HIV Disease Markers Research Articles

Dysbiosis in the oral bacterial and fungal microbiome of HIV-infected subjects is associated with clinical and immunologic variables of HIV infection.

BackgroundThe effect of smoking on microbial dysbiosis and the potential consequence of such shift on markers of HIV disease is unknown. Here we assessed the relationship of microbial dysbiosis with smoking and markers of HIV disease.MethodsOral wash was collected from: (1) HIV-infected smokers (HIV-SM, n = 48), (2) HIV-infected non-smokers (HIV-NS, n = 24), or (3) HIV-uninfected smokers (UI-SM, n = 24). Microbial DNA was extracted and their bacterial and fungal microbiota (bacteriome and mycobiome, respectively) were characterized using Ion-Torrent sequencing platform. Sequencing data were compared using clustering, diversity, abundance and inter-kingdom correlations analyses.ResultsBacteriome was more widely dispersed than mycobiome, there was no noticeable difference in clustering between groups. Richness of oral bacteriome in HIV-SM was significantly lower than that of UI-SM (P ≤ .03). Diversity of HIV-NS was significantly lower than that of HIV-SM or UI-SM at phylum level (P ≤ .02). Abundance of Phylum Firmicutes was significantly decreased in HIV-NS compared to HIV-SM and UI-SM (P = .007 and .027, respectively), while abundance of Proteobacteria was significantly increased in HIV-NS compared to HIV-SM and UI-SM (P = .0005 and .011, respectively). Fungal phyla did not differ significantly between the three cohorts. Cumulative smoking was positively correlated with Facklamia but negatively with Enhydrobacter, and current alcohol use was negatively correlated with Geniculata. Bacteria Facklamia exhibited weakly positive correlation with longer PI duration (r = 0.094, P = 0.012), and a negative correlation with nadir CD4 count (r = -0.345; P = 0.004), while Granulicatella was negatively correlated with nadir CD4 count (r = -0.329; P = 0.007). Fungus Stemphylium correlated negatively with nadir CD4 (r = -0.323; P = 0.008).ConclusionsDysbiosis of the oral microbiota is associated with clinical and immunologic variables in HIV-infected patients.

Plasma IP-10 Concentrations Correlate Positively with Viraemia and Inversely with CD4 Counts in Untreated HIV Infection.

Background:Chronic immune activation is a feature of HIV infection associated with accelerated HIV disease progression. There is conflicting data on the association of biomarkers of immune activation with traditional markers of HIV disease progression; CD4 counts and viral load (VL).Objective:The study aimed to determine the association of biomarkers of immune activation; interferon (IFN)-γ-induced protein 10 (IP-10) and soluble cluster of differentiation 14 (sCD14) in chronic HIV infection with traditional markers of HIV disease progression.Methods:We collected demographic data, enumerated CD4 counts and quantified VL in 183 antiretroviral therapy (ART)-naive adults with chronic HIV infection. Plasma concentrations of IP-10 and sCD14 were quantified in the ART-naive adults with chronic HIV infection and 75 HIV-uninfected controls.Results:IP-10 concentrations were significantly higher in the HIV-infected group (median; 257.40pg/ml, IQR; 174.08-376.32) than in the HIV-uninfected (median; 86.19pg/ml, IQR; 67.70-116.39) (P<0.001). Similarly, sCD14 concentrations were significantly higher in the HIV-infected (median; 1.45µg/ml, IQR; 1.02-2.16) group than in the controls (median; 0.89µ/ml, IQR; 0.74-1.18) (P<0.001). High log10 IP-10 concentrations were positively correlated with high log10 viral loads (Spearman’s correlation coefficient [R]=0.21, P=0.003) and inversely correlated with low CD4 counts (R= -0.19, P=0.011). In contrast, log10 sCD14 was not significantly associated with either log10 viral loads (R=0.03, P=0.707) nor CD4 count (R=-0.04, P=0.568).Conclusion:We conclude that plasma sCD14 and IP-10 were elevated in the HIV-infected patients compared to HIV-uninfected individuals possibly due to on-going immune activation. In addition, plasma high concentrations of IP-10 but not sCD14 concentrations are associated with high VL and low CD4 count.

