HIV-1-Specific CD4+ T Cell Responses in Chronically HIV-1 Infected Blippers on Antiretroviral Therapy in Relation to Viral Replication Following Treatment Interruption

The impact of transient viral load blips on anti-HIV-1 immune responses and on HIV-1 rebound following treatment interruption (TI) is not known. Clinical and immunological parameters were measured during 40 weeks of antiretroviral therapy (ART) and following TI in an observational cohort of 16 chronically HIV-1-infected subjects with or without observed viral load blips during ART. During therapy, blips in seven subjects were associated with higher anti-HIV-1 (p24) CD4⁺ T cell lymphoproliferative responses (p = 0.04), without a significant difference in T cell activation or total anti-HIV-1 CD8⁺ T cell interferon-γ (IFN-γ) responses when compared to nine matched non-blippers. Therapy interruption resulted in a significantly higher viral rebound in blippers by 8 week despite retention of higher lymphoproliferative p24 responses (p = 0.01) and a rise in CD3⁺ T cell activation (p = 0.04) and anti-HIV-1 CD8⁺ T cell responses in blippers by week 4 when compared to non-blippers. Past week 4 of interruption, therapy re-initiation criteria were also met by a higher frequency in blippers by week 14 (p < 0.04) with no difference between groups by week 24. These data support that blippers have higher anti-HIV lymphoproliferative responses while on ART but experience equal to higher viral rebound as compared to matched non-blippers upon TI.     

A novel HLA-B*44 allele, HLA-B*4459, identified in a renal patient with aberrant B44 serology and characterized by sequence-based typing

Human leukocyte antigen-B*4459 was first identified in a renal patient. The novel allele differs from B*44020101 by a single nucleotide change in exon 3 at nucleotide 453 (C-->G), which changes codon 127 from asparagine (AAC) to lysine (AAG) explaining some aberrant B44 serology results in 2003.     

Antibody Response to Achromobacter xylosoxidans during HIV Infection Is Associated with Lower CD4 Levels and Increased Lymphocyte Activation

Inflammation during HIV infection is associated with worse disease outcomes and progression. Many mechanisms have been indicted, including HIV itself, coinfections, and gut microbial translocation. Concerning microbial translocation, we hypothesized that adaptive immune responses to a specific bacterial species known to be present in gut-associated lymphoid tissue are higher among HIV-infected individuals than among HIV-uninfected controls and are associated with T cell activation and lower CD4 T cell counts. By characterizing the IgG response to Achromobacter xylosoxidans, we found that HIV-infected participants who were immunoresponsive (n = 48) had significantly lower CD4 percentages (P = 0.01), greater CD4 activation (percentages of RA⁻ CD38⁺) (P = 0.03), and higher soluble CD14 (P = 0.01). HIV-positive individuals had higher anti-A. xylosoxidans IgG titers than HIV-uninfected individuals (P = 0.04). The results suggest an abnormal adaptive immune activation to gut microflora during HIV infection.     

RANTES Production in HIV-1 Antigen-Stimulated Whole Blood Culture: Relationship with Type 1 Immune Response and Plasma Viral Load in Individuals Infected with HIV-1

Host factors which control replication and clearance of human immunodeficiency virus (HIV) are poorly understood. RANTES (regulated on activation, normal T cell expressed and secreted) and other β-chemokines may be HIV-1-suppressive factors but their role in the progression of HIV-1 infection is a subject of controversy. We investigated the relationship between production of RANTES and correlates of disease progression in 15 patients infected with HIV-1. We used whole blood culture to study the production of RANTES, interferon (IFN)-γ, interleukin (IL)-4 and IL-13 in response to supernatant of T cells infected with HIV-1. A defect of RANTES production was associated with a predominant type 2 and decreased type 1 cytokine profile (IL-4 and/or IL-13 > IFN-γ). We obtained a positive correlation between RANTES and IFN-γ ( P =  0.004) and the ratio of type 1 and type 2 cytokines IFN-γ/IL-4 ( P =  0.04) and IFN-γ/IL-13 ( P =  0.003), and a negative correlation between RANTES production and HIV-1 RNA copy number in plasma ( P =  0.01). The same pattern of correlation was observed between HIV-1 p24-stimulated production of RANTES and the plasma viral load ( P =  0.02, n  = 15). The measurement of RANTES produced by heparinized whole blood in response to HIV-1 antigens appears as a potentially valuable tool to assess the defect of type 1 immune response in individuals infected with HIV-1 and to define whether the absence of a RANTES response may play a role in the increased rate of HIV-1 replication.     

