Objectives
The aim of the study was to determine the modifications of the mutational archive in proviral HIV‐1 DNA occurring during 24 months of intermittent or continuous highly active ...antiretroviral therapy (HAART).
Methods
The study population included subjects enrolled in the Istituto Superiore di Sanità Pulsed Antiretroviral Therapy (ISS PART) clinical trial. All of these patients were on first‐line HAART and had plasma HIV‐1 RNA below 50 HIV‐1 RNA copies/mL. A genotypic resistance test was performed on HIV‐1 DNA extracted from peripheral blood mononuclear cells (PBMC) at baseline and after 24 months of follow‐up. Resistance‐associated mutations (RAMs) were defined according to the International AIDS Society (IAS) USA classification.
Results
Sixty‐nine subjects were included in the study 36 enrolled in arm A of the ISS PART (continuous HAART) and 33 enrolled in arm B (intermittent HAART). No major modifications of the mutational archive were found in either group after 24 months of follow‐up, in terms of both the proportion of subjects with mutations and the total number of mutations.
Conclusions
In this patient population, the mutational archive in HIV‐1 DNA extracted from PBMC was stable for 24 months, irrespective of HAART modality, whether continuous or intermittent.
To design a Health-related Quality of Life (HRQoL) instrument for HIV-infected people in the era of highly active antiretroviral therapy (HAART).
The self-administered questionnaire was developed by ...an Italian network including researchers, physicians, people living with HIV, national institutions and community-based organizations (CBO) through several steps: (1) review of existing HRQoL literature and questionnaires for HIV-infected people; (2) selection of relevant domains measuring HRQoL in HIV-infected people, and identification of new domains related to new aspects of HRQoL concerning HAART-treated individuals; (3) conduction of two pre-test analyses in independent groups of Italian HIV-positive people (n approximately =100) distributed throughout the country. The objectives of the first pre-test were to verify the usefulness of the questionnaire, to construct a form easily understandable by everyone, to define the domains and their significance; the second pre-test aimed at evaluating and reshaping the questionnaire based on a statistical analysis of the outcomes of first pre-test; (4) validation analysis. A large cohort of people with HIV infection was recruited for the last step.
The internal consistence reliability (Cronbach's alpha) was >or=0.70 for all domains. Most domains had Cronbach's coefficient >0.80. All domains demonstrated convergent and discriminant validity. The final version of ISSQoL includes two sections: HRQoL Core Evaluation Form (9 domains) and Additional Important Areas for HRQoL (6 domains). The ISSQoL was administered together with two additional forms: a Daily Impact of Symptoms Form and a Demographic Information Form. The Additional Important Areas for HRQoL include social support, interaction with medical staff, treatment impact, body changes, life planning, and motherhood/fatherhood.
The data reported in the present paper provide preliminary evidence of the reliability and validity of the ISSQoL questionnaire for the measurement of HRQoL in HIV-infected people. The direct involvement of HIV-positive people in all the phases of the project was a key aspect of our work.
Evaluates the impact of health-related quality of life (HRQoL) enfuvirtide-based (ENF-based) salvage regimens of treatment-experienced HIV patients, in an observational multicenter cohort study. ...Source: National Library of New Zealand Te Puna Matauranga o Aotearoa, licensed by the Department of Internal Affairs for re-use under the Creative Commons Attribution 3.0 New Zealand Licence.
The Italian National Institute of Health Quality of Life - Core Evaluation Form (ISSQoL-CEF) is a specific questionnaire measuring health-related quality of life for human immunodeficiency ...virus-infected people in the era of highly active antiretroviral therapy. The main goal of this study was to examine the construct validity of this questionnaire by confirmation of its hypothesized dimensional structure.
Baseline quality of life data from four clinical studies were collected and a confirmatory factor analysis of the ISSQoL-CEF items was carried out. Both first-order and second-order factor models were tested: Model 1 with nine correlated first-order factors; Model 2 with three correlated second-order factors (Physical, Mental, and Social Health); Model 3 with two correlated second-order factors (Physical and Mental/Social Health); Model 4 with only one second-order factor (General Health).
A total of 261 patients were surveyed. Model 1 had a good fit to the data. Model 2 had an acceptable fit to the data and it was the best of all hierarchical models. However, Model 2 fitted the data worse than Model 1.
