Non-acquired Immunodeficiency Syndrome Research Articles

Non-AIDS defining cancers in HIV-infected individuals: a concise review

Non-acquired immunodeficiency syndrome (AIDS)-defining cancers (NADCs) present a growing concern in human immunodeficiency virus (HIV)-infected individuals, impacting morbidity and mortality rates. This paper synthesizes current epidemiological data and explores the multifaceted relationship between HIV infection and NADC risk. Epidemiological studies indicate a shifting landscape of cancer incidence among HIV-infected populations, with a notable rise in NADCs over recent decades. Factors such as prolonged life expectancy due to effective antiretroviral therapy (ART) and aging of the HIV-infected population contribute to this trend. Despite the overall decline in AIDS-defining cancers, NADCs have emerged as a significant cause of morbidity and mortality in HIV-infected individuals. Immunodeficiency, chronic inflammation, and oncogenic viral co-infections, such as human papillomavirus and hepatitis C virus, compound the risk of developing NADCs. Diagnostic challenges persist, with delayed detection and suboptimal management contributing to poor outcomes. Treatment modalities for NADCs in HIV-infected individuals require careful consideration, balancing cancer-directed therapy with potential interactions with ART and immune reconstitution. Prevention strategies, including cancer screening and lifestyle modifications, are crucial in mitigating the burden of NADCs in this population. As the landscape of HIV care continues to evolve, understanding the epidemiology and clinical characteristics of NADCs is imperative for optimizing clinical management and improving outcomes in HIV-infected individuals.

Non-acquired immunodeficiency syndrome defining malignancies in people living with haemophilia and human immunodeficiency virus after direct-acting antiviral era.

Non-acquired immunodeficiency syndrome-defining malignancies (NADMs) are the crucial cause of mortality in people living with haemophilia and human immunodeficiency virus (PLWHH). We aimed to analyse the types and characters of NADMs in PLWHH after approval of direct-acting antivirals (DAA), considering that most PLWHH are infected with hepatitis C virus (HCV). We conducted a nationwide questionnaire mail survey across 395 HIV core facilities in Japan between May 2022 and February 2023. Eight-year data from 64 respondent hospitals (n = 328 PLWHH; 2015-2022) were collected; 35 NADM cases were identified and analysed. Standardised cancer incidence ratios (SCIRs) were calculated. The median age of PLWHH with NADMs was 51 years (interquartile range: 47-62 years); the SCIR was 2.08 (95% confidence interval [CI]: 1.48-2.90) for all malignancies (including carcinoma in situ). Liver cancer accounted for most NADMs (43% [15/35]). The SCIRs of liver cancer (23.09 [95% CI: 13.92- 38.30]) and papillary thyroid cancer (9.38 [2.35-37.50]) significantly increased after adjusting for general Japanese male sex and age. Among PLWHH with liver cancers, 73% (11/15) achieved HCV-sustained virological response. Notably, for patients aged ≤ 50 years, 47% (7/15) were affected by liver cancers, and 27% (4/15) succumbed to NADMs. This study presents the largest survey of NADMs in PLWHH after DAA approval. Our findings emphasised the elevated risk of malignancies in PLWHH, underscoring the need for early cancer screening and preventive measures, particularly against liver cancers, even in younger PLWHH.

Fatal Bladder Carcinoma in Woman with Human Immunodeficiency Virus: A Case Report

Background: Chronic human immunodeficiency virus (HIV) infection is associated with an increased incidence of Non-Acquired Immunodeficiency Syndrome (non-AIDS) defining cancers. To date, only a limited number of cases of bladder cancer have been linked with HIV infection in women. We sought to describe the clinical characteristics of HIV-associated bladder cancer. Methods: A 54-year-old female patient presented with symptoms of an occlusive syndrome. Medical examination was followed by a CT scan. The imaging revealed a significant finding. There was a noticeable process within the bladder. Further evaluation and management were recommended. Results: Spontaneous urinary cytology revealed the presence of malignant cells. An endoscopy was performed under spinal anesthesia, uncovering a large sessile tumor with necrotic areas located on the ventral aspect and dome of the bladder. Due to the severity of the condition, a palliative resection was carried out. Subsequent histological examination identified the tumor as a high-grade urothelial carcinoma, with evidence of muscle invasion. This diagnosis confirmed the aggressive nature of the disease, highlighting the necessity for further medical management and intervention. Conclusion: Bladder cancers in HIV-infected patients are rare but can occur in relatively young individuals with a low nadir CD4 cell count. These cancers often exhibit aggressive pathological features and can be fatal.

