Five human immunodeficiency virus type 1 phenotypic variants with different MT-2 cell tropisms correlate with prognostic markers of disease

OBJECTIVES: We correlated virologic and immunologic parameters of disease progression with cytopathogenicity of HIV isolates. STUDY DESIGN/METHODS: Human immunodeficiency virus type 1 (HIV-1) isolates from 207 patients with CD4+ cell counts < 500/mm3 were examined for biologic phenotype in MT-2 cells. We used a cross-sectional study design. RESULTS: Three subtypes of syncytium-inducing (SI) strains with different times of appearance of syncytia formation in cell culture and two subtypes of non-syncytium-inducing (NSI) isolates, with (NSI/MT2+) or without (NSI/MT2-) replicative capacity in MT-2 cells, were identified. Early SI strains were associated with the lowest CD4+ cell counts and the highest levels of viral load, and NSI/MT2- isolates correlated with the highest CD4+ cell counts and the lowest viral loads. Patients with late SI and NSI/MT2+ strains showed minimal differences in immunologic and virologic markers. CONCLUSIONS: Five HIV phenotypic variants that correlate significantly (P < 0.001) with markers of disease progression were identified.     

High IL-7 plasma levels may induce and predict the emergence of HIV-1 virulent strains in pediatric infection.

BACKGROUND: HIV-1 infection results in severe immunodeficiency when T-cell loss cannot be compensated. IL-7 is one of the main cytokines involved in the maintenance of T-cell homeostasis. However, IL-7 can also enhance HIV-1 replication in vivo and lead to an accelerated progression of AIDS. OBJECTIVE: The aim of our study was to evaluate if the increase of IL-7 levels in response to CD4+ T cell depletion could favor the emergence of HIV-1 strains with more aggressive phenotypes in pediatric infection. STUDY DESIGN: Plasma IL-7 levels were measured in 42 HIV-1 vertically infected infants at different times of infection, and HIV-1 isolates were obtained from primary cell cultures to determine replication rate and syncytium-inducing (SI) capability on MT-2 cell line. RESULTS: IL-7 levels were significantly higher in infants harboring HIV-1 SI strains compared to those with non-syncytium-inducing (NSI) viruses (p<0.0001). Likewise, IL-7 levels were higher in infants with rapid replicating viral strains versus those with slow replicating viruses (p=0.0006). Despite the strong negative correlation between IL-7 levels and CD4+ T lymphocyte counts (r=-0.55, p=0.0001), covariance analysis demonstrated that the high levels of IL-7 were associated with more virulent phenotype features (SI and rapid replicating strains) independently of CD4+ T cell depletion. In 19 of the 42 infants, longitudinal follow-up studies showed that SI to NSI phenotype switch can occur after HAART administration, with a reduction in IL-7 levels and an increase in CD4+ T cell counts. CONCLUSIONS: IL-7 response to T-cell depletion may enhance T-cell production, but at the same time may foster HIV-1 disease progression favoring the emergence of more virulent HIV-1 strains characterized by SI capability and rapid replication rate.     

Comparison of human immunodeficiency virus biological phenotypes isolated from cerebrospinal fluid and peripheral blood

Quantitative human immunodeficiency virus (HIV) cultures were carried out on cerebrospinal fluid (CSF), peripheral blood mononuclear cells (PBMCs), and plasma from patients with HIV in order to compare the infectious HIV load. The HIV strains isolated were studied for syncytiuminducing (SI) capacity, using the MT-2 cell line, in order to compare the HIV strain phenotype of blood and CSF isolates. Forty-two patients with HIV-1 infection were enrolled in the study, 33 of whom had neurological symptoms and 9 of whom were without neurological symptoms. HIV was isolated from 16 (38%) of the 42 CSF cultures, with a low mean titer of 6.3 ± 3.4 tissue-culture-infective doses (TCID) per milliliter. Patients with HIV-positive CSF culture had a viral load in PBMCs of 40.5 ± 15.5 TCID per 10⁶ PBMC and in plasma of 104.7± 9.3 per milliliter. Two (15%) of the 13 CSF isolates were Sl strains, compared to 17 (56.6%) of the 30 PBMC isolates and 13 (54%) of the 24 plasma isolates (P<0.05). Five of the nine patients from whom CSF and blood strains were obtained had the same viral biological phenotype. This study suggests that different HIV variants may be found in different body fluids and/or cells. © 1995 Wiley-Liss, Inc.     

