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Biomedical subjects

Renato Maserati

Publications and source records attributed to Renato Maserati.

At least 19 recordsLinked to original sources
PubMed2006

Cervical intraepithelial neoplasia and cervicovaginal shedding of human immunodeficiency virus.

OBJECTIVE: Although human immunodeficiency virus (HIV) infection is a well-known risk factor for cervical intraepithelial neoplasia (CIN), the influence of CIN on cervicovaginal shedding of HIV is poorly understood. The purpose of this study was to evaluate the association between CIN and the shedding of HIV in cervicovaginal secretions. METHODS: Two hundred sixteen HIV-seropositive patients were followed up by Pap test, colposcopy, and targeted cervical biopsies for a median of 16 months (range 0-94). A diagnosis of low-grade CIN was made on the basis of Pap test and either colposcopy or cervical biopsy. High-grade CIN was diagnosed solely on the basis of cervical biopsy. At each follow-up visit, we measured HIV-1 RNA in plasma, proviral HIV-1 DNA, and cell-associated and cell-free HIV-1 RNA in cervicovaginal secretion by competitive polymerase chain reaction (cRT-PCR) and reverse transcriptase PCR. The univariable and multivariable associations between the occurrence of CIN and the presence of HIV-related nucleic acids in cervicovaginal secretions were evaluated with logistic generalized estimating equations. RESULTS: Overall, at enrollment and during the follow-up period, a diagnosis of either low-grade or high-grade CIN was made in 14.4% (99/689) and 6.7% (46/689) of the visits, respectively. The presence of measurable levels of plasma HIV-1 RNA was a significant risk factor for the detection of cervicovaginal HIV-1 DNA (odds ratio [OR] 1.86, 95% confidence interval [CI] 1.32-2.61, P < .001), cell-associated (OR 1.69, 95% CI 1.18-2.43, P = .004), and cell-free HIV-1 RNA (OR 1.84, 95% CI 1.28-2.63, P = .001). After the adjustment for the effect of plasma HIV-1 RNA, CD4(+) positive cell counts less than 200 mm(3), and bacterial vaginosis, the detection of cell-associated (OR 1.75, 95% CI 1.23-2.49, P = .006) and cell-free HIV-1 RNA (OR 2.0, 95% CI 1.39-2.87, P = .001) in cervicovaginal secretions was significantly associated with the diagnosis of CIN. CONCLUSION: The presence of CIN lesions is a significant risk factor for genital HIV shedding. Given the high prevalence of cervical disease among HIV-positive women, this finding could have important epidemiological implications in both heterosexual and perinatal transmission of HIV. LEVEL OF EVIDENCE: II-2.

Cervix Mucus↗
PubMed2006

Influence of hepatitis C genotypes on lipid levels in HIV-positive patients during highly active antiretroviral therapy.

BACKGROUND: The independent role of HCV genotype 3 (HCV-3) in dyslipidaemia following highly active antiretroviral therapy (HAART) is still unexplored. METHODS: Analysis of data from a cohort of 307 HIV/HCV-coinfected patients and 415 HIV-monoinfected controls was conducted. Patients with available lipid levels at baseline and minimum 3-month follow-up were ranked into three groups by HCV status (HCV-3, other HCV genotypes or HCV negative). Univariate and multivariate GEE models were performed to assess factors correlated with lipid serum levels as coefficient (Coef., defined as mean difference [mg/dl] across the follow-up). Univariate and multivariate logistic regression analyses were performed for prediction of relevant hypertriglyceridaemia (> or = 500 mg/dl) and relevant hypercholesterolaemia (> or = 240mg/dl) at 3 months of follow-up. RESULTS: HCV-3 correlated with lower triglyceridaemia (Coef.=-38.22; P=0.001), independently from the other considered variables, including age, gender and use of stavudine or lopinavir. Even though HCV infection per se appeared to be protective, HCV-3 in particular was also independently associated with lower cholesterolaemia (Coef.=-46.35; P<0.001). At logistic regression analyses, HCV-3, but not HCV-non-3, was associated with lower risk of relevant hypercholesterolaemia (odds ratio [OR] 0.06; P=0.01) and relevant hypertriglyceridaemia (OR 0.11; P=0.05), independently from other considered variables. CONCLUSIONS: Our data confirm that HCV coinfection per se is associated with lower risk of hypercholesterolaemia after HAART. This effect was particularly attributed to HCV-3, which was the only genotype associated with lower triglyceridaemia during HAART.

