Human Immunodeficiency Virus Infected Subjects Research Articles

Depletion of CD4+ lymphocytes in human immunodeficiency virus-infected subjects

Depletion of CD4+ lymphocytes in human immunodeficiency virus-infected subjects

Changes in Fat Mitochondrial DNA and Function in Subjects Randomized to Abacavir-Lamivudine or Tenofovir DF–Emtricitabine With Atazanavir-Ritonavir or Efavirenz: AIDS Clinical Trials Group Study A5224s, Substudy of A5202

The effect of nonthymidine nucleoside reverse-transcriptase inhibitors (NRTIs) on fat mitochondrial DNA (mtDNA) content and function is unclear. A5202 randomized antiretroviral therapy-naive human immunodeficiency virus-infected subjects to abacavir-lamivudine (ABC/3TC) versus tenofovir DF-emtricitabine (TDF/FTC) with efavirenz (EFV) or atazanavir-ritonavir (ATV/r). A5224s, substudy of A5202, enrolled 269 subjects with fat measurements by dual-energy x-ray absorptiometry and computed tomography. A subset of subjects underwent fat biopsies at baseline and week 96 for mtDNA content (real-time polymerase chain reaction) and oxidative phosphorylation nicotinamide adenine dinucleotide (reduced) dehydrogenase (complex I) and cytochrome c oxidase (complex IV) activity levels (immunoassays). Intent-to-treat analyses were performed using analysis of variance and paired t tests. Fifty-six subjects (87% male; median age, 39 years) were included; their median body mass index, CD4 cell count, and fat mtDNA level were 26 kg/m(2), 227 cells/μL, and 1197 copies/cell, respectively. Fat mtDNA content decreased within the ABC/3TC and TDF/FTC groups (combining EFV and ATV/r arms; median change, -341 [interquartile range, -848 to 190; P = .03] and -400 [-661 to -221; P < .001] copies/cell, respectively), but these changes did not differ significantly between the 2 groups (P = .57). Complex I and IV activity decreased significantly in the TDF/FTC group (median change, -12.45 [interquartile range, -24.70 to 2.90; P = .003] and -8.25 [-13.90 to -1.30; P < .001], optical density × 10(3)/µg, respectively) but not the ABC/3TC group. Differences between the ABC/3TC and TDF/FTC groups were significant for complex I (P = .03). ABC/3TC and TDF/FTC significantly and similarly decreased fat mtDNA content, but only TDF/FTC decreased complex I and complex IV activity levels. NCT00118898.

SEROPREVALENCE OF HEPATITIS B VIRUS AMONG HUMAN IMMUNODEFICIENCY VIRUS PATIENTS ATTENDING ANTIRETROVIRAL TREATMENT (ART) CENTRE, AGBOR, NIGERIA

The prevalence of some infectious diseases (Hepatitis B) has changed with the incidence of HIV/AIDS pandemic. This study was carried out to determine the prevalence of hepatitis B virus (HBV) infection in human immunodeficiency virus (HIV) infected patients undergoing treatment in the Antiretroviral Treatment Centre Agbor, Delta State,Nigeria. A total of 538 HIV infected subjects were recruited for this study, comprising 156(29%) males and 382(71%) females aged between 1-70 years and were screened for Hepatitis B. Of the 538 samples , 12(7.7%) males and 8(2.0%) females were sero-positive for HBV. The highest seroprevalence (5.9%) was observed in the group aged 46-60 years, followed by the age group of 1-15 years (4.0%) and 31-45 years (3.5%). The lowest prevalence of (0%) was observed in the group aged 61-70 years. The difference in seroprevalence between the groups aged 1-15 years and 46-60 was statistically significant (P &lt; 0.001) .Enlightenment campaigns should be intensified as well as immunization against Hepatitis B in order to achieve Hepatitis B free population.

