Function In HIV-infected Patients Research Articles

"Cannabinoids' Short-Term Effects on Immune Phenotype and Function in HIV-Infected Patients: A Review"

Smoking marijuana and 9- tetrahydrocannabinol (THC) (dronabinol, Marinol) is used for treating anorexia and weight loss caused by the human immunodeficiency virus-1 (HTV-1). However, there have been concerns that these chemicals may have a negative influence on the immune systems of HTV-infected persons. The writer has conducted randomised, potential, controlled trial in adults who have HIV-infection and who have been receiving protease inhibitor-that contains high active antiretroviral therapy to assess the usage of marijuana cigarette (3.95 percent THC), dronabinol (2.5 mg), and an oral placebo in adults who have HIV-infection receiving protease inhibitor-containing highly active antiretroviral therapy (HAART). Immunological presentation (flow cytometric quantification of cellular subpopulations, B cells, and natural killer [NK] cells) and immunological function (induced cytokine production, NK cell activity, and lymphoproliferation) tests were carried out at the beginning and on a regular basis.

Incidence Rate and Time to Occurrence of Renal Impairment and Chronic Kidney Disease among Thai HIV-infected Adults with Tenofovir Disoproxil Fumarate Use

Background: Tenofovir disoproxil fumarate (TDF) is a major antiretroviral therapy for Thai human immunodeficiency virus (HIV) infected adults. TDF is associated with a decrease in renal function. There is limited data about the use of TDF with the incidence and time to renal impairment and chronic kidney disease (CKD) in Thai HIV-infected adults. Objectives: To study the association of TDF with the incidence rate and duration of renal impairment and CKD in Thai patients. Methods: A retrospective cohort study in Thai naïve HIV-infected adults was conducted to compare the incidence rate and time to renal impairment and CKD in TDF and non-TDF groups. The incidence rate was analyzed by person-time. Time to renal impairment and CKD were analyzed by Kaplan-Meier curves and log-rank tests. Results: A total of 1,400 patients were enrolled. The incidence rates of renal impairment in TDF and non-TDF groups were 27.66/1,000 and 5.54/1,000 person-years. The rate ratio was 4.99 (95% confidence interval [CI] 2.66–9.35). The incidence rates of CKD in both groups were not significantly different. Themean difference of eGFR between the TDF and non-TDF groups was 1.92 ml/min/1.73 m2 (p = 0.022). Time to onset of renal impairment between the TDF and non-TDF groups was found to differ by approximately 20 months. Conclusion: The incidence rate of renal impairment was about five times higher in the TDF group. A rapid decline of eGFR occurred in the first 2–3 years of treatment. Therefore, the renal function of HIV-infected patients should be monitored so that the severity of renal impairment could be evaluated and CKD could be prevented.

Derangement in Enzymatic and Non-Enzymatic Markers of Liver Function in Human Immunodeficiency Virus (HIV) Infected Patients in Makurdi, North Central Nigeria

Liver disease has emerged as a critical issue in the management of human immunodeficiency virus (HIV) victims. This study was carried out to investigate the derangement in indices of liver function in HIV-infected patients in Makurdi, North Central Nigeria. One hundred and fifty males and females adults within the age range of 21- 50 years were enrolled for this study. One hundred of these participants were confirmed HIV positive, out of which fifty were on various antiretroviral drugs including the nucleoside / nucleotide reverse transcriptase inhibitors and the non-nucleoside transcriptase inhibitors classes of antiretroviral drugs. The remaining fifty persons who were HIV- negative served as the control group. Blood samples from the studied persons were analysed for alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, total protein, albumin, total bilirubin and conjugated bilirubin using automated clinical chemistry analyser, Hitachi 902 (Roche Diagnostic GMBH, Germany). The HIV- patients with or without antiretroviral drugs had their serum levels of alanine aminotransferase, aspartate aminotransferase and alkaline phosphatase significantly raised (p< 0.05) compared with the control subjects. A significant rise (p< 0.05) was observed in serum level of total protein in the HIV patients who were yet to commence antiretroviral drugs when compared to the control subjects. However, the albumin levels of the HIV patients on the antiretroviral drugs and those who were yet to commence the antiretroviral drugs decreased significantly (p< 0.05) when compared with that of the control. The total bilirubin level of the HIV patients on antiretroviral drugs showed significant increase (p< 0.05) compared with the control subjects and the HIV patients who were not on antiretroviral drugs. This study reveals that both HIV infection itself and the antiretroviral drugs cause hepatic malfunction

Acute supplementation with beetroot juice improves endothelial function in HIV-infected individuals.

