associations with the likelihood of meeting the definition of HIVAW were for individuals with Medicaid and hospitalization(s) post-HIV index date; race and ART status were not associated.Conclusions:Findings suggest HIVAW remains prevalent in PWH. ART use was not found to be associated with HIVAW. HIVAW was highest among those with Medicaid coverage or any hospitalization(s). Further research is needed to better understand additional factors associated with and contributing to HIVAW.

Characteristics of new HIV diagnoses over 1995-2019: A clinic-based study in Montréal, Canada.

Characterization of populations at risk of acquiring HIV is required to inform the public health response to HIV. To identify potential changing needs in HIV prevention and care cascade, we aim to describe how the demographic profiles and exposure categories of newly diagnosed HIV positive individuals attending a large sexual health clinic in Montréal (Canada) evolved since the beginning of the antiretroviral therapy era in the mid-1990s. Using diagnosis data from participants of the Clinique médicale l'Actuel cohort of HIV-positive patients, we examined the distribution of exposure categories (sexual orientation, sexual behaviours, injection drug use, being born in an HIV-endemic country) by gender and year of diagnosis. Time trends in mean age and in the proportion of patients with late (CD4 <350 cells/μL) or advanced stage (CD4 <200 cells/μL) of HIV infection at diagnosis were assessed through meta-regressions. A total of 2,612 patients diagnosed with HIV between January 1st, 1995 and December 31st, 2019 were included. Overall, mean age was 35 years (standard deviation: 10 years) and remained stable over time. The proportion of patients with advanced stage of HIV infection decreased from 16% in 1995 to 4% in 2019. Although men who have sex with men (MSM) consistently accounted for the highest proportion of new diagnoses (77%, 2,022/2,612 overall), their proportion decreased since 2013. There was also a concomitant decrease in the proportion of people who inject drugs, with none of the newly diagnosed participants reporting injection drug use since 2017, and an important increase in the proportion of patients born in an HIV-endemic country (24%, 7/29 in 2019), especially among women. Compared to patients from non-endemic countries, those from HIV-endemic countries were characterized by higher proportions of heterosexuals (88% vs 17%) and of women (52% vs 7%), and were twice likely to get diagnosed at an advanced stage of HIV infection (32% vs 15%). In absolute numbers, MSM continue to account for the largest exposure category. However, patients from HIV-endemic countries, who tend to be diagnosed at later stages of HIV infection, constitute an increasing proportion of newly diagnosed individuals. These persons could face distinct barriers to rapid diagnosis. Tailoring HIV testing strategies and other prevention interventions to the specific unmet prevention needs of these individuals is warranted.

Cardiometabolic Complications in Youth With Perinatally Acquired HIV in the Era of Antiretroviral Therapy.

Antiretroviral therapy (ART) scale-up has dramatically reduced rates of pediatric HIV mortality and morbidity. Children living with perinatally acquired HIV (PHIV) are now expected to live through adolescence and well into adulthood, such that adolescents now represent the largest growing population living with HIV. This review aims to discuss the prevalence and mechanisms for cardiometabolic comorbidities in the setting of newer ART regimens and the research gaps that remain. Data highlight the continued risks of subclinical cardiometabolic complications in PHIV in the setting of newer ART. Novel techniques in imaging and omics may help identify early cardiometabolic abnormalities in this young population and potentially identify early changes in the mechanistic pathways related to these changes. Further studies to determine risk and management strategies of the cardiometabolic effects in PHIV adolescents, beyond ART, are warranted. Focus should be on prevention of these complications in youth to avoid new epidemic of diabetes and cardiovascular disease when these youths become aging adults.

The Integrity of Retinal Morphology in Non-immunocompromised People Living with HIV on Antiretroviral Therapy.