Abstract 64: Microvascular Endothelial Dysfunction, Oxidative Stress and Reduced Arginine: Adma in Premenopausal Women With HIV

Cardiovascular disease (CVD) is common in persons infected with the human immunodeficiency virus (HIV) who are receiving highly active antiretroviral therapy (HAART). Since CVD generally begins with microvascular dysfunction, we tested the hypothesis that women with HIV have microvascular endothelial dysfunction. We related this to reactive oxygen species (ROS), NOS substrate: inhibitor ratio (arginine: ADMA) and inflammation. Subcutaneous microvascular arterioles (SMAs) were isolated from gluteal skin biopsies from 11 premenopausal, virally suppressed African American HIV positive women receiving HAART but without CVD risk factors and 10 healthy matched controls in the Women’s Interagency HIV Study (WHIS). Preconstricted SMAs were mounted in a Mulvany-Halpern myograph and relaxed with graded concentrations of acetylcholine (ACh). Endothelium derived relaxation (EDR), endothelium-derived relaxation factor (EDRF; NOS-dependent relaxation), endothelium derived hyperpolarizing factor (EDHF; K + -channel dependent relaxation) and endothelium derived contracting factor (EDCF; ACh-induced contraction with relaxation pathways inhibited) were related to plasma cytokines (array) and plasma arginine: ADMA ratio (measured by capillary zone electrophoresis).Compared to controls, HIV infected subjects had reduced EDRs (50±6 vs 78±3%; P&lt; 0.01), EDRF (27±4 vs 38±3%, P&lt; 0.05), EDHF(18±4 vs 39±4%, P&lt; 0.05) and decreased NO activity (0.18±0.05vs 0.69±0.17ΔUnits, P&lt; 0.05 from DAF-FM fluorescence).They had an ACh-induced EDCF (21±2vs7±3%, P&lt; 0.01) and increased microvascular ROS (0.14±0.04 vs 0.04±0.04 Δunits; P&lt; 0.01 from tempo-9ACfluorescence). Plasma cytokines in HIV subjects showed enhanced inflammation and plasma arginine: ADMA concentrations were reduced (178±12 vs 203±13 μmol/ μmol; P&lt; 0.005). In conclusion, pre-menopausal women receiving HAART with virally suppressed HIV who were free of CVD risk factors developed defective microvascular EDRF and EDHF with reduced NO and NOS substrate: inhibitor ratio. They had inflammation and their microvessels developed a new ACh-induced EDCF and enhanced ROS. These profound microvascular disturbances in apparently healthy young women may herald the development of premature CVD.

Acute coronary syndrome in HIV patients: from pathophysiology to clinical practice.

A majority of human immunodeficiency virus (HIV) infected subjects in developed countries have access to highly active anti-retroviral therapy (HAART), which is associated with significantly improved long term survival. In this setting, clinical attention needs to be focused on the impact of premature atherosclerotic cardiovascular disease (CVD), which already represents a leading cause of morbidity and mortality in these patients. While the higher prevalence of traditional risk factors remains the main culprit of increased CVD risk, HIV infection itself and antiretroviral toxicity are confounding proatherogenic factors. It is therefore critical to treat modifiable risk factors, keeping close attention to drug interactions in these patients with high cardiovascular risk profile.

HHVs AND LYMPHOPROLIFERATIVE DISORDERS

Similarly to Epstein-Barr virus (EBV), the human herpesvirus-8 (HHV-8) is a γ-herpesvirus, recently recognized to be associated with the occurrence of rare B cell lymphomas and atypical lymphoproliferations, especially in the human immunodeficiency virus (HIV) infected subjects. Moreover, the human herpesvirus-6 (HHV-6), a β-herpesvirus, has been shown to be implicated in some non-malignant lymph node proliferations, such as the Rosai Dorfman disease, and in a proportion of Hodgkin’s lymphoma cases. HHV-6 has a wide cellular tropism and it might play a role in the pathogenesis of a wide variety of human diseases, but given its ubiquity, disease associations are difficult to prove and its role in hematological malignancies is still controversial. The involvement of another β-herpesvirus, the human cytomegalovirus (HCMV), has not yet been proven in human cancer, even though recent findings have suggested its potential role in the development of CD4+ large granular lymphocyte (LGL) lymphocytosis. Here, we review the current knowledge on the pathogenetic role of HHV-8 and human β-herpesviruses in human lymphoproliferative disorders.