Human immunodeficiency virus patients with low CD4 counts are more likely to have precancerous polyps identified during index colonoscopy.

Antiretroviral treatment (ART) has improved the life expectancy of patients living with human immunodeficiency virus (HIV). As these patients age, they are at increased risk for developing non-acquired immunodeficiency syndrome defining malignancies (NADMs) such as colon cancers. To determine which factors are associated with the development of precancerous polyps on screening colonoscopy in patients with HIV and to investigate whether HIV disease status, measured by viral load and CD4 count, might influence precancerous polyp development. A retrospective review of records at two urban academic medical centers was performed for HIV patients who had a screening colonoscopy between 2005-2015. Patients with a history of colorectal cancer or polyps, poor bowel preparation, or inflammatory bowel disease were excluded. Demographic data such as sex, age, race, and body mass index (BMI) as well as information regarding the HIV disease status such as CD4 count, viral load, and medication regimen were collected. Well-controlled patients were defined as those that had viral load < 50 copies, and poorly-controlled patients were those with viral load ≥ 50. Patients were also stratified based on their CD4 count, comparing those with a low CD4 count to those with a high CD4 count. Using colonoscopy reports in the medical record, the size, histology, and number of polyps were recorded for each patient. Precancerous polyps included adenomas and proximal serrated polyps. Data was analyzed using Fisher's exact tests and logistic regression through SAS 3.8 software. Two hundred and seven patients met our inclusion criteria. The mean age was 56.13 years, and 58% were males. There were no significant differences in terms of age, race or ethnicity, insurance, and smoking status between patients with CD4 counts above or below 500. BMI was lower in patients with CD4 count < 500 as compared to those with count > 500 (P = 0.0276). In patients with CD4 > 500, 53.85% of patients were female, and 70.87% of patients with CD4 < 500 were male (P = 0.0004). Only 1.92% of patients with CD4 ≥ 500 had precancerous polyps vs 10.68% of patients with CD4 < 500 (P = 0.0102). When controlled for sex, BMI, and ART use, patients with CD4 < 500 were 9.01 times more likely to have precancerous polyps [95% confidence interval (CI): 1.69-47.97; P = 0.0100]. Patients taking non-nucleoside reverse transcriptase inhibitors were also found to be 10.23 times more likely to have precancerous polyps (95%CI: 1.08-97.15; P = 0.0428). There was not a significant difference noted in precancerous polyps between those that had viral loads greater or less than 50 copies. Patients with low CD4 counts were more likely to have precancerous polyps on their screening colonoscopy although the etiology for this association is unclear. We also found an increased risk of precancerous polyps in patients taking non-nucleoside reverse transcriptase inhibitors, which is contradictory to prior literature showing ART has decreased the risk of development of NADMs. However, there have not been studies looking at colorectal cancer and ART by drug class, to our knowledge. Further prospective studies are needed to determine the effect of HIV control and therapies on polyp development.

Human Immunodeficiency Virus and Clonal Hematopoiesis.

The evolution of antiretroviral therapies (ART) has tremendously improved the life expectancy of people living with human immunodeficiency virus (HIV) (PLWH), which is currently similar to the general population. However, as PLWH are now living longer, they exhibit various comorbidities such as a higher risk of cardiovascular disease (CVD) and non-acquired immunodeficiency syndrome (AIDS)-defined malignancies. Clonal hematopoiesis (CH) is the acquisition of somatic mutations by the hematopoietic stem cells, rendering them survival and growth benefit, thus leading to their clonal dominance in the bone marrow. Recent epidemiologic studies have highlighted that PLWH have a higher prevalence of CH, which in turn is associated with increased CVD risk. Thus, a link between HIV infection and a higher risk for CVD might be explained through the induction of inflammatory signaling in the monocytes carrying CH mutations. Among the PLWH, CH is associated with an overall poorer control of HIV infection; an association that requires further mechanistic evaluation. Finally, CH is linked to an increased risk of progression to myeloid neoplasms including myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML), which are associated with particularly poor outcomes among patients with HIV infection. These bidirectional associations require further molecular-level understanding, highlighting the need for more preclinical and prospective clinical studies. This review summarizes the current literature on the association between CH and HIV infection.