HIV-1-specific cytolytic T-lymphocyte activity correlates with lower viral load, higher CD4 count, and CD8+CD38-DR- phenotype: comparison of statistical methods for measurement.

OBJECTIVES: The objective of this study was to use novel statistical methods to determine the correlation between HIV-1-specific cytolytic T-lymphocyte (CTL) activity and HIV-1 plasma viral load, in a blinded study of HIV-infected patients at various stages of clinical disease. METHODS: Peripheral blood mononuclear cells (PBMC) were collected and stored at enrollment and 2 weeks later, from 15 HIV-infected individuals who were receiving stable antiretroviral therapy for the previous 6 weeks and during the study period. HIV-1-specific CTL activity was measured using an antigen-specific PBMC in vitro stimulation method. Measurements of plasma viral load, as well as CD4+ and CD8+ T lymphocytes expressing T-cell activation markers (DR and CD38) were also performed at each time point. CTL activity was quantified using three separate statistical methods: area under the net HIV-specific lysis curve (AUC), lytic units (LU20), and linear regression (LR) of net HIV-specific lysis. RESULTS: HIV-1 nef-, pol- and gag-specific CTL activity (AUC method) was significantly higher in subjects with a plasma viral load < or = 30,000 RNA copies/ml, than in those with viral load >30,000 RNA copies/ml. When plasma viral load was analyzed as a continuous variable, there was a strong correlation between higher CTL activity and lower viral load for nef (r2 = .77; p < .001), pol (r2 = .63; p < .001) and gag (r2 = 0.75; p < .001) targets by the AUC, but not for the LU20 analysis. Using the LR analysis, which is less dependent on in vitro PBMC growth than the AUC analysis, an independent association was demonstrated between nef- and gag-specific CTL activity and lower viral load. Measurement of CTL activity was also significantly correlated with a higher percentage of circulating CD8+DR-CD38- T lymphocytes. CONCLUSIONS: In this blinded study using an in vitro stimulation of frozen PBMC, higher HIV-1 nef-, pol-, and gag-specific CTL activity correlated with lower plasma viral load, particularly in patients with a CD4 count <500 cells/mm3. Two new statistical methods for estimating CTL activity, AUC and LR analyses, were superior to the standard lytic unit (LU20) method for demonstrating this correlation. These data also demonstrated that higher circulating CD8+ T lymphocytes with a DR-CD38-phenotype, correlate with a lower plasma viral and load and higher HIV-specific CTL activity. This suggests that lymphocytes with this double-negative phenotype may include circulating HIV-specific CD8+ CTL.     

Homeostatic chemokines CCL19 and CCL21 promote inflammation in human immunodeficiency virus‐infected patients with ongoing viral replication

CCL19 and CCL21 and their receptor CCR7 are expressed constitutively within lymphoid organs, regulating lymphocyte homing. Recent studies suggest that these chemokines may have inflammatory properties. We hypothesized a role of CCL19/CCL21 in human immunodeficiency virus (HIV) infection by promoting inflammation. We examined the expression of CCL19 and CCL21 in mononuclear cells from peripheral blood mononuclear cells (PBMC) and bone marrow mononuclear cells (BMMC) in HIV‐infected patients before and during highly active anti‐retroviral therapy (HAART). We also examined the ability of CCL19/CCL21 to promote inflammatory responses in these patients. PBMC from untreated HIV‐infected patients (n = 29) released enhanced levels of CCL19 spontaneously compared with cells from controls (n = 20), particularly in those with symptomatic disease (n = 15, P < 0·01 versus controls). During HAART (n = 9), there was a decrease in the spontaneous CCL19 release and an increase in the phytohaemagglutinin‐stimulated CCL19 release in both PBMC (P < 0·01) and BMMC (P < 0·05). In patients with enhanced HIV replication there was an increased proportion of inflammatory CD8⁺CCR7^‐CD45RA^‐ T cells in peripheral blood [P < 0·01 and P < 0·05 versus controls, untreated (n = 9) and treatment failure (n = 8), respectively]. In vitro, CCL19/CCL21 promoted an inflammatory response in PBMC when accompanied by high viral load, irrespective of HAART. The HIV‐tat protein significantly boosted the inflammatory effect of CCL19/CCL21 in PBMC. These findings link a dysregulated CCL19/CCL21/CCR7 system in HIV‐infected patients to persistent inflammation and HIV replication, not only in untreated HIV infection, but also in treatment failure during HAART.     

