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Biomedical subjects

A Lazzarin

Publications and source records attributed to A Lazzarin.

At least 325 records · Page 18Linked to original sources
PubMedDate not supplied

Four drug-HAART in primary HIV-1 infection: clinical benefits and virologic parameters.

BACKGROUND: From a theoretical standpoint, primary HIV infection (PHI) represents a great chance to modify the natural history of the disease. In this study we purposed a four drugs regimen with zidovudine, lamivudine, ritonavir and saquinavir to treat aggressively the infection and achieve a complete immune reconstitution. METHODS: This is an Italian multicentric open label study. Adult patients with PHI were eligible for the study if they met at least one clinical criterion and one laboratory criterion of the following. Clinical criteria: Signs and symptoms of acute retroviral syndrome within the past 70 days, exposure to HIV-1 within the last 3 months, a preceding negative antibody test within the past 6 months. Laboratory criteria: Detectable p24 antigen with neutralization in serum; detectable HIV-RNA in plasma; indeterminate Western blot test with negative or low positive value HIV antibody in ELISA test. RESULTS: Since April 1997 to April 1999 40 patients with PHI have been enrolled; 80% of this cohort referred symptoms related to acute antiretroviral syndrome. Treatment has been withdrawn in 17 patients (12 for intolerance, 3 for toxicity and 2 for failure). At baseline the mean CD4+ T cells count and CD4/CD8 ratio were 537 (range 55-1287) and 0.58 (range 0.1-1.03) and the mean plasma HIV-RNA level was 5.9 log copies/ml (range 3-7.15). Plasmatic HIV-1 RNA levels of all patients dropped below 200 copies/ml in 68% of patients at week 12, 81% at week 24, 93% after 12 months and 100% after 18 months. Immunological parameters have been improved and have achieved normal range since 6th month. CONCLUSIONS: A rapid virologic suppression and immunological reconstitution are associated with PHI therapy. However early treatment should be weighted against the potential disadvantages such as immediate adverse events (intolerance and drug toxicity) and long term manifestation (metabolic disorders).

Acquired Immunodeficiency Syndrome↗
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Primary HIV infection: molecular approaches in diagnosis and monitoring.

OBJECTIVE: The aim of this study was to evaluate, in patients with primary HIV infection (PHI), the modification of HIV molecular parameters (HIV, RNA, and DNA) induced by highly active antiretroviral therapy (HAART) in peripheral blood mononuclear cells (PBMC) and in lymphoid tissue (LNMC). METHODS: Nineteen patients with primary HIV infection, 4 women and 15 men with an average age of 35 years (range 27-62), were included in this study. Ten patients received 4 drugs: zidovudine plus lamivudine plus saquinavir plus ritonavir, 7 patients received 3 drugs: zidovudine plus lamivudine plus saquinavir and 2 patients received a different combination of 3 drugs: zidovudine plus lamivudine plus indinavir. As control group we included 8 patients who had been enrolled in a placebo-controlled trial of zidovudine between 1991 and 1995: four received placebo and 4 were treated with zidovudine alone. Peripheral blood samples and lymphoid tissue obtained by echo-driven fine needle biopsies were drawn to monitor molecular HIV parameters. A quantitative in house PCR method in the HIV gag region was used to monitor viral DNA burden and the NASBA system for viremia. RESULTS: A certain heterogeneity in the baseline values of HIV, DNA, and RNA was observed. Early HAART determined a rapid recovery of the CD4 cell number with normalisation of the CD4/CD8 ratio in most patients. HIV-RNA levels dropped to undetectable levels after a few months of therapy and HIV-DNA was consistently reduced although it never reached undetectable levels. Lymph-node biopsies were well tolerated due to the non-invasive sampling, however an optimisation of the method is needed to improve cell recovery. In the valuable samples the amount of HIV DNA recovered is comparable to that from peripheral blood samples, both at baseline and at follow-up.

