Low CD4 Group Research Articles

Thiamine deficiency underlies persistent gut dysbiosis and inflammation in people living with HIV on antiretroviral therapy

BackgroundAntiretroviral therapy (ART) has significantly improved the prognosis for people living with human immunodeficiency virus (PLWH). However, alterations in the gut microbiota of PLWH affect their metabolic environment and may contribute to chronic inflammation and premature aging, despite effective ART. Given that inflammation in the body have been shown to be risk factors for age-related diseases, elucidating changes in the gut microbiota and metabolic levels over time in individuals would be for understanding the dynamics in the body that lead to disease development.MethodsThe study assessed changes in blood markers, gut microbiota, and metabolic environment of PLWH on ART for four years, with participants divided into two groups based on median CD4 cell count (580/µL).ResultsThe high-CD4 group was more obese than the low-CD4 group, but there was no significant difference in comorbidities, such as diabetes, hypertension, and dyslipidemia. An investigation of the alterations in gut microbiota over a 4-year period revealed a reduction in specific groups of bacteria that produce short-chain fatty acids (SCFAs) and an increase in the occurrence of Enterobacteriaceae. In addition, a decline in bacterial thiamine synthesis was predicted, and a decreased abundance of the Ruminococcus gauvreauii group, which relies on supplementation with thiamine from symbiotic bacteria, was observed. The abundance of Collinsella and Catenibacterium at baseline was positively correlated with the predicted number of thiamine-synthesizing pathway. The presence of Catenibacterium at follow-up was inversely correlated with the rate of increase in plasma levels of lipopolysaccharide-binding protein, an indicator of a leaky gut. In terms of assessing the diversity of gut microbiota, a trend towards an increase in opportunistic bacteria with different genetic distances was observed in the high-CD4 group at follow-up.ConclusionThese observations suggested that, despite effective ART, the thiamine-deficient environment in the gut continues to reduce thiamine-requiring bacteria, such as certain SCFA-producing bacteria. As a result, secondary effects, such as proliferation of opportunistic bacteria and chronic inflammation associated with increased intestinal permeability, proceed in PLWH. Thus, certain essential nutrient deficiencies for gut metabolic environment may disrupt the symbiotic relationship between gut bacteria and increase the risk of developing inflammatory diseases.

Comparative immunogenicity and neutralizing antibody responses post heterologous vaccination with CoronaVac (Sinovac) and Vaxzevria (AstraZeneca) in HIV-infected patients with varying CD4+ T lymphocyte counts

ABSTRACT The immune response to heterologous coronavirus disease (COVID-19) vaccination in people living with HIV (PLWH) is still unclear. Herein, our prospective cohort study aimed to compare the immune response of heterologous vaccination with CoronaVac (Sinovac) and Vaxzevria (AstraZeneca) between PLWH having CD4 counts ≤ 200 cells/µL (low CD4+) and > 200 cells/µL (high CD4+). Anti-receptor-binding domain (RBD) immunoglobulin G (IgG) levels and the percentage inhibition of neutralizing antibodies (nAbs) were analyzed at 2 and 12 weeks after immunization. Participants in the low and high CD4+ groups had mean CD4+ counts of 139 and 575 cell/µL, respectively. Two and 12 weeks after immunization, in the low CD4 group, the median anti-RBD-IgG levels were 159 IU/mL and 143 IU/mL, respectively, whereas the nAb level was 71% and decreased to 47.2%, respectively. Contrarily, the median anti-RBD-IgG levels in the high CD4+ group were 273 IU/mL and 294 IU/mL, respectively, whereas the nAb levels were 89.3% and relatively stable at 81.6%. However, although immune responses between the two study groups were not significantly different, a decline in nAb levels was observed at 12 weeks in the low CD4+ group. Therefore, a COVID-19 booster vaccine dose is suggested for immunoprotection.