HIF1A Overexpression Is Associated with Poor Prognosis in a Cohort of 731 Colorectal Cancers

Tissue hypoxia commonly occurs in tumors. Hypoxia- inducible factor (HIF)-1 and HIF-2, which are essential mediators of cellular response to hypoxia, regulate gene expression for tumor angiogenesis, glucose metabolism, and resistance to oxidative stress. Their key regulatory subunits, HIF1A (HIF-1α) and endothelial PAS domain protein 1 (EPAS1; HIF-2α), are overexpressed and associated with patient prognosis in a variety of cancers. However, prognostic or molecular features of colon cancer with HIF expression remain uncertain. Among 731 colorectal cancers in two prospective cohort studies, 142 (19%) tumors showed HIF1A overexpression, and 322 (46%) showed EPAS1 overexpression by immunohistochemistry. HIF1A overexpression was significantly associated with higher colorectal cancer-specific mortality in Kaplan-Meier analysis (log-rank test, P < 0.0001), univariate Cox regression (hazard ratio = 1.84; 95% confidence interval, 1.37 to 2.47; P < 0.0001) and multivariate analysis (adjusted hazard ratio = 1.72; 95% confidence interval, 1.26 to 2.36; P = 0.0007) that adjusted for clinical and tumoral features, including microsatellite instability, TP53 (p53), PTGS2 (cyclooxygenase-2), CpG island methylator phenotype, and KRAS, BRAF, PIK3CA, and LINE-1 methylation. In contrast, EPAS1 expression was not significantly associated with patient survival. In addition, HIF1A expression was independently associated with PTGS2 expression (P = 0.0035), CpG island methylator phenotype-high (P = 0.013), and LINE-1 hypomethylation (P = 0.017). EPAS1 expression was inversely associated with high tumor grade (P = 0.0017) and obesity (body mass index ≥ 30 kg/m²) (P = 0.039). In conclusion, HIF1A expression is independently associated with poor prognosis in colorectal cancer, suggesting HIF1A as a biomarker with potentially important therapeutic implications.Tissue hypoxia commonly occurs in tumor, and adaptation to tissue hypoxia appears to be one of important characteristics of malignant cells.^1,2 Hypoxia-inducible factor (HIF)-1 and HIF-2 play a key role in cellular adaptation to hypoxia and regulate the expression of genes responsible for glucose metabolism, angiogenesis, and cell survival.^1,2,3 Thus, HIF and related pathways are potential therapeutic targets.^4,5 Cellular HIF levels are regulated not only by the oxygen-dependent pathway (eg, VHL and prolyl hydroxylase, EGLN) but also by the oxygen-independent pathway (eg, glycogen synthase kinase 3, the phosphatidylinositol 3-kinase pathway, the mitogen-activated protein kinase kinase/extracellular signal-regulated kinase pathway).^6,7 HIF and hypoxia signaling influence a wide variety of pathways including those related to vascular endothelial growth factor (VEGF), cyclins, and MTOR.^1,2 Thus, cellular HIF levels may modify responsiveness to drugs targeting those pathways or hypoxia signaling, and it is of particular interest to examine HIF expression in human cancers. Key regulatory subunits of HIF, HIF1A (the official symbol for HIF-1α), and endothelial PAS domain protein 1 (EPAS1; the official symbol for HIF-2α) are differentially overexpressed^8,9 and have distinct functions in human cancers.^9,10,11 HIF1A expression leads to increased tumor growth and metastasis in some studies,^12,13,14,15 whereas HIF1A inhibits tumor growth by cell cycle arrest or apoptosis induction in other studies.^16,17,18,19 Similar paradoxical effects of EPAS1 have also been reported; EPAS1 appears to promote cancer development and progression in neuroblastoma and renal carcinoma,^20,21,22 whereas it appears to inhibit tumor growth in other cancers including colon cancer.^23,24,25Previous data on HIF1A, EPAS1, and clinical outcome in colorectal cancer have been inconclusive. A study of 90 rectal cancer patients showed poor prognosis associated with HIF1A but not with EPAS1.²⁶ In contrast, another study of 87 colorectal cancer patients reported poor prognosis associated with EPAS1 but not with HIF1A.²⁷ Among studies assessing only HIF1A, some reported its independent prognostic effect^28,29 whereas others did not.^30,31 However, all previous studies^{26,27,28,29,30,31} were limited by small sample sizes (N <136). Considering the increasing importance of the HIF pathway as a potential target for cancer treatment,^1,2,6 the assessment of HIF1A and EPAS1 expression and clinical outcome using a large number of colorectal cancers is needed.We therefore examined prognostic effects of HIF1A and EPAS1 expression among 731 colorectal cancer patients identified in two prospective cohort studies. Moreover, because we concurrently assessed other important molecular events including mutations in KRAS, BRAF, and PIK3CA, LINE-1 hypomethylation, microsatellite instability (MSI), and the CpG island methylator phenotype (CIMP), we could evaluate the effect of HIF1A or EPAS1 expression after controlling for these potential confounders.     

