Data from 197 patients for whom highly active antiretroviral therapy (HAART) failed, who started a new regimen chosen under the guide of resistance testing results interpreted by experts, were ...retrospectively studied, provided that at least 2 determinations of adherence and plasma drug concentrations were performed during the follow-up. Univariate and multivariable logistic regression analyses were conducted, using confirmed virologic response at week 24 as outcome measure (i.e., achievement of undetectable HIV plasma viral load at any time point before week 24 and its maintenance up to week 24). Suboptimal drug concentrations (odds ratio OR: 0.3; 95% confidence interval CI 0.2-0.7; p = 0.006) and suboptimal adherence (OR: 0.4; 95% CI 0.2-0.8; p = 0.014) were both negative independent predictors of sustained virologic response, while the use of boosted protease inhibitor-containing regimens resulted to be protective (OR: 2.4; 95% CI 1.1-5.3; p = 0.032).
Background
Baseline and follow-up predictors of new AIDS-defining events (ADE) or death among patients who started HAART with CD4
+
T-cell counts ≥200 cells/mm
3
have rarely been assessed ...simultaneously.
Methods
A prospective observational cohort study (1996–2002) is reported. HIV-infected patients initiating HAART with a CD4
+
T-cell count ≥200 cells/mm
3
were studied. Baseline and time-varying factors were tested for the prediction of new ADE/death using Cox regression models.
Results
A total of 896 subjects were studied over a median of 5.1 years. The incidence of a new ADE was 1.6 (95% confidence interval 1.3–2.1) per 100 person-years. Among baseline factors, higher CD4
+
T-cell counts before HAART were associated with lower risk of ADE/death, but not after adjustment for time-varying factors. On a multivariable analysis including both baseline and time-varying covariates, longer delay from HIV diagnosis to HAART was an independent predictor of ADE/death (per year, hazard ratio HR 1.06; P=0.025) and was independent of CD4
+
T-cell count before treatment. Longer time spent with HIV RNA <400 copies/ml (per month, HR 0.96; P=0.003) and higher latest CD4
+
T-cell count (per log
2
cells/mm
3
, HR 0.65; P<0.001) were found to be protective.
Conclusions
Patients with higher CD4
+
T-cell counts before HAART initiation had a better prognosis. However, except for the delay in starting HAART, viro-immunological evolution outweighed the effect of baseline factors. Moreover, suppressing HIV replication for as long as possible could improve the clinical outcome. Prospective randomized clinical trials to assess the optimal timing of HAART initiation are both feasible and urgently needed.
Peripheral blood lymphocytes from 33 patients with idiopathic IgA nephropathy (IgAN) and 15 healthy controls were stimulated in vitro by Protein A from Staphylococcus Cowan I; immunoglobulin (Ig) ...production was measured by a reverse hemolytic plaque assay to evaluate the quantity of cells secreting Ig. In addition, serum Ig levels, circulating IgG, IgA and IgM immune complexes (ICs) and the Fc and C3b receptor mediated phagocytosis of peripheral monocytes were measured. The laboratory findings in different phases of the disease were compared. The mean level of IgA-plaque forming cells (IgA PFC) in IgAN patients with normal renal function was significantly higher (p less than 0.001) than the mean control value. In contrast, they were reduced significantly in those patients who were subjected to periodic hemodialysis (p less than 0.001). Disease activity produced a significant increase in IgG PFC and IgA PFC, high IgG and IgM serum levels, high circulating IgG ICs, and low C3b-mediated phagocytic function of the peripheral macrophages. These findings demonstrate that IgAN is associated with an increased number of IgG and IgA-secreting cells in the peripheral blood of patients during the active phase of the disease and that the concurrent presence of high levels of circulating Ig ICs may be responsible for the gross hematuria, as their deposition in the glomeruli could activate the complement system.
Objectives: The objective was to study genotypic correlates of discordant interpretations of amprenavir (APV) resistance between a rules-based algorithm and either recombinant phenotype or virtual ...phenotype. Methods: HIV resistance mutations found in patients from the GenPheRex study were interpreted with VGI-TRUGENE (version 5.0; VGI) and compared with either recombinant-phenotype (Antivirogram, r-PHT) or virtual-phenotype (Virtual-Phenotype, v-PHT) interpreted through Virco biological cut-offs. Results: Among 180 samples available, 56 (31.1%) were discordant with the observed genotype interpretation results, as a result of being judged as sensitive by r-PHT or v-PHT but resistant by VGI (S/R). Only the I84V mutation was almost invariably found in concordant resistant isolates compared with S/R isolates (60% versus 0%, respectively; P < 0.0001). Notwithstanding this, the number of multi-protease inhibitor-associated mutations (PAMs) was significantly higher in the concordant resistant isolates; the prevalence of >3 PAMs was 56.52% versus 33.93% in R/R and S/R isolates, respectively (P = 0.01). Correspondence analysis confirmed the relevance of PAMs, although additional mutations appeared to be correlated with APV resistance. Conclusions: The rate of discordance between rules-based and either r-PHT or v-PHT interpretations for APV was high. Mutation I84V and accumulation of >3 PAMs were found to be associated with resistance as interpreted with all systems tested. However, our results indicate that a number of mutations may have an impact on APV resistance, but that they are missed by current interpretation algorithms and this merits further investigations.
Objectives
To assess prevalence and predictive factors of viro‐immunological discordant trends in a cohort of heavily pretreated patients.
Methods
Factors associated with viro‐immunological ...discordant trends either as categorical or continuous measures have been studied in 159 heavily pretreated HIV‐positive patients from a multicentre prospective study of real‐ vs. virtual‐phenotype. Univariate and multivariate logistic regressions were used to assess risk factors for categorical discordant responses, ceasing follow‐up at week 32 since enough patients had been on the original drug combination for a sufficient amount of time to evaluate their immune response. Complementary linear regression analysis was performed over the entire 48 weeks' follow‐up considering CD4 and plasma viral load (pVL) as continuous measures.
Results
Among 58 virological responder patients (≥1 log10 HIV‐1 RNA copies/mL decrease) and 101 virologically non‐responders, immunological discordances (increase in CD4 count of<or ≥100 cells/μL) were observed in 58.6% and 38.6%, respectively. Baseline CD4 count was associated with discordant responses in both groups. Multivariable linear regression over the entire 48 weeks' follow‐up demonstrated significant correlation between absolute decrease in pVL and increase in CD4 count (HR 28.06, 95%CI 35.32–20.79; P<0.001), also the use of protease inhibitors (PIs) in the salvage regimen (HR 36.57, 95%CI 15.45–57.68; P<0.001) and >8 months on treatment (HR 41.64, 95%CI 19.27–64.01; P<0.001) correlated with highly significant immune recovery.
Conclusions
These data confirm that therapy, possibly including PIs, should be continued in heavily pretreated patients and that hard‐to‐reach pVL undetectability is not essential to obtain immunologic recovery; however, this is strongly increased by the degree of pVL reduction that should be achieved.
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