Association between the gut microbiome and organic acid profiles in a Japanese population with HIV infection

IntroductionAn increased incidence of metabolic syndrome has been observed in human immunodeficiency virus (HIV)-infected individuals. In contrast, gut dysbiosis is involved in various pathogeneses, including vascular endothelial disorders. Organic acids, including short-chain fatty acids (SCFAs), are essential for maintaining gut homeostasis. Therefore, this study aimed to explore the gut microbiome profile and organic acids in a Japanese population infected with HIV. MethodsForty-nine patients with HIV infection on combination antiretroviral therapy (cART) were enrolled and divided into the high and low CD4 groups based on a CD4 cutoff of 350 cells/μL. Stool samples were analyzed by 16S ribosomal RNA next-generation sequencing and high-performance liquid chromatography. The association between the gut microbiome, including bacterial taxa and organic acids, was statistically analyzed. ResultsThe fecal microbial community composition was significantly different between HIV patients with CD4 counts above and below 350 cells/μL. The relative abundance of Roseburia, Prevotella, Prevotella_9, and [Clostridium]_methylpentosum_group were significantly enriched in the high CD4 group. Fecal succinic acid tended to be more abundant in the low CD4 group, and acetic, propionic, and butyric acids tended to be more abundant in the high CD4 group. Roseburia was positively correlated with butyric acid levels. Prevotella_9 and Prevotella were negatively correlated with succinic acid levels and positively correlated with acetic and propionic acid levels. ConclusionsThis study showed intestinal dysbiosis bordering on a CD4 count of 350 in patients with HIV infection undergoing cART. These findings might help in understanding intestinal damage and systemic inflammation in HIV infection.

Weight gain in patients starting Dolutegravir-based ART according to baseline CD4 count after 48 weeks of follow up.

Excessive weight gain is a current concern among People Living with HIV (PLHIV) starting ART. To evaluate the weight gain after 48-weeks of ART in naive patients, according with baseline CD4 count. PLHIV starting 3TC+TDF+DTG with at least 48-weeks of follow up in two AIDS referral centers were stratified by baseline CD4 count (lower or higher than 200 cells/mm3). Data on CD4 count, HIV viral load, weight/Body Mass Index (BMI), lipids and glucose levels were collected at baseline, 24 and 48 weeks of treatment. For analysis purpose, patients were categorized according to their BMI progression. A total of 270 patients were included in the study. Mean CD4 count were 78.3±61.7 and 536.7±273 cells/mm3 for low and high CD4 count groups, respectively (p < 0.001). Baseline BMI was significantly lower in low CD4 group (21.7vs. 23.6 Kg/m2, p < 0.001). Patients in low CD4 group gained more weight than those in high CD4 group (11.2±8.5kg vs. 2.2±4.2 Kg, p=0.004). Overall weight gain was higher in women, regardless group (13.1±7.9 Kg vs. 1.4±3.6 Kg for women and men, respectively, p < 0.001). The proportion of overweight/obesity significantly increased in low CD4 group. Viral suppression rate was high for both groups. At week 48 the overall proportion of overweight/obesity was like that reported for the Brazilian population. Weight gain in the present study indicates a "return to health" phenomenon. Excessive weight gain was more frequent in women.

T-Lymphocyte Gene-Regulated CCL5 and Its Association with Extrahepatic Metastasis in Hepatocellular Carcinoma.