HIV-Associated Conditions in Older Adults.

Geriatric practices will see more people living with human immunodeficiency virus (HIV), as their life expectancy is close to the general population due to effective antiretroviral therapy (ART). Geriatricians focus more on HIV-associated, non-acquired immunodeficiency syndrome (AIDS) disorders than HIV alone. We will review the most common chronic illnesses and conditions associated with aging and HIV. Even though fall frequency in older adults living with HIV is similar to or lower than in people without HIV, fall assessment is appropriate, especially in the high-risk elderly living with HIV. HIV also impacts motor function and memory loss, especially in advanced cases. ART doesn't cross the blood-brain barrier, leading to major neurocognitive disorders with age. The etiology of HIV and cardiovascular disease (CVD) is multifactorial, including the effect of ART. Pitavastatin and pravastatin cause fewer interactions with ART.While the treatment for HIV decreases the risk of opportunistic infections, it may cause several bone-related abnormalities, including low bone mineral density (BMD), osteoporosis, and fractures. Polypharmacy is associated with disability and mortality and may increase the risk of ART drug-drug interaction. The oral health status of HIV-infected patients is commonly inadequate, and the presence of dental care managers may improve clinical outcomes and increase medication adherence. Furthermore, people aging with HIV (PAWH) have an increased mortality risk when co-infected with coronavirus disease 2019 (COVID-19). In summary, older adults living with HIV may face unique challenges. Therefore, providing comprehensive medical care and psychosocial support through an interdisciplinary team can significantly impact their lives.

Clinical Analysis of Non-AIDS Patients with Pulmonary Cryptococcosis and the Change in Their Clinical Features over 30 Years in a Tertiary Hospital in Beijing, China.

Over the past few decades, the clinical features of pulmonary cryptococcosis (PC) have progressed; however, there is a lack of data on the manifestations of PC over time. To investigate the differences in the clinical characteristics of PC across different time periods, we retrospectively reviewed 130 non-acquired immunodeficiency syndrome (AIDS) patients diagnosed with pathologically or microbiologically confirmed PC from 1990-2020. Among the 130 patients with PC, 24 (18.5%) exhibited immunosuppression, and 44 (33.8%) had underlying diseases. In radiology, 118 (90.8%) presented with subpleural lesions, and 68 (53.1%) presented with nodules with diameters ranging from 1-5 cm. Seventy-five (57.7%) patients underwent surgery alone. The clinical features of PC at different time periods showed that hospitalization days decreased (P = 0.009), and the number of patients with symptoms decreased over time. The number of patients exhibiting isolated lesions decreased (P = 0.022), and the number of patients exhibiting subpleural lesions increased (P = 0.020). In addition, the number of patients with lesions presenting 3-10 mm nodules increased (P = 0.028). In conclusion, an increasing number of patients have been diagnosed with PC over the last 30 years. The timing of PC diagnosis has shifted to the early stages of disease progression. Pulmonary lesions caused by cryptococcosis are easily misdiagnosed and may require unnecessary surgical treatment. Further research is needed to identify the lung lesions caused by cryptococcosis.

Renal Cell Carcinoma Associated With HIV/AIDS: A Review of the Epidemiology, Risk Factors, Diagnosis, and Treatment

Renal cell carcinoma (RCC), one of the most common genitourinary tumors, is induced by many factors, primarily smoking, obesity, and hypertension. As a non-acquired immunodeficiency syndrome (AIDS)-defining cancer, human immunodeficiency virus (HIV) may also play a critical role in the incidence and progression of RCC. It is evident that individuals who are infected with HIV are more likely than the general population to develop RCC. The age of RCC diagnosis among HIV-positive patients is younger than among HIV-negative individuals. However, many other characteristics remain unknown. With the increase in RCC incidence among HIV-infected patients, more research is being conducted to discover the relationship between RCC and HIV, especially with regard to HIV-induced immunodeficiency, diagnosis, and treatment. Unexpectedly, the majority of the literature suggests that there is no relationship between RCC and HIV-induced immunodeficiency. Nonetheless, differences in pathology, symptoms, or treatment in HIV-positive patients diagnosed with RCC are a focus. In this review, we summarize the association of RCC with HIV in terms of epidemiology, risk factors, diagnosis, and treatment.