Prevalence of Metabolic Syndrome Among Human Immunodeficiency Virus–Infected Subjects Is Widely Influenced by the Diagnostic Criteria

The aim of this study was to compare the prevalence of metabolic syndrome in human immunodeficiency virus (HIV)-infected patients treated with highly active antiretroviral therapy (HAART), using the National Cholesterol Education Program Adult Treatment Panel III (NCEP ATP III), European Group for the Study of Insulin Resistance (EGIR), and International Diabetes Federation (IDF) definitions. A cross-sectional study was carried out with 159 consecutive adult HIV-infected subjects (120 males and 39 females) under HAART. Anthropometric and laboratory parameters were measured by standard methods. Hyperinsulinemia was defined by a fasting concentration >75th percentile of values obtained in healthy individuals (107.5 pmol/L). The prevalence of ATP III-defined metabolic syndrome was 10.1%; it was 28.3% according to EGIR criteria and 15.1% using the IDF definition. The concordance between the definitions was low (kappa coefficient ranging between 0.134 and 0.296). All subjects with EGIR-defined metabolic syndrome had hyperinsulinemia, but only 50% of those with ATP III-defined metabolic syndrome and 62.5% in the IDF metabolic syndrome population had hyperinsulinemia. The inclusion of hyperinsulinemia as a criterion in the EGIR metabolic syndrome definition made it more discriminative than the ATP III definition, both in men and women, and than the IDF definition in men to identify metabolic syndrome in HIV-infected subjects under HAART.

Alteraciones osteoarticulares en la infección por el VIH

The aim of this paper is to present the most relevant musculoskeletal disorders, their diagnosis and treatment to the scientific community and the professionals in charge of patients with human immunodeficiency virus (HIV) infection. These recommendations have been agreed by a panel of experts from the National AIDS Plan (PNS) and the AIDS Study Group (GESIDA). The group have reviewed the efficacy and safety results of clinical trials, cohort studies and pharmacokinetic studies published in biomedical journals (PubMed and Embase), or presented at conferences. Three levels of evidence have been defined according to the sources of data: level A, randomized controlled trials; level B, cohort or case-control; and level C, descriptive studies and expert opinion. Based on this evidence, the authors have decided to recommend, consider or not recommend for each situation. The decrease in bone mineral density is common in HIV-infected patients on antiretroviral treatment, especially during the first year (from 2 to 4%), with a subsequent partial recovery. A dual energy x-ray absorptiometry (DEXA) scan is recommended in patients over 50 years old with HIV infection, history of bone fractures and/or risk factors. Treatment with bisphosphonates has been shown to be effective. Osteoarticular infections are more frequent than in the non-infected population. The level of immunosuppression, risk practice, and antiretroviral treatment should be considered for a proper diagnosis and therapeutic approach. Laboratory and imaging procedures recommended for the study of musculoskeletal processes in HIV infected subjects are the same as in the general population. Osteonecrosis and decreased bone mineral density are the most frequent alterations in children. An early diagnosis of bone disorders is needed. The influence of modifiable risk factors must be avoided and initiate treatment when necessary. Bisphosphonates have been effective in osteoporosis.

The kidney function trends in human immunodeficiency virus/acquired immune deficiency syndrome (HIV/AIDS) patients at the Nylon DistrictHospital, Douala, Cameroon

Human immunodeficiency virus (HIV) related kidney disease is one of the leading causes of death and affects predominantly people of black descent. Data is unavailable on the presence of kidney disease amongst HIV positive patients in Cameroon and a high prevalence of the disease depicts a high incidence of HIV associated nephropathy. A cohort study was carried out from May to August 2010 at the Nylon District Hospital Douala to investigate the Kidney function trends amongst seropositive individuals. Kidney function tests like serum urea, serum creatinine, creatinine clearance, proteinuria and urine chemistry was measured amongst 329 participants amongst whom 100 (30.4%) were HIV negative and 229 (69.6%) were HIV positive. The age range of the study population was 18 to 60 years, with mean age of 35.122 ± 0.543. There were 94(28.6%) males and 235 (71.5%) females. The percentage of HIV seropositivity was higher in females than in males (74.3% vs. 25.7% p < 0.05).Although, Serum creatinine, creatinine clearance and proteinuria were significantly higher in the control group than in the HIV infected subjects (p < 0.0001, p = 0.046 and p = 0.001, respectively), these values were not indicative of renal pathology. Considering only HIV positive individuals the mean serum creatinine was significantly higher in the Antiretoviral treatment (ART) naive group when compared to those who were already on ART. These findings indicate that renal function is not affected by the seropositivity status of individuals. Key words: Kidney function, human immunodeficiency virus/acquired immune deficiency syndrome(HIV/AIDS) seropositivity, Cameroon.

