Treatment Of HIV-infected Patients Research Articles

Time to Initiate Antiretroviral Therapy Between 4 Weeks and 12 Weeks of Tuberculosis Treatment in HIV-Infected Patients

Optimal timing for initiation of antiretroviral therapy (ART) among HIV-infected patients with tuberculosis (TB) is not well established. HIV/TB-coinfected patients were randomized to initiate tenofovir/lamivudine/efavirenz at 4 weeks (4-week group) or 12 weeks (12-week group) of TB treatment. The primary outcome was 1-year all-cause mortality. Of 156 patients, 79 were in 4-week group and 77 in 12-week group. Overall, median (interquartile range) CD4 was 43 (47-106) cells per cubic millimeter and median (interquartile range) HIV-1 RNA was 5.8 (5.4-6.3) log copies per milliliter. Eleven (7%) mortalities occurred in a total follow-up period of 137 patient-years. Seven percent (6/79, 8.76 per 100 patient-years) mortalities were in 4-week group, and 6% (5/77, 7.25 per 100 person-years) mortalities were in 12-week group [relative risk (RR) = 0.845, 95% confidence interval (CI) = 0.247 to 2.893]. Twenty-eight (35%) patients in 4-week group and 25 (32%) patients in 12-week group were hospitalized (RR = 1.142, 95% CI = 0.588 to 2.217). Grade 2-4 adverse events were 39% (31/79) in 4-week group and 34% (26/77) in 12-week group (RR = 1.267, 95% CI = 0.659 to 2.435). In multivariate analysis, "low albumin" (RR = 2.695, 95% CI = 1.353 to 5.475) and "low baseline CD4 count" (RR = 4.878, 95% CI = 1.019 to 23.256) were the independent predictors of mortality. Immune reconstitution inflammatory syndrome was more frequent in 4-week group with an incidence of 8.86 versus 5.02 per 100 person-months in 12-week group over the first 6 months of ART (P = 0.069). In middle-income countries where ART is initiated at CD4 count of <350 cells per cubic millimeter, immediate initiation of ART in HIV-infected patients with active TB was not associated with survival advantage when compared to initiation of ART at 12 weeks.

Acute psychosis related to use of trimethoprim/sulfamethoxazole in the treatment of HIV-infected patients with Pneumocystis jirovecii pneumonia: a multicentre, retrospective study

A recent study reported that trimethoprim/sulfamethoxazole caused acute psychosis in four renal transplant patients with Pneumocystis jirovecii pneumonia. We aimed to investigate the incidence of and factors associated with trimethoprim/sulfamethoxazole-related acute psychosis in HIV-infected patients with P. jirovecii pneumonia. We reviewed the medical records of HIV-infected patients who presented with P. jirovecii pneumonia and received trimethoprim/sulfamethoxazole at six major hospitals in Taiwan from July 2009 to May 2011. Acute psychosis was defined as the occurrence of hallucinations or delusions following the initiation of trimethoprim/sulfamethoxazole during hospitalization. During the study period, 135 patients receiving trimethoprim/sulfamethoxazole for P. jirovecii pneumonia were enrolled and 16 (11.9%; 95% CI, 6.3%-17.4%) developed acute psychosis after a median duration of 5 days of trimethoprim/sulfamethoxazole treatment (range, 3-11 days). The incidence increased from 0% (0/16) in patients who received a daily trimethoprim dose of ≤12 mg/kg to 23.5% (4/17) in those who received a daily trimethoprim dose of >18 mg/kg. In multivariate logistic regression analysis, a higher daily dose of trimethoprim/sulfamethoxazole (OR, per 1 mg increase of trimethoprim, 1.40; 95% CI, 1.12-1.76; P = 0.0035) and use of adjunctive steroids (OR, 4.43; 95% CI, 1.14-17.15; P = 0.031) were associated with acute psychosis. In this case series, 11.9% of HIV-infected patients developed acute psychosis while receiving trimethoprim/sulfamethoxazole for P. jirovecii pneumonia. While the study was limited by its retrospective design, the risk appeared to increase with increasing daily dose of trimethoprim/sulfamethoxazole in those vulnerable patients with multiple risks for acute psychosis.