Adult↗
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Early production of HIV-1 neutralising antibodies in patients following highly active antiretroviral treatment (HAART) during primary HIV infection.

We investigate the effects of highly active antiretroviral therapy (HAART) on humoral immune responses during a 24-month follow up of 15 HIV patients with acute primary HIV infection. The patients were divided into three groups on the basis of the therapeutic protocol they were following at the time of entry: a) five naive patients (untreated or treated with only ZDV or AZT); b) five patients following a triple combination of ZDV+ lamivudine (3TC)+ saquinovir (SQV); and c) five patients on a four-drug combination of ZDV+3TC+SQV+ ritonavir (RTV). The results show that the early introduction of HAART greatly reduces plasma viremia levels and restores the number of CD4 cells. A significant correlation was found between anti HIV neutralising activity and the four-drug, but not the three-drug combination. The reduction in infectivity was directed against viruses of different clades and associated with immunoglobulin fractions. Moreover, the neutralising antibodies in the HAART-treated patients appeared after two weeks of treatment and remained stable throughout the 24 months of follow up. The early appearance of neutralising antibodies represent an important component of immune responses during primary HIV infection, may contribute towards immune reconstitution in patients on HAART, and give further information that may be useful in developing new strategies designed to eradicate the disease.

Acquired Immunodeficiency Syndrome↗
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Analysis of serum and plasma beta chemokines in primary HIV infection (PHI).

The levels of certain beta-chemokines in biological fluids do not necessarily reflect their circulating concentrations as they may be dramatically influenced by ex vivo release during sample manipulation. In the present study beta-chemochine levels were evaluated in sequential paired plasma and serum samples collected from a cohort of 18 patients with primary HIV infection (PHI), as well as from 17 HIV-seronegative individuals. In plasma of PHI patients, a significant increase of RANTES (mean 119.1 vs 15.85 ng/ml; p=0.0001) and MIP-1beta (mean 53.4 pg/ml vs 33.6 pg/ml; p=0.0001) was documented. Intra-patient covariance analysis demonstrated no significant association between the variations of RANTES in plasma and serum or between RANTES levels and platelet counts. Reproducibility tests of RANTES measurements in plasma from PHI patients showed a mean coefficient of variation of 1.8%. These data demonstrate that the plasma levels of RANTES and, to a lesser extent, MIP-1beta are persistently perturbed during the early phase of HIV infection. Furthermore they indicate that plasma and serum levels are not directly correlated, being influenced by different physiological phenomena that occur during the ex vivo preparation procedures of the two biological fluids.

Chemokine CCL4↗
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Cyclosporin A in combination with HAART in primary HIV-1 infection.

HAART is the cornerstone of HIV therapy, and has significantly reduced morbidity and mortality associated with HIV disease. The institution of HAART during the primary HIV-1 infection has a more profound influence on the ultimate pattern and rate of disease progression than therapy commenced later on. However, it also well demonstrated that HAART alone is not able to eradicate the virus, unless over a life-long period of time. There is therefore the need to develop alternative strategies aimed at modulating the immune responses in order to achieve the long-term control of HIV even once HAART is discontinued. Among immunomodulant agents, cyclosporin A in combination with HAART might play a role in the treatment of people with primary HIV-1 infection.

Acquired Immunodeficiency Syndrome↗
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Comparison of protease genotype and phenotype in HIV-1 infected patients exposed to more than one protease inhibitor.

Many patterns of mutations selected by HIV-1 protease inhibitors have been described, but in most cases isolates with these patterns have been obtained from pre-clinical studies or after failures of monotherapies. We compared genotype and phenotype in HIV-1 infected patients who have failed more than one PI-including regimen. Phenotypic resistance could arise also in the absence of specific primary mutations and in the presence of different substitutions among those known to confer resistance to ritonavir, indinavir or nelfinavir. The number of secondary mutations was significantly associated with phenotypic resistance for each protease inhibitor. Thus, more study of mutational patterns in heavily pretreated patients is warranted; in the mean time treatment choices might be optimized if phenotyping could integrate genotyping within this setting.

