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Biomedical subjects

L Perrin

Publications and source records attributed to L Perrin.

At least 91 records · Page 5Linked to original sources
PubMed1997

The qualitative nature of the primary immune response to HIV infection is a prognosticator of disease progression independent of the initial level of plasma viremia.

Following infection of the host with a virus, the delicate balance between virus replication/spread and the immune response to the virus determines the outcome of infection, i.e., persistence versus elimination of the virus. It is unclear, however, what relative roles immunologic and virologic factors play during primary viral infection in determining the subsequent clinical outcome. By studying a cohort of subjects with primary HIV infection, it has been demonstrated that qualitative differences in the primary immune response to HIV, but not quantitative differences in the initial levels of viremia are associated with different clinical outcomes.

CD4 Lymphocyte Count↗
PubMed1997

Genetic polymorphism of CCR5 gene and HIV disease: the heterozygous (CCR5/delta ccr5) genotype is neither essential nor sufficient for protection against disease progression. Swiss HIV Cohort.

Homozygous (delta ccr5/delta ccr5) and heterozygous (CCR5/delta ccr5) deletions in the beta-chemokine receptor 5 (CCR5) gene, which encodes for the major co-receptor for macrophage-tropic HIV-1 entry, have been implicated in resistance to HIV infection and in protection against disease progression, respectively. The CCR5/delta ccr5 genotype was found more frequently in long-term nonprogressors (LTNP) (31.0%) than in progressors (10.6%, p < 0.0001), in agreement with previous studies. Kaplan-Meier survival analyses showed that a slower progression of disease, i.e. higher proportion of subjects with CD4+ T cell counts > 500/microl (p = 0.0006) and a trend toward a slower progression to AIDS (p = 0.077), was associated with the CCR5/delta ccr5 genotype. However, when LTNP were analyzed separately, no significant differences in CD4+ T cell counts (p = 0.12) and viremia levels (p = 0.65) were observed between the wild-type (69% of LTNP) and the heterozygous (31.0%) genotypes. Therefore, there are other factors which play a major role in determining the status of nonprogression in the majority of LTNP. Furthermore, there was no evidence that the CCR5/delta ccr5 genotype was associated with different rates of disease progression in the group of progressors. Taken together, these results indicate that the CCR5/delta ccr5 genotype is neither essential nor sufficient for protection against the progression of HIV disease.

HIV Infections↗
PubMed1997

Acute human immunodeficiency virus type 1 disease as a mononucleosis-like illness: is the diagnosis too restrictive?

The purpose of this study was to describe the frequency and duration of clinical features at the time of acute human immunodeficiency virus type 1 (HIV-1) disease in 218 patients with documented symptomatic primary HIV-1 infection. The mean duration of acute HIV-1 disease was 25.1 days (median, 20.0 days) and did not differ by gender, age, and risk factor. The frequency and mean duration of clinical features occurring in >50% of patients were as follows: fever, 77.1% and 16.9 days; lethargy, 65.6% and 23.7 days; cutaneous rash, 56.4% and 15 days; myalgia, 54.6% and 17.7 days; and headache, 50.9% and 25.8 days. Only 15.6% of patients presented with a typical mononucleosis-like illness (MLI) defined as fever, pharyngitis or sore throat, and cervical adenopathy, and 10% had no features of an MLI. A meningitis-like syndrome occurred in 20 patients (9.2%). Acute HIV-1 disease is more diverse than previously reported, and the absence of fever or other MLI features does not rule out acute HIV-1 disease.

Acute Disease↗
PubMed1997

Toxicity, efficacy, plasma drug concentrations and protease mutations in patients with advanced HIV infection treated with ritonavir plus saquinavir. Swiss HIV Cohort Study.