Trends & predictors of non-AIDS comorbidities among people living with HIV and receiving antiretroviral therapy in Lebanon.

Combined antiretroviral therapy (cART) increased the life expectancy of people living with Human Immunodeficiency Virus (HIV) (PLHIV) and remarkably reduced the morbidity and mortality associated with HIV infection. Consequently, PLHIV are experiencing non-acquired immunodeficiency syndrome (AIDS) associated comorbid conditions including diabetes, hyperlipidemia, hypertension, and cardiovascular disease. The aim of this study is to determine the frequency of non-AIDS associated comorbid conditions among a cohort of PLHIV on cART in Lebanon.Data were collected between November 2018 and December 2019 from 105 voluntary participants. A standardized questionnaire was used to collect demographic and behavioral data including lifestyle, smoking, physical activity, substance use and abuse in addition to co-infections and family history of non-communicable diseases. Moreover, data on occurrence and treatment of cardiovascular disease, hypertension, diabetes, lipid and metabolic disorders as well as mental health were collected. Blood samples were used to assess the levels of fasting blood sugar (FBS), glycosylated hemoglobin (HbA1C), triglycerides (TG), low-density lipoprotein (LDL), high-density lipoprotein, total cholesterol, and serum creatinine.Hypertension (29.5%) and hyperlipidemia (29.5%) followed by diabetes (23.7%) and cardiovascular disease (9.7%) were mainly reported among study participants. Higher rate of comorbid conditions was observed among participants >40 years of age than those ≤40 years with both hypertension and hyperlipidemia most commonly reported. Older age (odds ratio [OR] 7.6; 95% CI: 1.83-31.98; P = .005) is associated with higher odds of having hyperlipidemia. Moreover, participants on cART for ≥10 years are 5 times more likely to have hyperlipidemia (OR 5; 95% CI: 1.08-22.73; P = .039). Our results also showed that study participants did not experience anxiety, depression or somatic symptoms and that there was no association between these mental disorders and older age or comorbidities.Our results provide important information on HIV trends and associated comorbidities in Lebanon and can be used to improve the management of non-communicable diseases among PLHIV.

HIV/AIDS Associated Lymphoma: Review.

Lymphoma is one of the hematologic malignancies that occur at a higher rate in human immunodeficiency virus-infected individuals. It is one of the most frequent neoplastic causes of death in those individuals. Non-Hodgkin’s lymphoma and Hodgkin’s lymphomas are acquired immunodeficiency syndrome defining lymphoma and non-acquired immunodeficiency syndrome defining lymphoma, respectively. Non-Hodgkin’s lymphoma is the most common type of lymphoma in human immunodeficiency virus-positive people. The lymphoma that develops in patients infected with the human immunodeficiency virus/acquired immunodeficiency syndrome is heterogeneous in terms of morphology, pathogenesis pathways, and cellular derivation. A narrative review was conducted on the basis of relevant literature on the current topic to summarize the current epidemiology, pathogenesis, laboratory diagnosis, and treatment of lymphoma in human immunodeficiency virus-infected patients. The finding showed that although the incidence of non-Hodgkin’s lymphoma has decreased after the advent of highly active antiretroviral therapy, it has remained higher in human immunodeficiency virus-infected people than in the general population. On the other hand, the incidence of Hodgkin’s lymphoma has increased after the introduction of highly active antiretroviral therapy. Therefore, it is recommended that people living with human immunodeficiency virus/ acquired immunodeficiency syndrome be screened for the development of lymphoma to increase their survival time and quality of life, and further research is required regarding the pathogenesis, treatment, and laboratory diagnosis of human immunodeficiency virus/ acquired immunodeficiency syndrome-associated lymphoma.

Research Progress on the Relationship between the NLRP3 Inflammasome and Immune Reconstitution in HIV-Infected Patients Receiving Antiretroviral Therapy.