The findings of in this study, consistent with the results of previous study, pointed out the construct validity of the ISSQoL-CEF.
Myotonic dystrophy is an autosomal dominant disease affecting many organ systems, including the heart. Abnormalities of the cardiac conduction system are a frequent and well-documented finding in ...this neuromuscular disease, whereas overt signs of heart failure are rarely reported. However, controversy exists about the prevalence of preclinical left ventricular (LV) dysfunction in patients with myotonic dystrophy who have no symptoms of heart failure. To address this issue, load-independent LV function indexes were compared in patients with myotonic dystrophy and in normal subjects. LV measurements were obtained with M-mode echocardiography in 43 consecutive patients with myotonic dystrophy (mean age 35 +/- 14 years) who had no clinical evidence of heart failure, and in 35 sex- and age-matched controls. A cuff sphygmomanometer was used to determine blood pressure. No difference was found between patients and control subjects in the percentage of LV ejection fraction predicted for end-systolic stress (103 +/- 7 vs 103 +/- 7%; p = 0.97) or in the end-systolic stress/volume index ratio (2.9 +/- 0.5 vs 2.7 +/- 0.4 dyne7/cm3; p = 0.09). Similarly, no significant difference in LV myocardial function was detected between the 19 patients with a mild degree of the neuromuscular disease and in the 24 with a moderate or severe degree of the disease. Finally, LV myocardial function was compared between patients with myotonic dystrophy and atrioventricular or intraventricular conduction disturbances (n = 8) and those without these disturbances (n = 35), but no significant difference in the percentage of LV ejection fraction predicted for end-systolic stress or in the end-systolic stress/volume index ratio could be detected.
To define the impact of coinfection with hepatitis B virus (HBV) or hepatitis C virus (HCV) on viroimmunological response to raltegravir-based salvage regimens that also include new HIV inhibitors ...such as maraviroc, darunavir and etravirine.
We used data from a national observational study of patients starting raltegravir-based regimens to compare virological suppression and CD4 cell change from baseline in patients with and without concomitant HBV or HCV infection.
Overall, 275 patients (107 coinfected and 168 non-coinfected) were evaluated. Coinfected patients were more commonly former intravenous drug users and had a longer history of HIV infection and higher baseline aminotransferase levels. Both HIV-RNA and CD4 response were similar in the two groups. Mean time to first HIV-RNA copy number <50 copies/mL was 4.1 months (95% CI 3.5-4.6) in non-coinfected patients and 3.9 months (95% CI 3.3-4.5) in coinfected patients (hazard ratio 1.039, 95% CI 0.761-1.418, P = 0.766, log-rank test). The risk of developing new grade 3-4 hepatic adverse events was significantly higher in coinfected patients (hazard ratio 1.779, 95% CI 1.123-2.817, P = 0.009). The two groups of coinfected and non-coinfected patients had similar rates of interruption of any baseline drug (hazard ratio 1.075, 95% CI 0.649-1.781, P = 0.776) and of raltegravir (hazard ratio 1.520, 95% CI 0.671-3.447, P = 0.311). Few AIDS-defining events and deaths occurred.
Viroimmunological response to regimens based on raltegravir and other recent anti-HIV inhibitors is not negatively affected by coinfection with HBV or HCV. Liver toxicity, either pre-existing or new, is more common in coinfected patients, but with no increased risk of treatment interruption.
To evaluate the evolution of HIV-1 coreceptor tropism in proviral DNA of patients during maraviroc-based therapy.
Fourteen heavily high active antiretroviral therapy (HAART)-treated patients with a ...CCR5 Trofile profile were monitored over a 24 month period from the start of maraviroc therapy. Whole-blood samples were obtained at different timepoints, and coreceptor tropism was determined for proviral DNA from the V3-loop region sequence using the Geno2Pheno algorithm false positive rate (FPR): 20%.
At the start of maraviroc treatment, 13/14 patients were viraemic (median: 4.33 log copies/mL). Concordance in R5 tropism (R5/R5) was observed between circulating HIV-RNA (Trofile) and HIV-DNA provirus in 10/14 patients (median FPR = 54.0%), while 4 patients showed a CXCR4-tropic R5/X4 variant in their provirus (FPR: 5.8%, 5.7%, 16.6% and 1.1%, respectively). All R5/R5 patients showed a stable HIV-1 DNA coreceptor usage. Two out of four R5/X4 patients showed a tropism shift in their archived provirus and, after 6 months a prevalence of R5-tropic virus was detected in DNA. The other two R5/X4 patients harboured the 11/25 genotype, and maintained X4 tropism in provirus during the study. Virological response did not reveal differences in RNA decay and CD4+ cell recovery in patients with discordant tropism.