Extrahepatic metastasis in hepatocellular carcinoma (HCC) greatly limits the prognostic survival of HCC patients. Levels of preoperative peripheral lymphocyte subsets and cytokines in the serum for predicting extrahepatic spread of hepatocellular carcinoma are still not common in clinical practice. The aim of this study is to investigate the value and mechanisms of peripheral lymphocyte subsets and cytokines in predicting extrahepatic spread of HCC. We used a retrospective design to analyze data pertaining to a total of 380 patients with HCC who were examined for peripheral T-lymphocyte subsets before receiving microwave ablation. We performed Cox regression analysis to screen out independent risk factors and used pathology specimens from the patients and public databases of liver cancer to investigate the correlation between cytokines and intra-tumor immune cells. The CD4low group had better metastasis-free 1-year, 3-year, and 5-year survival rates compared to the CD4high group (80% vs 69%, 67% vs 51%, and 57% vs 39%, respectively; HR 1.7 (1.2, 2.3), P = 0.0019). Similarly, the CD8high group had better metastasis-free 1-year, 3-year, and 5-year survival rates compared to the CD8low group (65% vs 78%, 46% vs 64%, and 34% vs 54%, respectively; HR 0.6 (0.4, 0.8), P < 0.001). Patients with the CD4high/CD8low phenotype had significantly worse metastasis-free survival times compared to other patients (HR 2.0 (1.5, 2.8), P < 0.001). Additionally, T lymphocyte-specific genes (CD4, CD8) were correlated with CCL5 expression, which was also positively correlated with the level of intra-tumoral infiltrating CD8 T cells and the prognosis of HCC patients. Both CD4+ and CD8+ T lymphocyte subsets were independent risk factors for extrahepatic metastasis in HCC. Serum CCL5 levels could indicate the infiltration level of intra-tumoral CD8+ T cells and the risk of extrahepatic metastasis in HCC patients, aiding in patient risk stratification for metastasis.

Peripheral blood CD4+ T cell count predicts recurrence of condyloma acuminatum after photodynamic therapy in HIV-positive patients.

Few studies have reported postoperative relapse of condyloma acuminatum (CA) after 5-aminolevulinic acid photodynamic therapy (ALA-PDT) in human immunodeficiency virus (HIV) positive patients. The clinical data of HIV-positive CA patients treated with ALA-PDT from October 2018 to December 2019 were analyzed retrospectively. Univariate and multivariate Cox regression was used to analyze the variables related to postoperative recurrence. Pearson correlation test was employed to analyze the correlation between CD4+ T cell count and postoperative recurrence rate. Kaplan-Meier method was used to compare the CA recurrence after ALA-PDT in low CD4 group and high CD4 group. A total of 38 HIV-positive patients with CA were included in the study. Among them, 26 patients experienced CA recurrence within 6 months, and the recurrence rate was 68.4%. CD4+ T cell count was 187.0 (79.0-596.0) cells/μl in relapsed patients and 406.0 (89.0-612.0) cells/μl in non-relapsed patients, showing a statistically significant difference (p=.005). Pearson correlation coefficient analysis revealed a negative correlation between CD4+ T cell count and postoperative recurrence rate (p=.005, r=-.443). Univariate regression analysis showed that CD4+ T cell count was correlated with postoperative recurrence, hazard ratio (HR) was 0.99 [95% Confidence interval (CI)=0.99-1.0, p=.012]. Multivariate Cox regression analysis showed that with the low CD4+ T cell count as the reference, the high CD4+ T cell count was negatively correlated with postoperative recurrence (HR=0.09, 95% CI 0.01-0.87, p=.038). Peripheral blood CD4+ T cell count can predict the CA recurrence rate after ALA-PDT in HIV-positive patients.

Biomarkers of Endothelial Activation in Black South African HIV-Positive Subjects are Associated with Both High Viral Load and Low CD4 Counts.

The prevalence of cardiovascular death in the HIV-infected population is higher than in uninfected individuals. Growing evidence suggests that HIV infection itself is directly linked to endothelial activation and dysfunction. Therefore, the aim of this study was to investigate whether endothelial activation is present in African subjects with HIV infection and identify its possible determinants. Eighty HIV-infected treatment-naive cases, categorized into two groups based on CD4 count (38 subjects with CD4 count ≤350 cells/mm3 and 42 subjects with CD4 count >350 cells/mm3), were compared with 60 HIV-uninfected controls. A small subgroup of the HIV-infected participants (n = 13) were followed up for 18 months following initiation of antiretroviral therapy (ART). Anthropometric data, fasting lipid and glucose levels, viral load, and CD4 counts were measured as were serum levels of intercellular adhesion molecule-1 (ICAM-1), endothelial leukocyte adhesion molecule-1, vascular cell adhesion molecule-1 (VCAM-1), monocyte chemoattractant protein-1, von Willebrand factor (vWF), tumor necrosis factor alpha (TNF-α), interleukin-6 (IL-6), and interleukin-8 (IL-8). The HIV-infected low CD4 group had higher levels of ICAM-1 (p < .05), VCAM-1 (p < .0005), TNF-α (p < .005), and vWF (p < .005), compared with the controls. In the HIV-infected cohort, VCAM-1 levels were negatively associated with CD4 counts (β = -0.474; p < .0005), whereas vWF levels were positively associated with viral load (β = 0.344; p < .01). Levels of ICAM-1 and VCAM-1 were reduced by ART (p < .05 vs. baseline for both), however, levels of IL-6, IL-8, and TNF-α increased (p < .005 vs. baseline for all). Endothelial activation and inflammation are evident in African ART-naive HIV-infected patients; the former is attenuated, and the latter is increased after 18 months of ART. In HIV-infected subjects, both immunological dysregulation and viral load are associated with biomarkers of endothelial activation.