A novel antiviral approach

Viral infections are often the etiological agents of severe acute and chronic human diseases. Their peculiar biology usually leads to the need of design specific therapies for each virus, and the eradication of the viruses and the healing of the patients very often are not reached also after decades of theoretical and applied researches. HIV is a classical example of how the efforts of the researchers may be disappointed in eradicating a virus infection in an infected patient. Here I present a hypothesis for a new antiviral approach that may be suitable for the treatment of HIV infected patients. The same approach, with opportune modifications, may be also applied as healing strategy for a wide set of viruses infections. In brief, my idea is to use the retrotranscription machinery and the packaging system of HIV infected cells to amplify the interfering effects of siRNAs directed against HIV genes and transcripts. The coding sequences for the interfering RNAs are brought to the infected cells via modified HIV virions deficient for structural viral genes that will use the resident viral activities of HIV infected cell as helpers. The use of this strategy will probably lead to an intracellular, intercellular and systemic amplification of the specific virus-targeted interfering activities. Moreover this strategy may show novel levels of interference: a competition between the deficient and wild type viruses for the packaging molecules and the possibility of homologous recombination between the deficient and wild type viruses that may lead in turn to the formation of recombinant non infectious viruses, and the removing of wild type provirus sequence from the host genome of infected cells by recombination.

Antimicrobial Photodynamic Therapy in the Treatment of Oral Candidiasis in HIV-Infected Patients

Antimicrobial photodynamic therapy (aPDT) has been used to combat local infections, and it consists of the combination of a photosensitizer, a light source, and reactive oxygen species (ROS) to kill microbial cells. In this study, we evaluated the effectiveness of aPDT in the treatment of candidiasis in HIV-infected patients. Twenty-one patients were divided into three groups. Control group (CG) was treated with the conventional medication for candidiasis (fluconazole 100 mg/day during 14 days). Laser group (LG) was subjected to low-level laser therapy (LLLT), wavelength 660 nm, power of 30 mW, and fluence of 7.5 J/cm(2), in contact with mucosa during 10 sec on the affected point. An aPDT group (aPDTG) was treated with aPDT, that is, combination of a low-power laser and methylene blue 450 μg/mL. Pre-irradiation time was 1 min. Parameters of irradiation were the same ones as for the LG, and patients were single irradiated. Patients were clinically evaluated and culture analysis was performed before, immediately after, and 7, 15, and 30 days after the treatment. Our results showed that fluconazole was effective; however, it did not prevent the return of the candidiasis in short-term. LLLT per se did not show any reduction on Candida spp. aPDT eradicated 100% of the colonies of this fungus and the patients did not show recurrence of candidiasis up to 30 days after the irradiation. These findings suggest that aPDT is a potential approach to oral candidiasis treatment in HIV-infected patients.

Syphilis and neurosyphilis in human immunodeficiency virus-infected patients: A retrospective study at a teaching hospital in Taiwan