Human immunodeficiency virus (HIV) is associated with lower nitric oxide (NO) bioavailability and vascular dysfunction. Nitrate-rich beetroot juice (BJ) has been shown to acutely increase NO availability and vascular function in healthy and individuals at high risk for cardiovascular disease. Thus, we tested the effects of BJ ingestion on flow-mediated dilation (FMD) and pulse wave velocity (PWV) measurements in healthy and HIV-infected patients. Thirteen HIV-infected individuals (age, 36 ± 10 years) and 18 healthy (age, 27 ± 8 years) participated in the study. Individuals were submitted to vascular tests such as FMD and pulse PWV at pre (T0) and at 120 min (T120) after BJ and placebo (PLA) ingestion. The %FMD at T0 of the control group was significantly higher than the %FMD at T0 of the HIV individuals in both interventions. BJ improved the %FMD at T120 when compared with T0 in the HIV and control groups. There was no change in %FMD after PLA ingestion in the control and HIV groups. There were no differences between groups (control vs HIV), time points (T0 vs T120), and interventions (BJ vs PLA) for PWV. Our findings showed that nitrate-rich BJ ingestion acutely improved vascular function in healthy and HIV-infected patients. Clinical Trials Registry no. NCT03485248. Novelty: HIV is associated with lower NO bioavailability and vascular dysfunction. Acute supplementation with nitrate-rich BJ has been shown to acutely increases NO bioavailability. We showed for the first time that BJ acutely improves endothelial function in HIV-infected patients.

Assessment of the Effect of HAART on Renal Function of HIV Patients Attending the Bamenda Regional Hospital, Cameroon

Background: Management of HIV involves a life-long administration of a cocktail of antiretroviral drugs, some of which have been known for their nephrotoxicity. Despite the increasing access to this combination therapy, Highly Active Antiretroviral Therapy (HAART) information on its renal effect is still scarce and contradictory. The aim of this study was to assess the effect of HAART on the renal function of HIV-infected patients attending the Bamenda Regional Hospital, Cameroon. Methods: This was a comparative hospital-based cross-sectional study involving HIV positive and negative individuals who visited the Day clinic of the Bamenda Regional Hospital during the study period. Spectrophotometry was used to quantify the renal markers. Glomerular Filtration Rate was determined by the 24 hours creatinine clearance method. Blood urea nitrogen was calculated from serum urea concentrations. Renal impairment was then classified according to the National Kidney Foundation clinical practice guideline. Data were analysed on SPSS version 21 using Student t-test, ANOVA, and Pearson’s correlation. The level of significance was set at p<0.05. Results: A total of 201 participants were enrolled in this study, of which 144(71.6%) were females. Their ages ranged between 22 to 60 years with a mean age of 37.4 ± 9.6 years. The participants were divided into 3 study groups; HIV negative, HAART-naïve and the HAART experienced groups. The HAART experienced group had a significantly higher mean BUN and BUN-Creatinine ratio (p= 0.001 and 0.003 respectively) as well as the least creatinine clearance (p= 0.017) when compared to the other groups meanwhile the HAART-naive group had a significantly higher mean urine protein (p= 0.026) when compared to the other two categories. There was no association between renal dysfunction and the HAART regimen as well as adherence to treatment. Conclusion: This study demonstrated that though the participants on HAART had decreased renal function, the mean Creatinine clearance was not statistically different from that of the participants not yet on HAART. this is indicative that the decreased renal function could be as a result of the devastating effect of HIV. It further demonstrates no association between decreased renal function to the type of HAART regimen used, duration on HAART as well as the patient’s adherence to treatment.

Muscle Strength and Aerobic Capacity in HIV-Infected Patients: A Systematic Review and Meta-Analysis.

