Effect of anti-retroviral therapy on oxidative stress in hospitalized HIV-infected adults with and without TB.

BackgroundHIV infection and opportunistic infections cause oxidative stress (OS), which is associated with tissue damage. Anti-retroviral therapy (ART) is used to treat HIV and decrease the risk of opportunistic infections, but it is unclear whether ART reduces OS. Association of ART with OS was investigated.MethodsWe stratified a convenience sample of frozen serum or plasma from HIV-infected, ART-naïve (n=21); HIV-infected, ART-treated (n=14); HIV and PTB co-infected, ART-naïve (n=21); HIV and PTB co-infected, ART-treated (n=25) patients. Controls (n=21) were HIV-negative adults without TB symptoms. Concentration of OS markers namely: transaminases (ALT and AST), gamma glutamyl transpeptidase (GGT), albumin, total protein, malondialdehyde (MDA), vitamin C, and total anti-oxidant status (TAS) were determined.ResultsAST (p<0.001), GGT (p<0.001), total protein (p=0.001) and MDA (p<0.001) were higher in HIV patients compared to controls. Vitamin C (P<0.0001) and albumin (p<0.01) were lower in HIV-patients relative to controls. ART was only associated with higher albumin (p=0.001), higher GGT (p=0.02) and lower vitamin C (p=0.009). HIV and PTB co-infection was only significantly associated with higher GGT (p=0.01) and AST (p=0.03).ConclusionWe identified severe OS among HIV-patients. ART was associated with both increased and reduced markers of OS hence suggesting that ART may not attenuate OS

Renal and Electrolyte Disturbances in HIV infected patients

BACKGROUND & OBJECTIVES: HIV/AIDS patients may have renal involvement also, however, Indian data are sparse. The present study was done to find the prevalance of renal diseases in HIV/AIDS patients attending ART Centre, Govt. Rajaji hospital Madurai. METHODS: A previously designed proforma will be used to collect the demographic and clinical details of the patients. Two hundred patients will be selected randomly. All the patients will undergo detailed clinical evaluation, appropriate investigations such as CD4+ count, Blood sugar, Blood urea, serum creatinine, Serum electrolytes, urine routine and USG abdomen. The study group will be divided into two groups: Group A ART naive patients and Group B HIV patients on ART. RESULTS: About 60% of study population were in the age group of 21-40 years and 36% of study populalation were in the age group of 41-60 year. Around 62% of study population were ART NAIVE and 38% were on ART. Gender distribution is of around 65% male and 35% female. Blood urea and creatinine level was raised in 33 patients (16.5%) of study population, among them 9 patients (27%) on ART and 24 patients (73%) were ART NAÏVE. Around 45% patients have CD4 count between 200-500 and 32% patients have CD4 count 501-1000. Mean urea level in the study population was found to be 30.140 ; with a standard deviation of 15.372. Mean serum creatinine in the study population is 1.109 with a standard deviation of 0.618. Blood urea and creatinine levels are raised in ART naïve patients than patients on ART, p value were 0.038 and 0.047 respectively, it is statistically significant which indicates urea and creatinine level was higher in ART NAÏVE patients and lower in patients taking ART. Around 72 (36%) patients were found to be having hyponatremia. Mean serum sodium in the study population is 133.7 with a standard deviation of 7.199. Around 41 (20.5% ) patients were found to be having hypokalemia . Mean serum potassium in the study population is 3.892 with a standard deviation of 0.894. Serum sodium and potassium level was found to be decreased in more ART naïve patients than those on ART, p value were < 0.027 and < 0.015 respectively which is statistically significant and indicates Na+ and K+ level was significantly lower in ART NAÏVE patients compared to patients on ART. Proteinuria present in 33 patients (16.5%) of study population, among them 9 patients (27%) on ART and 24 patients (73%) were ART NAÏVE. Significant proteinuria was higher in ART NAÏVE patients and lower in patient taking ART. USG abdomen showed increased cortical echoes in 30 patients (15%) of study population, among them 7 patients (23%) on ART and 23 patients (77%) were ART NAÏVE. Renal cortical echoes were higher in ART NAÏVE patients and low occurence in patient taking ART. Cortico medullary differentiation was maintained in all patients. INTERPRETATION & CONCLUSIONS: Renal involvement seems to be common in Indian patients with HIV. Elevated Blood urea, serum creatinine and proteinuria could be an early marker of HIV associated renal lesions and screening for their presence may be beneficial. A low occurrence of renal involvement found in patients already on ART suggests some renoprotective effect of ART. Hyponatremia, hypokalemia and hyperkalemia are common electrolyte disorders in HIV infected patients. Among them hyponatremia and hypokalemia incidence is more in ART NAIVE patients than patient on ART. This indicates decreased incidence of electrolyte disturbances on patients on ART may be due to less oppurtunistic infections in them. The present findings need to be confirmed with further studies with larger sample size and prolonged period of follow up