Some studies have reported that the risk factors for neurosyphilis in patients with human immunodeficiency virus (HIV) and syphilis co-infection, include CD4 cell counts ≤350cells/μL and rapid plasma reagin (RPR) titer ≥1:32. However, neurosyphils can develop even in patients with CD4 cell counts >350cells/μL or RPR titer <1:32. In this study, we evaluated the outcome of syphilis to treatment in HIV-infected patients, and analysed the predictors of neurosyphilis in this population. We retrospectively reviewed medical records of HIV-infected patients with syphilis who visited the China Medical University Hospital between January 2000 and December 2009. Neurosyphilis was defined by white blood cell (WBC) counts >20cells/μL in the cerebrospinal fluid (CSF) sample or elevated Venereal Disease Research Laboratory (VDRL) titers of the CSF samples. Treatment failure was defined as less than 4-fold decrease in the serum RPR titer at or beyond 12 months post-treatment in case of early syphilis, and, at or beyond 24 months in case of late syphilis. One hundred and twenty-one HIV-infected patients (average age, 32 years) with syphilis were included in this study. Of 63 patients who had follow-up of serologic responses, 30 (47.6%) failed to respond to treatment. CD4 cell counts ≤200cells/μL was the indicator for treatment failure (P=.029). Lumbar puncture was performed in 65 patients, and 14 patients were diagnosed with neurosyphilis. At the time of lumbar puncture, 31 and 19 of the 65 patients showed CD4 cell counts of >350cells/μL and RPR of <1:32, respectively. An HIV viral load (VL) ≥10000copies/mL was found to be associated with the development of neurosyphilis (P=.016). In HIV-infected patients with syphilis, RPR titer should be evaluated more frequently when CD4 count ≤200cell/μL is associated with treatment failure. Lumbar puncture for the diagnosis of neurosyphilis should be considered in patients with HIV and syphilis co-infection, even in patients with CD4 cell counts >350cells/μL, and particularly when the HIV VL ≥10000copies/mL.

Mutations in HIV-1gagandpolCompensate for the Loss of Viral Fitness Caused by a Highly Mutated Protease

During the last few decades, the treatment of HIV-infected patients by highly active antiretroviral therapy, including protease inhibitors (PIs), has become standard. Here, we present results of analysis of a patient-derived, multiresistant HIV-1 CRF02_AG recombinant strain with a highly mutated protease (PR) coding sequence, where up to 19 coding mutations have accumulated in the PR. The results of biochemical analysis in vitro showed that the patient-derived PR is highly resistant to most of the currently used PIs and that it also exhibits very poor catalytic activity. Determination of the crystal structure revealed prominent changes in the flap elbow region and S1/S1' active site subsites. While viral loads in the patient were found to be high, the insertion of the patient-derived PR into a HIV-1 subtype B backbone resulted in reduction of infectivity by 3 orders of magnitude. Fitness compensation was not achieved by elevated polymerase (Pol) expression, but the introduction of patient-derived gag and pol sequences in a CRF02_AG backbone rescued viral infectivity to near wild-type (wt) levels. The mutations that accumulated in the vicinity of the processing sites spanning the p2/NC, NC/p1, and p6pol/PR proteins lead to much more efficient hydrolysis of corresponding peptides by patient-derived PR in comparison to the wt enzyme. This indicates a very efficient coevolution of enzyme and substrate maintaining high viral loads in vivo under constant drug pressure.

Drug safety evaluation profile of stavudine plus lamivudine for HIV-1/AIDS infection

Introduction: The lamivudine (3TC) + stavudine (d4T) combination is still widely used as part of first-line therapy for HIV-1-infected patients in low-resource countries. This review is intended to assess the benefits and risks in terms of safety of d4T + 3TC-based combination antiretroviral therapy (ART) for the treatment of HIV-1 infection.Areas covered: The most relevant papers related to the safety of d4T + 3TC-based ART were selected and summarized.Expert opinion: In industrialized countries, the 3TC + d4T combination is not recommended for initial therapy because of long-term metabolic toxicities associated with d4T. In developing countries, it may have a role in the treatment of HIV-infected patients if there is no other chance for starting antiretroviral therapy.