Correlation of mucocutaneous manifestations of HIV-infected patients in an ART center with CD4 counts.

As the search for reliable clinical indicators for management of human immunodeficiency virus/AIDS continues, mucocutaneous manifestations of HIV are considered among key clinical indicators for prediction of underlying degree of immunosuppression, systemic opportunistic infections, and disease progression. (1) To study the prevalence of mucocutaneous manifestations in HIV-seropositive patients attending the ART center of our hospital (2) To correlate mucocutaneous manifestations with CD4 cell counts. A total of 200 HIV-seropositive patients of adult age group visiting our hospital were included in the study. Information on demographics such as age, sex, transmission route, socioeconomic status, educational status, CD4 counts, and mucocutaneous findings was collected through interview administered survey and case records followed by oral and cutaneous examination. Mean CD4 cell count of asymptomatic HIV/AIDS patients was 580.96 cells/mm3. In comparison with the CD4 cell count of asymptomatic HIV-positive patients, (mean 580.96 cells/mm3) CD4 cell count of HIV-positive patients with various mucocutaneous manifestations (mean 409.65 cells/mm3) was correlated using student t-test and was statistically significant (P = 0.017). This study revealed maximum mucocutaneous lesions in the CD4 count range of 200-500. Nail changes accounted for the most common cutaneous manifestation with 53%, and pigmentation accounted for the most common oral manifestation with 39%. Mucocutaneous manifestations can arouse one to suspect the diagnosis of HIV infection in an otherwise healthy unwary patient. They can serve as a dependable marker of HIV disease.

HIV Infection Is Independently Associated with Increased CT Scan Lung Density

Noninfectious pulmonary complications are common among HIV-infected individuals and may be detected early by quantitative computed tomography (CT) scanning. The association of HIV disease markers with CT lung density measurement remains poorly understood. One hundred twenty-five participants free of spirometry-defined lung disease were recruited from a longitudinal cohort study of HIV-infected and HIV-uninfected individuals to undergo standardized CT scan of the chest. Parenchymal density for the entire lung volume was calculated using computerized software. Qualitative assessment of CT scans was conducted by two radiologists masked to HIV status. Linear regression models were developed to determine the independent association of markers of HIV infection on inspiratory scan mean lung density (MLD). HIV-infected participants had a significantly higher MLD (denser lung) compared to HIV-uninfected participants (-815 Hounsfield unit [HU] vs -837 HU; P = 0.002). After adjusting for relevant covariates, HIV infection was independently associated with 19.9 HU higher MLD (95% CI 6.04 to 33.7 HU; P = 0.005). In qualitative assessment, only ground glass attenuation and cysts were noted more commonly among HIV-infected individuals compared to HIV-uninfected individuals (34% vs 17% [P = 0.045] and 27% vs 10% [P = 0.03], respectively). No qualitative radiographic abnormalities attenuated the association between HIV infection and increased MLD. HIV infection is independently associated with increased lung density. Although qualitative CT abnormalities were common in this cohort, only ground glass attenuation and cysts were noted more frequently in HIV-infected participants, suggesting that the increased lung density observed among HIV-infected individuals may be associated with subclinical inflammatory lung changes.

Factors associated with fractures in HIV-infected persons: which factors matter?

Growing evidence suggests that tenofovir disoproxil fumarate decreases bone density among patients with HIV, but there are conflicting reports as to whether this decrease in bone density translates to higher fracture risk. We aimed to determine what factors were associated with an increased risk of fracture for patients with HIV, in particular whether tenofovir is associated with elevated fracture risk. We conducted a retrospective cohort study at two tertiary care hospitals in Boston, MA, between 2001 and 2012 to determine whether tenofovir use is associated with elevated all-site fracture risk, as compared to other antiretroviral medications. We also examined other potential factors associated with fracture among patients with HIV. We identified 1981 HIV-infected patients who had at some point used tenofovir and 682 patients who had not. The mean age was 43years, and 72% were male. The hepatitis C co-infection rate was 28%, about 40% had nadir CD4 count <200, and about 40% had a history of an AIDS-defining illness. We did not find an association between risk of fracture and tenofovir disoproxil fumarate (TDF) (adjusted RR (aRR) 0.8, 95% CI 0.6-1.1). However, co-infection with hepatitis C did increase risk of fracture (aRR 1.6, 95% CI 1.1-2.3), as did nadir CD4 count <200 (aRR 3.1, 95% CI 1.9-5.0) and history of AIDS-defining illness (aRR 1.6, 95% CI 1.1-2.2). There was no association found between fracture and tenofovir use, but there were associations between co-infection with hepatitis C and markers of advanced HIV disease and fracture.