Body Mass Index and CD4+ T-Lymphocyte Recovery in HIV-Infected Men with Viral Suppression on Antiretroviral Therapy

Abstract

Purpose: To better characterize the relationship between body mass index (BMI) and CD4+ T-lymphocyte recovery in HIV disease.Methods: We analyzed the association between baseline BMI and CD4+ T-lymphocyte increases, as well as the association between BMI and immune activation (CD38 and HLA-DR co-expression on CD4+ and CD8+ T-lymphocytes), in male HIV-infected patients who achieved viral suppression on antiretroviral therapy (ART).Results: Baseline BMI predicted change in CD4+ T-lymphocyte count at weeks 96 ( P = .03, n = 461) and 144 ( P = .005, n = 357) but not at week 48 ( P = .38, n = 558). Relative to men with a normal BMI, overweight and obese men had increases at week 144 that were 35 and 113 cells/ mm³ higher, respectively, while underweight men had CD4+ T-lymphocyte increases that were 94 cells/mm³ lower. No significant correlations between baseline BMI and cellular immune activation were seen.Conclusions: BMI predicts CD4+ T-lymphocyte gains in men started on ART.     

Decreased Dipeptidyl Peptidase IV Enzyme Activity of Plasma Soluble CD26 and Its Inverse Correlation with HIV-1 RNA in HIV-1 Infected Individuals

Human plasma contains soluble CD26/dipeptidyl peptidase IV (sCD26/DPPIV) although its physiological significance remains unclear. To determine whether the plasma sCD26 levels have clinical relevance in HIV-1 infected individuals, the concentration and DPPIV enzyme activity of plasma sCD26 were measured. While there is no significant difference between the plasma levels of sCD26 in 90 HIV-1 infected individuals and in 79 uninfected controls, specific DPPIV enzyme activity of sCD26 was significantly decreased HIV-1 infected individuals (P < 0.0001). Specific DPPIV enzyme activity was correlated with the levels of CD4+ T cells (r = 0.247; P < 0.02), CD8+ T cells (r = 0.236; P < 0.03), and adenosine deaminase (r = 0.227; P < 0.05) and had an inverse correlation with HIV-1 RNA (Spearman's r = 0.474; P = 0.0012). Furthermore, recombinant sCD26 enhanced the in vitro PPD-induced response of lymphocytes from HIV-1 infected individuals with decreased specific DPPIV enzyme activity. These results suggest that the specific DPPIV enzyme activity of plasma sCD26 may contribute to the immunopathogenesis of HIV infection.     