Identification of potential drug–drug interactions between antiretroviral drugs from prescriptions in the private health-care sector in South Africa

The aim of this study was to identify potential drug-drug interactions (DDIs) between antiretroviral drugs (ARVs) and to determine whether prescribed daily doses (PDDs) from prescriptions can be used in the evaluation of these interactions. A quantitative, retrospective drug utilization study was performed on 49,995 and 81,096 ARV prescriptions from a South African pharmacy benefit management company, which were prescribed to 7664 and 10,162 HIV patients for 2005 and 2006, respectively. Potential DDIs identified across different age groups were 778 for 2005 and 1155 for 2006; the majority occurred in patients aged 19 to ≤45 years. The potential DDIs identified between ARVs were all interacting at clinical significance level 2 according to guidelines indicated by Tatro. These results demonstrate that potential DDIs were identified between ARVs mostly in three ARV combinations: Kaletra(®) (lopinavir/ritonavir) and efavirenz, lopinavir/ritonavir and nevirapine and combinations of indinavir and ritonavir. There is a need for more education on the prescribing protocols for ARVs in the treatment of HIV-infected patients in the private health-care sector in South Africa.

Kidney transplantation in HIV positive patients. Two case reports from Hospital de Clínicas de Porto Alegre initial experience

Recently kidney transplantation has become an accepted treatment modality for the treatment of HIV infected patients with end-stage renal diseases. For such treatment it is required stability of clinical and laboratory parameters related to HIV infection and the use of highly active antiretroviral therapy. In this report we present the first two cases in Brazil of patients with HIV infection transplanted with organs from deceased donors performed successfully in our institution. The interactions between immunosuppressive and antiretroviral drugs, the co-infections, cardiovascular risk profile and the high incidence of acute rejection remain the major problems to be dealt with in these patients.

Risk Factors for Late Presentation for Care among HIV-Infected Patients in Guadeloupe: 1988-2009

Objective: The objective of this study was to identify the factors associated with presentation for care with CD4 cell count ≥ 500/ mm3, n=627) patients were included between 1 January 1988 and 31 December 2009. Factors associated with late presentation (CD4 count <200 cells/μL) were assessed using descriptive statistics and ordered multivariable logistic regression. Results: At the time of diagnosis, 40.21% of patients had than less 200 CD4 lymphocytes/mm3. Age older than 30 years OR: 1.55[1.14-2.10], p=0.005, male gender OR: 1.83[1.58-2.12], p<0.0001, access to care before 1992 OR: 1.56[1.03-2.02], p=0.038 and alcohol use OR: 8.80[2.26-34.36], p=0.002 were independently associated with a low CD4 cell count. Conclusion: The findings of this study (underline the need to expand HIV testing beyond the usual facilities) may be of value in helping to achieve earlier access to treatment in HIV-infected patients in order to minimize the individual risk of morbidity and mortality.

Incomplete Immune Recovery in HIV Infection: Mechanisms, Relevance for Clinical Care, and Possible Solutions

Treatment of HIV-infected patients with highly active antiretroviral therapy (HAART) usually results in diminished viral replication, increasing CD4+ cell counts, a reversal of most immunological disturbances, and a reduction in risk of morbidity and mortality. However, approximately 20% of all HIV-infected patients do not achieve optimal immune reconstitution despite suppression of viral replication. These patients are referred to as immunological nonresponders (INRs). INRs present with severely altered immunological functions, including malfunction and diminished production of cells within lymphopoetic tissue, perturbed frequencies of immune regulators such as regulatory T cells and Th17 cells, and increased immune activation, immunosenescence, and apoptosis. Importantly, INRs have an increased risk of morbidity and mortality compared to HIV-infected patients with an optimal immune reconstitution. Additional treatment to HAART that may improve immune reconstitution has been investigated, but results thus far have proved disappointing. The reason for immunological nonresponse is incompletely understood. This paper summarizes the known and unknown factors regarding the incomplete immune reconstitution in HIV infection, including mechanisms, relevance for clinical care, and possible solutions.