The rainbow cohort: 96 week follow-up of saquinavir-containing regimens in previously antiretroviral therapy (ART)-naïve and pre-treated but protease inhibitor (PI)- naïve hiv-infected patients

<p>Abstract</p> <p>Objective</p> <p>We have previously reported data from the German cohort of the multinational observational prospective RAINBOW survey which assessed the tolerability and efficacy of ritonavir-boosted saquinavir (SQV/r)-containing regimens over 48 weeks in routine clinical practice. This analysis presents data from antiretroviral (ART)-naïve and pretreated but protease inhibitor (PI)-naïve patients treated in a long-term one line (96 weeks) follow-up of the initial study.</p> <p>Methods</p> <p>All ART-and PI-naïve patients from the initial RAINBOW cohort who had recorded data to one line 96 weeks of treatment were eligible for inclusion in the current analysis. Efficacy assessments included the proportion of patients with HIV-1 RNA < 50 and < 400 copies/mL and changes in CD4 cell count from baseline to week 96. Tolerability assessments included changes in liver enzymes and lipid levels from baseline to week 96. For evaluation of efficacy, intent-to-treat analysis, in which missing values were recorded as failure (ITT), and last-observation-carried-forward (LOCF) analysis were used. Metabolic parameters were assessed using LOCF analysis.</p> <p>Results</p> <p>The analysis included 175 ART-naïve and 109 pretreated but PI-naïve patients. After 96 weeks, a similar proportion of patients in the ART-naïve and in the pretreated but Pi-naïve group had HIV-1 RNA levels < 400 copies/mL (68.0% and 70.6% [ITT], respectively; 96.6% and 90.8% [LOCF], respectively). The proportion of patients with HIV RNA < 50 copies/mL was higher in the ART-naïve group compared with the pretreated but PI-naïve group (61.1% and 56.9% [ITT], respectively; 84.0% and 75.2% [LOCF], respectively). Median change in CD4 cell count from baseline to week 96 was'+263 cells/mm³(IQR 170; 384. LOCF; p < 0.0001) in the ART-naïve group, and one line +181 cells/mm³(IQR 60; 309. LOCF; p < 0.0001) in the pretreated but PI-naïve group. Treatment was well tolerated, with only 2.5% of patients withdrawing from treatment due to side effects. There were no clinically relevant changes in liver enzyme levels. Overall total cholesterol, triglyceride, and low-and high-density lipoprotein levels increased to week 96, although levels remained within normal ranges in the majority of ART-naïve and pretreated patients.</p> <p>Conclusions</p> <p>This follow-up analysis confirms the long term efficacy and tolerability of SQV/r in ART-naïve and pretreated but PI-naïve patients in the real-life clinical setting.</p

Anti-retroviral therapy increases the prevalence of dyslipidemia in South African HIV-infected patients