Effect of rosuvastatin on plasma coenzyme Q10 in HIV-infected individuals on antiretroviral therapy

Background: Coenzyme Q10 (CoQ10) deficiency has been associated with statin-induced myopathy, and supplementation with CoQ10 may reduce inflammation markers. The effects of statins on CoQ10 and its anti-inflammatory properties have not been investigated in HIV-positive patients.Objective: The objectives of this study were to examine the effect of rosuvastatin on CoQ10 and CoQ10/LDL ratio over 24-week SATURN-HIV trial, explore the associations between CoQ10 levels and markers of vascular disease, inflammation, and immune activation, and assess whether changes in CoQ10 affected the anti-inflammatory effects of statin therapy or were associated with myalgia symptoms.Methods: This was a secondary analysis of the SATURN-HIV trial, a 96-week randomized clinical trial of 10 mg daily rosuvastatin vs. placebo in HIV-infected patients on antiretroviral therapy. We assessed the statin treatment effect on CoQ10 levels and CoQ10/LDL ratios and whether changes in these markers were related to myalgias. Relationships between CoQ10, subclinical vascular disease, and biomarkers of inflammation and immune activation were explored using Spearman correlations and multivariable regression models.Results: Overall, 147 patients were included. Median age was 46 years; 78% were male and 68% African American. At baseline, CoQ10 levels and CoQ10/LDL ratio were modestly correlated with markers of HIV disease, immune activation, and carotid distensibility. After 24 weeks of statin therapy, CoQ10 levels decreased (p = 0.002 for between group difference) and CoQ10/LDL ratio increased (p = 0.036). In the statin treatment arm, we did not find evidence of a relationship between changes in CoQ10 or CoQ10/LDL ration and changes in markers of inflammation or immune activation. There was a borderline statistically significant association between changes in CoQ10 and myalgia symptoms [OR 4.0 per 0.1 mg/L decrease in CoQ10, p = 0.07].Conclusion: Twenty-four weeks of 10 mg daily rosuvastatin decreases CoQ10 concentration and increases CoQ10/LDL ratio in HIV-infected patients on antiretroviral therapy.

Unhealthy Alcohol Use is Associated with Monocyte Activation Prior to Starting Antiretroviral Therapy.

Alcohol use may accelerate HIV disease progression, but the plausible biological mechanisms have not been clearly elucidated. HIV-positive persons who were not on antiretroviral therapy (ART) completed the baseline assessment for a longitudinal study examining the association of alcohol use with HIV disease markers. Oversampling drinkers, baseline samples were tested for markers of monocyte activation (soluble CD14 [sCD14]), inflammation (interleukin-6 [IL-6]-6), and coagulation (d-dimer). We defined "unhealthy alcohol use" as testing positive using the Alcohol Use Disorders Identification Test-Consumption (≥3 for women and ≥4 for men) in the past 3 months or testing positive using a biomarker of heavy drinking, phosphatidylethanol (≥50 ng/ml). Multiple linear regression was used to examine the associations of unhealthy alcohol use with sCD14, log10 IL-6, and d-dimer. Compared to those who were abstinent from alcohol, unhealthy drinkers had significantly higher sCD14 levels (mean = 1,676 vs. 1,387 ng/ml; mean difference [95% confidence interval (CI)] = 289 [83, 495], p < 0.01). In analyses adjusted for demographic factors, current cigarette smoking, and HIV disease markers, unhealthy drinkers continued to display significantly higher sCD14 levels compared to those who were abstinent from alcohol (adjusted mean = 1,670 vs. 1,406 ng/ml; adjusted mean difference [95% CI] = 264 [47, 480], p = 0.02). Unhealthy alcohol use was not significantly associated with IL-6 or d-dimer levels. Unhealthy alcohol use was independently associated with a marker of monocyte activation (i.e., higher sCD14) that predicts mortality in treated HIV infection. Longitudinal research should examine whether unhealthy alcohol use predicts changes in sCD14 prior to and following ART initiation.