Anti-infective treatment in HIV-infected patients during perioperative period

ObjectiveTo investigate anti-infective treatments in HIV-infected surgical patients during the perioperative period.MethodsA retrospective study of sepsis and surgical site infections (SSIs) was conducted in 266 HIV-infected patients. The patients were divided into 3 groups based on CD4+ T cells counts in the preoperative period: group A (0–199 cell/ul), group B (200–349 cell/ul) and group C ([greater than or equal to] 350 cell/ul). When the CD4 count was below 350 cells/uL, anti-retrovirus therapy was started. For patients whose preoperative CD4 counts were [less than or equal to] 200 cells/uL, preoperative antibiotic medication was started.ResultsPatients in group A were more likely to get sepsis than patients in the other two groups (p0.01). Among 82 patients with clean wounds, only one patient got SSIs. All patients with dirty wounds had acquired SSIs after surgery. There were only 6 patients dead at 30 days after surgery, a death rate of 2.3%. Sepsis appeared in 110 patients (41%).ConclusionsComplete evaluation of surgical risk and suitable perioperative anti-infective treatment may lead to better outcome for HIV-infected surgical patients.

Serum paraoxonase-3 concentration in HIV-infected patients. Evidence for a protective role against oxidation

We investigated the influence of the HIV infection on serum paraoxonase-3 (PON3) concentration and assessed the relationships with lipoprotein-associated abnormalities, immunological response, and accelerated atherosclerosis. We studied 207 HIV-infected patients and 385 healthy volunteers. Serum PON3 was determined by in-house ELISA, and PON3 distribution in lipoproteins was investigated by fast-performance liquid chromatography (FPLC). Polymorphisms of the PON3 promoter were analyzed by the Iplex Gold MassArray(TM) method. PON3 concentrations were increased (about three times) in HIV-infected patients with respect to controls (P < 0.001) and were inversely correlated with oxidized LDL levels (P = 0.038). Long-term use of nonnucleoside reverse transcriptase inhibitor (NNRTI)-based antiretroviral therapy was associated with a decrease of PON3 concentrations. In a multivariate linear regression analysis, these relationships were still strong when the main confounding covariates were considered. PON3 was mainly found in HDL in HIV-infected patients, but a substantial amount of the protein was detected in LDL particles. This study reports for the first time an important increase in serum PON3 concentrations in HIV-infected patients that is associated with their oxidative status and their treatment with NNRTI. Long-term, prospective studies are needed to confirm the possible influence of this enzyme on the course of this disease and its possible utility as an analytical biomarker.

Pharmacokinetic Profiling and Bioequivalence Assessment of Two Marketed Brands of Nevirapine Tablets in Healthy Indian Volunteers

Nevirapine (CAS 129618-40-2), a non-nucleoside reverse transcriptase inhibitor, has been effectively used for treatment of HIV-infected patients. A randomized, two-way, crossover study was conducted in 24 fasting, healthy, Indian male subjects to compare plasma pharmacokinetic profile and single-dose tolerability of a new nevirapine tablet formulation (test, T) with that of a reference (R) tablet. Each volunteer received T and R formulations separated by at least 19 days of drug free wash-out period. Plasma concentrations of nevirapine, determined up to 288 h post dose by a sensitive and validated HPLC assay, were utilized to assess pharmacokinetic parameters such as the maximum observed plasma concentration (Cmax), time to Cmax (tmax), and area under plasma concentration curve (AUCinfinity). The primary plasma pharmacokinetic parameters of anti-retroviral substances, Cmax and AUCinfinity, were comparable for either of the formulations. Oral absorption of nevirapine was almost complete within 5 h. Geometric mean ratios (% reference) of AUCinfinity and Cmax and their 90% confidence intervals were 96.9 [93.69-100.24] and 100.8 [94.61-107.4], respectively. As the 90% confidence intervals of the geometric mean ratio were entirely within 80 to 125% for log-transformed parameters, the two formulations were considered bioequivalent in the extent and rate of absorption. Both formulations exhibited similar tolerability under fasting conditions.