Amino Acid Substitution↗
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Selective enrichment of CD30-expressing cells within the blast region of lymphocytes from patients with primary HIV infection (PHI).

Individuals experiencing a primary infection with HIV (PHI) are known to undergo a potent activation of their humoral and cellular immune response. We investigated the expression of CD30 in peripheral blood mononuclear cells (PBMC) from 15 PHI patients before their initiation of HAART, since elevated levels of its soluble form, sCD30, have been previously documented in the plasma/sera of PHI patients. We also analyzed other lymphocyte-associated activation markers, including CD69, CD25 and HLA-DR. When looking at total lymphocytes, HLA-DR was expressed on the majority of lymphocytes, followed evenly by CD69 and CD25, and last by CD30. Of note, we observed that 13 out of these 15 patients displayed a characteristic expansion of lymphocytes with larger morphology (termed blasts). When a morphologic gate was drawn on these blasts, the percentage of CD25-, CD69-positive cells remained substantially unchanged, that of HLA-DR-positive cells augmented, but the the most striking increase occurred in the percentage of CD30-expressing lymphocytes. Therefore, although all of the molecules studied are considered lymphocyte activation markers, CD30 is most likely to be expressed within cycling/proliferating cells of the lymphoblast fraction during the earliest phases of HIV infection.

Antigens, CD↗
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Primary HIV-1 resistance in recently and chronically infected individuals of the Italian Cohort Naive for Antiretrovirals.

The risk of acquiring HIV-1 drug resistance at time of infection has become a public health problem following the widespread use of antiretroviral drugs in developed countries. Although a number of studies have reported data regarding the prevalence of HIV-1 primary resistance in developed countries over the past years, limited knowledge is available regarding the proportion of mutations related to drug resistance in antiretroviral naive subjects with chronic HIV-1 disease. In this study, we evaluated the prevalence of mutations in the reverse-transcriptase (RT) and protease region both in a representative group of recently HIV-1 infected subjects (n=68) and a cohort of chronically-infected HIV-positive patients (n=347) enrolled in the Italian Cohort of Antiretroviral Naive patients (I.CO.NA.). In recently infected individuals, the overall prevalence of mutations for nucleoside RTI (NRTIs) was 10/68 (14.7%). The distribution of mutations by calendar year were 0, 1 in 1996, 9, 3 in 1997 and 1, 0 in 1998 for NRTIs and protease inhibitors (PIs) respectively. Thymidine associated mutations were identified in six subjects (8.8%), five of whom had one mutation [41L, 70K (n=2), 215Y] and one had two mutations (67N+219Q). Four subjects (5.9%) showed the changes associated with resistance to lamivudine (184V or 118I). No non nucleoside-RTI (NNRTI) mutations were present in the study period. Primary PIs mutations (two 46L and two 82I) were present in four subjects (5.9%). Of note, mutations related to resistance to more than one class of antiretrovirals were present in one (1.5%). Among patients with chronic infection a large proportion (88.5%) carried no mutations in RT region, 11.5% individuals carried one or more mutations associated with resistance to NRTI (7.8%), or NNRTI (4.9%), with 4 patients carrying mutations to both classes. Among mutations associated with high-level resistance to RTI, T215Y was found in only 2 patients, M184V in 2 cases, T69D in another case, and K103N in only 1 patient, for a total of 6 patients (one carrying both T215Y and M184V) (1.7%). Primary mutations associated with substantial resistance to PIs were found in only 5/347 patients (1.4%); all the other patients carried only secondary mutations. Prevalence of mutations associated with high-level resistance to antiretroviral drugs is stable in recently infected individuals and low in patients with established HIV infection. The potential impact of transmitted mutations on the response to first regimen in individuals carrying transmitted mutations needs to be assessed by prospective studies.