Evaluation of immunoglobulin classes (IgA, IgG and IgM) levels and complement fixation activity in HIV infected subjects

The study was designed to evaluate the immunoglobulin A, G and M levels and complement fixation activity in HIV infected participants, who were not administered antiretroviral therapy (ART). Eighty (80) HIV infected participants, aged between 15 – 55 years (38 ±10 years), were recruited for the study. Forty five (45) of the participants were classified as symptomatic HIV (stage ii), while the remaining 35 were classified asasymptomatic HIV (stage i). Similarly, 40 seronegative participants served as control. Blood samples were collected from the participants for the determination of HIV status by immunochromatography, HIV confirmation by Western blot, determination of immunoglobulin levels by immunoturbidimetry, and complement activity by complement fixation test. The IgG and IgA were significantly increased in symptomatic HIV infection compared with asymptomatic HIV infection (p0.05). The complement fixation activities decreased in HIV infected patients compared with the values in HIV seronegatives. The increase in IgA concentration with HIV infected participants may suggest existence of mucosal infections, while theincrease in IgG concentration in HIV infected participants may suggest evidence of increased opportunistic infection requiring IgG response. The low level of complement activity in HIV infected participants maypredispose individuals with HIV infection to disease commonly controlled through immunological activity of the complement. Keywords: Human Immunodeficiency Virus (HIV), immunoglobulins (IgA, IgG and IgM), complements.

The risk of HIV and HCV infections among injection drug users in northeast India

Injection drug users (IDUs) and their associated risk behavior are responsible for driving the human immunodeficiency virus (HIV) epidemic in northeast India. So a group of IDUs from two northeastern states (Mizoram and Nagaland) of India were studied to find the prevalence of HIV, co-infection with hepatitis C virus (HCV), hepatitis B virus (HBV), and associated risk behaviors. Out of the 400 IDUs enrolled, 398 consented for HIV, HCV, and hepatitis B surface antigen (HbsAg) test. Of them, 10.8% were HIV-1 antibody positive, 47.8% had HCV antibody, and 3.8% had detectable HBsAg. Among the HIV infected subjects, 79.1% were co-infected with HCV and 6.9% had triple infection. Heroin users showed a higher association with HIV (OR = 7.3, 95% CI: 2.5–21.5, p=0.0003) and HCV infection (OR = 7.6, 95% CI: 3.5–16.6, p<0.0001) than Spasmo-proxyvon (dextropropoxyphene, a synthetic opiod analgesic). In summary, apart from the known risk variables among IDUs, type of injecting drugs also influences the HIV/HCV transmission pattern among the IDUs.

Lipodystrophy and anti-retroviral therapy as predictors of sub-clinical atherosclerosis in human immunodeficiency virus infected subjects

Background and objective Although anti-retroviral therapy (ART) prolonged survival in HIV-infected persons, an increase in cardiovascular disease has also been observed. A frequent complication of ART is the development of lipodystrophy (LD) with its multiple phenotypes that may be associated with cardiovascular disease. We assessed the contribution of chronic HIV infection, ART use and LD to the presence of sub-clinical atherosclerosis as evaluated by coronary artery calcium (CAC) imaging. Methods Observational cross-sectional study of 372 HIV-infected patients receiving ART who attended a cardiometabolic clinic (48.2 ± 8-year old; 74% men). All patients underwent CAC surveillance with computed tomography and the Agatston score was used to quantitate CAC. Presence of CAC was defined as a score >10. Multivariable logistic regression was used to evaluate associations between HIV clinical factors, ART and LD with the presence of CAC. Findings CAC was found in 134 patients (36%) with a median CAC score of 50 (range 10; 1243). Lipoatrophy alone (OR 3.82, 95% CI: 1.11; 13.1), fat accumulation alone (OR 7.65, 95% CI: 1.71; 37.17) and mixed lipodystrophy phenotypes (OR 4.36, 95% CI: 1.26; 15.01) were strongly associated with presence of CAC after adjusting for age, sex, hypertension and cumulative exposure to ART. Conclusion CAC is common among long-term ART users. The association between CAC and LD underscores the potential atherosclerosis risk inherent with ART and the need to undertake routine cardiovascular surveillance in patients treated with these drugs.