The abnormal distribution of NK cell subsets before HAART treatment may be related to the level of immune reconstitution in HIV patient

BackgroundHIV infection leads to the damage of NK cells, which is closely associated with the disease's progression, but whether it affects immune reconstitution after Highly Active Antiretroviral Therapy (HAART) is not clear. MethodsFrom March 9 to October 31, 2017, a total of 75 confirmed cases with HIV in Wenzhou were collected and analyzed. NK cell subsets were measured and compared among three groups: the control group, the group whose CD4+ T cell counts <200/μL (named as low-CD4 group) and the group whose CD4+ T cell counts ≥200/μL (named as high-CD4 group). The lymphocytic subsets were dynamically monitored in patients with HIV after HAART. ResultsPatients in low-CD4 group have lower proportion of CD3−CD56dimCD16+ NK cell subset, but have higher proportion of CD3−CD56−CD16+ NK cell subsets, which were compared with patients in high-CD4 group (All P values <0.01). There is a positive correlation between the proportion of CD3−CD56−CD16+ NK cell subset and CD4+ T cell counts (r = 0.628, p < 0.001). Patients in the low-CD4 group have higher expression of PD-1 and PS on NK cells than patients in the high-CD4 group (All P values < 0.05). The odds ratio of the proportion of the CD3−CD56−CD16+ NK cell subset before treatment for HAART efficacy was 0.826 (p < 0.001). ConclusionsThere are abnormalities in the proportion and function of NK cell subsets in HIV patients, which are associated with disease progression. The proportion of the CD3−CD56−CD16+ NK cell subset before treatment is related with HAART efficacy.

Longitudinal changes in plasma Caspase-1 and Caspase-3 during the first 2 years of HIV-1 infection in CD4Low and CD4High patient groups.

Over 95% of CD4 cell death occurs by Caspase-1-mediated pyroptosis during HIV infection. Caspase-3-mediated apoptosis accounts for the death in a small proportion of infected CD4 cells. To date, there have been no reports on the dynamics of Caspase-1 and Caspase-3 and their relationship with disease progression in acute HIV-1 infection. In this study, two distinct HIV-1 patient groups were enrolled. The CD4High group maintained a CD4 level above450 cells/μl while CD4 levels in the CD4Low group dropped below 250 cells/μl within 2 years after infection. Blood samples were collected at 1, 2, 3, 4, 6, 12 and 24 months after HIV infection. Plasma Caspase-1 and Caspase-3 levels in the two patients groups were determined by a single-step ELISA using commercially available monoclonal antibodies. The results showed that Caspase-1 and Caspase-3 levels in the CD4High group increased rapidly and then decreased within a short time during early HIV-1 infection. In contrast, Caspase-1 and Caspase-3 levels in the CD4Low group were obviously increased after 1 year of HIV-1 infection.