Genotypic Determination of HIV Tropism in a Cohort of Patients Perinatally Infected With HIV-1 and Exposed to Antiretroviral Therapy

The aim of this study was to determine the coreceptor tropism by performing genotypic HIV-1 tropism testing in a cohort of patients perinatally infected with HIV-1 and exposed to antiretroviral therapy. Genotypic coreceptor tropism was determined in patients with HIV-1 RNA<100 copies/mL using PBMC samples by gp120 V3 sequencing followed by geno2pheno interpretation (set at a false positive rate [FPR] of 20%) and in patients with >100 copies/mL using plasma samples (set at a FPR of 20%), according to European guidelines. Out of 55 patients, 50 had an HIV-1 subtype B strain, and mean (SD) age was 18.2 (4.6) years. The median duration of antiretroviral therapy was 13 years (range, 3–23). Thirty-three (60%) patients harbored the R5 virus. At the time of the testing, the median CD4+ T lymphocyte cell count and percentage were 705 cells/mm³ (474–905) and 32.5% in group R5 and 626 cells/mm³ (450–755) and 31.7% in group X4/D-M, respectively. The nadir of CD4+ T-cell count in groups R5 and X4/D-M were 322 cells/mm³ (230–427) and 340 cells/mm³ (242–356), respectively. These differences were not statistically significant. Fifteen patients had HIV-1 RNA >50 copies/mL. The median HIV-1 RNA and HIV-1 DNA were comparable in both groups without a statistical difference. The study provides an overview of the prevalence of coreceptor tropism in a cohort of patients who were vertically infected with HIV-1. The high prevalence of X4/D-M-tropic strains may simply reflect the long-term exposure to HIV.     

Lower expression of plasma-derived exosome miR-21 levels in HIV-1 elite controllers with decreasing CD4 T cell count

Exosome-derived miR-21 was independently associated with CD4 T cell decline in HIV-1-infected elite controllers (OR 0.369, 95% CI 0.137–0.994, p = 0.049). Also, a negative correlation between miR-21 expression and MCP-1 level was found (r = −0.649, p = 0.020), while no correlation between soluble biomarkers or cellular immune activation was found.     

CD4 T-cell count and HIV-1 infection in adults with uncomplicated malaria

BACKGROUND: HIV-1-negative children with malaria have reversible lymphocyte and CD4 count decreases. We assessed the impact of malaria parasitemia on the absolute CD4 count in both HIV-1-infected and non-HIV-infected adults. METHODS: In Ndola, Zambia, at the health-center level, we treated 327 nonpregnant adults for confirmed, uncomplicated, clinical malaria. We assessed HIV-1 status, CD4 count, and HIV-1 viral load (if HIV-1-infected) at enrollment and at 28 and 45 days after treatment. RESULTS: After successful antimalarial treatment, the median CD4 count at day 28 of follow-up increased from 468 to 811 cells/microL in HIV-1-negative and from 297 to 447 cells/microL in HIV-1-positive patients (paired t test, P < 0.001 for both). CD4 count increment was inversely correlated with CD4 count at day 0 in both HIV-1-negative (P < 0.001) and HIV-1-positive patients (P = 0.03). After successful treatment, the proportion of patients with CD4 count <200/microL at day 45 decreased from 9.6% to 0% in HIV-1-negative and from 28.7% to 13.2% in HIV-1-positive malaria patients (P < 0.001 for both). In patients with detectable but mostly asymptomatic parasitemia, CD4 count and, if HIV-1-infected, viral load at day 45 of follow-up were similar to those observed at enrollment. CONCLUSION: Interpretation of absolute CD4 count might be biased during or just after a clinical malaria episode. Therefore, in malaria-endemic areas, before taking any decision on the management of HIV-1-positive individuals, their malaria status should be assessed.     