Non-immunocompromised people living with HIV (NIPLHIV) share a similar immunocompetence to non-HIV (HIV) people with an elevated cluster of differentiation 4 (CD4) count in the era of antiretroviral therapy (ART). This has reduced the incidence of HIV retinopathy, thus raising the question of the integrity of the retinal morphology in NIPLHIV with longer life expectancy. The study assessed the retinal thickness and volume of NIPLHIV without retinitis on ART and attempted to find associations with linear parameters of cerebral atrophy. The study was conducted at a public hospital in South Africa. All people living with HIV were on ART with CD4 counts above 350 cells/mm3 and viral loads less than 10,000 copies/mL. The Heidelberg Spectralis ocular coherence tomographer assessed the retinal thickness and volume for comparison between 30 NIPLHIV and 30 HIV-negative participants. A subset of the HIV group obtained a computed tomography scan to determine the bicaudate ratio and the sylvian fissure ratio to assess cerebral atrophy. Independent t tests were performed to identify differences in retinal thickness and volume. Multivariate linear regressions measured associations between retinal thickness and volume with cerebral atrophy. The NIPLHIV group had a thicker mean global temporal subfields at Early Treatment Diabetic Retinopathy Study (ETDRS) 3 mm (P = .047) and ETDRS 6 mm (P = .03). The mean global temporal subfield volume at ETDRS 3 mm was also increased in the NIPLHIV group (P = .02). Nasal macula retinal nerve fiber layer thickness and the inferior inner nuclear layer macula volume were directly related to the bicaudate ratio, whereas the volumes at the outer retinal layer subfields of the macula were inversely related to sylvian fissure ratio in NIPLHIV. Macula thickness and volumetric differences do exist in NIPLHIV. Practitioners should keep NIPLHIV under retinal morphometric surveillance because they live longer. Associations of cerebral atrophy with retinal morphology may be used to monitor cerebral atrophy in NIPLIV on ART.

Outcomes of men with HIV and germ cell cancer: Results from an international collaborative study.

Previous studies have shown that men with HIV and germ cell cancer (HIV-GCC) have inferior overall survival (OS) in comparison with their HIV-negative counterparts. However, little information is available on treatments and outcomes of HIV-GCC in the era of combination antiretroviral therapy (cART). This study examined men living with HIV who were 18 years old or older and had a diagnosis of histologically proven germ cell cancer (GCC). The primary outcomes were OS and progression-free survival (PFS). Data for 89 men with a total of 92 HIV-GCCs (2 synchronous GCCs and 1 metachronous bilateral GCC) were analyzed; among them were 64 seminomas (70%) and 28 nonseminomas (30%). The median age was 36 years, the median CD4 T-cell count at GCC diagnosis was 420 cells/µL, and 77% of the patients on cART had an HIV RNA load < 500 copies/mL. Stage I disease was found in 44 of 79 gonadal GCCs (56%). Among 45 cases with primary disseminated GCC, 78%, 18%, and 4% were assigned to the good-, intermediate-, and poor-prognosis groups, respectively, of the International Germ Cell Cancer Collaborative Group. Relapses occurred in 14 patients. Overall, 12 of 89 patients (13%) died. The causes of death were refractory GCC (n = 5), an AIDS-defining illness (n = 3), and other causes (n = 4). After a median follow-up of 6.5 years, the 5- and 10-year PFS rates were 81% and 73%, respectively, and the 5- and 10-year OS rates were 91% and 85%, respectively. The 5- and 10-year PFS and OS rates of men with HIV-GCC were similar to those reported for men with HIV-negative GCC. Patients with HIV-GCC should be managed identically to HIV-negative patients. Men living with HIV are at increased risk for germ cell cancer (GCC). Previous studies have shown that the survival of men with HIV-associated germ cell cancer (HIV-GCC) is poorer than the survival of their HIV-negative counterparts. This study examined the characteristics, treatments, and outcomes of 89 men with HIV-GCC in the era of effective combination antiretroviral therapies. The long-term outcomes of men with HIV-GCC were similar to those reported for men with HIV-negative GCC. Patients with HIV-GCC should be managed identically to HIV-negative patients.

Global Prevalence of Anemia and the Impact of Antiretroviral Therapy Among People Living With HIV: A Systematic Review and Meta-Analysis