Acute Disease↗
PubMedDate not supplied

Molecular and phylogenetic characterization of HIV variants in Italian primary HIV infections (PHI): identification of non-B subtype variants.

The distribution of Human Immunodeficiency Virus type 1 (HIV-1) clades is evaluated in primary HIV-1 infections (PHIs) occurring through sexual transmission in Lombardia, the Italian region with the highest prevalence/incidence of HIV-1 infections. The two primary inclusion parameters for enrollment were sexual transmission and < 1 year seroconversion. Thirty-four enrolled patients have been analysed so far at the molecular level, to characterize their infecting HIV-1 population. Two HIV-1 genomic regions with different rates of genetic variability, the hypervariable C2-V3 fragment of the env gene and the conserved 5' end of the gag p17, were amplified by Polymerase Chain Reaction (PCR) in peripheral blood mononuclear cells (PBMCs) and characterized by direct DNA sequence analysis. Pairwise nucleotide alignment and phylogenetic analyses show that, although with a high range of nucleotide variability, 32 out of the 34 HIV-1 isolates identified in this PHI cohort fall under the clade B genotype. The two remaining isolates, detected in a couple formed by a Nigerian woman and her Italian partner, consistently cluster with clade G standards in both sub-genomic regions. The amino acid sequences confirm this classification, showing clade-specific residues both in the V3 and p17 regions. These data suggest that the B clade is still prevalently associated with acute primary HIV-1 infections occurring in Italy through sexual transmission. However, the significant intra-clade variability and the identification of non-B clades strongly indicate the relevance of continuous molecular monitoring of the HIV-1 isolates circulating in Italy, for prognostic evaluations as well as preventive and therapeutic strategies.

Acute Disease↗
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HIV-1 DNA and RNA kinetics in primary HIV infection.

BACKGROUND: HIV-1 reservoir is early established during PHI. It is reduced, but not extinguished by early therapy: DNA containing cells are still detectable after months of successful viremia suppression. To define the best method to measure low level viral replication, we determined the extent of HIV reservoir in 11 acutely infected patients and evaluated how it is renewed even during successful treatment. METHODS: Eleven acutely infected HIV patients were included in the study. Three where not treated with antiretroviral drugs while 8 underwent early aggressive antiretroviral treatment (HAART) which, in 3 cases, was associated to cyclosporin A (CsA) administration. HIV viremia was monitored by commercially available methods while HIV-DNA and cellular RNA quantitation were obtained by in house PCR and RT-PCR respectively, in the gag region. RESULTS: Significant CD4 recover and HIV viremia suppression were reached in a mean period of three to six months in all treated patients. The course of the HIV-DNA and of cellular HIV RNA reduction showed a similar trend. This variation was slower, if compared to plasma viremia and never reached undetectable levels, justifying the rebound of viremia observed at therapy interruption. CONCLUSIONS: These data suggest and confirm that complete abolition of viral replication is not achieved and viral reservoir may be re-expanded even after short term rebound of viremia. Scheduling of possible structured therapy interruption should be designed based on multiple virological parameters and on the individual characteristics of the patients.

Adult↗
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Granulocyte/monocyte apheresis induces sustained increases in CD4 T cells in HIV-1 infected patients with poor CD4 T cell restoration after suppression of viral replication by HAART.