Effect of Interleukin-28B Polymorphism on Interleukin-28 Expression and Immunological Recovery amongst HIV-1-Infected Individuals Following Antiretroviral Therapy

Purpose: Type III interferon is well known to have diverse antiviral and immunomodulatory activities. Studies describing the association of interleukin (IL)-28 polymorphisms in treatment-experienced HIV participants are limited. This study was aimed to determine the association of IL-28B gene polymorphisms with immunological recovery in HIV patients on 6–9 months of antiretroviral therapy (ART). Methods: Eighty treatment-naive HIV patients were recruited, of which 48 patients were followed up after 6–9 months of ART. Whole blood samples were collected before and after 6–9 months of ART. CD4, CD8 and CD3 counts were enumerated flow cytometry. IL-28B polymorphisms (rs12979860 and rs8099917) were profiled by polymerase chain reaction (PCR)-restriction fragment length polymorphism. The IL-28 mRNA and plasma HIV-1 viral load were estimated using real-time PCR and plasma IL-28 level by ELISA. Results: The CD4, CD4/CD3%, IL-28 mRNA and reversal of CD4/CD8 ratio were significantly increased following 6–9 months of ART (P < 0.01). The rs12979860 CC genotype and rs12979860:rs8099917 (CC: TT) haplotype showed significant association with higher CD4+ T-cell count amongst treatment-naive HIV-infected individuals (P < 0.05). In addition, there was a significant association of rs12979860 CC genotype with increase in CD4/CD3% following 6–9 months of ART. IL-28 mRNA showed correlation with the HIV-1 viral load, and there was a significant increase in the IL-28 mRNA expression following 6–9 months of ART. Conclusion: Our preliminary findings suggest that IL-28 polymorphisms could influence both immunological recovery and therapeutic response in HIV infection. Hence, functional studies are warranted to understand the mechanistic basis of IL-28-mediated host genetic influence on HIV therapeutic response.     

Association of HIV-1 viral phenotype in the MT-2 assay with perinatal HIV transmission

A case-control design study was used to investigate the association of maternal HIV-1 phenotype in MT-2 cells at or near the time of delivery with perinatal transmission of HIV-1, controlling for maternal CD4 percentage and duration of rupture of membranes, in 48 transmitting and 96 non-transmitting HIV-1-infected mothers who gave birth between 1990 and 1995. The non-syncytium-inducing (NSI) phenotype was more commonly seen in transmitting mothers compared with non-transmitting mothers (90% vs. 75%, p =.04). In a multivariable logistic regression model, the following maternal characteristics were significantly associated with HIV transmission: NSI phenotype (odds ratio [OR] = 6.08; 95% confidence interval [CI]: 1.73-21.35) and log(10) viral load (OR = 2.11; CI: 1.19-3.74). Finally, the association of NSI phenotype with transmission was stronger in transmitting women who received azidothymidine during pregnancy compared with transmitters who did not.     

Effect of the Serotonin Receptor Agonist,Buspirone, on Immune Function in HIV-Infected Individuals: A Six-Month Randomized,Double-Blind,Placebo-Controlled Trial