Purpose Data on the prevalence of dyslipidaemia and associated risk factors in HIV-infected patients from sub-Saharan Africa is sparse. We performed a cross-sectional analysis in a cohort of HIV-infected South African adults. METHODS: We studied HIV-infected patients who were either antiretroviral therapy (ART)-naive or receiving non-nucleoside reverse transcriptase inhibitor (NNRTI)-based or protease inhibitor (PI)-based ART. Evaluation included fasting lipograms, oral glucose tolerance tests and clinical anthropometry. Dyslipidemia was defined using the NCEP ATPIII guidelines. RESULTS: The median age of the participants was 34 years (range 19-68 years) and 78% were women. The prevalence of dyslipidemia in 406 ART-naive and 551 participants on ART was 90.0% and 85%, respectively. Low HDL-cholesterol (HDLC) was the most common abnormality [290/406 (71%) ART-naïve and 237/551 (43%) ART- participants]. Participants on ART had higher triglycerides (TG), total cholesterol (TC), LDL-cholesterol (LDLC) and HDLC than the ART-naïve group. Severe dyslipidaemia, (LDLC> 4.9 mmol/L or TG >5.0 mmol/L) was present in <5% of participants. In multivariate analyses there were complex associations between age, gender, type and duration of ART and body composition and LDLC, HDLC and TG, which differed between ART-naïve and ART-participants. CONCLUSION: Participants on ART had higher TG, TC, LDLC and HDLC than those who were ART-naïve but severe lipid abnormalities requiring evaluation and treatment were uncommon

Impact of HIV infection and zidovudine therapy on RBC parameters and urine methylmalonic acid levels

Background. Anaemia is a common complication of human immunodeficiency virus (HIV) infection. The aim of this study was to investigate the impact of HIV infection and zidovudine on red blood cells (RBC) parameters and urine methylmalonic acid (UMMA) levels in patients with HIV infection. Material and Methods. A cross-sectional study involving 114 subjects, 94 of which are HIV-infected nonanaemic and 20 HIV negative subjects (Cg) as control. Full blood count parameters and urine methylmalonic acid (UMMA) level of each subject were determined. Associations were determined by Chi-square test and logistic regression statistics where appropriate. Results. Subjects on zidovudine-based ART had mean MCV (93 fL) higher than that of control group (82.9 fL) and ART-naïve (85.9 fL) subjects and the highest mean RDW. Mean UMMA level, which reflects vitamin B12 level status, was high in all HIV-infected groups but was significantly higher in ART-naïve subjects than in ART-experienced subjects. Conclusion. Although non-zidovudine therapy may be associated with macrocytosis (MCV > 95 fL), zidovudine therapy and ART naivety may not. Suboptimal level of vitamin B12 as measured by high UMMA though highest in ART-naïve subjects was common in all HIV-infected subjects

Co-occurrence of shedding Herpes Simplex Virus type-2 (HSV-2), Human Papilloma Virus (HPV) and Human Immunodeficiency Virus 1 (HIV-1) in the female genital tract among HIV-infected women

Introduction: Human Immunodeficiency Virus remains as one of the largest pandemics in the world, with the prevalence of more than 70% of HIV-infected individual reside in Sub-Saharan Africa. Moreover, other sexually transmitted viral infection such as Human Papillomavirus and Herpes Simplex Virus also show a high prevalence in Sub-Saharan Africa. Recent studies show the presence of other viral STI in the genital region may have increased HIV shedding in the genital region. However, it not clearly known if the presence of ART or HIV may affect the shedding of other viral STI in the genital region and if the combination of other viral STI treatment and ART is necessary to treat an individual with multiple STI infection. Methods: This is a secondary data analysis study, based on analysing the data collected from a single-site, double-blinded randomized control study (2-IUD study). The research site was the Gugulethu Community Health Centre, Cape Town, South Africa and samples were collected between 2014 and 2018. Analysis was conducted on genital tract specimens of study participants obtained via the Menstrual Cup (MC) and Endocervical Swabs (ECS), collected at baseline, 3 and 6 months’ follow up visit from randomly selected 52 ART-Naïve participants and 56 age-matched women from the ART-Using group of the primary study. Logistic regression models were constructed to measure the associations between possible risk factors and viral STIs. Results are presented as odds ratios (OR) with 95% confidence intervals (CI). Results: ART-Naïve women had higher rates of HIV shedding in the genital tract at each visit. However, more than half of women using ART, most of them virally suppressed, had detectable genital HIV at one or more visits. Most of the participants showed pre-exposure to HSV-2, but shedding of HSV-2 was substantially less common. HPV was detected in 72% of the participants, with no significant difference by ART status. Overall, 70.3% of samples had at least one viral pathogen detected - 60.4% among ART-Using women compared to 82.8% in ART-Naïve women (P<0.001). Compared to ART-Naïve women, ART-Using women were significantly less likely to have co-occurrence of viral shedding overall. However, ART-Using women with higher VL had levels of viral co-occurrence similar to those of ART-Naïve women. Conclusion: Our analysis demonstrated that the ART-Using women were less likely to shed HIV, HSV-2, HPV and viral STI co-infection in the genital tract compared to ART-Naïve women. This may be be driven by plasma VL levels where ART-Using women with lower VL are less likely to shed these viruses compared to women with elevated VL, including those not on ART