Human immunodeficiency virus (HIV) infection is characterized not only by severe immunodeficiency but also by persistent inflammation and immune activation. These characteristics persist in people living with HIV (PLHIV) receiving effective antiretroviral therapy (ART) and are associated with morbidity and mortality in nonacquired immunodeficiency syndrome (AIDS) events. ART can inhibit HIV replication and promote immune reconstitution, which is currently the most effective way to control AIDS. However, despite effective long-term ART and overall suppression of plasma HIV RNA level, PLHIV still shows chronic low-level inflammation. The exact mechanisms that trigger chronic inflammation are unknown. Activation of the inflammasome is essential for the host response to pathogens, and some recent studies have confirmed the role of the inflammasome in the pathogenesis of inflammatory diseases. The NLRP3 inflammasome has been widely studied, which is a pyrin domain-containing protein 3 belonging to the family of nucleotide-binding and oligomerization domain-like receptors (NLRs). Recent studies suggest that inflammasome-mediated pyroptosis is associated with CD4+ T cell loss in the absence of persistent infectious HIV replication. This article reviews the mechanism of the NLRP3 inflammasome and its correlation with immune reconstitution in PLHIV treated with ART.

Plasma MicroRNA Signature Panel Predicts the Immune Response After Antiretroviral Therapy in HIV-Infected Patients.

BackgroundApproximately 10–40% of people with human immunodeficiency virus (HIV) infection are unable to obtain successful improvements in immune function after antiretroviral therapy (ART). These patients are at greater risk of developing non-acquired immunodeficiency syndrome (AIDS)-related conditions, with the accompanying increased morbidity and mortality. Discovering predictive biomarkers can help to identify patients with a poor immune response earlier and provide new insights into the mechanisms of this condition.MethodsA total of 307 people with HIV were enrolled, including 110 immune non-responders (INRs) and 197 immune responders (IRs). Plasma samples were taken before ART, and quantities of plasma microRNAs (miRNAs) were determined using reverse transcriptase-quantitative polymerase chain reaction (RT-qPCR). Candidate biomarkers were established through four phases: discovery, training, validation, and blinded test. Binary logistic regression was used to analyze the combined predictive capacity of the identified miRNAs. The effect of one miRNA, miR-16-5p, on T cell function was assessed in vitro.ResultsExpression of five miRNAs (miR-580, miR-627, miR-138-5p, miR-16-5p, and miR-323-3p) was upregulated in the plasma of INRs compared with that in IRs. Expression of these miRNAs was negatively correlated with both CD4+ T cell counts and the increase in the proportion of CD4+ T cells after one year of ART. These five miRNAs were combined in a predictive model, which could effectively identify INRs or IRs. Furthermore, we found that miR-16-5p inhibits CD4+ T cell proliferation by regulating calcium flux.ConclusionWe established a five-miRNA panel in plasma that accurately predicts poor immune response after ART, which could inform strategies to reduce the incidence of this phenomenon and improve the clinical management of these patients.

Alterations in the oral microbiome in HIV infection: causes, effects and potential interventions.

A massive depletion of CD4+ T lymphocytes has been described in early and acute human immunodeficiency virus (HIV) infection, leading to an imbalance between the human microbiome and immune responses. In recent years, a growing interest in the alterations in gut microbiota in HIV infection has led to many studies; however, only few studies have been conducted to explore the importance of oral microbiome in HIV-infected individuals. Evidence has indicated the dysbiosis of oral microbiota in people living with HIV (PLWH). Potential mechanisms might be related to the immunodeficiency in the oral cavity of HIV-infected individuals, including changes in secretory components such as reduced levels of enzymes and proteins in saliva and altered cellular components involved in the reduction and dysfunction of innate and adaptive immune cells. As a result, disrupted oral immunity in HIV-infected individuals leads to an imbalance between the oral microbiome and local immune responses, which may contribute to the development of HIV-related diseases and HIV-associated non-acquired immunodeficiency syndrome comorbidities. Although the introduction of antiretroviral therapy (ART) has led to a significant decrease in occurrence of the opportunistic oral infections in HIV-infected individuals, the dysbiosis in oral microbiome persists. Furthermore, several studies with the aim to investigate the ability of probiotics to regulate the dysbiosis of oral microbiota in HIV-infected individuals are ongoing. However, the effects of ART and probiotics on oral microbiome in HIV-infected individuals remain unclear. In this article, we review the composition of the oral microbiome in healthy and HIV-infected individuals and the possible effect of oral microbiome on HIV-associated oral diseases. We also discuss how ART and probiotics influence the oral microbiome in HIV infection. We believe that a deeper understanding of composition and function of the oral microbiome is critical for the development of effective preventive and therapeutic strategies for HIV infection.