The attitudes of British surgical trainees about the treatment of HIV-infected patients

As the incidence of HIV increases, the occupational risk of human immuno deficiency virus (HIV) infection also increases, leading to heightened anxiety within surgical practice. This study assessed the attitudes of surgeons treating HIV-infected patients. Seventy surgical trainees working in two district general hospitals were requested to complete a survey assessing their attitudes regarding the surgical management of HIV-infected patients. A needle-stick injury was reported by 64% of the trainees. Fifty-four percent of trainees were concerned about acquiring HIV from patients when performing a surgical procedure. There was a significant difference between the number of trainees worried about treating a patient with HIV and the number of trainees wearing eye protection when performing invasive procedures (p < 0.002). Eighty-six percent of trainees were confident they could treat HIV patients safely, but only 63% were aware of the hospital protocol for needle-stick injuries. There appears to be increasing concern among surgical trainees about carrying out surgical procedures on HIV-infected patients. Despite equipment being fully available, many trainees are not considering the full use of protective theatre garments to minimize the risk of HIV contamination. Further education and training is required to stress the importance of the increasing HIV prevalence and the need for safety during surgical practice.

Alteration of CD8+ T cell effector diversity during HIV‐1 infection with discordant normalization in effective antiretroviral therapy

Although the impairment of HIV-specific T lymphocytes is evident during chronic HIV-infection, it is unclear whether the increased CD8+ T cells associates with either selective or overall change of effector functional phenotype. Instead of study on HIV-specific T cells only, analyzing bulk T cell populations represent a neglected area of T cell impairment, which go far beyond HIV-specific T cells. In this study, we determined the diversity of CD8+ T cells in term of cytolytic molecule expression (perforin, granzyme A, and granzyme B) and cytokine production ability (IFN-gamma, TNF-alpha, and IL-2) using intracellular staining and flow cytometry technique. The results were compared between healthy individuals, untreated, and antiretroviral therapy (ART) treated HIV infected patients. We demonstrated the presence of four different subsets of CD8+ T cells that expressed different combinations of cytolytic molecules. We also identified seven different subsets of cytokine producing cells based on different combination of IFN-gamma, TNF-alpha, and IL-2. Results showed significant alterations of these cell subsets that expressed different combination of cytolytic effector molecules or cytokines in HIV infected patients. Furthermore, cytolytic molecule expressing cell subsets are not normalized in effective ART treated patients, whereas the selective population of cytokine producing cells returned to normal value. The effector diversity of CD8+ T cells changed in HIV infected patients. Although effective ART altered functional diversity of these cells, long-term suppression of viral replication may be required to normalize the selected CD8+ T cell effector phenotype in HIV infected patients.

Frequency of HLA B∗5701 allele carriers in abacavir treated-HIV infected patients and controls from northeastern Brazil

In clinical practice, using pharmacogenetics has risen in importance since the technologies for genomic variation searches for different responses to drugs became widespread, easier, more rapid, and affordable for a specialized laboratory. The main pharmacogenetics studies have mostly involved drug resistance monitoring in oncology patients;1 however, other applications are being developed to detect genetic molecular markers associated with resistance or hypersensitivity/adverse reactions to antiretroviral drug treatment in Human Immunodeficiency Virus (HIV)-infected patients.2 HIV treatment is known to be limited by adverse drug reactions and the development of resistance. One significant example is the strong association of the Abacavir hypersensitivity reaction with HLA-B*5701 in HIV-positive patients.3 Abacavir, a common drug for treating HIV-infected patients, is an efficient nucleoside reverse-transcriptase inhibitor with a beneficial long-term toxicity profile, often used with other antiretroviral agents. However, Abacavir can yield adverse effects such as immunologically-driven hypersensitivity in 5 to 8% of HIV-positive subjects during the first six weeks of use.2 Hypersensitivity symptoms immediately reverse after the interruption of Abacavir.4 The hypersensitivity reaction to Abacavir has been reportedly associated with the presence of the major histocompatibility complex class I allele HLA-B*5701 and this association has been confirmed in several replication studies in different ethnic groups of HIV-positive patients.3 In our study, we searched for the presence of HLA B*5701 in 96 HIV-positive patients treated with Abacavir and in 243 healthy subjects from Northeastern Brazil (Recife, Pernambuco) to verify the percentage of HLA B*5701 allele carriers in HIV patients and in the general population from Northeast Brazil. This area is known to harbor a tri-hybrid population resulting from contributing African (44%), Caucasian (34%), and native American (22%) genomes.5

P4-S2.02 Regulatory T cells and Fox P3 levels in naive and HAART treated HIV-1 infected patients in Thailand

BackgroundThe frequency and expression levels of FoxP3 in regulatory T-cells (T-regs) from advanced-stage HIV-infected patients are controversial. Thus, the aims of this study were to compare these parameters of T-regs...