Impact of Antiretroviral Therapy on the Incidence of Tuberculosis: The Brazilian Experience, 1995–2001

The human immunodeficiency virus (HIV) fuels tuberculosis (TB) epidemics. In controlled clinical trials, antiretroviral therapy (ART) reduces TB incidence in HIV-infected patients. In this study we determine if, under programmatic conditions, Brazil's policy of universal ART access has impacted TB incidence among HIV-infected patients.We abstracted clinical information from records of HIV-infected patients managed in the public sector in 11 Brazilian states between 1/1/1995 and 12/31/2001. Case ascertainment (TB and HIV) utilized guidelines (with added stringency) published by Brazil's Ministry of Health. We determined TB incidence and hazards ratio (HR) for ART-naïve and ART-treated [including highly active ART (HAART)] patients employing Cox proportional hazards analysis.Information from 463 HIV-infected patients met study criteria. The median age of the study population was 34 years, 70% were male, and mean follow-up to primary endpoints--TB, death, and last clinic visit--was 330, 1059, and 1125 days, respectively. Of the 463 patients, 76 (16%) remained ART-naïve. Of the patients who never received HAART (n = 157) 81 were treated with ART non-HAART. Of the patients who received any ART (n = 387), 306 were treated with HAART (includes those patients who later switched from ART non-HAART to HAART). Tuberculosis developed in 39/463 (8%) patients. Compared to HAART- and ART non-HAART-treated patient groups, TB incidence was 10- (p<0.001) and 2.5-fold (p = 0.03) higher in ART-naïve patients, respectively. The median baseline absolute CD4+ T-lymphocyte count for patients who developed TB was not significantly different from that of patients who remained TB free. In multivariate analysis, the incidence of TB was statistically significantly lower in HAART-treated [HR 0.2; 95% (CI 0.1, 0.6); p<0.01] compared to ART naïve patients. A baseline CD4+ T-lymphocyte count <200 cells/mm(3) [HR 2.5; (95% CI 1.2, 5.4); p<0.01], prior hospitalization [HR 4.2; (95% CI 2.0, 8.8); p<0.001], prior incarceration [HR 4.1; 95% CI 1.6, 10.3); p<0.01], and a positive tuberculin skin test [HR 3.1; (95% CI 1.1, 9.0); p = 0.04] were independently and positively associated with incident TB.In this population-based study we demonstrate an 80% reduction in incident TB, under programmatic conditions, in HAART-treated HIV-infected patients compared to ART-naïve patients

Liver function tests of HIV/AIDS patients at the nylon district hospital, Douala, Cameroon