OBJECTIVE: To assess the safety, efficacy and plasma drug levels of the combination of ritonavir plus saquinavir for the treatment of advanced HIV infection. DESIGN: Multicentre pilot study. PATIENTS: Eighteen protease inhibitor-naive patients, with intolerance or contraindication to reverse transcriptase inhibitors, a median CD4 cell count of 12 x 10(6)/l (range, 1-50 x 10(6)/l), and a median HIV viraemia of 5.25 log10 copies/ml (range, 4.00-6.13 log10 copies/ml). METHODS: Patients received 600 mg twice daily of both ritonavir and saquinavir. Viraemia was measured at baseline and at weeks 5, 9 and 13. Response was defined as a drop of viraemia of more than 1 log10 at week 5. Plasma drug levels were determined after at least 3 weeks of combined treatment: samples were collected before and 1, 2, and 4 h after the morning ingestion of both drugs. The protease gene was sequenced at baseline and under treatment. RESULTS: Among the 16 patients evaluable at week 5, 11 were responders, and among these patients, six remained responders at week 13 (two with undetectable viraemia). Study discontinuations were due to side-effects (n = 4), patient choice (n = 3), protocol violation (n = 1) and death (n = 1). Responders had higher drug levels than non-responders (P < 0.01 for saquinavir, P = 0.04 for ritonavir). In two non-responders, development of multiple new mutations at positions 10, 20, 48, 82, 84 and 90 was observed after 5-13 weeks. CONCLUSION: The response to ritonavir plus saquinavir in advanced HIV infection is unpredictable. A minority of patients respond with disappearance of HIV viraemia. In other patients, rapid cumulative emergence of protease mutations conferring resistance to treatment cannot always be prevented by good compliance and relatively high plasma drug levels.

Acquired Immunodeficiency Syndrome↗
PubMed1997

Impact of PUVA therapy on HIV viremia: a pilot study.

BACKGROUND: Treatment by ultraviolet radiation (UV) during human immunodeficiency virus (HIV) infection is controversial, since exposure of HIV-infected cells in vitro to UV enhances HIV replication in vitro. METHODS: Four consecutive AIDS patients with psoriasis and CD4 count lower than 20/mm3 were treated with 8-methoxypsoralen and UVA (PUVA). HIV viremia expressed as long of HIV-1 RNA copies/ml of plasma was quantified 10 min before and 1 h following UVA exposure, every week during PUVA therapy and at the end of treatment. The Psoriasis Area Surface Index (PASI) score was used to quantify the severity of psoriasis. RESULTS: No significant change in HIV-1 RNA level was observed in the 18 paired samples analyzed before and 1 h after PUVA (median: -0.05 log HIV-1 RNA, range: -0.50-0.21, p = 0.10). After 12-31 UVA exposure for a total dose of 15.5-196 J/cm2 over a period of 6-15 weeks, viremia changes from baseline in the 4 patients were -0.61, -0.07, 0.36 and 0.39 log HIV RNA. In 1 patient without antiviral treatment, a persistent decrease in viremia and transient increase in CD4 cell count were observed. PUVA was well tolerated and associated with significant improvement of the PASI score in 3 patients. CONCLUSION: HIV viremia is not significantly modified by PUVA therapy in AIDS patients with psoriasis.

Acquired Immunodeficiency Syndrome↗
PubMed1997

Zidovudine plus didanosine in primary HIV-1 infection.

Viraemia levels in the months following primary HIV-1 infection (PHI) predict the subsequent course of the infection. Inhibition of viral replication in PHI patients might improve their clinical prognosis. In this study, we evaluated the antiviral efficacy of the association of two reverse transcriptase inhibitors--zidovudine at 250 mg twice daily and didanosine at 200 mg twice daily--in 12 patients treated for at least 6 months (median 10 months, range 6-15 months). We compared values for viraemia, proviral DNA and CD4:CD8 ratios in these patients with two historical control groups consisting of 16 untreated patients and 15 patients on zidovudine therapy. Significantly lower viraemia was observed between 3 and 12 months in patients on zidovudine-didanosine therapy. Viraemia levels lower than 200 HIV-1 RNA copies/ml were observed in 3/12 patients on zidovudine-didanosine therapy after 3 months, in 8/12 after 6 months and in 3/5 after 12 months. Only one of the 31 historical control patients had undetectable viraemia. For proviral DNA, smaller differences between groups were observed, although with time proviral DNA became undetectable (< 1 copy/7.5 x 10(5) lymphocytes) in four patients from the zidovudine-didanosine group versus one in the control groups. Finally, the CD4:CD8 ratio was significantly higher in the zidovudine-didanosine group and none of the patients in this group developed HIV-1-associated clinical complications. These data suggest a higher efficacy of combined therapy compared with zidovudine monotherapy in PHI patients and indicate that control of viraemia for at least 1 year is achievable in PHI patients.

Acquired Immunodeficiency Syndrome↗
PubMed1996

[Prevalence of transmission of zidovudine-resistant viruses in Switzerland. l'Etude suisse de cohorte VIH].