Severe Lower Respiratory Tract Infections Associated with Human Parainfluenza Viruses 1–3 in Children Infected and Noninfected with HIV Type 1

The aim of this study was to compare the clinical course of severe lower respiratory tract infections associated with human parainfluenza virus types 1–3 (HPIV 1–3) in hospitalised children infected with the human immunodeficiency virus type 1 (HIV-1) versus that in hospitalised children not infected with HIV-1. Children were enrolled prospectively as part of a broader study that evaluated the aetiology of lower respiratory tract infections in HIV-1-infected and -noninfected children from March 1997 through March 1999. HPIV types 1–3 were isolated from nasopharyngeal aspirate samples that were analysed using immunofluorescein monoclonal antibody assays. Thirty percent (24 of 80) of the children from whom HPIV was isolated were infected with HIV-1. Sixty-six percent (47of 62) and 22% (14 of 62) of the HPIV isolates that were typed were subtypes 3 and 1, respectively. The clinical presentation of severe lower respiratory tract infection was similar in both HIV-1-infected and -noninfected children, except that the former were less likely to have wheezing (4.2% vs. 28.6%, P=0.01). Furthermore, the duration of hospitalisation was longer in HIV-1-infected children than in HIV-1-noninfected children (median 11.5 days [range 1–15 days] vs. median 7.5 days [range 1–22 days]; P=0.02), and mortality was higher (5 of 24 [20.8%] infected children vs. 0 of 56 noninfected children; P=0.001). Importantly, four of five (80%) of the HIV-1-infected children who died had other concurrent illnesses or predisposing factors for severe HPIV-associated disease. HPIV-associated lower respiratory tract infection causes greater morbidity and mortality in HIV-1-infected children than in HIV-1-noninfected children; however, this may be due to other concurrent illnesses in HIV-1-infected children. Electronic Publication     

Monocarboxylate Transporters 1 and 4 Are Associated with CD147 in Cervical Carcinoma

Due to the highly glycolytic metabolism of solid tumours, there is an increased acid production, however, cells are able to maintain physiological pH through plasma membrane efflux of the accumulating protons. Acid efflux through MCTs (monocarboxylate transporters) constitutes one of the most important mechanisms involved in tumour intracellular pH maintenance. Still, the molecular mechanisms underlying the regulation of these proteins are not fully understood. We aimed to evaluate the association between CD147 (MCT1 and MCT4 chaperone) and MCT expression in cervical cancer lesions and the clinico-pathological significance of CD147 expression, alone and in combination with MCTs. The series included 83 biopsy samples of precursor lesions and surgical specimens of 126 invasive carcinomas. Analysis of CD147 expression was performed by immunohistochemistry. CD147 expression was higher in squamous and adenocarcinoma tissues than in the non-neoplastic counterparts and, importantly, both MCT1 and MCT4 were more frequently expressed in CD147 positive cases. Additionally, co-expression of CD147 with MCT1 was associated with lymph-node and/or distant metastases in adenocarcinomas. Our results show a close association between CD147 and MCT1 and MCT4 expressions in human cervical cancer and provided evidence for a prognostic value of CD147 and MCT1 co-expression.     

Viral load and CD4 count dynamics after HIV-1 seroconversion in homosexual and bisexual men in Rio de Janeiro, Brazil