Temporal Trends in Patient Characteristics and Outcomes Among Children Enrolled in Mozambique's National Antiretroviral Therapy Program.

During 2004-2009, >12,000 children (<15 years old) initiated antiretroviral therapy (ART) in Mozambique. Nationally representative outcomes and temporal trends in outcomes were investigated. Rates of death, loss to follow-up (LTFU) and attrition (death or LTFU) were evaluated in a nationally representative sample of 1054 children, who initiated ART during 2004-2009 at 25 facilities randomly selected using probability-proportional-to-size sampling. At ART initiation during 2004-2009, 50% were male; median age was 3.3 years; median CD4% was 13%; median CD4 count was 375 cells/μL; median weight-for-age Z score was -2.1. During 2004-2009, median time from HIV diagnosis to care initiation declined from 33 to 0 days (P = 0.001); median time from care to ART declined from 93 to 62 days (P = 0.004); the percentage aged <2 at ART initiation increased from 16% to 48% (P = 0.021); the percentage of patients with prior tuberculosis declined from 50% to 10% (P = 0.009); and the percentage with prior lymphocytic interstitial pneumonia declined from 16% to 1% (P < 0.001). Over 2652 person-years of ART, 183 children became LTFU and 26 died. Twelve-month attrition was 11% overall but increased from 3% to 22% during 2004-2009, mainly because of increases in 12-month LTFU (from 3% to 18%). Declines in the prevalence of markers of advanced HIV disease at ART initiation probably reflect increasing ART access. However, 12-month LTFU increased during program expansion, and this negated any program improvements in outcomes that might have resulted from earlier ART initiation.

Magnitude of Anemia and Associated Factors among Pediatric HIV/AIDS Patients Attending Zewditu Memorial Hospital ART Clinic, Addis Ababa, Ethiopia

Background. Anemia is one of the most commonly observed hematological abnormalities and an independent prognostic marker of HIV disease. The aim of this study was to determine the magnitude of anemia and associated factors among pediatric HIV/AIDS patients attending Zewditu Memorial Hospital (ZMH) ART Clinic in Addis Ababa, Ethiopia. Methods. A cross-sectional study was conducted among pediatric HIV/AIDS patients of Zewditu Memorial Hospital (ZMH) between August 05, 2013, and November 25, 2013. A total of 180 children were selected consecutively. Stool specimen was collected and processed. A structured questionnaire was used to collect data on sociodemographic characteristics and associated risk factors. Data were entered into EpiData 3.1.1. and were analyzed using SPSS version 16 software. Logistic regressions were applied to assess any association between explanatory factors and outcome variables. Results. The total prevalence of anemia was 22.2% where 21 (52.5%), 17 (42.5%), and 2 (5.0%) patients had mild, moderate, and severe anemia. There was a significant increase in severity and prevalence of anemia in those with CD4+ T cell counts below 350 cells/μL (P < 0.05). Having intestinal parasitic infections (AOR = 2.7, 95% CI, 1.1–7.2), having lower CD4+ T cell count (AOR = 3.8, 95% CI, 1.6–9.4), and being HAART naïve (AOR = 2.3, 95% CI, 1.6–9.4) were identified as significant predictors of anemia. Conclusion. Anemia was more prevalent and severe in patients with low CD4+ T cell counts, patients infected with intestinal parasites/helminthes, and HAART naïve patients. Therefore, public health measures and regular follow-up are necessary to prevent anemia.

Associations of host genetic variants on CD4⁺ lymphocyte count and plasma HIV-1 RNA in antiretroviral naïve children.