Zidovudine (ZDV) was the most widely used anti-HIV drug between 1987 and 1995, and, as already reported, transmission of ZDV-resistant viruses occurs. Several mutations of the reverse transcriptase gene have been identified; one of them affects the 215 codon and is associated with a high degree of resistance. We have determined, using selective PCR, the prevalence of transmission of 215 mutant isolates in 134 patients with primary HIV infection (PHI) and have identified 8 patients with 215 mutant virus between 1989 and 1995 in Switzerland. Mutant resistant viruses have been isolated from patients treated with most antiviral drugs. A systematic search for mutant viruses may provide useful information for the adaptation of treatment strategies.

Adolescent↗
PubMed1996

Lack of monomeric IgM anti-hepatitis C virus (HCV) core antibodies in patients with chronic HCV infection.

Antibodies of the IgM class against the hepatitis C virus core antigen are found in up to 70% of patients with either acute or chronic hepatitis C. The sedimentation rate of such IgM was analyzed by rate-zonal centrifugation of nine sera taken from seven patients, two acutely and five persistently infected with hepatitis C virus. All patients had circulating high-molecular weight (i.e. pentameric) IgM, indicating that the production of low molecular weight IgM, commonly observed in other persistent viral infections, does not apply to hepatitis C virus and cannot be used to distinguish acute from chronic hepatitis C virus infection.

Chronic Disease↗
PubMed1996

The Drosophila teashirt homeotic protein is a DNA-binding protein and modulo, a HOM-C regulated modifier of variegation, is a likely candidate for being a direct target gene.

The Drosophila teashirt (tsh) gene has an homeotic function which, in combination with HOM-C genes, determines thoracic and abdominal (trunk) identities. Analysis of TSH protein distribution during embryogenesis using a specific polyclonal antibody shows that it is nuclear. The protein is present with regional modulation in several tissues within the trunk, suggesting additional tsh functions to those already studied. We identified a candidate tsh target shared with some HOM-C genes, the modifier of variegation gene modulo (mod). The TSH zinc-finger protein recognizes in vitro two specific sites within a 5' control element of the mod gene which responds in vivo to tsh activity. TSH is therefore a DNA binding protein and might directly control mod expression.

Animals↗
PubMed1996

Inhibition of syncytia-inducing (SI) virus by autologous serum from HIV-1-infected individuals.

BACKGROUND: Progression from HIV infection to AIDS is often accompanied or even predicted by a switch of the virus to a more pathogenic or syncytia-inducing (SI) phenotype concomitant with the development of HIV variants escaping neutralizing antibodies. OBJECTIVE: Here we studied the capacity of sera to neutralize autologous SI-HIV or the laboratory strain III(B) and compared these data to the viral load in HIV-1-infected patients. METHODS: The SI phenotype of HIV was detected by co-cultivation of peripheral blood mononuclear cells (PBMCs) with MT2 cells in 112 patients stratified by their CD4 cell counts. Sera at dilutions of 1 : 15 and 1 : 75 were added to MT2 co-cultures with autologous PBMCs as well as with HIV-1/IIIB-infected H9 cells to study the inhibitory capacity. The p24 antigenemia was detected by enzyme-linked immunosorbent assay (ELISA) and the circulating HIV RNA was determined using the polymerase chain reaction (PCR). RESULTS: The SI virus was detected in PBMCs from 31/65 patients with < or = 200 CD4+ cells, 8/28 patients with 201-499 CD4+ cells, and 1/19 patients with > or = 500 CD4+ cells. Sera from 16/40 patients inhibited the autologous SI-HIV. In sera from patients with < or = 200 CD4+ cells, p24 antigen could be detected in 17/34 (50%) patients with non-syncytia-inducing (NSI) phenotype and in 7/19 (37%) patients carrying SI-HIV without serum inhibition. In contrast, all 12 sera with inhibitory activity to the autologous SI-HIV were negative for p24 antigen. A similar tendency was seen in patients with higher CD4+ T-cell counts. The mean load of circulating HIV RNA did not differ among groups of patients. Independently of their neutralizing activity to the autologous SI virus, the majority of sera were able to neutralize the laboratory HIV-1/III(B). CONCLUSIONS: While most of the patients' sera neutralized the laboratory HIV-1/III(B) strain, only some sera were able to inhibit the autologous SI-HIV. In these cases, the detectable SI-HIV may still be controlled by the immune system in vivo, which is consistent with a low p24 antigenemia.