PURPOSE: Reliable predictors of HIV disease progression are scarce in developing countries, where most HIV infections occur. We describe early virologic and immunologic events among men who have sex with men in Rio de Janeiro, Brazil. METHODS: Seroconverters from 2 high-risk cohorts were followed for up to 36 months with periodic laboratory evaluations, plasma viral load, and CD4 count assessments. Viral load and CD4 count mean trajectories were computed. For the modeled viral loads, mean and median values were 24,480 (4.36 log10) and 19,720 (4.29 log10) copies/mL (range 14,880-58,090), respectively. Median CD4 count was 373 cells/microL (range 260-508). Overall variation on viral loads ranged from 4.3 to 5.2 log10 copies/mL with a visible increase in the viral load starting at approximately 600 days (n = 12) after estimated time of seroconversion. The initial period of HIV infection was characterized by an increase in CD4 count (n = 29) followed by a steep decline starting at approximately 200 days (508 cells, 95% CI: 425 to 569). A gradual decrease was observed in the median CD4 count thereafter, reaching 281 (95% CI: 100 to 466) at 1000 days after the estimated date of seroconversion. CONCLUSIONS: Although viral load dynamics resembled those observed in developed countries, CD4 counts seem to decline at a faster rate than in the Multicenter AIDS Cohort Study (MACS) cohort. Clinical and survival data are needed to assess the impact of interventions, such as antiretroviral therapy, on the clinical course of HIV infection in Brazil.     

Characterization of HLA-B*5516, -B*1313, -B*9512, and -DRB1*1457 alleles identified in a southwest Chinese population

The human leukocyte antigen (HLA)-B*5516 allele differs from the B*5502 by a single 97 T --> C substitution (His to Tyr at position 33) in exon 2. The B*1313 allele results from 419 T --> A and 420 A --> C substitutions, encoding a Leu to Tyr substitution at 140 in exon 2 of the B*1301 allele. The B*9512 allele differs from B*1502 by a single 360 G --> C substitution (Gln to His at 120) in exon 3. The DRB1*1457 allele appears to be a hybrid molecule generated by recombination between the DRB1*13 and DRB1*14 alleles. The serological equivalents of these new alleles are HLA-B22, -B13, -B15, and DR13, respectively. Family studies detected two rare haplotypes: A*11, B*9512, DRB1*14 and A*24, B*52, Cw*07, DRB1*1457, DRB3*020201, DQB1*050301. The gene frequencies of these alleles in the Chinese population are less than 0.0001.     

Interaction between KIR3DL1 and HLA-B*57 supertype alleles influences the progression of HIV-1 infection in a Zambian population

KIR and HLA loci are both highly polymorphic, and some HLA class 1 products bind and trigger cell-surface receptors specified by KIR genes. We examined whether KIR genes act in concert with HLA-B locus to control HIV-1 infection in a sample of Zambian patients. DNA samples from 88 Zambian patients with HIV-1 were examined. Patients were classified as either slow progressors (SP; n = 54) or rapid progressors (RP; n = 34) to AIDS. All were typed for HLA-B and KIR genes. Our results reveal an association between B*57 supertype (B*57s, which includes B*57 and B*58 alleles) and delayed progression to AIDS (p = 0.0007 by pc = 0.015; OR = 5.25). We also observed an increase incidence of Bw4-I80 in patients with slow progression (p = 0.001 by pc = 0.003, OR = 5). This increase was found to be secondary to B*57s. The presence of both KIR3DL1 and B*57S has a significant effect on progression to AIDS (p = 0.0008; OR = 5.61). B*57s genotypes with another HLA-B allele different from those in the trans position, which also had a specificity different to Bw4-I80 (Bw4-T80 or Bw6), was also greater in the SP than in the RP group (p = 0.00003; OR = 10.11). The presence of the inhibitory allele KIR3DL1 in combination with the HLA-B*57s alleles that contain the Bw4-I80 epitope, has a highly protective effect against progression to AIDS in Zambian patients.     

The DC-SIGNR 7/5 Genotype is Associated with High Dendritic Cell Counts and Their Subsets in Patients Infected with HIV-1

Purpose

The aim of this study was to assess peripheral blood dendritic cell (DC) frequencies and Dendritic Cell-specific intracellular adhesion molecule 3 grabbing non-integrin related (DC-SIGNR) genotyping in healthy individuals, injecting drug users and HIV-1 infected individuals and correlate with different clinical parameters from north India.