Predictive Value of Pharmacokinetics-Adjusted Phenotypic Susceptibility on Response to Ritonavir-Enhanced Protease Inhibitors (PIs) in Human Immunodeficiency Virus-Infected Subjects Failing Prior PI Therapy

The activities of protease inhibitors in vivo may depend on plasma concentrations and viral susceptibility. This nonrandomized, open-label study evaluated the relationship of the inhibitory quotient (IQ [the ratio of drug exposure to viral phenotypic susceptibility]) to the human immunodeficiency virus type 1 (HIV-1) viral load (VL) change for ritonavir-enhanced protease inhibitors (PIs). Subjects on PI-based regimens replaced their PIs with ritonavir-enhanced indinavir (IDV/r) 800/200 mg, fosamprenavir (FPV/r) 700/100 mg, or lopinavir (LPV/r) 400/200 mg twice daily. Pharmacokinetics were assessed at day 14; follow-up lasted 24 weeks. Associations between IQ and VL changes were examined. Fifty-three subjects enrolled, 12 on IDV/r, 33 on FPV/r, and 8 on LPV/r. Median changes (n-fold) (FC) of 50% inhibitory concentrations (IC(50)s) to the study PI were high. Median 2-week VL changes were -0.7, -0.1, and -1.0 log(10) for IDV/r, FPV/r, and LPV/r. With FPV/r, correlations between the IQ and the 2-week change in VL were significant (Spearman's r range, -0.39 to -0.50; P < or = 0.029). The strongest correlation with response to FPV/r was the IC(50) FC (r = 0.57; P = 0.001), which improved when only adherent subjects were included (r = 0.68; P = 0.001). In multivariable analyses of the FPV/r arm that included FC, one measure of the drug concentration, corresponding IQ, baseline VL, and CD4, the FC to FPV was the only significant predictor of VL decline (P < 0.001). In exploratory analyses of all arms, the area under the concentration-time curve IQ was correlated with the week 2 VL change (r = -0.72; P < 0.001). In conclusion, in PI-experienced subjects with highly resistant HIV-1, short-term VL responses to RTV-enhanced FPV/r correlated best with baseline susceptibility. The IQ improved correlation in analyses of all arms where a greater range of virologic responses was observed.

Steady-State Pharmacokinetics of Abacavir in Plasma and Intracellular Carbovir Triphosphate following Administration of Abacavir at 600 Milligrams Once Daily and 300 Milligrams Twice Daily in Human Immunodeficiency Virus-Infected Subjects

Abacavir (ABC) is administered either at 600 mg once daily (ABC 600 mg QD) or 300 mg twice daily (ABC 300 mg BID) in anti-human immunodeficiency virus (anti-HIV) combination therapy. Although ABC plasma pharmacokinetics following each regimen has been well defined, no study has directly compared the regimens with respect to pharmacokinetics of ABC's active intracellular anabolite, carbovir-triphosphate (CBV-TP). In an open-label, two-period, crossover study, 34 HIV-infected male and female subjects stabilized on antiretroviral regimens containing either ABC 600 mg QD or ABC 300 mg BID received their usual doses on days -1 and 1 and then switched regimens for days 2 to 11. Serial blood samples collected on days 1 and 11 were assayed for plasma ABC and intracellular CBV-TP concentrations using validated high-performance liquid chromatography-tandem mass spectrometry methods. Pharmacokinetic parameters were calculated using noncompartmental methods. Analysis of variance with a mixed-effect model was performed for treatment and gender comparisons. In 27 evaluable subjects, the regimens provided bioequivalent ABC daily areas under the concentration-time curve from 0 to 24 h (AUC(0-24)) and comparable CBV-TP concentrations at the end of the dosing interval (C(tau)). As expected, ABC QD resulted in 109% higher ABC maximum concentrations of drug in plasma (C(max)) than did ABC BID. ABC QD also resulted in 32% higher CBV-TP AUC(0-24) and 99% higher CBV-TP C(max) than did ABC BID. Females had a 38% higher weight-adjusted ABC AUC(0-24) and 81% higher weight-adjusted CBV-TP AUC(0-24) than did males. Virologic suppression was maintained during regimen switch, and no tolerability differences between regimens were observed. In conclusion, this study showed that ABC 600 mg QD and ABC 300 mg BID regimens led to similar intracellular CBV-TP C(tau) values, thus providing pharmacokinetic support for the interchangeability of these two regimens. Women had higher intracellular CBV-TP exposure than did men.