Adult↗
PubMed2005

Improved lipid profiles and maintenance of virologic control in heavily pretreated HIV-infected patients who switched from stavudine to tenofovir treatment.

A retrospective chart analysis of 66 human immunodeficiency virus type 1 (HIV-1)-infected patients whose treatment was switched from stavudine to tenofovir without any other treatment changes was conducted. The mean total cholesterol values decreased significantly within 3 months after the tenofovir substitution and remained significantly less than baseline values during 18 months of follow-up (mean decrease, 36 mg/dL; P = .002). Regimens containing tenofovir provided effective control of HIV-1 infection, with stable CD4+ cell counts and continued suppression of plasma HIV-1 level following the treatment switch from stavudine.

Adenine↗
PubMed2005

The effect of vaginal candidiasis on the shedding of human immunodeficiency virus in cervicovaginal secretions.

OBJECTIVE: The purpose of this study was to evaluate the influence of symptomatic vulvovaginal candidiasis on the shedding of HIV-1 in cervicovaginal secretions of HIV-1-infected women. STUDY DESIGN: We obtained paired blood and cervicovaginal lavage samples from 66 HIV-infected women with symptomatic vulvovaginal candidiasis, and 249 HIV-infected control patients without genital infection. HIV-1 RNA in plasma, proviral HIV-1 DNA, HIV-1 RNA transcripts, and cell-free HIV-1 RNA in cervicovaginal secretions were quantitatively evaluated by competitive polymerase chain reaction (cPCR) and reverse transcriptase PCR (cRT-PCR). We used logistic regression on ordered data to assess the influence of vulvovaginal candidiasis on the HIV-1 load in cervicovaginal secretions adjusting for potential confounders. RESULTS: Overall, the amount of HIV-1 RNA in plasma was significantly correlated with HIV-1 DNA (Spearman rank 0.153 +/- 0.059, P = .006), HIV-1 RNA transcripts (Spearman rank 0.169 +/- 0.058, P = .003), and cell free HIV-1 RNA (Spearman rank 0.185 +/- 0.059, P = .001) load in cervicovaginal secretion. Forty-eight out of 182 (26.4%) patients who tested negative for HIV-1 RNA in plasma were positive for HIV-DNA in their cervicovaginal secretions. In logistic regression analysis vulvovaginal candidiasis was significantly associated with increasing loads of HIV-1 RNA transcripts (Odds ratio [OR] 1.97, 95% CI 1.09-3.57, P = .025) and cell free HIV-1 RNA (OR 2.03, 95% CI 1.10-3.73, P = .02) in cervicovaginal secretions. CONCLUSION: In HIV-infected women, vulvovaginal candidiasis is associated with an increased number of copies of cell-associated and cell-free HIV-1 RNA in cervicovaginal secretions.

Bodily Secretions↗
PubMed2005

A case of a progressive multifocal leukoencephalopathy patient with four different JC virus transcriptional control region rearrangements in cerebrospinal fluid, blood, serum, and urine.

JC virus (JCV) is the etiological agent of progressive multifocal leukoencephalopathy (PML), a fatal demyelinating disease of the central nervous system (CNS). During the acquired immunodeficiency syndrome (AIDS) epidemic, it was the cause of the death in up to 8% of AIDS patients. The genomic organization of JCV and, in particular, the hypervariability of the transcriptional control region (TCR), a regulatory noncoding region, are well known. Given that the TCR plays a central role in the viral replication of JCV, a crucial role in the determination of the neurotropism and in the pathogenic capabilities of the virus is also suspected. Here the authors describe a case of PML that did not respond to highly active antiretroviral therapy (HAART) therapy. There was a simultaneous presence of JCV strains with four different TCR structures in urine, peripheral blood cells, serum, and cerebrospinal fluid (CSF) samples. These data confirmed that the presence of the archetype TCt is restricted to urine, while also suggesting that the degree of the rearrangement varies and increases from the peripheral blood to CSF.