Abstract

Purpose: Previous studies have shown that agents modulating the cAMP/PKA pathway have a beneficial effect on immune reconstitution in HIV-infected individuals. Here we evaluate the effect of buspirone on immune function as measured by CD4 and CD8 T-cell counts, CD4/CD8 T-cell ratio, HIV viral load, and response to pokeweed mitogen (PWM) in antiretroviral naive HIV-1-infected individuals. Method: Twenty-three HIV-infected patients with CD4 T-cell counts above 300 per μL were enrolled in a 6-month double-blinded placebo controlled trial. No patients received antiretroviral therapy during the study. Blood samples were drawn prior to treatment, after 1 week, 1 month, 3 months, and 6 months, and as a follow-up sample 1 month after completion of study. Results: A significant decrease in CD8 + T-cell counts (p = .02) and an increase in CD4/CD8 ratio (p = .0003) in buspirone-treated patients compared to placebo-treated patients was observed. There were no significant differences in CD4 T-cell counts, HIV viral load, or proliferative response to PWM between those receiving placebo and those receiving buspirone. Conclusion: Buspirone treatment leads to significant changes in CD8 T-cell count and in CD4/CD8 ratio. Thus, agents affecting the adenosine 3', 5'-cyclic monophosphate/protein kinase A type 1 (cAMP/PKA-1) pathway may be candidates for positive immune modulation in patients with HIV-1 infection.     

Quantitation of hepatitis C virus RNA in peripheral blood mononuclear cells in HCV-monoinfection and HIV/HCV-coinfection

Peripheral blood mononuclear cells (PBMCs) represent an extrahepatic hepatitis C virus (HCV) reservoir, the significance of which is unclear due to limited studies and varying test methodologies. In this study, a commercial viral load assay for measuring cell‐associated PBMC HCV RNA was evaluated. HCV RNA was extracted from PBMCs, sorted CD14+, and CD19+ cells and corresponding plasma samples using the Abbott m2000 and Real‐Time HCV assay. Test performance and influence of HIV seropositivity on plasma and PBMC HCV RNA were studied. Among 51 patients, 67 and 62 unique patient samples had detectable plasma and PBMC HCV viral load, respectively. The median PBMC viral load was 535 IU/1 M cells (range 29–5,190). CD19+ cells had significantly higher viral load than CD14+ cells (median log₁₀ HCV viral load 2.63 vs. 1.50 IU/ml; P< 0.001). Stability of PBMC viral load over time was demonstrated in untreated patients; all patients with an undetectable plasma HCV viral load after HCV treatment also demonstrated undetectable PBMC viral load. Repeated testing in nine samples yielded consistent PBMC viral load, differing by only 1.3‐fold (range 1.0–1.7‐fold). Among samples with detectable plasma HCV RNA, the correlation between PBMC and plasma viral load was moderate (r = 0.66) and was greater among HCV mono‐infected compared to HIV/HCV co‐infected subjects (r = 0.80 vs. 0.52). Measurement of cell‐associated PBMC HCV RNA using a commercial assay demonstrated promising test characteristics. Differences in PBMC HCV viral load based on HIV‐coinfection status and the significance of greater copy number in B‐cells requires further study. J. Med. Virol. 84:431–437, 2012. © 2011 Wiley Periodicals, Inc.     

Persistently biased T-cell receptor repertoires in HIV-1-infected combination antiretroviral therapy-treated patients despite sustained suppression of viral replication

In most HIV-1-infected patients, highly active antiretroviral therapy (HAART) reduces plasma viral load to <50 copies/mL and increases CD4+ T-cell number and function. However, it is still unclear whether alterations of T-cell receptor (TCR) beta-chain variable region (BV) repertoire, tightly related to disease progression, can be fully recovered by long-term treatment with HAART. This study analyzed the evolution of both T-cell subset composition and TCRBV perturbations in chronically HIV-1-infected patients with moderate immunodeficiency during 36 months of HAART. Despite persistently suppressed HIV replication, the rate of CD4+ T-cell repopulation, after an initial burst, progressively declined throughout the study period, resulting in a mean CD4+ T-cell count at the end of follow-up that was still significantly lower in HIV patients than in HIV-seronegative controls. This was seen in association with an incomplete restitution of both CD4 and CD8 TCRBV repertoire disruptions and was also demonstrated by the appearance of new TCRBV oligoclonal expansions occurring during HAART. In conclusion, these data indicate that 3 years of fully suppressive HAART may be not adequate to normalize CD4 counts and TCRBV repertoires in patients starting HAART with moderately advanced disease.     