Diagnostic value of the combinations of bronchoalveolar lavage fluid pathogen detection and cryptococcal antigen test in pulmonary cryptococcosis

Objective: To evaluate the diagnostic value of bronchoalveolar lavage fluid pathogen detection combined with cryptococcal antigen test(CrAg) for pulmonary cryptococcosis(PC). Methods: A retrospective case analysis was performed on non-acquired immunodeficiency syndrome patients admitted to Ninghai First Hospital for suspected PC from January 2018 to December 2019. Fifty-nine patients were included. Sixteen cases (8 males and 8 females) were diagnosed with PC, aged from 18 to 76 years[an average age of (52±14) years], while 43 cases were diagnosed as having Non-PC. All patients had undergone both serum CrAg test and BALF pathogen detection(cultures and direct examination) combined with BALF-CrAg test. The sensitivity and specificity of the combined method of BALF was evaluated, and a parallel comparison of the diagnostic efficiencies of the two methods were made. Results: Of the 16 confirmed PC cases, serum CrAg tests were positive in 11 and negative in 5 cases, while the combined method showed that 14 were positive and 2 were negative. Compared with the clinical final diagnosis, the sensitivity, specificity, positive predictive value and negative predictive value showed that the serum CrAg tests were 68.8% (11/16), 97.7% (42/43), 91.7% (11/12), 89.3% (42/47) respectively, versus 87.5% (14/16), 100.0% (43/43), 100% (14/14), 95.6% (43/45) by the combined method of BALF. The results displayed no statistical difference between the two diagnostic methods (P =1.000). Among the 5 initially serum CrAg-negative cases, 4 were later confirmed as proven PC via the combined method of BALF and the other one by percutaneous lung biopsy. Conclusion: The combined method of BALF pathogen detection with BALF-CrAg showed a similar statistical efficiency rate for diagnosing pulmonary cryptococcosis compared with serum CrAg tests. It may serve as an efficient diagnosis method for PC cases with negative serum CrAg tests.

Antiretroviral therapy for HIV controllers: Reasons for initiation and outcomes in the French ANRS-CO21 CODEX cohort.

BackgroundLess than 1% of Human Immunodeficiency Virus (HIV)-infected individuals are able to achieve spontaneous viral control without requiring antiretroviral therapy (ART). Whether these HIV controllers (HIC) are at risk of HIV-associated comorbidities and could benefit from ART is debated, but recent studies reported decreased T-cell activation upon ART initiation. We report the frequency of ART initiation, reasons to treat, treatment outcome on immunovirological parameters, and rate of side-effects and treatment discontinuation in the French cohort of HIC.MethodsParticipants included in the French multicenter Agence Nationale de Recherche sur le SIDA et les Hépatites (ANRS) Cohorte des extremes (CODEX) cohort of HIC between July 6, 2007 and January 3, 2018 were prospectively followed. ART initiation, indication, discontinuation, non-Acquired ImmunoDeficiency Syndrome (AIDS)-defining events, side-effects, and immunovirological parameters were recorded. Undetectable HIC (u-HIC) were defined as participants with strictly undetectable viral loads based on routinely used assays throughout the follow-up and blipper HIC (b-HIC) as participants with possible detectable viral loads above the detection threshold during follow-up.FindingsAmong 302 HIC followed for a median of 14.8 years [10.3–20.2], 90 (30%) received ART (7 u-HIC and 83 b-HIC). The main reasons for ART initiation were decreased CD4 T-cell counts (n = 36, 40%), loss of virological control (n = 13, 14%), and non-AIDS-defining events (n = 12, 13%). Sixteen (18%) participants experienced 17 grade 1–2 adverse events. In b-HIC, ART slightly increased the CD4/CD8 ratio (median +0.19, p < 0.0001) and decreased the frequency of circulating CD38+ HLA-DR.+ CD4 and CD8 lymphocytes (median -0.75%, p = 0.003, and -2%, p < 0.0001, respectively), but these changes were not observed for treated u-HIC. Thirteen (14%) participants discontinued ART (5 (38%) because of side-effects, and 10 remained HIC after treatment cessation (median follow-up: 305 days [235–728]).InterpretationOnly 30% of participants in this large cohort of HIC required ART during a median follow-up of 14.8 years. These results show that HIC status is very stable and vouch for a patient-centered treatment decision based on the individual benefit/risk balance.

