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Biomedical subjects

Pierre-Marie Girard

Publications and source records attributed to Pierre-Marie Girard.

At least 19 recordsLinked to original sources
PubMed2007

Salvage therapy with amprenavir, lopinavir and ritonavir is durably potent in HIV-infected patients in virological failure: 1-year results.

We report the results of the extended follow-up at one year of a randomized trial evaluating the virological efficacy of a salvage therapy combining lopinavir and amprenavir with either 200 or 400 mg/day ritonavir, along with optimized nucleoside reverse transcriptase inhibitors, in patients carrying multidrug-resistant isolates. The combination of amprenavir, lopinavir and ritonavir (400 mg/day) is durably potent, yielding a sustained virological response (HIV RNA < 50 copies) in 39% of cases.

Anti-HIV Agents↗
PubMed2006

Influence of pravastatin on carotid artery structure and function in dyslipidemic HIV-infected patients receiving antiretroviral therapy.

Forty-two pravastatin-treated HIV-positive patients and 42 sex, age, and smoking status-matched hypercholesterolemic HIV-positive patients not under lipid-lowering treatment were compared for differences in intima-media thickness (IMT) of the common carotid artery (CCA) and aortic stiffness. Pravastatin had no influence on carotid artery structure and function, or aortic stiffness. Age and body mass index were independent determinants of IMT of the CCA. Mean arterial pressure, age, duration of HIV infection and protease inhibitor exposure determined aortic stiffness.

Age Factors↗
PubMed2006

A novel hepatitis B virus mutation with resistance to adefovir but not to tenofovir in an HIV-hepatitis B virus-co-infected patient.

A molecular virology analysis performed in an HIV-hepatitis B virus (HBV) co-infected patient showed the emergence of an unusual HBV polymerase gene mutation (rt A181T) under adefovir therapy, conferring resistance to adefovir but not to tenofovir, as proved by in-vitro phenotypic analysis. This observation suggests that careful monitoring of co-infected patients is required to diagnose HBV resistance to nucleos(t)ide analogues, and that tenofovir may be active at least against some of the adefovir-resistant strains.

Adenine↗
PubMed2006

Differences in the frequency and function of HHV8-specific CD8 T cells between asymptomatic HHV8 infection and Kaposi sarcoma.

It is unclear how the immune response controls human herpesvirus 8 (HHV8; also known as Kaposi sarcoma-associated herpesvirus [KSHV]) replication and thereby prevents Kaposi sarcoma (KS). We compared CD8 T-cell responses to HHV8 latent (K12) and lytic (glycoprotein B, ORF6, ORF61, and ORF65) antigens in patients who spontaneously controlled the infection and in patients with posttransplantation, AIDS-related, or classical KS. We found that anti-HHV8 responses were frequent, diverse, and strongly differentiated toward an effector phenotype in patients who controlled the infection. Conversely, HHV8-specific CD8 cells were very rare in patients who progressed to KS, and were not recruited to the tumoral tissue, as visualized by in situ tetramer staining of KS biopsies. Last, HHV8-specific CD8 T cells were observed in a seronegative recipient of an HHV8infected graft who remained persistently aviremic and antibody negative, suggesting that specific cytotoxic T lymphocytes (CTLs) may provide protection from persistent HHV8 infection. These results support the crucial role of cellular immune responses in controlling HHV8 replication, in preventing malignancies in latently infected subjects, and in conferring genuine resistance to persistent infection. They may also have important implications for the design of prophylactic and therapeutic HHV8 vaccines, and for adoptive immunotherapy of KS.

Acquired Immunodeficiency Syndrome↗
PubMed2006

Major role of hepatitis B genotypes in liver fibrosis during coinfection with HIV.

BACKGROUND: Little is know about the determinants of liver fibrosis progression and genomic variability in hepatitis B virus (HBV) in HIV/HBV-coinfected patients. METHODS: A cross-sectional analysis examined common characteristics of HBV infection in an ongoing cohort study of 308 patients with both HIV-1-positive Western blot and plasma HBV surface antigen (HBsAg) seropositivity. Risk factors for liver fibrosis were studied in a subset of 104 patients for whom liver biopsy and complete HBV genomic analysis were available. Analysis was performed by exact multiple regression analysis. RESULTS: Mean age of the study population was 40.3 years, with a ratio male to female of 5.3 and a mean duration of HIV infection of 9.3 years. In the subset of 104 patients, plasma HBV e antigen (HBeAg) in HBV-replicative patients could not be detected in 28.4% and lamivudine-resistant mutants were detected in 67.8%. HBV genotype A was the most frequent genotype (73/104) and 25 patients were infected by the usually rare genotype G. METAVIR fibrosis score was rated F2-F4 in 70 patients. After adjustment for the most common known determinants of liver fibrosis, HBV genotype G [odds ratio (OR), 12.60; 95% confidence interval (CI), 1.72-infinite; P < 0.009], efavirenz exposure (OR, 3.55; 95% CI, 1.14-12.14; P < 0.03), and the duration of HIV infection (3.86; 95% CI, 1.27-12.64; P < 0.01) were strongly associated with the risk of grade F2-F4 fibrosis. CONCLUSION: HBV genotype G is a determinant of liver fibrosis in HIV/HBV-coinfected patients and HBV genotyping should be considered as part of the management of patients with multiple risk factors for rapid progression of liver fibrosis.

Adult↗
PubMed2006

Determinants of adherence to non-occupational post HIV exposure prophylaxis.