Increased risk of non-AIDS-related events in HIV subjects with persistent low CD4 counts despite cART in the CoRIS cohort

The aim was to analyze clinical complications in HIV-infected subjects who persistently maintain low CD4 levels despite virological response to cART in the Spanish CoRIS cohort. The main inclusion criteria were CD4 counts <200cells/mm3 at cART-initiation and at least 2years under cART achieving a viral load <500copies/mL. Those patients with CD4 counts <250cells/mm3 2years after cART were classified as the Low-CD4 group, and clinical events were collected from this time-point. Poisson regression models were used to calculate incidence rate ratios of death, AIDS-defining events, serious non-AIDS-defining events (NAE) and of each specific NAE category (non-AIDS-defining malignancies (non-ADM), cardiovascular, kidney- and liver-related events). Of 9667 patients in the cohort, a total of 1128 met the criteria and 287 (25.4%) were classified in the Low-CD4 group. A higher risk of death (aIRR: 4.71; 95% CI: 1.88–11.82; p-value=0.001) and of non-ADM were observed in this group (aIRR: 2.23; 95% CI: 1.07–4.63; p=0.03). Our results stress the need to control accelerated aging in this population to counter their increased risk of non-AIDS-defining diseases, particularly cancer, and are consistent with the concept that clinical complications are potentially affected by genetics and lifestyle.

Effect of Low CD4 Cell Count on Cervical Squamous Intraepithelial Lesions among HIV-Positive Women in Enugu, Southeastern Nigeria.

HIV-positive women are more likely to develop cervical neoplasm. HIV-positive women with low CD4 T-lymphocyte cell count may be more predisposed to cervical squamous intraepithelial lesions (SILs). This study aimed to determine the association between low cellular immunity of HIV positive women, and the prevalence and grade of cervical squamous intraepithelial lesions. Pap smear was carried out on two cohorts of Highly Active Anti Retroviral Therapy (HAART) experienced HIV-positive women (178 per group) at the AIDS Prevention Initiative in Nigeria-Centre for Disease Control Adult Anti-Retroviral clinic of the University of Nigeria Teaching Hospital, Enugu, Nigeria from June to November, 2012. The study group had CD4 cell count of < 200 cells/μl while the control group had CD4 cell count of ≥200 cells/μl. The mean CD4 cell counts of participants in the study (low CD4) group was 127.9 ± 47.49 cells/ml while that of the control (high CD4) group was 489.2 ± 186.36 cells/ml (p < 0.001). The prevalence of SIL was 10.2% (18/176) for the low CD4 group, and 5.7% (10/176) for the high CD4 group [OR = 1.9 (95% CI: 0.85, 4.22)]. The commonest category of SILs identified was Low-grade Squamous Intraepithelial Lesion (LSIL), thus 11 (6.3%) in the study versus 7 (4.0%) in the control group (p = 0.703). Prevalence of cervical SILs among HIV positive women on HAART in Enugu, Nigeria is low and has no significant relationship with their CD4 cell count.

Short communication: Longitudinal changes in peripheral blood NK cells during the first year of HIV-1 Infection in CD4Low and CD4High patient groups.

Natural killer (NK) cells may modulate the pathogenesis of primary HIV-1 infection. However, the relationship between the number and function of NK cells during an acute HIV-1 infection and HIV-1 disease progression remains to be elucidated. In this study, we enrolled two distinct patient groups. One group progressed to where their CD4 cell counts fell below 200 cells/μl within 2 years (CD4Low group), while the CD4 cell counts of the other group remained above 500 cells/μl for over 2 years (CD4High group). We compared the number and function of NK cells during the first year of HIV-1 infection between the two distinct groups. We found that the number of total NK cells and the number of cells in the CD56(dim)CD16(pos) subset rapidly decreased in both groups during early HIV-1 infection. The absolute number of total NK cells and CD56(dim)CD16(pos) NK cells was significantly higher in the CD4High group when compared to the CD4Low group during the first month of infection. No significant difference between the numbers of CD56(bright)CD16(neg) NK cells of the two groups was observed. However, more CD56(neg)CD16(pos) NK cells were found in the CD4Low group than in the CD4High group. We also found that NK cell function increased within the first 3 months of HIV-1 infection in the CD4High group and then exhibited a decreasing trend. However, in the CD4Low group, NK cell function did not increase significantly within the first 3 months of HIV-1 infection but then gradually increased. We concluded, therefore, that robust NK functioning cells that are present during an acute HIV-1 infection might be beneficial in controlling HIV-1 disease progression.