Maternal viral load,CD4 cell count and vertical transmission of HIV-1

HIV load and CD4 cell numbers were measured among 95 HIV infected women during pregnancy in order to determine their value as prognostic markers for transmission of virus from mother to infant. Among the 94 live births, 13 children were infected with HIV, 69 were uninfected and 12 were of unknown infection status. HIV RNA levels, as measured by nucleic acid sequence based amplification, were significantly higher (P < 0.001) in women who transmitted virus than among those who did not transmit and maternal viral load was a stronger predictor of transmission than CD4 cell number. The predicted rate of transmission relative to maternal HIV RNA was 2% at 1,000 copies, 11% at 10,000 copies and 40% at 100,000 copies/ml. Little variation in viral load occurred during pregnancy and there was an association between viral load and prematurity, the mean gestation at delivery decreasing by 1.3 weeks for every 10-fold increase in maternal HIV RNA (P = 0.007). This study demonstrates that a high level of maternal HIV RNA is a risk factor for transmission of virus to the infant and maternal viral load is of more value as a prognostic marker for transmission risk than CD4 cell number. High viral load is also associated with premature delivery. Maternal viral load is therefore a useful marker on which to base management decisions during pregnancy. J. Med. Virol. 54:113–117, 1998. © 1998 Wiley-Liss,Inc.     

Relationship between V3 genotype, biologic phenotype, tropism, and coreceptor use for primary isolates of human immunodeficiency virus type 1.

OBJECTIVES: The predictive value of positively charged amino acids at positions 11 and 25 within the V3 loop region of the human immunodeficiency virus type 1 (HIV-1) envelope gene for the syncytium-inducing (SI) phenotype was assessed. STUDY DESIGN/METHODS: Sequencing was performed on DNA extracted from primary peripheral blood mononuclear cells (PBMCs) and complementary DNA (cDNA) prepared from serial viral isolates from 10 HIV-1-seropositive subjects. Proviral DNA sequencing was also performed on biologic clones from most of these subjects. RESULTS: Positive charge at position 11 and/or 25 in 257 isolate cDNA, PBMC DNA, and biologic clone PBMC DNA sequences was compared with 69 phenotypic determinations, of which 62.3% were SI. V3 genotype was 51.2% sensitive and 85.8% specific for the SI phenotype, with positive and negative predictive values of 62.8% and 79.0%, respectively. Cellular tropism failed to correlate with V3 genotype, coreceptor use, or biologic phenotype. Exclusive use of CCR5 was associated with the nonsyncytium-inducing (NSI) phenotype. Overall, V3 loop charge was higher in SI than in NSI isolates (5.01 and 3.78, respectively; p = 0.0211). CONCLUSIONS: The predictive power of SI phenotype from V3 genotype is relatively weak, especially in a low SI prevalence population. The direct measurement of viral phenotype, cellular tropism, and coreceptor use in HIV-1 isolates is essential for accurate biologic characterization.     

HIV-1 DNA proviral load in treated and untreated HIV-1 sero-positive patients

As proviral human immunodeficiency virus type 1 (HIV-1) DNA can replenish and revive viral infection upon activation, its detection might offer significant therapeutic information, complementing the input provided by plasma RNA determination in the follow-up of infected individuals. A selected group of acutely infected subjects was studied to verify both total and 2-long terminal repeat (2-LTR) DNA proviral load during the acute phase of infection and thereafter. Patients were divided in two sex- and age-matched groups: 19 naive individuals who did not receive antiretroviral therapy during the observation period and 20 subjects treated according to current guidelines. Total and 2-LTR HIV-1 DNA proviral load, in addition to RNA viral load and CD4 cell count, were determined in peripheral blood mononuclear cells (PBMC) at baseline, 6 and 12 months after the first sampling. Total and 2-LTR HIV-1 DNA proviral load exhibited no significant variation at any time in the naive patients (total HIV-1 DNA ranging from 896 ± 731 to 715 ± 673 copies/10⁵ PBMC and 2-LTR HIV-1 DNA ranging from 94 ± 105 to 65 ± 44 copies/10⁵ PBMC), whereas a significant reduction in both total HIV-1 DNA (ranging from 997 ± 676 to 262 ± 174 copies/10⁵ PBMC) and 2-LTR HIV-1 DNA proviral load (ranging from 116 ± 55 to 26 ± 35 copies/10⁵ PBMC) was detected in highly active antiretroviral therapy (HAART) patients, together with a CD4⁺ T cell count increase and RNA load decrease. HAART negatively affects both the labile HIV burden and the integrated proviral DNA, at least in the initial period of successful treatment, suggesting that quantification of HIV-1 DNA proviral load may be an important parameter in monitoring HIV infection.     