Physical impairment is highly prevalent in HIV-infected patients. We conducted a systematic review of published studies that included studies comparing muscle function in HIV-infected patients to matched healthy controls, and studies comparing aerobic capacity in HIV-infected patients with that observed in matched healthy controls. Systematic review and meta-analysis. We searched for references on MEDLINE, SciELO, Cumulative Index to Nursing and Allied Health (CINAHL), and Scopus up to December 2017. Weighted mean differences and 95% confidence intervals (CIs) were calculated, and heterogeneity was assessed using the I test. A total of 30 studies, covering 2148 healthy controls and 2161 HIV-infected patients, fulfilled the inclusion criteria. The average muscle strength and aerobic capacity were significantly lower in HIV-infected patients. Meta-analysis revealed moderate-quality evidence of weaker muscle strength and aerobic capacity in HIV-infected patients. A significant difference in lower-body strength of 1.07 (95% CI: 0.29 to 1.84) was found for participants in the healthy control group compared with HIV group. A significant difference in aerobic capacity (peak VO2) of 8.4 (95% CI: 4.8 to 12.0) was found for participants in the healthy control group compared with HIV group. Muscle strength and aerobic capacity of HIV-infected patients are reduced in comparison with healthy controls. Additional studies are needed to define the best interventions to improve the physical function in HIV-infected patients.

HIV associated kidney diseases: Clarifying concordance between renal failure in HIV infection and histopathologic manifestations at kidney biopsy

Patients with HIV infection have a wide spectrum of renal diseases. Some are known to be the direct effect of the viral infection while others are renal diseases that also occur in uninfected populations. HIV associated nephropathy (HIVAN) is considered to be a subtype of primary focal and segmental glomerulosclerosis that is distinct in HIV infected patients. It is more frequent in the African-American population and associated with mutations of the apolipoprotein L1 (APOL1) gene. HIV associated immune complex kidney disease (HIVICD) encompasses a spectrum of HIV associated renal diseases characterized by the presence of immune complex deposition within glomeruli. Thrombotic microangiopathy (TMA) is a complication of HIV infection that presents with hemolytic anemia, thrombocytopenia, and renal failure. TMA in HIV patients is associated with very high mortality. Lastly, the multitude of antiretroviral drugs used for treatment of HIV infections can result in nephrotoxicity. Although a kidney biopsy may not be the first line study for renal disease, knowledge of the different histopathologic features of HIV-associated and unassociated diseases is of paramount importance in the treatment and subsequent outcome of renal function in HIV infected patients. In this review we will describe the histopathologic features and discuss the pathophysiology of the entities previously named.

Maraviroc Intensification Improves Endothelial Function in Abacavir-Treated Patients, an Open-Label Randomized Cross-Over Pilot Study

BackgroundThe increased risk of abacavir in cardiovascular disease (CVD) in HIV-infected patients is still being debated. Maraviroc, a CCR5 blocker, has been shown to decrease immune activation and monocyte infiltration in atherosclerotic plaques in murine experiments. Therefore, we examined the effect of maraviroc intensification on flow-mediated dilatation (FMD) in abacavir-treated HIV-infected patients and its effect on immunological and inflammatory parameters.MethodsA open-label prospective crossover study with a duration of 16 weeks: 8 weeks of intervention (maraviroc intensification) and 8 weeks of control (unchanged cART regimen). FMD, HIV-specific variables, expression of HIV co-receptors, markers of inflammation and coagulation and cellular markers of immune activation were measured at weeks 0, 8 and 16. The changes (Δ) in these variables were compared between intervention and control periods using non-parametric tests. To evaluate the relation with the change in FMD, linear regression modeling was used.ResultsTwenty-one male patients with suppressed plasma HIV-RNA, on cART, had a known HIV infection for 9.2 years (IQR 6.9–13.5) with abacavir use for 6.5 years (2.8–9.3). A significantly increased FMD of 0.73% (IQR −0.25 to 1.70) was seen after maraviroc intensification compared to a decrease of −0.42% (IQR −1.89 to 0.25; p = 0.049) in the control period. There was a negative relation between ΔFMD with ΔD-dimer (β −22.70, 95% CI −39.27; −6.13, p = 0.011) and ΔCD95+ CD4+ T cells (β −0.16, 95% CI −0.28; −0.04, p = 0.013), adjusted for age and duration of HIV.ConclusionMaraviroc intensification modestly improves endothelial function in HIV-infected patients on an abacavir-containing regimen.Trial registrationNCT01389063.Electronic supplementary materialThe online version of this article (doi:10.1007/s40121-016-0115-0) contains supplementary material, which is available to authorized users.

Disrupted Homeostatic Cytokines Expression in Secondary Lymph Organs during HIV Infection.