Longitudinal changes in total, 2-LTR circular, and integrated HIV-1 DNA during the first year of HIV-1 infection in CD4Low and CD4High patient groups with HIV-1 subtype AE.

The level of viral DNA in early HIV-1 infection is an important parameter in the prediction of disease progression. Few data have been published on the dynamics of HIV-1 DNA during the first year of HIV infection. In this study, two distinct HIV-1 patient groups were enrolled. Group 1 (CD4High group) maintained their CD4 above 450 cells/μL within 1 year, while Group 2 (CD4Low group) progressed to CD4 below 300 cells/μL. The amounts of total, 2-long terminal repeat (2-LTR) circular, and integrated HIV-1 DNA were determined in the peripheral blood mononuclear cells at 1, 3, 6, and 12 months after HIV infection. Reductions in the amount of total and integrated HIV-1 DNA were detected in the CD4High group during the first year of HIV infection but not in the CD4Low group. Disease progression may be related to the body's ability to control HIV-1 DNA during early HIV-1 infection.

Compare mDCs and pDCs between two distinct patients groups in acute HIV-1 infection.

The role of DCs in primary HIV-1 infection remains uncertain. In this study, we enrolled two different groups of subjects with acute HIV-1 infection. One group progressed to CD4 counts below 200 cells/μl within 2 years of HIV-1 infection (CD4 Low Group), while the other group maintained CD4 counts above 500 cells/μl (CD4 High Group). We did not find statistical difference in the pDC number between the two groups during acute HIV-1 infection. However, the mDC number was significantly lower in the CD4 Low Group than in the CD4 High Group.

Development of a rapid cell‐fusion‐based phenotypic HIV‐1 tropism assay

IntroductionA dual split reporter protein system (DSP), recombining Renilla luciferase (RL) and green fluorescent protein (GFP) split into two different constructs (DSP1–7 and DSP8–11), was adapted to create a novel rapid phenotypic tropism assay (PTA) for HIV-1 infection (DSP-Pheno).MethodsDSP1–7 was stably expressed in the glioma-derived NP-2 cell lines, which expressed CD4/CXCR4 (N4X4) or CD4/CCR5 (N4R5), respectively. An expression vector with DSP8–11 (pRE11) was constructed. The HIV-1 envelope genes were subcloned in pRE11 (pRE11-env) and transfected into 293FT cells. Transfected 293FT cells were incubated with the indicator cell lines independently. In developing the assay, we selected the DSP1–7-positive clones that showed the highest GFP activity after complementation with DSP8–11. These cell lines, designated N4R5-DSP1–7, N4X4-DSP1–7 were used for subsequent assays.ResultsThe env gene from the reference strains (BaL for R5 virus, NL4-3 for X4 virus, SF2 for dual tropic virus) subcloned in pRE11 and tested, was concordant with the expected co-receptor usage. Assay results were available in two ways (RL or GFP). The assay sensitivity by RL activity was comparable with those of the published phenotypic assays using pseudovirus. The shortest turnaround time was 5 days after obtaining the patient's plasma. All clinical samples gave positive RL signals on R5 indicator cells in the fusion assay. Median RLU value of the low CD4 group was significantly higher on X4 indicator cells and suggested the presence of more dual or X4 tropic viruses in this group of patients. Comparison of representative samples with Geno2Pheno [co-receptor] assay was concordant.ConclusionsA new cell-fusion-based, high-throughput PTA for HIV-1, which would be suitable for in-house studies, was developed. Equipped with two-way reporter system, RL and GFP, DSP-Pheno is a sensitive test with short turnaround time. Although maintenance of cell lines and laboratory equipment is necessary, it provides a safe assay system without infectious viruses. With further validation against other conventional analyses, DSP-Pheno may prove to be a useful laboratory tool. The assay may be useful especially for the research on non-B subtype HIV-1 whose co-receptor usage has not been studied much.