CD4 T-lymphocyte (CD4) counts and HIV plasma RNA concentration (RNA) are 2 key HIV disease markers. The complex interplay between virus and host genetics may contribute to differences in viral set point and CD4 status. Determining the effects of host genetic variation on HIV disease markers is often complicated by the use of antiretroviral therapy. In this study, the association between genetic variants and baseline HIV RNA and CD4 counts was examined in a large cohort of antiretroviral naïve children. Specimens from 1053 HIV-infected children were screened for single nucleotide polymorphisms in 78 regions from 17 genes. Linear regression with a robust variance estimator was used to test the association between genetic markers with HIV RNA and CD4 count, controlling for age, race/ethnicity and study. False discovery rate (FDR) controlling was used to adjust for multiple testing. The study population was 60% black, 26% Hispanic and 13% white; median age 2.35 years; 55% female. Baseline median CD4 count was 780/mm; median log10 HIV RNA was 5.17 copies/mL. For analyses of the associations of genetic makers with baseline CD4 count, 6 HLA and 4 additional markers exhibited P < 0.05, but none met the criteria for statistical significance with FDR controlled at 0.05. For baseline HIV RNA, HLA DRB1*15, DRB1*10, B-27/57, B-14, Cw-8, B-57 were statistically significant with FDR controlled at 0.05. These results provide strong evidence that HLA DRB1*15, DRB1*10, B-27/57, B-14, Cw-8, B-57 are associated with HIV RNA and play a role in HIV pathogenesis in infected children.

Immune Activation Is Associated With Increased Gut Microbial Translocation in Treatment-Naive, HIV-Infected Children in a Resource-Limited Setting

Gut damage resulting in microbial translocation (MT) is considered a major cause of immune activation (IA) in HIV infection, but data in children are limited, particularly in the absence of antiretroviral therapy. Sixty perinatally HIV-infected, antiretroviral therapy-naive children, aged 2-12 years, were evaluated for plasma levels of lipopolysaccharide, DNA sequences encoding bacterial 16 second ribosomal DNA (16S rDNA) and soluble CD14 concurrently with markers of CD4 and CD8 T-cell IA and immune exhaustion (IE), CD4 counts, and plasma viral load. At study entry, participants were classified into immune categories (ICs): IC1 (CD4% > 25), IC2 (CD4% 15-25), and IC3 (CD4% < 15). Age-matched HIV-uninfected children served as controls. Data were evaluated at study entry and at 12 months. Levels of MT, IA, and IE were increased in patients as compared with controls, were highest in patients in IC3 group, and did not change over 12 months. MT products lipopolysaccharide and 16S rDNA correlated with each other and each correlated with plasma viral load, soluble CD14, and T-cell IA and IE. There was a correlation of IA with IE. CD4 counts and percentage were inversely correlated with MT products and underlying CD4 activation. In a natural history cohort of HIV-infected children not on therapy, MT was more pronounced in the most severely immunocompromised patients and was associated with IA. Strategies to reduce MT may help to reduce IA and prevent CD4 depletion.

Knowledge of disease markers and quality of patient–provider interaction among adolescents with perinatally acquired HIV: implications for transition to adult care

During the early years of the AIDS epidemic, youth born with perinatally acquired HIV (PHIV) were not expected to survive childhood. Today, they are living well into young adulthood, necessitating a transition from pediatric to adult infectious disease care. Previous research has emphasized the importance of disease-specific knowledge in preparing adolescents for a successful transition. Additional research has found that the quality of patient–provider relationships is associated with the intent to seek and continue care among adolescents. Among adults living with HIV, high-quality patient–provider interactions are related to improved medication adherence. The purpose of this study was to investigate the association between knowledge of disease markers (CD4 count and viral load) and quality of patient–provider interactions among 40 adolescents with PHIV (mean age 17.3 years), 90% of whom were African-American, with attention to implications for transition readiness. Twelve participants (30%) accurately defined what a CD4 count is, and only two participants accurately reported their own CD4 counts. Less than half of the participants correctly defined viral load, and only eight participants (20%) knew their own viral load. Seventeen participants (42.5%) answered all four questions incorrectly. All participants completed the Adolescent Patient Provider Interaction Scale, which indicated that the majority of adolescents experienced positive interactions with providers. Knowledge of disease markers was positively associated with patient–provider interaction. The significant association between disease marker knowledge and quality of patient–provider interactions suggests that adolescents with higher quality interactions with their providers possess greater knowledge about the disease and their own status. Poor understanding of HIV disease markers may adversely influence the transition to adult care. However, the strong patient–provider relationship offers a vehicle to promote increasing medical autonomy among adolescents, including understanding of important disease-related markers.