Formulation preference, tolerability and quality of life assessment following a switch from lopinavir/ritonavir soft gel capsule to tablet in human immunodeficiency virus-infected patients

BackgroundLopinavir/ritonavir (LPV/r) tablet compared to the soft gel capsule (SGC) formulation has no oleic acid or sorbitol, has no refrigeration or food-restriction requirements, and has less pharmacokinetic variability. We compared the tolerability, quality of life (QoL), and formulation preference after switching from LPV/r SGC to the tablet formulation.MethodsIn a prospective, single-arm, cohort study-design, 74 human immunodeficiency virus (HIV) infected subjects stable on LPV/r-based therapy were enrolled prior to (n = 25) or 8 weeks (n = 49) after switching from SGC to tablet. Baseline data included clinical laboratory tests, bowel habit survey (BHS) and QoL questionnaire (recalled if enrolled post-switch). Global Condition Improvement (GCI)-score, BHS-score, QoL-score, and formulation preference data were captured at weeks 4 and 12.ResultsAt week 12 post-enrollment; the tablet was preferred to the SGC (74% vs. 10%, p < 0.0001). GCI-overall-tolerability score was 2.46 ± 3.30 on a scale of -7 to +7, with 90% admitting to feeling better or about the same. Stool frequency, consistency, volume, and ± blood improved, however the improvement was significant in "consistency" only (p = 0.03). Aggregate Bowel Habit-Profile improved (BHS-score change = -0.227, p = 0.01). Inverse relationship existed between GCI and BHS (slope = -1.2, p = 0.02) at week-4, suggesting that improved overall-tolerability was related to better gastrointestinal (GI)-tolerance. QoL-scores were stable. Mean reductions in total cholesterol of 9.20 mg/dL (p = 0.02), in triglycerides of 33 mg/dL (p = 0.04), and in HDL of 4.50 mg/dL (p = 0.01) unrelated to lipid-lowering therapy, were observed at week 12.ConclusionsLPV/r-tablet was well tolerated and preferred to the SGC in HIV infected subjects, with stable QoL and appreciable improvement in GI-tolerability. The unexpected changes in lipid profile deserve further evaluation.

Predictive Value of Pharmacokinetics-Adjusted Phenotypic Susceptibility on Response to Ritonavir-Enhanced Protease Inhibitors (PIs) in Human Immunodeficiency Virus-Infected Subjects Failing Prior PI Therapy

Predictive Value of Pharmacokinetics-Adjusted Phenotypic Susceptibility on Response to Ritonavir-Enhanced Protease Inhibitors (PIs) in Human Immunodeficiency Virus-Infected Subjects Failing Prior PI Therapy

Nutritional status and serum zinc and selenium levels in Iranian HIV infected individuals.

BackgroundHuman immunodeficiency virus infected individuals are prone to malnutrition due to increased energy requirements, enteropathy and increased catabolism. Trace elements such as zinc and selenium have major role in maintaining a healthy immune system. This study was designed to evaluate the nutritional status of Iranian subjects who were newly diagnosed with human immunodeficiency virus infection and to compare serum level of zinc and selenium in these patients with those of the sex and aged match healthy subjects.MethodsAfter an interview and physical examination, nutritional assessment was done based on clinical and anthropometric parameters. Body mass index (normal range 18.5–27 kg/m2 based on age) of less than 16, 16–16.9 and 17–18.4 kg/m2 were considered as severe, moderate and mild malnutrition respectively. Serum level of zinc and selenium were measured by graphite furnace atomic absorption.ResultsSevere, moderate and mild malnutrition were detected in 15%, 38% and 24% of human immunodeficiency virus infected individuals respectively. Compared with the healthy control group, serum level of zinc and selenium in the human immunodeficiency virus infected subjects were significantly lower (P = 0.01 and P = 0.02 respectively).ConclusionMalnutrition found to be prevalent in Iranian human immunodeficiency virus infected individuals and low serum zinc and selenium levels are common in this population.