Research has firmly established that infection by human immunodeficiency virus (HIV) leads to structural disruption in secondary lymph organs (SLOs) and that IL-7 expression by SLOs is downregulated in simian immunodeficiency virus (SIV)-infected rhesus macaques. However, the foregoing has not been demonstrated in HIV-infected patients. As well, SLO-produced chemokines and cytokines, other than IL-7, have not been tested. In this study, SLOs in HIV-infected patients exhibit decreased levels of lymphoid cytokines, such as IL-7 and C–C motif chemokine ligand 21 (CCL21), due to lower expression of lymphotoxin (LT)-β. Previous research has shown that LT-β is produced mainly by CD4+T cells in rhesus macaques, while our study found the same level of LT-β expressed by CD4+T and CD8+T cells in humans. CD8+T cells substitute for depleted CD4+T cells LT-β production. Only the total number of CD3+T cells can account for the majority of LT-β in human SLOs. This study indicates a possible mechanism and a potential target for improvement of SLO function in HIV-infected patients, a novel adjuvant therapy for AIDS.

The influence of espresso coffee on neurocognitive function in HIV-infected patients

ABSTRACTThe aim of our study was to evaluate the impact of coffee intake on cognitive function in persons living with HIV (PLWH). 130 PLWH with CD4 > 200 cells/mm3, undetectable viral load, treated with HAART were included. A structured interview was applied and relevant clinical and laboratory data were assessed, including coffee intake. For neuropsychological assessment, the HIV Neurobehavioral Research Center Battery was chosen. Univariate nonparametric statistics and multivariate regression model were used. A significant association between espresso coffee use and a better cognitive function was verified in five of the eight psychometric measurements. In the multivariate analysis, after variable adjustment, linear regression analysis showed that coffee intake was a positive predictor for attention/working memory, executive functions and Global Deficit Score. Although the mechanisms behind the influence of caffeine on cognitive functioning are controversial, regular espresso coffee intake may have favourable effects on cognitive deterioration caused by HIV.

Is Abnormal Urine Protein/Osmolality Ratio Associated with Abnormal Renal Function in Patients Receiving Tenofovir Disoproxil Fumarate?

BackgroundRisk factors for and optimal surveillance of renal dysfunction in patients on tenofovir disoproxil fumarate (TDF) remain unclear. We investigated whether a urine protein-osmolality (P/O) ratio would be associated with renal dysfunction in HIV-infected persons on TDF.MethodsThis retrospective, single-center study investigated the relationship between parameters of renal function (estimated glomerular filtration rate (eGFR) and P/O-ratio) and risk factors for development of kidney dysfunction. Subjects were HIV-infected adults receiving TDF with at least one urinalysis and serum creatinine performed between 2010 and 2013. Regression analyses were used to analyze risk factors associated with abnormal P/O-ratio and abnormal eGFR during TDF therapy.ResultsPatients were predominately male (81%); (65%) were Caucasian. Mean age was 45.1(±11.8) years; median [IQR] TDF duration was 3.3 years. [1.5–7.6]. Median CD4+ T cell count and HIV viral load were 451 cells/μL [267.5–721.5] and 62 copies/mL [0–40,150], respectively. Abnormal P/O-ratio was not associated with low eGFR. 68% of subjects had an abnormal P/O-ratio and 9% had low eGFR. Duration of TDF use, age, diabetes and hypertension were associated with renal dysfunction in this study. After adjustment for age, subjects on TDF > 5 years had almost a four-fold increased likelihood of having an abnormal P/O-ratio than subjects on TDF for < 1yr (OR 3.9; 95% CI 1.2–14.0; p = 0.024).ConclusionAbnormal P/O-ratio is common in HIV-infected patients on TDF but was not significantly associated with low eGFR, suggesting that abnormal P/O-ratio may be a very early biomarker of decreased renal function in HIV infected patients.

Effects of a 2-Year Supervised Exercise Program Upon the Body Composition and Muscular Performance of HIV-Infected Patients.