HIV-associated neurocognitive disorder

Neurological involvement in HIV is often associated with cognitive impairment. Although severe and progressive neurocognitive impairment has become rare in HIV clinics in the era of potent antiretroviral therapy, most patients with HIV worldwide have poor outcomes on formal neurocognitive tests. In this Review, we describe the manifestations of HIV-associated neurocognitive disorder in the era of effective HIV therapy, outline diagnosis and treatment recommendations, and explore the research questions that remain. Although comorbid disorders, such as hepatitis C infection or epilepsy, might cause some impairment, their prevalence is insufficient to explain the frequency with which it is encountered. HIV disease markers, such as viral load and CD4 cell counts, are not strongly associated with ongoing impairment on treatment, whereas cardiovascular disease markers and inflammatory markers are. New cerebrospinal fluid and neuroimaging biomarkers are needed to detect and follow impairment. Ongoing research efforts to optimise HIV therapy within the CNS, and potentially to intervene in downstream mechanisms of neurotoxicity, remain important avenues for future investigation. Ultimately, the full control of virus in the brain is a necessary step in the goal of HIV eradication.

Critical Consciousness, Racial and Gender Discrimination, and HIV Disease Markers in African American Women with HIV

Critical consciousness, the awareness of social oppression, is important to investigate as a buffer against HIV disease progression in HIV-infected African American women in the context of experiences with discrimination. Critical consciousness comprises several dimensions, including social group identification, discontent with distribution of social power, rejection of social system legitimacy, and a collective action orientation. The current study investigated self-reported critical consciousness as a moderator of perceived gender and racial discrimination on HIV viral load and CD4+ cell count in 67 African American HIV-infected women. Higher critical consciousness was found to be related to higher likelihood of having CD4+ counts over 350 and lower likelihood of detectable viral load when perceived racial discrimination was high, as revealed by multiple logistic regressions that controlled for highly active antiretroviral therapy (HAART) adherence. Multiple linear regressions showed that at higher levels of perceived gender and racial discrimination, women endorsing high critical consciousness had a larger positive difference between nadir CD4+ (lowest pre-HAART) and current CD4+ count than women endorsing low critical consciousness. These findings suggest that raising awareness of social oppression to promote joining with others to enact social change may be an important intervention strategy to improve HIV outcomes in African American HIV-infected women who report experiencing high levels of gender and racial discrimination.

Relationship of plasma cytokines and clinical biomarkers to memory performance in HIV

Chronic systemic immune activation and inflammatory processes have been linked to brain dysfunction in medically stable HIV-infected people. We investigated the association between verbal memory performance and plasma concentrations of 13 cytokines measured using multiplexed bead array immunoassay in 74 HIV-seropositive individuals and 50 HIV-seronegative controls. Memory performance was positively related to levels of IL-8 and IFN-γ, and negatively related to IL-10 and IL-18 and to hepatitis C infection. Memory performance was not significantly related to HIV disease markers. The results indicate the importance of systemic immune and inflammatory markers to neurocognitive function in chronic and stable HIV disease.

GSTM1 null‐allele polymorphism, oxidative stress and HIV disease progression in an HIV‐infected population

ObjectiveTo examine the effects GSTM1 null‐allele polymorphism on oxidative stress (OS) and disease progression in HIV+ adults.MethodsGSTM1 genotype was determined by quantitative PCR. OS (mitochondrial 8‐oxo‐2′‐deoxyguanosine, and Complex I and IV) and HIV disease (CD4 count and viral load) markers were measured in 129 HIV+ adults. Those with BMI &gt;;28kg/m2 were excluded. Gene copies were not quantified, thus the Hardy‐Weinberg formula was not applicable.ResultsFunctional GSTM1 occurred in 66% (62/94) Blacks, and 33% (11/33) of the Caucasians. Those with functional GSTM1 had higher CD4 count (β=5.55, p=0.04), and lower viral load (β=−1.11, p=0.001), and mitochondrial 8‐oxo‐2′‐deoxyguanosine (β−0.28, p=0.03). Complex I activity (β=7.53. p=0.04) was increased over time compared to those with null‐allele GSTM1, controlling for other variables affecting OS.ConclusionThe presence of a functional GSTM1 genotype is associated with improved antioxidant activity over time. GSTM1 null‐allele polymorphism appears to have a detrimental effect on immune function and viral load control, suggesting a potential benefit from antioxidants in HIV infected patients with the defective gene.Supported by NIDA