Current antiretroviral regimens (HAART) are generally effective in reducing viral replication to undetectable levels and inducing a raise in CD4 T cells. However, in approximately 5 to 15% of patients suppression of viral replication is not followed by an increase in CD4 T cells. Such patients may be at increased risk for opportunistic infections. Here we report the results from a phase II open label randomised trial on 30 patients classified as poor responders to HAART who were either subjected to eight consecutive cycles of selective monocyte apheresis or maintained under HAART alone. The results show that monocyte apheresis results in increased CD4 T cell counts which are maintained for at least 31 weeks after last apheresis. This effect was observed only on patients with complete suppression of viral replication. Other effects of monocyte apheresis included a strong reduction of TNF-alpha production in patients with high baseline levels of this cytokine and activation of resting T cells during the apheresis cycles. In two patients with high cellular HIV DNA load apheresis was followed by a 98% reduction, suggesting purging of infected cells. There was no evidence of increased viral replication during or after the apheresis cycles. The data show that monocyte apheresis is safe, well tolerated and may be indicated in patients who respond poorly to HAART.

Adult↗
PubMedDate not supplied

Implementation of an Italian multicentric care network for early HIV infection diagnosis: 1999-2001 report.

BACKGROUND: Diagnosis of a new HIV infection during the primary phase (PHI) is sometimes misleading in a primary care setting. Since 1999 the Italian network for the study of acute HIV infection (ISAI) has been operative. At the time of PHI diagnosis the case is reported to the coordinating centre and enrolled in the National Register which records all epidemiological, demographic and clinical information. PATIENTS AND METHODS: From 1999 to September 2001, 51 symptomatic or asymptomatic patients with diagnosis of primary HIV infection were signalled to the coordinating centre. At screening, assessments were: interview to collect demographic and epidemiological data, clinical history (regarding PHI signs and symptoms) and, if available, relevant index case information; physical examination; routine hematology and chemistry; lymphocyte count; plasma HIV-RNA. In a subset of patients PBMC HIV-DNA, HIV-RNA, resistance genotyping and HIV subtype characterization were assessed. RESULTS: 74.5% of patients were males and all but four were Italian. Hetero and homosexual contacts were the prevalent route of HIV transmission. Forty-five patients (89%) were symptomatic and the most frequent signs and symptoms were: fever, lymphadenopathy, malaise and pharyngodinia. Baseline reverse-transcriptase (RT) and protease (PR) genotyping analysis was available for 29 patients. Only one of 29 patients harbored a virus with a resistance-associated mutation in the RT region (215Y); NNRTI mutations were identified in 3 of 29 patients. In the remaining 20 (69%) patients no mutations were found in the RT region. Sequence data from PR region were successfully obtained in 21 patients. Only one of these had a high-level resistance mutation (46L); in an additional 10 cases 1 or more secondary mutations were identified. The remaining 10 patients harbored a PR region wild type virus. One patient presenting two secondary mutations in the PR region, even if highly adherent and tolerant to drug regimen, showed a slow viral load decrease. CONCLUSIONS: Our cohort confirms the uptrend of new infections through unsafe sexual contacts involving both homosexual and heterosexual couples. Genotype sequencing for antiretroviral resistant viral variants describes a low prevalence of RT resistance-associated mutations, as well as primary mutations in the PR region. On the contrary, a higher prevalence of PR gene polymorphisms and mutations is not known with any certainty to confer resistance to NRTI and NNRTI. The identification of antiretroviral drug resistant HIV strains is strategic for clinical and therapeutical intervention, even though from a public health point of view cost-efficacy must be considered.

AIDS Serodiagnosis↗
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Potential role of immune modulation in the effective long-term control of HIV-1 infection.

Recent advances in HIV-1 pathogenesis, and in defining virological and immunological responses to highly active antiretroviral therapy (HAART), along with the identification of the numerous drawbacks of HAART, have clearly demonstrated that the eradication of the virus is not a feasible therapeutic goal, and that there is an urgent need to develop other approaches to fight HIV-1 infection. Novel therapeutic approaches of immune modulation have recently been evaluated in pilot clinical trials. First, treating primary HIV-1 infection with cyclosporin A (CsA) coupled with HAART to target massive immune activation extends the benefits achieved with HAART during primary HIV-1 infection and might contribute to the establishment of a more favourable immunological set-point affecting the ultimate pattern and rate of disease progression. Second, treating chronic HIV-1 infection in patients with long-term suppression of virus replication induced by HAART, with the addition of mycophenolate mofetil (MMF) reduces the pool of activated CD4+ T lymphocytes able to support productive HIV-1 infection, and might have an indirect impact on the pool of resting, latently infected CD4+ T cells, contributing to its depletion in vivo. The important question is clearly whether these results will have an impact on the clinical management of patients with HIV-1 infection, determining the precise therapeutic function of drugs like CsA and MMF, thus investigating the effects of these drugs on residual viral replication and the decay of the latent reservoir, on long-term immunological benefit, and, ultimately, on clinical benefit.