Journal Article↗
PubMed1996

Prognostic value of viremia in patients with long-standing human immunodeficiency virus infection. Swiss HIV Cohort Study Group.

Human immunodeficiency virus (HIV) viremia was evaluated in 73 patients with long-standing infection to investigate its relationship with clinical or biologic parameters and to assess its use as a predictor of clinical progression and death. After adjustment for other parameters, baseline HIV RNA level was significantly associated with baseline clinical stage and CD4 cell count. During follow-up (mean, 14.6 months), 16 patients died; 34 others had clinical progression of disease. In multivariate analysis, mortality was better predicted by baseline CD4 cell count (relative hazard [RH] for 100-cell decrease, 3.5; 95% confidence interval [CI], 1.5-8.2; P = .003) than by HIV RNA (P = .28) or clinical stage. HIV RNA level was the best predictor of clinical progression (RH for 1 log increase, 2.8; 95% CI, 1.6-4.9; P < .001). Monitoring of HIV RNA level may help to identify patients who might benefit from antiretroviral or prophylactic therapy.

Adult↗
PubMed1996

Combined therapy with zidovudine and L-697,661 in primary HIV infection.

OBJECTIVE: To decrease viraemia levels in primary HIV infection by using a combination of zidovudine (ZDV) and L-697,661. DESIGN: Four primary HIV-infected patients were treated for 6 months with ZDV, 250 mg twice daily, in association with the non-nucleoside reverse transcriptase inhibitor L-697,661 500 mg three times daily. Viraemia, proviral DNA, CD4 and CD8 cell counts were measured serially during 18 months. RESULTS: Viraemia decreased to undetectable levels (< 200 RNA copies/ml) in two patients. A third patient had a marked decrease followed by a rebound during therapy; viraemia levels did not vary markedly in the fourth patient. A rebound in viraemia levels was observed within 15 days of discontinuation of therapy in the three responding patients. Proviral levels evolved in parallel with viraemia but were always detectable in all patients. In the three patients with an initial decrease of viraemia, CD4 cell counts were within the normal range 2 months after initiation of therapy and did not markedly decrease after discontinuation of therapy. In the two patients with partial or no response of viraemia, mutations associated with low level of resistance to L-697,661 appeared during treatment. CONCLUSION: A marked decrease of viraemia can be achieved in some primary HIV-infected patients with combined therapy. Six months of treatment does not prevent a rebound of viraemia, which was observed within 15 days of interruption of therapy.

Adult↗
PubMed1996

Plasma levels of soluble CD30, tumour necrosis factor (TNF)-alpha and TNF receptors during primary HIV-1 infection: correlation with HIV-1 RNA and the clinical outcome.

OBJECTIVES: The immunological and virological events associated with primary HIV-1 infection have a major impact on the course of HIV-1 disease, and the identification of early predictors during primary HIV infection is critical for the therapeutic strategy. DESIGN AND METHODS: Eighteen consecutive patients with primary HIV infection were followed for a median of 398 days. Clinical status, CD4+ T-cell counts, and plasma samples were obtained weekly from enrollment until week 6, then at weeks 12, 24 and 52, and every 6 months thereafter. Seroconversion was assessed by anti-HIV-1/2 antibodies and Western blot analysis. HIV-1 RNA in plasma was quantified by Amplicor HIV Monitor test. Samples were assayed for immune complex-dissociated p24 antigen, tumour necrosis factor (TNF)-alpha, soluble TNF receptor (sTNFR)-1, sTNFR-II, sCD30 and sCD8 by enzyme immunoassays. Outcome was defined as entering clinical category B or C according to the Centers for Disease Control and Prevention criteria. As a control group, we included 23 HIV-1-negative healthy blood donors. RESULTS: Plasma levels of sCD30, TNF-alpha and sTNFR were significantly higher in HIV-1-infected patients than in controls, and were positively correlated with each other and with values of HIV-1 RNA. Patients who developed an outcome (n = 4) had significantly higher levels of sCD30, TNF-alpha and sTNFR compared with those who did not. Multivariate logistic regression analysis showed that sCD30 and TNF-alpha were the best predictors of outcome independently of CD4+ T-cell counts. CONCLUSIONS: During primary HIV infection, a persistent immune activation may be associated with a poor clinical outcome. The identification of sCD30 and TNF-alpha levels in plasma as early predictors of outcome in primary HIV infection, may direct the implementation of early therapeutic strategies in patients with elevated risk of disease progression.

Antigens, CD↗