Adult↗
PubMed2005

Limited sampling strategy for the estimation of systemic exposure to the protease inhibitor nelfinavir.

Therapeutic drug monitoring (TDM) of antiretroviral drugs has been proposed as a means of optimizing response to highly active antiretroviral therapy (HAART) in HIV infection because suboptimal exposure to these agents may lead to the development of resistant viral strains and subsequent therapeutic failure. The area under the curve (AUC), though considered to make the best estimate of total drug exposure, requires repeated blood sampling. The authors investigated the predictability of individual nelfinavir (NFV) concentrations at different time points for the AUC and tried to find the best sampling time for the abbreviated AUC to predict NFV total body exposure. A total of 99 NFV AUC0-12h values were measured in 99 patients receiving a 1250-mg oral dose twice a day. Venous blood samples were collected at baseline (predose, 0) and 1, 2, 3, 4, 5, 6, 8, and 12 hours postdose. A stepwise forward-selection, multiple-regression technique was chosen to assess the relative importance of single and combination concentration time points to predict the AUC calculated from the entire pharmacokinetic profile. Data were split into a development set and a validation set. The development set contained 49 randomly selected HIV patients. Of these, 22 HIV patients were coinfected with HCV, 7 with and 15 without cirrhosis. One-point predictors provided the lowest prediction precision, but predictive performance improved after the first 2 hours postdose. Plasma concentrations at 0 and 4 hours after the oral dose were most predictive if 2 variables were used in the regression equation. The AUC could be estimated from data for these 2 samples by using the following equation: AUC0-12 = 3.0 + 2.7 (C0) + 6.4 (C4), r = 92. The predictive performance of 2-point predictors at 0 and 4 hours (C0 + C4) was validated by comparing their ability to predict the full AUC in a validation set representative of HIV/HCV patients (n = 28) and HIV/HCV patients, with (n = 8) and without (n = 14) cirrhosis. The results showed a mean bias ranging from +2.7% in HIV/HCV patients to -6.0% in HCV coinfection with cirrhosis. The authors conclude that this result is clinically significant. The limited sampling strategy (LSS) described could be used in clinical practice for the easy assessment of the total exposure to NFV in HIV/HCV patients, both with and without cirrhosis.

Area Under Curve↗
PubMed2005

Clinical pharmacokinetics of nelfinavir and its metabolite M8 in human immunodeficiency virus (HIV)-positive and HIV-hepatitis C virus-coinfected subjects.

In order to evaluate the potential risk of nelfinavir (NFV) accumulation in human immunodeficiency virus (HIV)-hepatitis C virus (HCV)-coinfected patients with liver disease, we investigated the concentrations of NFV and M8, the active metabolite of NFV, in plasma HIV-positive (HIV+) patients coinfected with HCV. A total of 119 HIV+ subjects were included in our study: 67 HIV+ patients, 32 HIV+ and HCV-positive (HCV+) patients without cirrhosis, and 20 HIV+ and HCV+ patients with cirrhosis. Most of the enrolled patients (chronically treated) were taking NFV at the standard dosage of 1,250 mg twice a day. To assay plasma NFV and M8 concentrations, patients underwent serial plasma samplings during the dosing interval at steady state. Plasma NFV and M8 concentrations were measured simultaneously by a high-performance liquid chromatography method with UV detection. The HIV+ and HCV+ patients with and without cirrhosis had significantly lower NFV oral clearances than the HIV+ and HCV-negative individuals (28 and 58% lower, respectively; P < 0.05), which translated into higher areas under the concentration-time curves for cirrhotic and noncirrhotic patients. The NFV absorption rate was significantly lower in cirrhotic patients, resulting in a longer time to the maximum concentration in serum. The mean ratios of the M8 concentration/NFV concentration were significantly lower (P < 0.05) in HIV+ and HCV+ subjects with cirrhosis (0.06 +/- 0.074) than in the subjects in the other two groups. The mean ratios for M8 and NFV were not statistically different between HIV+ and HCV-negative patients (0.16 +/- 0.13) and HIV+ and HCV+ patients without cirrhosis (0.24 +/- 0.17), but the interpatient variability was high. Our results indicate that the pharmacokinetics of NFV and M8 are altered in HIV+ and HCV+ patients, especially those with liver cirrhosis. Therefore, there may be a role for therapeutic drug monitoring in individualizing the NFV dosage in HIV-HCV-coinfected patients.