Lipodystrophy and Insulin Resistance in Combination Antiretroviral Treated HIV-1–Infected Patients: Implication of Resistin

Little information is available with respect to the involvement of resistin in lipodystrophy and metabolic disturbances in HIV-1-infected patients treated with combination antiretroviral therapy (cART). We determined whether the resistin (rest) -420C>G single-nucleotide polymorphism and plasma resistin are associated with the development of lipodystrophy and metabolic disturbances in HIV-1-infected patients treated with cART. The study group comprised 299 HIV-1-infected patients treated with a stable cART for at least 1 year (143 with lipodystrophy and 156 without) and 175 uninfected controls. Anthropometric, clinical, and metabolic variables were determined. Homeostasis model assessment for insulin resistance was used to evaluate insulin resistance. Plasma resistin levels were determined by enzyme-linked immunosorbent assay. The rest -420C>G was assessed using restriction fragment length polymorphism. Student t test, 1-way and 2-way analysis of variance, χ2 test, and Pearson and Spearman correlations were performed for statistical analysis. Genotypes containing the rest -420G variant allele were significantly more common in HIV-1-infected patients without lipodystrophy compared with those with lipodystrophy (P = 0.037). Infected patients had significantly greater plasma resistin levels than uninfected controls (P < 0.001). Among infected patients, plasma resistin levels were significantly lower in patients with lipodystrophy with respect to those without (P = 0.034). In infected patients, plasma resistin levels had a significant positive correlation with insulin and homeostasis model assessment for insulin resistance: P < 0.001 and P = 0.002 in the lipodystrophy subset and P = 0.002 and P = 0.03 in the nonlipodystrophy subset, respectively. In our cohort of white Spaniards, the rest -420C>G single-nucleotide polymorphism may be associated with cART-related lipodystrophy. Plasma resistin correlates with insulin resistance in infected patients with and without lipodystrophy.

CD8-EOMEShigh T cells define a subpopulation of CD8 memory cells that restore CD127high expression after cART treatment in HIV infected patients. (105.27)

Abstract After acute viral infection a small population of effector CD8 T cells upregulate CD127 expression and develop into long lived resting memory T cells. During chronic infections, such as HIV, there is an accumulation of CD8 T cells with effector/memory-like phenotype. These observations led to the hypothesis that there is a developmental impairment in the long lived resting memory T cells within that setting. The transcription factors RUNX3 and Eomesodermin (EOMES) are important in the development of long lived memory CD8 T cells. We studied the dynamics of CD127 expression, RUNX3 and EOMES in patients with HIV infection and different levels of viremia. Consistent with other reports, CD127 expression was decreased in the memory CD8 T cell subset. The CD8 memory CD127low T cells showed increased expression of RUNX3 and EOMES mRNA, as well as effector molecules perforin and granzyme B. In patients with suppressed viremia, we could identify two populations of CD8 T cells expressing EOMEShigh and EOMESint. The EOMESint cells showed a short-lived effector phenotype (perforin+, granzyme B+, CD127low) and the EOMEShigh cells showed a memory-like phenotype (perforin-, CD127high). These results suggest that in human CD8 T cells, EOMES is necessary for the maintenance of long lived memory CD8 T cells and its expression was influenced by HIV-RNA levels and the associated inflammatory environment (R=0.4, p=0.01). These findings provide new insights into the pathogenesis of HIV infection.