Effect of GSTM1-Polymorphism on Disease Progression and Oxidative Stress in HIV Infection: Modulation by HIV/HCV Co-Infection and Alcohol Consumption

ObjectiveTo examine the effects of GSTM1 null-allele polymorphism on oxidative stress and disease progression in HIV infected and HIV/hepatitis C (HCV) co-infected adults.MethodsHIV-infected and HIV/HCV co-infected participants aged 40–60 years old with CD4 cell count >350 cells/ µl, were recruited. GSTM1 genotype was determined by quantitative PCR. Oxidative stress (mitochondrial 8-oxo-2’-deoxyguanosine [8-oxo-dG], malondialdehyde [MDA], oxidized glutathione and Complexes I and IV), apoptosis and HIV disease (CD4 count and viral load) markers were measured. Gene copies were not quantified, thus the Hardy-Weinberg formula was not applicable.ResultsOf the 129 HIV-infected participants, 58 were HIV/HCV co-infected. GSTM1 occurred in 66% (62/94) in those of African descent, and 33% (11/33) of the Caucasians. Those with GSTM1 coding for the functional antioxidant enzyme Glutathione S-transferase (GST), had higher CD4 cell count (β=3.48, p=0.034), lower HIV viral load (β=−0.536, p=0.018), and lower mitochondrial 8-oxo-dG (β=−0.28, p=0.03). ART reduced oxidative stress in the participants with the GSTM1 coding for the functional antioxidant enzyme. HIV/HCV co-infected participants with the GSTM1 coding for the functional antioxidant enzyme also had lower HIV viral load, lower 8-oxo-dG and lower rate of apoptosis, but also higher oxidized glutathione. Alcohol consumption was associated with lower HIV viral load but higher oxidized glutathione in those with the GSTM1 genotype coding for the functional antioxidant enzyme.ConclusionThe GSTM1 genotype coding for the functional antioxidant enzyme is associated with lower HIV disease severity, and with lower oxidative stress, compared to GSTM1 null-allele polymorphism. HCV co-infection and alcohol use may be associated with increased oxidative stress even in the presence of the GSTM1 coding for the functional antioxidant enzyme. The null-gene, on the contrary, appears to have a detrimental effect on immune function, viral load control, and antioxidant status, suggesting a potential benefit from antioxidants in HIV infected patients with the defective gene.

Gender-specific effects of an augmented written emotional disclosure intervention on posttraumatic, depressive, and HIV-disease-related outcomes: A randomized, controlled trial.

Trauma histories and symptoms of PTSD occur at very high rates in people with HIV and are associated with poor disease management and accelerated disease progression. The authors of this study examined the efficacy of a brief written trauma disclosure intervention on posttraumatic stress, depression, HIV-related physical symptoms, and biological markers of HIV disease progression. HIV-infected men and women were randomized to four 30-min expressive writing sessions in either a treatment (trauma writing) or an attention control (daily events writing) condition. The disclosure intervention augmented the traditional emotional disclosure paradigm with probes to increase processing by focusing on trauma appraisals, self-worth, and problem solving. Outcomes were assessed at baseline, 1-, 6-, and 12-month follow-up. Hierarchical linear modeling (N = 244, intent-to-treat analyses) revealed no significant treatment effects for the group as a whole. Gender by treatment group interactions were significant such that women in the trauma-writing group had significantly reduced posttraumatic stress disorder (PTSD) symptoms (p = .017), depression (p = .009), and HIV-related symptoms (p = .022) compared with their controls. In contrast, men in the trauma-treatment condition did not improve more than controls on any outcome variables. Unexpectedly, men in the daily-event-writing control group had significantly greater reductions in depression then men in the trauma-writing group. Treatment effects were magnified in women when the analysis was restricted to those with elevated PTSD symptoms at baseline. A brief (4-session) guided written emotional disclosure intervention resulted in significant and meaningful reductions in PTSD, depression, and physical symptoms for women with HIV, but not for men.