Adolescent↗
PubMed2004

Colour-Doppler ultrasonography of carotid vessels in patients treated with antiretroviral therapy: a comparative study.

OBJECTIVES: To evaluate the correlation between antiretroviral therapy (ART) and lesions of the carotid vessels using an ultrasound colour-Doppler technique. DESIGN: A total of 293 HIV-1 infected patients underwent epiaortic vessel ultrasonography: 105 on treatment with protease inhibitors (PI) (group I), 125 PI-naive patients treated with a non-nucleoside reverse transcriptase inhibitor-including regimen (group II), and 63 patients treated with two nucleoside reverse transcriptase inhibitors or naive to ART (group III). METHODS: Intima characteristics, pulsation and resistance indexes, and minimal, peak and mean speed were evaluated using a colour power doppler. Atherosclerotic plaques were described. Independent risk factors and values for glycaemia, cholesterolaemia and triglyceridaemia were considered. Statistical analysis included the Wilcoxon tests, the chi test, the Cochran Armitage trend test and the Mantel-Haenszel test and, when necessary, logistic regression analysis. RESULTS: Of the 150 group I patients, 55 (52.4%) presented acquired lesions of the vascular wall at ultrasonography, whereas similar lesions were found in 19 out of 125 (15.2%) patients in group II and in nine of 63 (14.3%) in group III. ART, age, smoking and CD4 T-cell count were the main predictive risk factors for vascular lesions. However, the highest significance was with the use of PI. CONCLUSIONS: These data confirm the higher prevalence of premature carotid lesions in the PI-treated patients. A periodic ultrasonographic study of the vascular wall should be included in the follow-up of HIV infected patients.

Adult↗
PubMed2004

Granule-dependent mechanisms of lysis are defective in CD8 T cells of HIV-infected, antiretroviral therapy-treated individuals.

BACKGROUND: HIV-specific cytotoxic T-cell (CTL) responses are defective in HIV-infected patients undergoing antiretroviral therapy (ART). This defect has been attributed to the decreased antigenic burden secondary to ART-associated suppression of HIV-replication, and is responsible for the rebounds of viraemia that occur when patients interrupt therapy. CTL are stimulated by type 1 cytokines and can kill targets via granule-dependent (perforin and granzymes) and -independent (tumour necrosis factor-alpha, CD95) mechanisms. METHODS: Granule-dependent and granule-independent mechanisms of CTL killing, as well as type 1 cytokine production by CD4 T cells, were analysed in 57 chronically HIV-infected ART-treated or ART-untreated individuals. RESULTS: The results can be summarized as follows: the frequency of gp160 (env)-specific interferon-gamma-secreting CD8 T lymphocytes correlates positively with HIV viraemia in ART-treated and -untreated patients; Env-specific perforin- and granzymes-expressing CD8 T lymphocytes, and Env-stimulated perforin and granzymes mRNA, are reduced in ART-treated patients independently of HIV viral load and of type 1 cytokine production; tumour necrosis factor-alpha production is increased in ART-treated individuals; and Env-specific immature CD8+28+27+ cells are only marginally augmented in ART-treated patients, Similar results are observed in cytomegalovirus-specific CD8 T cells and peripheral blood mononuclear cells. CONCLUSIONS: A defect of CTL function that selectively affects the granule-dependent mechanisms of lysis is observed in ART-treated individuals. Because interferon-gamma production is higher in these patients, this could be a defect primarily involving CTL. These data suggest an independence of CD8 T-cell numbers and their lytic ability in HIV-infected, ART-receiving patients. Immunomodulants are needed to successfully treat HIV infection.

Adult↗
PubMed2004

Dissociation of serum and liver hepatitis C virus RNA levels in patients coinfected with human immunodeficiency virus and treated with antiretroviral drugs.