High CCR5 Density on Central Memory CD4+ T Cells in Acute HIV-1 Infection Is Mostly Associated with Rapid Disease Progression

CD4+ central memory T cells play a critical role in the pathogenesis of simian immunodeficiency virus disease, and the CCR5 density on the surface of CD4 T cells is an important factor in human immunodeficiency virus (HIV)-1 disease progression. We hypothesized that quantifying central memory cells and CCR5 expression in the early stages of HIV-infection could provide useful prognostic information. We enrolled two different groups of acute HIV-infected subjects. One group progressed to CD4 T cell numbers below 250 cells/µl within 2 years (CD4 Low group), while the other group maintained CD4 cell counts above 450 cells/µl over 2 years (CD4 High group). We compared the CCR5 levels and percentage of CD4 subsets between the two groups during the 1st year of HIV infection. We found no differences between the two groups regarding the percentage of naïve, central memory and effector memory subsets of CD4 cells during the 1st year of HIV-1 infection. CCR5 levels on CD4+ CM subset was higher in the CD4 Low group compared with the CD4 High group during the 1st year of HIV-1 infection. High CCR5 levels on CD4 central memory cells in acute HIV infection are mostly associated with rapid disease progression. Our data suggest that low CCR5 expression on CD4 central memory cells protects CD4 cells from direct virus infection and favors the preservation of CD4+ T cell homeostasis.

Frequent detection of anti-tubercular-glycolipid-IgG and -IgA antibodies in healthcare workers with latent tuberculosis infection in the Philippines.

Anti-tubercular-glycolipid-IgG (TBGL-IgG) and -IgA (TBGL-IgA) antibodies, and the QuantiFERON-TB Gold test (QFT) were compared in healthcare workers (HCWs, n = 31) and asymptomatic human immunodeficiency virus-carriers (HIV-AC, n = 56) in Manila. In HCWs, 48%, 51%, and 19% were positive in QFT, TBGL-IgG, and -IgA, respectively. The TBGL-IgG positivity was significantly higher (P = 0.02) in QFT-positive than QFT-negative HCWs. Both TBGL-IgG- and -IgA-positive cases were only found in QFT-positive HCWs (27%). The plasma IFN-γ levels positively correlated with TBGL-IgA titers (r = 0.74, P = 0.005), but not TBGL-IgG titers in this group, indicating that mucosal immunity is involved in LTBI in immunocompetent individuals. The QFT positivity in HIV-AC was 31% in those with CD4+ cell counts >350/μL and 12.5% in low CD4 group (<350/μL). 59 % and 29% were positive for TBGL-IgG and -IgA, respectively, in HIV-AC, but no association was found between QFT and TBGL assays. TBGL-IgG-positive rates in QFT-positive and QFT-negative HIV-AC were 61% and 58%, and those of TBGL-IgA were 23% and 30%, respectively. The titers of TBGL-IgA were associated with serum IgA (P = 0.02) in HIV-AC. Elevations of TBGL-IgG and -IgA were related to latent tuberculosis infection in HCWs, but careful interpretation is necessary in HIV-AC.

Hematological abnormalities in HIV-infected patients

Anemia, neutropenia, and thrombocytopenia are commonly observed in HIV-infected patients. This study was undertaken to evaluate the prevalence of cytopenias and their association with CD4 count. Furthermore, the association of hemoglobin concentration with mortality was also investigated. We reviewed the data of 701 HIV-infected patients followed at our institution. Blood cell counts, hemoglobin concentration, CD4 count, and viral load were recorded. We also recorded the mortality rate after 1 year in the groups with CD4 <200/μl and ≥ 200/μl according to hemoglobin concentration. Of the total patients, 37.5% had anemia; 61.1% (110/180) were in the low CD4 group and 29.4% (153/521) were in the high CD4 group (p<0.01). Mean neutrophil counts were 2.610 × 10(9)/l and 3.204 × 10(9)/l in the low CD4 and high CD4 groups, respectively (p<0.01); mean platelet counts were 218.639 × 10(9)/l and 234.807 × 10(9)/l for the low CD4 and the high CD4 groups, respectively (p=0.03). Patients whose hemoglobin concentration was below the median value had a higher death rate in both the low CD4 (14 vs. 4 deaths, p=0.013) and high CD4 (8 vs. 1 death, p=0.0158) groups. We found an association between CD4 count and hemoglobin level, neutrophil count, and platelet count, and that anemia was independently associated with a higher mortality.