Adjuvants, Immunologic↗
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The effect of HAART on humoral immune response in primary HIV-1 infected patients.

The effect of Highly Active Antiretroviral Therapy (HAART) on binding and neutralizing antibody responses to human immunodeficiency virus type-1 (HIV-1) during primary and chronic infection was investigated. Seven patients HAART treated during primary infection, six HAART treated during chronic infection and five patients treated only with ZVD (Zidovudine) were analysed. HAART inhibited the development of anti env antibodies during primary infection. Administering HAART during primary infection usually did not substantially affect the development of weak neutralizing antibody responses against autologous virus. However, we demonstrated that very early treatment, during seroconversion, induce in some cases, a strong neutralizing antibodies against autologous virus. These results may be relevant for understanding how HAART may elicit a strong protective responses and may be useful in developing new strategies designed to achieve a long term control of the HIV infection.

Acute Disease↗
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Anti-nef antibodies and other predictors of disease progression in HIV-1 seropositive injecting drug users.

A cross-sectional and retrospective longitudinal study has been conducted in three Italian infectious disease centres to evaluate the role of anti-nef antibodies and other markers (HIV-1 p24 antigen, p24 Ag; Beta 2-microglobulin, B2-M; and number of CD4+ lymphocytes) as predictors of disease progression in HIV seropositive injecting drug users (IDUs). The selected patients were: 1) HIV-seropositive IDUs in different stages of HIV infection; 2) HIV-seropositive IDUs who had developed AIDS, from whom serial serum samples were available during the asymptomatic stage, and 3) HIV seropositive IDUs who remained asymptomatic through a follow-up period of the same duration as the patients who developed AIDS. Absence of anti-nef antibodies was associated with symptomatic HIV infection. A significant association between the absence of anti-nef antibodies, the presence of p24 Ag, high levels of B2-M, a number of CD4+ lymphocytes less than 500/ml at first visit and disease progression was found. Subjects who were persistently positive for antibody to nef were less likely to develop AIDS than those who were transiently or persistently negative. This difference was statistically significant (p = 0.03). The results of this study show that absence or disappearance of anti-nef antibodies may be used as predictor of disease evolution in HIV seropositive IDUs. This study also confirms the usefulness of other markers, such as p24 Ag, B2-M and number of CD4+ lymphocytes previously shown to be predictive of rapid disease progression for predicting the course of HIV seropositive IDUs.

AIDS-Related Complex↗
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Genetic heterogeneity of hepatitis C virus (HCV) in clinical strains of HIV positive and HIV negative patients chronically infected with HCV genotype 3a.