We examined hepatitis C virus (HCV) RNA levels in serum, peripheral blood mononuclear cells (PBMC), and the liver for 135 patients with chronic HCV infections, 44 of whom were human immunodeficiency virus (HIV) positive and treated with highly active antiretroviral therapy (group A), 66 of whom were HIV negative (group B), with abnormal serum alanine aminotransferase (ALT) values, and 25 of whom were HIV negative, with ALT values of </=1.5 times the normal value (group C). Patients had not been treated with interferon, with or without ribavirin, at the time of the study. A statistically significant correlation between HCV RNA levels in the liver and serum was reproducibly documented, whereas this was inconsistent for serum and PBMC. A comparative evaluation of HCV RNA levels in the liver and PBMC showed significantly lower values for group A than for groups B and C (P < 0.01 and P < 0.0001, respectively). In contrast, HCV RNA levels in serum were significantly higher for group A than for group B (P < 0.001). A dissociation between HCV RNA levels in serum and the liver was found for patients with HIV-HCV coinfections. Although the relative contribution of extrahepatic reservoirs, including lymphoid cells, to HCV RNA levels in serum is unclear, it may be speculated that a low intrahepatic HCV burden is caused by restored immunocompetence after successful antiretroviral therapy in coinfected patients.

Antiretroviral Therapy, Highly Active↗
PubMed2004

Strategies to decrease viral load rebound, and prevent loss of CD4 and onset of resistance during structured treatment interruptions.

BACKGROUND: Toxicity and other drug adherence-related factors have contributed to decreased compliance to antiretroviral regimens amongst HIV-infected patients. Irregular therapy disruption causes loss of CD4 T cells, onset of drug resistance and rapid rebound of plasma viral load (VL). However, an appropriate choice of drugs and properly scheduled structured treatment interruptions (STIs) may limit VL rebound, maintain CD4 counts and minimize resistance. METHODS: We conducted a clinical study of STIs, RIGHT 901, involving 60 drug-naive patients with chronic HIV infection (CD4 >300, VL >10,000) randomized to receive didanosine-stavudine-indinavir (IDV group) or didanosine-stavudine-hydroxyurea (HU group), for 12 weeks. Subsequently, all patients were randomized again to start STI (short induction) or to continue the therapy for an additional 24 weeks before starting STI (long induction). Both groups underwent four STI cycles and then stopped therapy as long as viraemia remained below 10,000 copies/ml before reinitiating another four cycles of STI. RESULTS: During continuous therapy VLs were suppressed at similar rates in both the HU and IDV groups, while a blunted CD4 count was documented in the HU group. Following the first stop median VL rebounded close to baseline values in both groups, however, during the following STI median VL rebound decreased in the HU group, while in the IDV group VL continued to rebound to values close to baseline, and the difference between the two groups was statistically significant. Moreover, patients treated with HU had a constant and stable CD4 increase during STI, whereas CD4 counts fluctuated in the IDV group, with sharp falls during treatment interruptions and partial CD4 recovery following treatment restart. Even in the presence of IDV resistance predisposing mutations at baseline, no genotypic change in the protease sequence was observed during STI. A relevant mutation in the reverse transcriptase sequence (K70R) emerged in one patient interrupting treatment after 36 weeks of continuous therapy and in one patient after four STI cycles. Side effects (no major events) were similar among groups. CONCLUSIONS: An appropriate choice of STI schedule and regimens containing drugs less prone to resistance and/or able to prevent CD4 fluctuation may contribute to optimizing STI for chronically infected patients with respect to limiting viral rebound, improving CD4 counts and maintaining a resistance profile comparable to continuous highly active antiretroviral therapy.

Anti-HIV Agents↗
PubMed2003

Real versus virtual phenotype to guide treatment in heavily pretreated patients: 48-week follow-up of the Genotipo-Fenotipo di Resistenza (GenPheRex) trial.