Background : There is a lack of research investigating long-term effects of exercise training upon the body composition and muscle function in HIV-infected patients (PHIV). The study investigated the influence of a 2-year supervised exercise program on body composition and strength of PHIV under highly active antiretroviral therapy (HAART).Methods : A training program including aerobic, strength and flexibility exercises was performed by 27 PHIV (17 men/ 10 women; age: 48.7±7.0 years; HAART: 150.7±65.3 months) during 1 year and 18 PHIV (10 men/ 8 women; age: 50.6±5.2 years; HAART: 176.6±53.1 months) during 2 years. Body composition and knee isokinetic strength were assessed at baseline and at the end of each year of intervention.Results : Body composition remained stable along the whole experiment vs baseline (1-year - total muscle mass: Δ men=1.1%, P=0.21; Δ women=1.4%, P=0.06; trunk fat: Δ men=-0.1%, P=0.65; Δ women=-1.5%, P=0.45; 2 years - total muscle mass: Δ men=2.7%, P=0.54; Δ women=-1.9%, P=0.71; trunk fat: Δ men=4.4%, P=0.96; Δ women=10.0%, P=0.30). After 1-year, peak torque increased in men (Δ extension=4.2%, P=0.01; Δ flexion=12.2%, P=0.04) and total work reduced in women (Δ extension=-15.4%, P=0.01, Δ flexion=-17.5%, P=0.05). All strength markers remained stable vs baseline after 2 years of intervention (P>0.05). Only men showed significant reduction in the risk of disability due to sarcopenia (P=0.05) after 1 year of intervention, which remained stable after 2 years.Conclusion : Long-term exercise training preserved strength and muscle mass in PHIV under HAART. Exercise programs should be part of HIV therapy to prevent sarcopenia of this population along the years.Trial Registration : ACTRN12610000683033; UTN U1111-1116-4416.

Lactonase activity and kidney function in HIV-infected patients under combined antiretroviral therapy

Lactonase activity and kidney function in HIV-infected patients under combined antiretroviral therapy

Reduction on titers of natural antibodies to ApoB-D peptide is associated with reduction on endothelial function in HIV-infected patients

Reduction on titers of natural antibodies to ApoB-D peptide is associated with reduction on endothelial function in HIV-infected patients

Herpes virus entry mediator, which decreases in HIV infection, can enhance the suppressive activity of regulatory T cell and predict recovery of CD4+T-cells during HAART.

Co-signaling molecules have been demonstrated to regulate regulatory T cells' (Tregs) function during human immunodeficiency virus (HIV) infection. A recently reported co-signaling molecule called herpes virus entry mediator (HVEM), a member of the tumor necrosis factor receptor family, can both enhance and inhibit the immune response. HVEM was also reported to enhance the suppressive function of regulatory T cells in mice. However, it remains unknown whether HVEM can regulate Treg function in HIV-infected patients or whether HVEM affects HIV disease progression. In this study, we found that the blockage of the HVEM could weaken Tregs' suppressive activity to effector T cells (Teffs). HVEM expression is reduced during the asymptomatic phase of HIV infection and fairly predictive of the recovery of CD4+T-cells in response to highly active anti-retroviral therapy (HAART), more so than nadir CD4+T-cell count or viral load. Taken together, these findings demonstrate the importance of HVEM in relation to Treg function and HIV disease progression, which would have therapeutic implications and provide insight into the pathogenesis of acquired immune deficiency syndrome (AIDS).

Variation and significance of helper T cells and regulatory T cells in the peripheral blood before and after antiretroviral treatment of human immunodeficiency virus-1 infected patients

Objective To investigate the changes and clinical significance of helper T cells (Th)22, Th17, Th1 and regulatory T cells (Treg) in the peripheral blood before and after antiretroviral treatment (ART) of human immunodeficiency virus (HIV)-1 infected patients. Methods Forty HIV-infected patients were recruited into this study, and 30 healthy subjects were recruited as controls. Peripheral blood of the patients was collected at baseline and after 3 months of ART treatment. The frequencies of Th22, Th17, Th1 and Treg were detected by flow cytometry. Tests for homogeneity of variance and paired t test for comparison was adopted. Spearman rank test was used for correlation analysis. Results The frequencies of peripheral Th22, Th17, Th1 and Treg from HIV-infected patients before treatment were significantly decreased compared to the healthy controls ([0.59±0.47]% vs [1.65±0.56]%[t=8.544, P 0.05). However, the Th1 frequency showed no difference compared to the baseline. The frequency of Treg in the HIV infected patients was significantly increased compared with the healthy controls ([10.76±3.76]% vs [7.01±1.88]%, t=5.003, P<0.01). However, it gradually decreased along with the ART treatment ([9.22±2.56]% after 2 months; [8.57±2.36]% after 3 months), which was still higher than that of healthy controls (t=2.984, P=0.004). The ratios of Th22/Treg, Th17/Treg and Th1/Treg of the HIV-infected patients were significantly decreased in comparison with the healthy controls (0.05±0.03 vs 0.25±0.10, t=11.69, P<0.01; 0.46±0.27 vs 1.07±0.42, t=7.728, P<0.01; 1.56±0.89 vs 3.37±1.02, t=7.052, P<0.01), and those were significantly increased after 3 months of treatment (0.17±0.10[t=6.852, P<0.01], 0.81±0.46[t=4.253, P<0.01] and 2.31±1.27[t=3.030, P<0.01]). Correlation analysis showed that the ratio of Th17/Treg of the HIV-infected patients was positively correlated with the peripheral CD4+ T cell count (r=0.312 5, P=0.049 6), and negatively correlated with HIV RNA viral load (r=-0.474 7, P=0.002 0). The ratio of Th1/Treg of the HIV-infected patients was positively correlated with the peripheral CD4+ T cell count (r=0.333 5, P=0.035 5). Conclusions Th22, Th17, Th1 and Treg cells in the peripheral blood of HIV-infected patients are closely related to CD4+ T cell count. ART can partially recover immune imbalance, and help to rebuild immune function of HIV-infected patients. Key words: Acquired immunodeficiency syndrome; Antiretroviral therapy; T-Lymphocytes, regulatory; Th22; Th17; Th1