A relatively good correlation between RNA and DNA tropism was observed at baseline. Proviral DNA tropism remained stable over 24 months of maraviroc-based therapy, indicating that determination of proviral DNA V3 sequence could be used in tropism prediction in clinical practice. The data also confirm the importance of the 11/25 rule in predicting viral tropism.
Background
AIDS defining events occur infrequently in the presence of CD4 counts above 200 cells/µL. It is, however, uncertain for most of the AIDS defining conditions whether this threshold can be ...considered equally safe in patients with a previously very low CD4 nadir.
Methods
We evaluated in detail all the AIDS defining events observed during a 48‐week clinical trial in 1251 nucleoside reverse transcriptase inhibitor‐experienced patients who started protease inhibitors (PIs) at CD4 counts below 50 cells/µL. The type of event, immunological status at the moment of event and time between start of PI treatment and event occurrence were analysed cumulatively and by event type; event rates were calculated.
Results
Concomitant data on CD4 counts were available for 338 AIDS defining events (81% of total events). Median time between start of treatment with PI and event was 94.5 days and median absolute CD4 value at the occurrence of event was 20 per µL. Only 14 events (in 12 patients) were observed above the threshold of 200 CD4 cells/µL. An analysis of the 67 deaths with concomitantly available CD4 counts (57%) showed a median CD4 count of 10 cells/µL, with only four deaths occurring in the presence of a CD4 count above 100 cells/µL.
Conclusions
Very few clinical AIDS defining conditions were observed in patients who start PIs at very low CD4 counts and with treatment restore absolute values in CD4 counts above 200 cells/µL. This threshold can therefore be considered a clinically effective goal of treatment with respect to occurrence of all AIDS defining conditions in patients starting PIs in very advanced HIV disease.
Background
Most of the studies evaluating rash in HIV‐positive patients have focused on nonnucleoside reverse transcriptase inhibitors (NNRTI), particularly nevirapine, and little is known about the ...occurrence of rash and the risk factors for its development in patients receiving regimens not based on NNRTI.
Methods We evaluated all cases of rash observed during a 48‐week randomized multicentre trial in 1251 nucleoside‐experienced patients who started treatment with protease inhibitors (ritonavir or indinavir) at CD4 counts below 50 cells/μL. Incidence rates for rash were calculated according to gender, clinical status, age, use of highly active antiretroviral therapy (HAART), Pneumocystis carinii pneumonia (PCP) prophylaxis and use of individual antiretroviral drugs at enrolment. Differences between groups defined according to the above characteristics were tested for statistical significance using the log‐rank test in a Kaplan‐Meier survival analysis. All factors that gave results in the univariate analyses below the significance level of 0.05 were included in a multivariate analysis using a Cox regression model.
Results During a follow‐up period of 9690 person‐months, 66 patients (5.3%) developed rash (0.68 events/100 person‐months). In the univariate analyses, risk of rash did not differ with trial treatment (indinavir or ritonavir), clinical status, PCP prophylaxis, or age. During follow‐up, rash was observed in 7.5% of enrolled women and in 4.5% of enrolled men (P=0.03). Serious rash occurred in 4.5% of enrolled women and in 1.6% of enrolled men (P=0.003). Use of HAART (P<0.001) and inclusion of zidovudine and of zalcitabine in the prescribed regimen (P=0.02) appeared to be associated with a lower risk of rash. In the multivariate analysis, the variables that remained significantly predictive of rash were gender (risk for women compared to men: 1.65, 95% confidence interval (CI): 1.00–2.72, P=0.048) and use of a non‐HAART regimen (risk for non‐HAART patients compared to HAART: 2.73, 95% CI: 1.49–5.02, P=0.001).
Conclusions In our study, about 5% of HIV‐positive patients who started treatment with protease inhibitors at very low CD4 counts developed rash, generally in the first few weeks after treatment. Risk was significantly higher in women and in patients who did not receive a HAART regimen. Our data indicate that women have a higher risk of rash than men, also with regimens that do not include NNRTI.
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