Global Disparities in Skin Cancer Services at HIV Treatment Centers across 29 Countries

Global Disparities in Skin Cancer Services at HIV Treatment Centers across 29 Countries

Plasma Extracellular Vesicle Subtypes May be Useful as Potential Biomarkers of Immune Activation in People With HIV

Background:Extracellular vesicles (EVs) are intercellular messengers with epigenetic potential since they can shuttle microRNA (miRNA). EVs and miRNA play a role in human immunodeficiency virus (HIV) infection immunopathogenesis. Chronic immune activation and systemic inflammation during HIV infection despite effective antiretroviral therapy (ART) are associated with non-acquired immunodeficiency syndrome (AIDS) comorbidities in people living with HIV (PLWH). Analysis of plasma EVs and their miRNA content may be useful as immune activation or inflammatory biomarkers in PLWH receiving ART. In this study, we hypothesized that the number, size, and miRNA of large and small EVs could reflect immune activation associated with an elevated CD8 T-cell count or a low CD4/CD8 ratio in PLWH.Methods:Plasma EVs subtype purified from PLWH and uninfected controls were sized using dynamic light scattering and quantified using flow cytometry and acetylcholine esterase (AChE) activity. Expression of mature miRNAs miR-92, miR-155, miR-223 was measured by quantitative reverse-transcriptase polymerase chain reaction in EVs and leucocytes.Results:HIV infection induces increased production of small EVs in plasma. EV subtypes were differentially enriched in miR-92, miR-155, and miR-223. Positive correlations between CD8 T-cell count and large EVs abundance and small EVs AChE activity were observed. CD4/CD8 ratio was negatively correlated with small EV AChE activity, and miRNA-155 level per small EV was negatively correlated with CD8 T-cell count.Conclusions:These findings suggest that quantifying large or small EVs and profiling miRNA content per EV might provide new functional biomarkers of immune activation and inflammation.

Association between Use of Methadone, Other Central Nervous System Depressants, and QTc Interval-Prolonging Medications and Risk of Mortality in a Large Cohort of Women Living with or at Risk for Human Immunodeficiency Virus Infection.

To evaluate the association between use of methadone, other central nervous system (CNS) depressants, and QTc interval-prolonging medications and risk of mortality among human immunodeficiency virus (HIV)-infected and at-risk HIV-uninfected women. Multicenter, prospective, observational cohort study (Women's Interagency HIV Study [WIHS]). A total of 4150 women enrolled in the WIHS study between 1994 and 2014 who were infected (3119 women) or not infected (1031 women) with HIV. Data on medication utilization were collected from all study participants via interviewer-administered surveys at 6-month intervals (1994-2014). Mortality was confirmed by National Death Index data. With age defining the time scale for the analysis, Cox proportional hazards models were used to estimate hazard ratios (HRs) for all-cause mortality in HIV-infected and -uninfected women and non-acquired immunodeficiency syndrome (AIDS) deaths in HIV-infected women. A total of 1046 deaths were identified, of which 429 were considered non-AIDS deaths. Use of benzodiazepines, CNS depressants (excluding methadone), and number of medications with conditional QTc interval-prolonging effects were each associated with all-cause mortality in multivariate models of HIV-infected women: hazard ratio (HR) 1.28, 95% confidence interval (CI) 1.01-1.60, p=0.037; HR 1.61, 95% CI 1.35-1.92, p<0.0001; and HR 1.15 per drug, 95% CI 1.00-1.33, p=0.047, respectively. Other explanatory variables for all-cause mortality in this model included HIV viral load, CD4+ cell count, renal function, hemoglobin and albumin levels, HIV treatment era, employment status, existence of depressive symptoms, ever use of injection drugs, and tobacco smoking. Of interest, use of CNS depressants (excluding methadone) was also associated with non-AIDS deaths (HR 1.49, 95% CI 1.49-2.2, p<0.0001). Although use of benzodiazepines and conditional QT interval-prolonging medications were associated with increased risk of non-AIDS mortality (HR 1.32 and 1.25, respectively), the effect was not statistically significant (p>0.05). In this cohort of HIV-infected and at-risk HIV-uninfected women, use of benzodiazepines, CNS depressants, and conditional QTc interval-prolonging medications were associated with a higher risk of mortality independent of methadone and other well-recognized mortality risk factors. Care must be taken to assess risk when prescribing these medications in this underserved and at-risk patient population.