Mild Decrease in Renal Function in HIV-Infected Patients on Antiretroviral Therapy: A Neglected Diagnosis

Background: Renal impairment is increasingly reported among HIV-Infected patients and has been associated to an increased chance of cardiovascular disease and death. Therefore, early identification of this problem could help to reduce morbidity and mortality among these individuals. The objective of the study was to determine the prevalence and associated factors with mild decrease in renal function of HIV-infected patients on highly-active antiretroviral therapy (HAART) and undetectable viral load in Brazil. Methods: Individuals between 18-70 years of age with time on HAART ≥ 12 months, viral load < 50 copies/mm3, and CD4 ≥ 200 cells/mm3, were consecutively enrolled at the outpatient clinic of Hospital de Clinicas de Porto Alegre, Brazil. Exclusion criteria were chronic kidney disease, pregnancy and known hepatic disease. Renal function was assessed by the Chronic Kidney Disease Epidemiology Collaboration equation. Mild decrease in renal function was defined as an estimated glomerular filtration rate between 89-60 mL/min/1.73m2, for a period of at least 3 months. Results: From the total of 213 enrolled volunteers, 193 were included in the final analysis. The mean age was 41.5 years, 102 were men (52.6%), and 156 (80.4%) were euro-descendants. Mild renal decline was diagnosed in 33.5% of the patients. Every other year of life (RR=1.05, 95%CI 1.03-1.06, p<0.001) and being euro-descendant (RR=1.94; 95%CI 1.07-3.78; p=0.049) were associated to mild decreases, whereas high body mass index (BMI) (RR=1.04, 95% CI 1.013-1007, p<0,001) was associated to normal function. Conclusions: Mild decrease in renal function was extremely common and more than expected in our cohort (33.5%) which deserves further attention while assisting HIV-positive individuals.

Hearing function in patients living with HIV/AIDS.