The role of complement and gp120-specific antibodies in virus lysis and CD4+ T cell depletion in HIV-1-infected patients

The substantial virus lysis was induced by HIV-1-infected patient serum and normal human complement serum in the presence of purified patient IgG. Non-infected CD4+ T cells coated with the whole virus or with a recombinant HIV-1 envelope gp120 and sensitised with patient IgG were also shown to be susceptible to complement-dependent lysis. The serum level of complement regulatory protein in a fluid phase, the C1-esterase inhibitor, was significantly correlated with serum concentration of C1q-circulating immune complexes (P=0.0062), but inversely with CD4+ T cell count (P< 0.0001). Accordingly, the disease progression in HIV-1-infected patients was significantly correlated with the level of complement activation as determined by serum level of C1-esterase inhibitor (P=0.0001), and inversely correlated with CD4+ cell count (P< 0.0001) and gp120-specific antibody titre (P=0.0086). These results strongly suggest that the complement activation by gp120-specific antibodies play a very important role in virus clearance, but also in depletion of infected as well as gp120-coated non-infected CD4+ bystander T cells during the course of HIV-1 infection.     

Fluctuations in HIV-1 viral load are correlated to CD4+ T-lymphocyte count during the natural course of infection

Viral load fluctuates during the natural course of asymptomatic HIV-1 infection. It is often assumed that these fluctuations are random around a set point or underlying growth trend. Using longitudinal data, we tested whether fluctuations in viral load can be better explained by changes in CD4+ T-cell count than by a set point or trend of exponential growth. The correspondence between viral load and CD4+ T-cell count could be described by a simple mathematical relation. Using a bootstrapping approach, the hypothesis that viral load fluctuations are random around a set point was rejected with p < .00005. The hypothesis that viral load fluctuations are random around a trend of exponential growth was rejected with p < .005. Viral load data was explained better by changes in CD4+ T-cell counts than by a set point or by a trend of exponential growth. The implications of this finding for improved prognostication are discussed.     

Impact of changes in antigen level on CD38/PD‐1 co‐expression on HIV‐specific CD8 T cells in chronic,untreated HIV‐1 infection

Excessive immune activation is a hallmark of chronic uncontrolled HIV infection. During the past years, growing evidence suggests that immune inhibitory signals also play an important role in progressive disease. However, the relationship between positive and negative immune signals on HIV‐specific CD8 T cells has not been studied in detail so far in chronic HIV‐1 infection. In this study, the expression of markers of positive (CD38) and negative (PD‐1) immune signals on virus‐specific CD8 T cells in chronic, untreated HIV‐1 infection was evaluated using intracellular cytokine staining. Viral escape mutations were assessed by autologous virus sequence analysis and subsequent peptide titration assays. Single‐epitope CD8 T‐cell responses toward Gag, Pol, and Nef were compared in 12 HIV‐1 controllers (viral load <5,000 cp/ml) and 12 HIV‐1 progressors (viral load >50,000 cp/ml) and a highly significant increase of CD38/PD‐1 co‐expression on virus‐specific CD8 T cells in progressors was found (P < 0.0001). The level of CD38/PD‐1 co‐expression was independent of epitope specificity. Longitudinal follow‐up revealed a clear drop in CD38/PD‐1 co‐expression on virus‐specific CD8 T cells after the suppression of antigen following either viral escape mutation or the initiation of HAART (P = 0.004). Antigen persistence with a fluctuating viral load revealed stable levels of CD38/PD‐1 co‐expression whereas significant rises in viral load were accompanied or even preceded by substantial increases in CD38/PD‐1 co‐expression. The CD38/PD‐1 phenotype clearly distinguishes HIV‐specific CD8 T‐cell responses between controllers and progressors. Whether it plays a causative role in disease progression remains debatable. J. Med. Virol. 82:358–370, 2010. © 2010 Wiley‐Liss, Inc.     