Prevalence of Systemic Hypertension Among HIV-Infected and HIV-Uninfected Young Adults in Baltimore, Maryland.

Adults with perinatally acquired human immunodeficiency virus (PHIV) infection may be at increased risk for nonacquired immunodeficiency syndrome (AIDS) diseases, including systemic hypertension (HTN). The purpose of this study was to examine the prevalence of HTN among young adults with PHIV compared with recently infected and uninfected young adults. We conducted a cross-sectional study of young adults with PHIV, frequency matched on race and sex to a stratified random sample of young adults with nonperinatally acquired HIV (NPHIV) and HIV-uninfected young adults. All of the subjects were aged 18 to 29 years. HTN was defined as two systolic blood pressure measurements ≥140 mm Hg or diastolic ≥90 mm Hg at least 3 months apart and/or prescription for an antihypertensive medication. Logistic regression was used to estimate adjusted prevalence odds ratios and 95% confidence intervals (CIs) for the association between HIV infection and HTN. A total of 324 patients were included-108 per exposure group. The prevalence of HTN was 23% among individuals with PHIV, 10% among individuals with NPHIV, and 8% among HIV-uninfected patients. PHIV patients had 3.4 (95% CI 1.48-7.66) times the base odds of having HTN compared with HIV-uninfected patients, and 2.7 (95% CI 1.23-5.71) times the odds compared with NPHIV patients. By multivariable analysis, PHIV patients had 4.7 and 2.9 times the odds of having HTN compared with HIV-uninfected patients and NPHIV patients, respectively, after controlling for sex, race, and family history of hypertension. Our findings suggest that HTN prevalence among PHIV young adults is significantly higher than sex- and race-matched NPHIV and HIV-uninfected patients of similar age.

Geriatric Syndromes in Older Adults Living with HIV and Cognitive Impairment.

Nearly half of the population living with human immunodeficiency virus (HIV) in the United States is now older than 50 years with at least 6% over age 65. Between 35% and 50% live with mild to moderate cognitive impairment. Older persons living with HIV (PLWH) also have a substantial burden of HIV-associated non-acquired immunodeficiency syndrome medical conditions and are at risk for frailty, geriatric syndromes, and early mortality compared with HIV-uninfected peers. We sought to define the magnitude of geriatric conditions and multimorbidity in PLWH older than 60 years who are living with symptomatic cognitive impairment. In a subset of participants, we examined associations between these geriatric conditions. Retrospective cohort study. HIV Elders Study at the University of California, San Francisco, Memory and Aging Center. Participants were HIV infected, virally suppressed, 60 years or older, and clinically diagnosed with mild neurocognitive disorder (MND). We conducted standardized assessment of geriatric conditions and everyday function and investigated multimorbidity burden using the Veterans Aging Cohort Study (VACS) index. Among 141 older PLWH with MND, 58% report incontinence, 55% meet criteria for pre-frailty, and a substantial proportion report dependence with instrumental activities of daily living (52%) or activities of daily living (41%). The mean VACS index score is 33 (standard deviation = 14), suggesting a 13.8% 5-year all-cause mortality risk. Older PLWH with symptomatic cognitive impairment carry a substantial burden of other geriatric conditions. Our work supports the need for comprehensive geriatric systems of care for cognitively impaired individuals aging with HIV. J Am Geriatr Soc 67:1913-1916, 2019.