During the earlier years of the HIV/AIDS epidemic, initial reports described sensorineural hearing loss in up to 49% of individuals with HIV/AIDS. During those years, patients commonly progressed to advanced stages of HIV disease and frequently had neurological complications. However, the abnormalities on pure-tone audiometry and brainstem-evoked responses outlined in small studies were not always consistently correlated with advanced stages of HIV/AIDS. Moreover, these studies could not exclude the confounding effect of concurrent opportunistic infections and syphilis. Additional reports also have indicated that some antiretroviral medications may be ototoxic; thus, it has been difficult to make conclusions regarding the cause of changes in hearing function in HIV-infected patients. More recently, accelerated aging has been suggested as a potential explanation for the disproportionate increase in complications of aging described in many HIV-infected patients; hence, accelerated aging-associated hearing loss may also be playing a role in these patients. We conducted a large cross-sectional analysis of hearing function in over 300 patients with HIV-1 infection and in 137 HIV-uninfected controls. HIV-infected participants and HIV-uninfected controls underwent a 2-hr battery of hearing tests including the Hearing Handicap Inventory, standard audiometric pure-tone air and bone conduction testing, tympanometric testing, and speech reception and discrimination testing. Three-way analysis of variance (ANOVA) and logistic regression analysis of 278 eligible HIV-infected subjects stratified by disease stage in early HIV disease (n = 127) and late HIV disease (n = 148) and 120 eligible HIV-uninfected controls revealed no statistically significant differences among the three study groups in either overall 4-frequency pure-tone average (4-PTA) or hearing loss prevalence in either ear. Three-way ANOVA showed significant differences in word recognition scores in the right ear among groups, a significant group effect on tympanogram static admittance in both ears and a significant group effect on tympanic gradient in the right ear. There was significantly larger admittance and gradient in controls as compared to the HIV-infected group at late stage of disease. Hearing loss in the HIV-infected groups was associated with increased age and was similar to that described in the literature for the general population. Three-way ANOVA analysis also indicated significantly greater pure-tone thresholds (worse hearing) at low frequencies in HIV patients in the late stage of disease compared with HIV-uninfected controls. This difference was also found by semi-parametric mixed effects models. Despite reports of "premature" or "accelerated" aging in HIV-infected subjects, we found no evidence of hearing loss occurring at an earlier age in HIV-infected patients compared to HIV-uninfected controls. Similar to what is described in the general population, the probability of hearing loss increased with age in the HIV-infected subjects and was more common in patients over 60 years of age. Interestingly, HIV-infected subjects had worse hearing at lower frequencies and have significant differences in tympanometry compared to HIV-uninfected controls; these findings deserve further study.

Invariant natural killer T (iNKT) cells in HAART-treated, HIV-positive patients with bone and cardiovascular impairment.

BackgroundInvariant Natural Killer T (iNKT) cells represent a determinant in the course of infections and diseases, however, their role in the pathogenesis of non-infectious co-morbidities in HIV-positive patients is unknown.MethodsFlow cytometry was used to investigate iNKT cell frequency, phenotype and function in HIV-infected patients on HAART with bone and/or cardiovascular disorders and in HIV-positive controls free from co-morbidities.ResultsiNKT cells from subjects with bone and cardiovascular impairment expressed high levels of CD161 and predominantly secreted TNF. iNKT cells from individuals with bone disease alone did not show any distinctive phenotypical or functional characteristics. The functional capacity of iNKT cells in patients with cardiovascular disorder was impaired with no cytokine release upon stimulation.ConclusioniNKT cells may have a role in non-infectious co-morbidities in treated HIV disease, possibly through the exacerbation of inflammation. Further studies are needed to investigate iNKT cells in the pathogenesis of non-communicable disorders in HIV infection.

A Prospective Cohort Study of Neurocognitive Function in Aviremic HIV-Infected Patients Treated With 1 or 3 Antiretrovirals

The evolution of neurocognitive performance in aviremic human immunodeficiency virus (HIV)-positive patients treated with <3 antiretrovirals is unknown. We prospectively included aviremic (≥1 year) HIV-positive patients, without concomitant major neurocognitive confounders, currently receiving boosted lopinavir or darunavir as monotherapy (n = 67) or triple antiretroviral therapy (ART) (n = 67) for ≥1 year. We evaluated neurocognitive function (7 domains) at baseline and after 1 year. We performed analysis of covariance to evaluate if 1 additional year of exposure to monotherapy compared with triple ART had an effect on Global Deficit Score (GDS) changes after adjustment for potential confounders. We also compared the evolution of neurocognitive performance and impairment rates. Intention-to-treat analysis showed that monotherapy did not influence 1-year GDS change after adjustment for significant confounders (age, ethnicity, duration of therapy, hepatitis C virus status, and HOMA-IR index); the adjusted effect was -0.04 (95% confidence interval, -.14 to .05; P = .38). Neurocognitive stability was observed with monotherapy and triple therapy (GDS crude mean change, -0.09 [95% confidence interval, -.16 to -.01] vs -0.08 [-.14 to -.02]), after 1 year of follow-up, similar proportions of patients changed neurocognitive status from impaired to unimpaired (monotherapy, 4 of 18 [22.2%]; triple therapy, 4 of 19 [21.1%]; P = .91) and vice versa (monotherapy, 5 of 44 [10.2%] and triple therapy, 3 of 45 [6.3%]; P = .48). Similar results were observed in an on-treatment analysis and with use of clinical ratings instead of GDS changes. The number of antiretrovirals included in the ART regimen does not seem to influence the evolution of neurocognitive function in HIV-infected patients with suppressed plasma viremia.