Early Depletion ofMycobacterium tuberculosis–Specific T Helper 1 Cell Responses after HIV‐1 Infection

The acid-fast bacillus Mycobacterium tuberculosis is often the first manifestation of acquired immunodeficiency syndrome in patients infected with human immunodeficiency virus (HIV). This study was conducted to better understand the mechanism underlying M. tuberculosis-specific pathogenicity early after onset of HIV infection. M. tuberculosis-specific T helper 1 (Th1) cells were studied in HIV negative (n=114) and chronically HIV infected (n=68) Tanzanian subjects by using early secreted antigenic target 6 (ESAT6) protein or tuberculin (purified protein derivative) with interferon-gamma ELISPOT and intracellular cytokine staining. In a longitudinal study, the effect of acute HIV infection on M. tuberculosis-specific Th1 cells was determined by polychromatic flow cytometric analysis in 5 subjects with latent M. tuberculosis infection who became infected with HIV. In tuberculosis (TB)-asymptomatic subjects (i.e., subjects with unknown TB status who did not show clinical signs suggestive of TB), chronic HIV infection was associated with a decreased percentage of subjects with detectable M. tuberculosis-specific Th1 cells (P< .001) a decrease which was not observed among subjects with active TB. Acute HIV infection induced a rapid depletion of M. tuberculosis-specific Th1 cells in 4 subjects remained TB asymptomatic, whereas the population of these cells remained stable in subjects who remained HIV negative (P< .01). Taken together, these data suggest a mechanism of rapid M. tuberculosis-specific Th1 cell depletion that may contribute to the early onset of TB in individuals with latent M. tuberculosis infection who become HIV infected.

Estimation of virological and immunological parameters in subjects from South India infected with human immunodeficiency virus type 1 clade C and correlation of findings with occurrence of neurological disease

Several studies carried out in Western countries have demonstrated that a number of virological and immunological markers such as viral loads, cytokines, beta(2)-microglobulin, neopterin, etc., are elevated in the serum and cerebrospinal fluid (CSF) of human immunodeficiency virus (HIV)-infected individuals with neurological disease. The neurological manifestations of HIV infection noted in Indian patients is different from those reported in Western countries. Moreover, few studies have investigated the role of virological and immunological parameters with respect to the progression of HIV-1 clade C infection in India. In this study, we measured virological (HIV-1 RNA levels) and immunological parameters (CD4 cell count and inflammatory markers) in the plasma and CSF of HIV-1-infected neurologically asymptomatic and symptomatic (with opportunistic infections and/or dementia) subjects. By using clade-specific polymerase chain reaction (PCR), we ascertained that all samples used for the study were infected with HIV-1 clade C. Among the various laboratory parameters evaluated, high viral loads in the CSF, low CD4 counts, and higher levels of interleukin (IL)-1alpha, IL-6, tumor necrosis factor alpha (TNFalpha), beta(2)-microglobulin, and neopterin were noted in HIV-infected subjects with neurological disease as compared to asymptomatic subjects. These data suggest that the markers evaluated in plasma and CSF samples correlated with occurrence of neurological disease in symptomatic individuals as compared to asymptomatic HIV infected subjects.

Influence of Antiretroviral Drugs on the Pharmacokinetics of Prednisolone in HIV-Infected Individuals

Corticosteroids are cytochrome P450 3A4 substrates, which have been associated with toxicities in patients receiving cytochrome P450 3A4 inhibitors such as human immunodeficiency virus protease inhibitors. In a study in healthy volunteers, ritonavir significantly increased prednisolone exposure. We investigated the influence of antiretroviral (ARV) medications on prednisolone pharmacokinetics in 3 groups of 10 human immunodeficiency virus-infected subjects. One group received lopinavir/ritonavir, and another efavirenz, as part of their ARV regimen; a third group did not receive ARV medications. Each subject received a single 20-mg prednisone dose followed by serial blood sampling for prednisolone. Prednisolone pharmacokinetics were compared among the groups. Area under the concentration-time curve was significantly lower in efavirenz recipients versus subjects receiving lopinavir/ritonavir (geometric mean ratio = 0.60, P = 0.01). Average prednisolone area under the concentration-time curve was higher in subjects taking lopinavir/ritonavir versus subjects not on ARVs; however, this difference was not significant (P > 0.05). These data indicate that prednisolone concentrations may fluctuate widely when human immunodeficiency virus-positive individuals established on efavirenz therapy change to lopinavir/ritonavir or vice versa.