Methods

Blood from 30 seronegative healthy individuals, 30 injecting drug users, and 30 patients infected with HIV-1 from North India were collected. Peripheral blood DC frequencies were determined by flow cytometry and repeat region polymorphism in DC-SIGNR was performed by PCR.

Results

There was a significantly lower number of DCs and their subsets in patients infected with HIV-1 compared to injecting drug users and healthy individuals. A significant positive correlation of DCs and their subsets with CD4⁺ T cells and negative correlation with HIV-1 viral load was found. A salient finding of this study was the association of the heterozygous 7/5 DC-SIGNR genotypes with higher percentage of DCs and their subsets and higher CD4⁺ T cell counts and lower viral load compared to the homozygous 7/7 DC-SIGNR genotypes in patients infected with HIV-1.

Conclusions

This is the first study to assess the DC subsets and its association with DC-SIGNR polymorphism in injecting drug users and HIV-1 infected patients and suggests the protective role of 7/5 DC-SIGNR genotypes in HIV-1 infection.     

Lower CD4+ T Lymphocyte Nadirs May Indicate Limited Immune Reconstitution in HIV-1 Infected Individuals on Potent Antiretroviral Therapy: Analysis of Immunophenotypic Marker Results of AACTG 5067

Background: Although initiation of potent antiretroviral therapy (ART) has significantly improved immune perturbations in individuals with AIDS, it is unclear which factors are most important in determining the degree of immune reconstitution.Methods: Whole blood was analyzed at baseline and week 12 in six groups of subjects (n = 81): those with acute or following immune reconstitution after Pneumocystis jirovecii (previously known as Pneumocystis carinii) pneumonia (PcP) (two groups) and cytomegalovirus (CMV) retinitis (two groups), HIV-infection without AIDS (one group), and healthy volunteers (one group). Absolute CD4+ and CD8+ T lymphocytes, naíve (CD45RA+) and memory (CD45RO+) CD4+ T lymphocytes and percentages of activated CD8+ T lymphocytes (CD8+/CD38+/HLA-DR), and CD28 expression on CD4+ and CD8+ T lymphocytes were enumerated.Results: The reconstituted CMV group, which had a history of a lower CD4+ T lymphocyte nadir compared to the reconstituted PcP group (15 cells/mm³ versus 48 cells/mm³; p = .013), had significantly lower absolute CD4+, CD8+ and naíve CD4+ T lymphocytes and a trend toward lower memory CD4+ T lymphocytes compared to the reconstituted PcP group. Moreover, no difference was noted between the reconstituted groups in the proportion of subjects with undetected HIV-1 RNA. The reconstituted subjects had significantly lower absolute CD4+, memory CD4+ and naíve CD4+ T lymphocytes than the HIV-positive controls and a significantly higher percentage of activated CD8+ T lymphocytes with a lower percentage of CD8+CD28 expression than the HIV-negative controls.Conclusion: The association of CD4+ T lymphocyte nadir with the extent of immune reconstitution in HIV-infected individuals suggests that HIV-1 may cause irreparable immune system damage despite potent ART.     

Characterization a novel HLA-B40 allele with serological Bw4 motif, HLA-B*4047, in the Finnish population and confirmation of B*270503 allele

We describe a novel HLA-B*40 allele assigned as B*4047*. The B*4047 allele was detected in a Finnish patient awaiting kidney transplantation. The patient had a "short" B60-like serological specificity with Bw4 association. After sequencing, the B*4047 allele was found to be identical to B*4001, except having five amino acid changes in exon 2, including the entire motif corresponding to Bw4 and w6 specificity. As a result of recombination or gene conversion, B*4047 has the Bw4 motif instead of expected Bw6. Screening of B40 alleles in the Finnish population revealed no other cases with this pattern, suggesting that this allele is rare. The sequence of B*270503 presented here provides the complete sequence for exons 2 and 3 for this allele. B*270503 allele differs from B*270502 by a single synonymous nucleotide substitution at non-variable position 489 in exon 3.