Expression Analysis of LEDGF/p75, APOBEC3G, TRIM5alpha, and Tetherin in a Senegalese Cohort of HIV-1-Exposed Seronegative Individuals

BackgroundHIV-1 replication depends on a delicate balance between cellular co-factors and antiviral restriction factors. Lens epithelium-derived growth factor (LEDGF/p75) benefits HIV, whereas apolipoprotein B mRNA-editing catalytic polypeptide-like 3G (APOBEC3G), tripartite motif 5alpha (TRIM5α), and tetherin exert anti-HIV activity. Expression levels of these proteins possibly contribute to HIV-1 resistance in HIV-1-exposed populations.Methodology/Principal FindingsWe used real-time PCR and flow cytometry to study mRNA and protein levels respectively in PBMC and PBMC subsets. We observed significantly reduced LEDGF/p75 protein levels in CD4+ lymphocytes of HIV-1-exposed seronegative subjects relative to healthy controls, whereas we found no differences in APOBEC3G, TRIM5α, or tetherin expression. Untreated HIV-1-infected patients generally expressed higher mRNA and protein levels than healthy controls. Increased tetherin levels, in particular, correlated with markers of disease progression: directly with the viral load and T cell activation and inversely with the CD4 count.Conclusions/SignificanceOur data suggest that reduced LEDGF/p75 levels may play a role in resistance to HIV-1 infection, while increased tetherin levels could be a marker of advanced HIV disease. Host factors that influence HIV-1 infection and disease could be important targets for new antiviral therapies.

Prevalence and predictors of kaposi sarcoma herpes virus seropositivity: a cross-sectional analysis of HIV-infected adults initiating ART in Johannesburg, South Africa

BackgroundKaposi sarcoma (KS) is the most common AIDS-defining tumour in HIV-infected individuals in Africa. Kaposi sarcoma herpes virus (KSHV) infection precedes development of KS. KSHV co-infection may be associated with worse outcomes in HIV disease and elevated KSHV viral load may be an early marker for advanced HIV disease among untreated patients. We examined the prevalence of KSHV among adults initiating antiretroviral therapy (ART) and compared immunological, demographic and clinical factors between patients seropositive and seronegative for KSHV.ResultsWe analyzed cross-sectional data collected from 404 HIV-infected treatment-naïve adults initiating ART at the Themba Lethu Clinic, Johannesburg, South Africa between November 2008 and March 2009. Subjects were screened at ART initiation for antibodies to KSHV lytic K8.1 and latent Orf73 antigens. Seropositivity to KSHV was defined as positive to either lytic KSHV K8.1 or latent KSHV Orf73 antibodies. KSHV viremia was determined by quantitative PCR and CD3, 4 and 8 lymphocyte counts were determined with flow cytometry. Of the 404 participants, 193 (48%) tested positive for KSHV at ART initiation; with 76 (39%) reactive to lytic K8.1, 35 (18%) to latent Orf73 and 82 (42%) to both. One individual presented with clinical KS at ART initiation. The KSHV infected group was similar to those without KSHV in terms of age, race, gender, ethnicity, smoking and alcohol use. KSHV infected individuals presented with slightly higher median CD3 (817 vs. 726 cells/mm3) and CD4 (90 vs. 80 cells/mm3) counts than KSHV negative subjects. We found no associations between KSHV seropositivity and body mass index, tuberculosis status, WHO stage, HIV RNA levels, full blood count or liver function tests at initiation. Those with detectable KSHV viremia (n = 19), however, appeared to present with signs of more advanced HIV disease including anemia and WHO stage 3 or 4 defining conditions compared to those in whom the virus was undetectable.ConclusionsWe demonstrate a high prevalence of KSHV among HIV-infected adults initiating ART in a large urban public-sector HIV clinic. KSHV viremia but not KSHV seropositivity may be associated with markers of advanced HIV disease.