Background: Anemia is the most frequent hematologic abnormalities among people living with human immunodeficiency virus (HIV) and is associated with HIV disease progression and high mortality of the patients. However, there is a wide variation of the prevalence of anemia among people living with HIV in different clinical settings and the impact of antiretroviral therapy (ART) on anemia is inconsistent. We aimed to obtain more precise estimates of prevalence of anemia and severity of anemia as well as the impact of ART among people living with HIV, which may be important for patients, caregivers, researchers and health policy-makers. Methods: We systematically searched PubMed, EMBASE, Web of Science, and Cochrane Library for original articles reporting the prevalence of anemia defined using age and sex-specific hemoglobin levels according to World Health Organization criteria among people living with HIV from inception to August 31, 2021. We used random effects meta-analyses to obtain pooled prevalence and 95% confidence intervals (CIs) of anemia and severity of anemia as well as odds ratio (OR) and 95% CI of association between ART and anemia among people living with HIV. Findings: We included 41 cross-sectional studies covering 143,357 people living with HIV. Among people living with HIV, the pooled prevalence of anemia was 47.30% (95% CI: 38.96%-55.63%) in overall, 42.77% (95% CI: 38.58%-47.96%) in males, and 48.61% (95% CI: 40.84%-58.37%) in females. The pooled prevalence of severity of anemia was 22.74% (95% CI: 20.76%-24.71%), 17.56% (95% CI: 12.74%-22.38%), and 4.33% (95% CI: 2.96%-5.69%) for mild, moderate and severe anemia, respectively. There was no significant association between ART and anemia (OR=0.80; 95% CI: 0.64, 1.01) among people living with HIV. Interpretation: Anemia is prevalent among people living with HIV and ART could not reduce the risk of anemia for patients. Thus, policies, strategies, and programs should be considered to identify the predictors of anemia among people living with HIV to reduce the burden of anemia among patients in the ART era. Funding Information: This work was supported by the National Natural Science Foundation of China (grant number: 71934002, 71874003) and National Key Research and Development Program of China (grant number: 2020YFC0846300). Declaration of Interests: The authors have no competing interests to declare.

Natural Bioactives as Potential Therapeutic Modalities Against NeuroAIDS.

With the introduction of antiretroviral therapy, the worldwide AIDS-related deaths have decreased, and life expectancy has increased, including the prevalence of AIDS-related neurological disorders or neuroAIDS. HIV-associated neurocognitive disorders such as mild neurocognitive disorder and asymptomatic neurocognitive impairment have largely remained stable or increased among the HIV-infected individuals in the combination antiretroviral therapy era. The emerging evidence that antiretrovirals with high CNS penetration effectiveness score contribute to the neurotoxicity and HIV-associated neurocognitive disorders has ushered the search for natural, nontoxic bioactive constituents having pre-established neuroprotective, anti-inflammatory, and restorative neurocognitive activity. In this review, we have highlighted the probable mechanism of neuroAIDS infection, the problem with the existing antiretroviral therapy, along with various bioactive constituents with in vivo, in vitro, or ex vivo evidence of their neuroprotective activity that can be used as an adjuvant with the current combination antiretroviral therapy regimen or can even serve as an alternate to the antiretrovirals for treatment of HIV associated neurocognitive disorder.

Web-Based Behavioral Intervention Utilizing Narrative Persuasion for HIV Prevention Among Chinese Men Who Have Sex With Men (HeHe Talks Project): Intervention Development.

BackgroundIn the era of potent antiretroviral therapy, a high level of condomless anal intercourse continues to drive increases in HIV incidence in recent years among men who have sex with men. Effective behavior change strategies for promoting HIV-preventive behaviors are warranted. Narrative persuasion is a novel health communication approach that has demonstrated its persuasive advantages in overcoming resistance to counterattitudinal messages. The efficacy of narrative persuasion in promoting health behavior changes has been well documented, but critical research gaps exist for its application to HIV prevention.ObjectiveIn this study, we aimed to (1) capitalize on narrative persuasion to design a web-based multisession intervention for reducing condomless anal intercourse among men who have sex with men in Hong Kong (the HeHe Talks Project) by following a systematic development process; and (2) describe the main components of the narrative intervention that potentially determine its persuasiveness.MethodsPersuasive themes and subtopics related to reducing condomless anal intercourse were initially proposed based on epidemiological evidence. The biographic narrative interview method was used to elicit firsthand experiential stories from a maximum variation sample of local men who have sex with men with diverse backgrounds and experiences related to HIV prevention; different types of role models were established accordingly. Framework analysis was used to aggregate the original quotations from narrators into collective narratives under 6 intervention themes. A dedicated website was finally developed for intervention delivery.ResultsA series of video-based intervention messages in biographic narrative format (firsthand experiential stories shared by men who have sex with men) combined with topic-equivalent argumentative messages were produced and programmed into 6 intervention sessions. The 6-week intervention program can be automatically delivered and monitored online.ConclusionsWe systematically created a web-based HIV prevention intervention derived from peer-generated stories. Strategies used to enhance the efficacy of the narrative intervention have been discussed within basic communication components. This paper describes the methods and experiences of the rigorous development of a narrative communication intervention for HIV prevention, which enables replication of the intervention in the future.