Pattern recognition can detect subtle field defects in eyes of HIV individuals without retinitis under HAART

ObjectivesTo use machine learning classifiers (MLCs) to seek differences in visual fields (VFs) between normal eyes and eyes of HIV+ patients; to find the effect of immunodeficiency on VFs and to compare the effectiveness of MLCs to commonly-used Statpac global indices in analyzing standard automated perimetry (SAP).MethodsThe high CD4 group consisted of 70 eyes of 39 HIV-positive patients with good immune status (CD4 counts were never <100/ml). The low CD4 group had 59 eyes of 38 HIV-positive patients with CD4 cell counts <100/ml at some period of time lasting for at least 6 months. The normal group consisted of 61 eyes of 52 HIV-negative individuals. We used a Humphrey Visual Field Analyzer, SAP full threshold program 24-2, and routine settings for evaluating VFs. We trained and tested support vector machine (SVM) machine learning classifiers to distinguish fields from normal subjects and high and CD4 groups separately. Receiver operating characteristic (ROC) curves measured the discrimination of each classifier, and areas under ROC were statistically compared.Results Low CD4 HIV patients: with SVM, the AUROC was 0.790 ± 0.042. SVM and MD each significantly differed from chance decision, with p < .00005. High CD4 HIV patients: the SVM AUROC of 0.664 ± 0.047 and MD were each significantly better than chance (p = .041, p = .05 respectively).ConclusionsEyes from both low and high CD4 HIV+ patients have VFs defects indicating retinal damage. Generalized learning classifier, SVM, and a Statpac classifier, MD, are effective at detecting HIV eyes that have field defects, even when these defects are subtle.

Dysregulation of β-Chemokines in the Lungs of HIV-1–Infected Patients

Summary: The β-chemokines, macrophage inflammatory protein (MIP)-lα, MIP-lβ, monocyte chemotactic protein (MCP)-1 and regulated-on-activation normal T cell, expressed and secreted (RANTES) are not only chemotactic for mononuclear cells but may be important in suppression of HIV-1 replication through competitive binding to the chemokine receptor, CCR5, which is critical to viral entry. In this study, bronchoalveolar cells (BACs) and autologous peripheral blood mononuclear cells (PBMCs) were obtained from HIV-1-infected participants who did not manifest clinical signs of lung disease with peripheral CD4 T-cell count >200/mm3 (n = 7, group with high CD4 count), or CD4 T-cell count <200/mm3 (n = 12, group with low CD4 count), and from healthy study subjects (n = 5). The capacity to express β-chemokines and CCR5 was assessed. Induction of MIP-lα by lipopolysaccharide (LPS) in BAC of HIV-1infected study subjects from the low CD4 group was less than BAC from healthy study subjects (p < .001), and also was less than in BACs from the group with a high CD4 group (p < .001). Moreover, the intracellular expression of MIP-lα in LPS-induced monocytes of HIV-1-infected patients was significantly less than that from healthy study subjects (p < .01). In addition, spontaneous expression of mRNAs for CCR5 and MIP-lα in BAC was significantly lower in HIV-1-infected patients compared with in healthy study subjects (p < .03 and p < .02, respectively). In contrast to the findings with MIP-lα, LPS stimulated MCP-1 in BAC from the group of HIV-1-infected patients with high CD4 count was significantly higher than healthy study subjects (p < .001). These dysregulations in the ability to express β-chemokines by BAC may be important in the progression of HIV-1 infection in the lung.