We compared viroimmunologic response after real phenotype (r-PHT) versus virtual phenotype (v-PHT) in patients failing highly active antiretroviral therapy (HAART). A total of 201 patients with >2 years of exposure, more than six experienced drugs, >1000 HIV RNA copies/mL, and on stable HAART for >6 months were randomized to the r-PHT or v-PHT arm. The primary end point was the proportion of HIV plasma viral load (pVL) <400 copies/mL. Secondary end points were absolute pVL change, proportion of pVL reduction >0.5 log(10) copies/mL, and absolute CD4 cell change. In the intention-to-treat-last observation carried forward analysis, study outcomes were not significantly different between arms over 48 weeks of follow-up: 20% and 24% pVL <400 copies/mL; 58% and 61% pVL reduction >0.5 log(10) copies/mL; -0.92 and -0.94(10) log copies/mL mean pVL decrease; and +41.6 and +94.4 cells/mm(3) mean absolute CD4 increase in the r-PHT and v-PHT arms, respectively. On-treatment analyses gave similar results. In the multivariate analysis of pVL <400 copies/mL, the following covariates were independent predictors at week 48: adherence (OR p= 0.25; p=.002), baseline CD4 (OR = 4.39; p=.007), intravenous drug use as risk factor for HIV acquisition (OR = 0.33; p=.024), and sensitivity score of the new regimens by biologic cut-offs (OR = 1.84; p=.029). Prescribed drugs for which patients were naive resulted in marginal prediction (OR = 1.93; p=.054). In conclusion, virologic and immunologic outcomes did not differ when r-PHT or v-PHT was used in this cohort of heavily pretreated patients. Several factors should be considered to take better advantage of resistance testing, including treatment history, clinical status, and patients' ability to adhere to treatment.

Adult↗
PubMed2003

Analysis of JC virus genotype distribution and transcriptional control region rearrangements in human immunodeficiency virus-positive progressive multifocal leukoencephalopathy patients with and without highly active antiretroviral treatment.

After the introduction of highly active antiretroviral therapy (HAART), the incidence of many acquired immunodeficiency syndrome (AIDS)-related opportunistic infections, but not of progressive multifocal leukoencephalopathy (PML), has been dramatically decreased. However, it has been shown that about 50% of the HAART-treated PML patients had a significantly prolonged (>6 months) survival time, in comparison to the short (<6 months) survival time of the classical form of PML. In order to verify if a particular genotype or genomic rearrangements of JC virus (JCV) could affect the clinical course of PML, the authors performed nucleotide sequencing of 25 virion protein (VP1) and 18 transcriptional control region (TCR) DNA amplified in the cerebrospinal fluid (CSF) of HAART-untreated PML patients, of 17 HAART-treated PML patients, and in the urine of 23 healthy individuals. In nontreated PML patients, 52% and 44% of amplified JCV were respectively type 1 and type 2, whereas in HAART-treated PML patients, 59% of the amplified JCV were type 1, 23% type 2, and 18% type 4, without differences between long and short survivors. In both groups, the amplified TCR had unique and extensive rearrangements, whereas archetype TCR without rearrangements was detected in all the healthy subjects and in the CSF of two long-survivor PML patients. The data obtained indicate that the introduction of HAART has induced changes in JCV genotype distribution and probably reduced the rate of rearrangements of TCR region among PML patients.

Acquired Immunodeficiency Syndrome↗
PubMed2002

B7-H1 is up-regulated in HIV infection and is a novel surrogate marker of disease progression.

The ligation of programmed death-ligand 1 (B7-H1) to T cells results in the preferential production of interleukin 10 (IL-10). We investigated if B7-H1 would be up-regulated in HIV infection, a disease characterized by increased IL-10 production, by measuring B7-H1, B7-1 (CD80), and B7-2 (CD86) expression and mRNA in 36 HIV-infected patients and in 22 healthy controls (HCs). Results showed that (1) B7-H1 expression and mRNA are augmented in cells of HIV patients; (2) increased IL-10 production in these patients is largely induced by B7-H1-expressing CD14(+) cells; (3) an inverse correlation is detected between B7-H1 expression and CD4 counts, whereas the up-regulation of B7-H1 is directly associated with HIV plasma viremia; (4) antiviral therapy results in the parallel down modulation of IL-10 production and B7-H1 expression/synthesis; and (5) B7-H1/CD80 and B7-H1/CD86 mRNA ratios are increased in peripheral blood mononuclear cells (PBMCs) of HIV patients compared with HCs. B7-H1 synthesis and expression are up-regulated in HIV infection, and the degree of dysregulation correlates with the severity of disease. Aberrant antigen presentation by antigen-presenting cells (APCs) that exhibit increased B7-H1 expression and IL-10 production in HIV infection could be responsible for T-lymphocyte unresponsiveness and loss of protective immunity. B7-H1 is a surrogate marker potentially involved in AIDS disease progression.