The clinical correlation between the degree of HCV variability and the response to anti-HCV treatment in HIV positive patients infected with HCV genotype 3a is unknown. In this study, 27 HIV positive and 5 HIV negative patients with HCV genotype 3a infection were treated with interferon-alpha-2b with or without ribavirin. Nine patients (5 HIV positive) achieved a sustained virological response (SR) and 23 (only one HIV negative) were non-responders (NR). Sequence analyses of the partial E2 domain and the non-structural 5A protein were performed at baseline in all patients, and before and during treatment in the HIV positive NRs. There was no difference in the mean number of amino acid mutations from HCV 3a prototype, within E2 region, between the HIV positive and HIV negative patients: 17 (range 11-25) vs 16 (range 14-17). The mean baseline number of mutations in E2 region, was similar in HIV positive SRs and NRs: 18 (range 14-25) vs 16 (range 11-19). Phylogenetic analysis of HCV paired serum samples at baseline and during treatment revealed identical E2 sequence in 5/21 HIV positive NR patients, whereas 6 other sequences were strictly related to baseline E2 domain and the remaining 10 were divergent. The mean number of amino acid mutations in the NS5A protein at baseline, was 1 (range 0-3) in HIV negative patients and 2 (range 0-4) in HIV positive ones. This region was highly conserved in all isolates of HIV positive NRs analysed during treatment. These results suggest that genetic variability at baseline within the E2 region and NS5A protein of HCV 3a strain obtained from HIV positive and HIV negative patients is not associated with treatment response. Furthermore, the anti-HCV treatment did not influence HCV heterogeneity within the E2 and NS5A domains in HIV positive patients infected with HCV genotype 3a.

Adult↗
PubMedDate not supplied

Characterization of GBV-C infection in HIV-1 infected patients.

BACKGROUND: GB virus C, a positive-stranded RNA virus, is classified in the family Flaviviridae. It is currently believed that persistent infection occurs in 25-50% of infected individuals, however, it still remains an "orphan" virus in search of a role in human pathology. Molecular epidemiological studies have demonstrated that GBV-C infection is present in about 1-1.4% of the healthy population in developed countries, that it shares routes of transmission with HIV and HCV and that the prevalence of GBV-C in these populations is higher than in blood donors. On the basis of the sequence variation among the isolates, GBV-C is classified into at least four major genotypes. Preliminary evidence has suggested that GBV-C is a lymphotropic virus that replicates mainly in the spleen and bone marrow. Recently, several reports have investigated the possible beneficial effect of GBV-C co-infection on HIV disease progression to AIDS, reduced mortality in HIV infected individuals and lower HIV viral loads, not leading to a definitive conclusion yet. AIM: To investigate the role of GBV virus C co-infection in two different subsets of HIV-infected patients, and to evaluate the prevalence of GBV-C genotypes in Northern Italy. METHODS: A total of 86 HIV positive patients were examined for GBV-C viremia (years after HIV sera conversion: 12 +/- 5). Control population (Group A): 46 patients (mean age 42 years) with <200CD4/ml during the observation period. Longterm non progressor population (Group B): 40 patients, (mean age 40 years) with >500 CD4/ml for at least 8 years and never treated with HAART. After extraction of viral RNA from plasma samples, amplification of a highly conserved region of 5'UTR was performed by nested RT-PCR. All positive samples were genotyped by sequencing, alignment with published sequences and phylogenetic analysis. CD4 cell count, HIV plasma levels were also evaluated. RESULTS: 9 out of 46 (19.56%) in Group A and 15 out of 40 (37.5%) in Group B had detectable GBV-C viremia (p=0.064, OR 2.47, percent confidence interval 0.94 to 6.51). No statistical difference was observed when disease stage was evaluated between the two groups. In Group B, after regression analysis for CD4 cell count decrease over the period observed, no significant difference was detected between GBV-C positive and negative patients. No significant difference was observed in Group B in HIV viremia and CD4 cell count at time of GBV-C detection between GBV-C infected patients and GBV-C negative patients. All Italian patients were genotype 2, the only African patient carried GBV-C genotype 1. CONCLUSIONS: Although previous results suggest that GBV-C virus may be a favorable marker for long term non progression of HIV disease, whether it plays a direct anti-HIV role or just takes advantage of non progessors' higher CD4 cell count to replicate more efficiently, still remains to be answered. Follow up of untreated patients and further evaluation of virological interactions, between the viruses and the host immune system, will be helpful to shed some light on these observations, offering new prognostic and eventually therapeutical tools for the management of HIV patients.

Adult↗