Background: Antiretroviral therapy (ART) which substantially reduces morbidity and mortality in human immunodeficiency virus (HIV) seropositive patients has been associated with hepatotoxicity. This study was aimed at investigating the effects of HIV infection and ART on liver function amongst HIV seropositive patients in Douala, Cameroon.Methods: A cross- sectional study was conducted from March to August, 2012 at the Nylon District Hospital, Douala. Demographic data were collected using a structured questionnaire.  Serum alanine and aspartate aminotransferases (ALT and AST), alkaline phosphatase (ALP) and gamma glutamyl transferase (GGT) activities were determined using colorimetric techniques.Results: The mean age of the study participants was 37.9 ± 6.02 years. A majority of the study participants (68.0%) were females. The mean CD4+ T lymphocyte cell count of HIV/AIDS patients on ART was significantly higher than the ART- naïve patients (p<0.05). The mean serum AST and ALT activities of ART-naïve patients were significantly higher than the control subjects (p<0.05). Similarly, the mean serum transaminases and GGT activities of HIV/AIDS patients on ART were significantly higher than the control subjects (p<0.05). The mean serum ALP and GGT activities of HIV/AIDS patients receiving ART were significantly higher than the ART- naïve patients (p<0.05).Conclusions: The present study provides evidence to suggest that both infection with HIV and treatment with ART are associated with liver injury.

Slow progression of pediatric HIV associates with early CD8+ T cell PD-1 expression and a stem-like phenotype

HIV non-progression despite persistent viraemia is rare among antiretroviral therapy (ART)-naïve adults, but relatively common among ART-naïve children. Previous studies indicate that ART-naïve paediatric slow-progressors (PSPs) adopt immune evasion strategies similar to those described in the SIV natural hosts. However, the mechanisms underlying this immunophenotype are not well understood. In a cohort of early-treated infants who underwent analytical treatment interruption (ATI) after 12 months of ART, expression of PD-1 on CD8+ T-cells immediately prior to ATI was the main predictor of slow progression during ATI (r=0.77, p=0.002). PD-1+ CD8+ T-cell frequency was also negatively correlated with CCR5 (r=-0.74, p=0.005) and HLA-DR (r=-0.63, p=0.02) expression on CD4+ T-cells and predicted stronger HIV-specific T-lymphocyte responses. In the CD8+ T-cell compartment of PSPs, we identified an enrichment of stem-like TCF-1+PD-1+ memory cells, whereas paediatric progressors and viraemic adults were populated with a terminally exhausted PD-1+CD39+ population. TCF-1+PD-1+ expression on CD8+ T-cells was associated with higher proliferative activity (r=0.41, p=0.03) and stronger Gag-specific effector functionality. These data prompt the hypothesis that the proliferative burst potential of stem-like HIV-specific cytotoxic cells could be exploited in therapeutic strategies to boost the antiviral response and facilitate remission in early-ART-treated infants with a preserved and non-exhausted T-cell compartment

Short-term Mortality Outcomes of HIV-Associated Cryptococcal Meningitis in Antiretroviral Therapy–Naïve and –Experienced Patients in Sub-Saharan Africa

Background: An increasing proportion of patients with HIV-associated cryptococcal meningitis have received antiretroviral therapy (ART) before presentation. There is some evidence suggesting an increased 2-week mortality in those receiving ART for 14 days. However, presentation and outcomes for cryptococcal meningitis patients who have recently initiated ART, and those with virologic failure and/or nonadherence, are not well described. / Methods: Six hundred seventy-eight adults with a first episode of cryptococcal meningitis recruited into a randomized, noninferiority, multicenter phase 3 trial in 4 Sub-Saharan countries were analyzed to compare clinical presentation and 2- and 10-week mortality outcomes between ART-naïve and -experienced patients and between patients receiving ART for varying durations before presentation. / Results: Over half (56%; 381/678) the study participants diagnosed with a first episode of cryptococcal meningitis were ART-experienced. All-cause mortality was similar at 2 weeks (17% vs 20%; hazard ratio [HR], 0.85; 95% CI, 0.6–1.2; P = .35) and 10 weeks (38% vs 36%; HR, 1.03; 95% CI, 0.8–1.32; P = .82) for ART-experienced and ART-naïve patients. Among ART-experienced patients, using different cutoff points for ART duration, there were no significant differences in 2- and 10-week mortality based on duration of ART. / Conclusions: In this study, there were no significant differences in mortality at 2 and 10 weeks between ART-naïve and -experienced patients and between ART-experienced patients according to duration on ART