Red blood cell deformability in patients with human immunodeficiency virus infection

Red blood cell (RBC) deformability is a major determinant of the ability of the RBC to pass repeatedly through the microcirculation. A decrease in RBC deformability leads to tissue perfusion and organ dysfunction. The purpose of this study was to measure the rigidity of RBCs from human immunodeficiency virus (HIV) seropositive individuals and investigate its relation to immune status and viral load. A filtration method based on the initial flow rate principle was used to determine the index of rigidity (IR) of 53 samples from HIV patients and 53 healthy individuals. The mean IR was significantly increased in patients with HIV compared to healthy individuals (P < 0.01). IR was inversely correlated with current CD4+ T-lymphocyte counts (P < 0.0001). High CD4 cell counts (>200cells/μl) are related to low IR values, independently of the viral load (VL). No differences in rigidity were noted between the VL groups, although there was a trend towards an increased IR in patients with high VL within the group of CD4<200. RBC deformability is decreased in HIV disease, in a degree mainly related to CD4 depletion. Further studies are needed to elucidate the underlying mechanisms and the role of VL in highly immunocompromised HIV patients.     

Comparison of Prognostic Importance of Latest CD4+ Cell Count and HIV RNA Levels in Patients with Advanced HIV Infection on Highly Active Antiretroviral Therapy

Abstract

The comparative prognostic importance of latest plasma HIV RNA levels (viral loads) and CD4+ cell counts among patients prescribed highly active antiretroviral therapy (HAART) has not been well characterized. Method: We assessed the prognostic value of latest CD4+ cell counts and latest viral loads for progression to AIDS or death and explored their interaction among 432 HIV-infected persons with advanced HIV who were prescribed a protease inhibitor (PI) as their first HAART regimen. Results: Pre-HAART median CD4+ cell count and viral load were 41 cells/mm³ and 126,331 copies/mL, respectively. After 12 months of HAART, the median CD4+ cell count was 154 cells/mm³; 39% of patients had a viral load of 400 copies/mL or lower. Over a median follow-up of 33 months, 109 (25%) of the 432 patients experienced an AIDS event or died. The hazard ratio for AIDS or death for those with latest CD4+ cell count <50 cells/mm³ versus ≥200 cells/mm³ was 13.9 (95% CI 6.5 to 29.7) without adjustment for latest viral load measurements and 9.5 (95% CI 4.0 to 22.5) after adjustment for latest viral load. In contrast, the hazard ratio for AIDS or death for those with viral load ≥100,000 versus <400 copies/mL was 4.2 (95% CI 2.3 to 7.7) without adjustment for latest CD4+ level and 1.2 (95% CI 0.6 to 2.4) with adjustment for latest CD4+ cell count. Conclusion: We conclude that when latest CD4+ cell count and viral load are considered separately, both are significantly related to AIDS or death; when these markers are jointly considered, the association of viral load with AIDS or death is substantially diminished. Latest CD4+ levels are more strongly related to AIDS or death than latest viral load levels in patients on HAART.     

Risk Factors for Esophageal Candidiasis in a Large Cohort of HIV-Infected Patients Treated with Nucleoside Analogues

 To assess the risk factors for esophageal candidiasis (EC), a cohort study and a case-control study were conducted using 1,368 French patients who were already participating in the Delta trial (which compared different types of antiretroviral therapy in HIV-infected patients) and who had no previous history of EC. During a median follow-up period of 19 months, 87 (6%) patients developed EC. The results of the cohort study showed an increased risk of EC associated with a low baseline CD4+ cell count (P<0.0001), a high baseline plasma HIV RNA level (P<0.0001) and prior zidovudine therapy (P=0.02) at entry to the study. The case-control study revealed an increased risk of EC in patients with a recent low CD4+ cell count (P<0.0002), recent antibacterial chemotherapy (P=0.01) and oral candidiasis (P<0.05). Cotrimoxazole prophylaxis also increased the risk of EC (P=0.04) in the case-control study.