Antigens, CD↗
PubMed2002

Early and late effects of highly active antiretroviral therapy: a 2 year follow-up of antiviral-treated and antiviral-naive chronically HIV-infected patients.

BACKGROUND: Control of HIV replication can be observed in highly active antiretroviral therapy (HAART)-treated and, occasionally, in HAART-naive patients. The immunological correlates of these situations were examined in a longitudinal study. DESIGN: A prospective study. Immunovirological analyses in 16 chronically HIV-infected, HAART-naive patients (time 0) who started HAART. Fifteen patients (short-term HAART) were re-evaluated after 24 months (time 1). Results were compared with those of 30 patients who received HAART for more than 12 months before the study period (long-term HAART) and were analysed at the same timepoints. Fifteen patients who were antiviral therapy naive (naive) at both timepoints were also studied. RESULTS: Over a 24-month period CD4 and CD8 cell counts and viraemia remained unchanged in naive and long-term HAART patients; CD4 cell counts increased and viraemia diminished in short-term HAART individuals. Antigen-stimulated proliferation was unmodified in naive and short-term HAART patients, but improved in long-term HAART individuals. Gp160-stimulated IL-2 and IFN-gamma production was augmented in long-term HAART patients and marginally modified in other patients. IL-7 production was unmodified in naive individuals, augmented in short-term HAART patients, and diminished in long-term HAART patients. Chemokine production was similar in all patients. Naive patients showed the highest CD8 cell counts at both timepoints. CONCLUSION: HAART has a major impact on the outcome of HIV infection, even if functional immune modulation in HAART-treated patients is evident only after long periods of therapy. Low but detectable HIV replication in HAART-naive patients with preserved immune functions might not be associated with CD4 cell reduction, functional immune defects, or changes in viraemia.

Antiretroviral Therapy, Highly Active↗
PubMed2002

Assessment of handwashing practices with chemical and microbiologic methods: preliminary results from a prospective crossover study.

BACKGROUND: Handwashing (HW) by clinical staff is the single most important measure for preventing transmission of nosocomial infection (NI). The primary objectives of this study were to improve the motivation and awareness of the importance of HW practices among health care workers (HCWs) and to assess the effectiveness of a new chemical system in checking HW compliance. In addition, we evaluated the efficacy and tolerability of 2 soap solutions used during regular working hours by HCWs at our institution. METHOD: A preliminary short training course was performed to promote HW compliance and awareness. We chose 2 surgical wards at our 1200-bed teaching hospital. Sampling of hands was conducted weekly during routine activities of HCWs without advance warning. We used the staff list as a sampling frame to select subjects. Data were collected anonymously. On the basis of a crossover study design, a plain soap and one containing 4% chlorhexidine gluconate (CHG) were used alternatively in each ward for 4 consecutive months. Hand samples were evaluated with microbiologic cultures and with a commercially available kit that measures adenosine triphosphate (ATP) bioluminescence. As additional process indicators, we examined the amount of hand soap and CHG solution distributed and rate of NIs. RESULTS: A total of 74 HCWs were evaluated for hand contamination. During the 4-month study, we found a significant reduction in colony-forming unit counts (P <.008) and ATP levels (P <.002) compared with baseline values. The results showed a positive correlation (r = 0.68, P <.0001) between the microbial counts detected by standard culture and ATP levels measured with the commercial kit. Plain soap (P <.003) was more effective than CHG in reducing colony-forming unit counts among HCWs in the vascular surgery ward. We documented a reduction in the NI rate and an increase in the consumption of soap and paper towels. CONCLUSION: HW compliance improved during the study period among HCWs. The method to measure ATP bioluminescence is simple and easy to perform and provides reliable results within a few minutes of sampling hands. It can be used extensively to test HW compliance among HCWs.

Adenosine Triphosphate↗