We conducted a study on 140 patients who sought advice at hospital after a non-occupational exposure. The full 28-day course of prophylactic antiretroviral therapy was completed by 109 patients. No HIV contamination was observed. Factors associated with suboptimal adherence were African ethnicity [odds ratio (OR) 13.3, 2.02-87.54] and oral sexual intercourse (OR 8.35, 1.66-41.99). Compliance with prophylactic antiretroviral therapy can be increased by addressing social and psychological barriers to adherence.

Adult↗
PubMed2006

Low genetic barrier to large increases in HIV-1 cross-resistance to protease inhibitors during salvage therapy.

HIV-1 resistance to protease inhibitors (PIs) is characterized by extensive cross-resistance within this drug class. Some PIs, however, appear less affected by cross-resistance and are often prescribed in salvage therapy regimens for patients who have failed previous PI treatment. To examine the capacity of HIV-1 to adapt to these treatment changes, we have followed the evolution of HIV-1 protease genotypes and phenotypes in 21 protease-inhibitor-experienced patients in whom 26 weeks of an aggressive salvage regimen associating lopinavir, amprenavir and ritonavir failed to suppress viral replication. Baseline genotypes exhibited a median of seven resistance mutations in the protease. After 26 weeks of treatment, changes in protease genotypes were seen in 13/21 patients. The evolution of these protease genotypes was rapid, with more than one-third of the changes occurring during the first 6 weeks. Although the mean number of additional mutations was small (2.15 new mutations at week 26) these mutations were sufficient to promote remarkable changes in resistance phenotype. In several patients, some of the new mutations were found to exist before salvage treatment as part of minority quasi-species. Thus, in the face of the strong pharmacological pressure exerted by combinations of PIs to which it has never been exposed, and in spite of limited cross-resistance to these drugs before salvage therapy, HIV-1 can rapidly adapt its resistance genotype and phenotype at a minimal evolutionary cost.

Drug Administration Schedule↗
PubMed2006

Salvage therapy with atazanavir/ritonavir combined to tenofovir in HIV-infected patients with multiple treatment failures: randomized ANRS 107 trial.

BACKGROUND: Ritonavir (RTV)-boosted atazanavir (ATV) and tenofovir disoproxil fumarate (TDF-DF) are promising in highly experienced patients because of their pharmacokinetic profile, activity, safety and resistance properties. METHODS: A 26-week study of the safety and efficacy of RTV-boosted ATV plus TDF-DF was conducted in 53 HIV-infected patients who were failing their current highly active antiretroviral therapy (HAART) regimen. Patients with history of failure to at least two protease inhibitors (PIs) and one non-nucleoside reverse transcriptase inhibitor (NNRTI) were randomized to either continue their current regimen (group 1) or replace the PI by ATV (300 mg once daily) boosted by RTV (100 mg; group 2) for 2 weeks. Then, all patients received the same combination of ATV, RTV and TDF-DF (300 mg) plus optimized NRTIs regimen. RESULTS: At baseline, median CD4+ T-cell count was 206/mm3, median viral load (VL) 5.0 log10/ml and median numbers of NRTI, NNRTI and PI resistance mutations were 7, 1 and 8, respectively. At week 2, median VL remained unchanged from baseline in group 2 as compared with group 1 (-0.1 vs -0.1 log10/ml). At week 26, a mild decrease in median VL from baseline of 0.2 log10/ml was observed, with 16 (31%) and 9 (17%) patients exhibiting a decrease in viral load of at least 0.5 and 1.0 log10/ml, respectively. Baseline phenotypic and genotypic resistance to ATV were the most predictive independent factors of virological response. The regimen was well tolerated. CONCLUSION: In these very advanced patients failing highly HAART, the combination of boosted ATV plus TDF-DF yielded low antiretroviral activity.

Adenine↗
PubMed2005

Impact of therapeutic immunization on HIV-1 viremia after discontinuation of antiretroviral therapy initiated during acute infection.

BACKGROUND: Treatment strategies that would induce durable virological control of human immunodeficiency virus (HIV)-1 in the absence of continued antiretroviral therapy (ART) are highly desirable.METHODS. We assessed, in a randomized, double-blind, placebo-controlled trial, whether the addition of therapeutic vaccines (ALVAC-HIV [vCP1452] or ALVAC-HIV and Remune) to ART initiated during acute infection could increase the probability of having a plasma viral load </=1000 HIV-1 RNA copies/mL 24 weeks after planned discontinuation of ART.RESULTS. All 79 randomized subjects completed the immunization schedule, and 78 discontinued ART with no major safety concerns. After immunization, subjects in the vaccine study arms had significantly increased HIV-1-specific CD4(+) and CD8(+) T cell responses, by interferon- gamma enzyme-linked immunospot assay, compared with those in the placebo study arm. Overall, 17.7% of subjects had </=1000 HIV-1 RNA copies/mL 24 weeks after discontinuation of ART, with no significant difference between the vaccine study arms and the placebo study arm (15.4% vs. 22.2%; difference, -6.8% [95% confidence interval, -26.8% to 10.0%]; P=.54).CONCLUSION. Therapeutic immunization and ART, compared with ART alone, generated HIV-1-specific cellular immunity but did not lead to better virological control of HIV-1 24 weeks after discontinuation of ART. Our trial design appears to be feasible and safe for testing future immune-boosting strategies.

AIDS Vaccines↗
PubMed2005

Risk factors for CD4 lymphopenia in patients treated with a tenofovir/didanosine high dose-containing highly active antiretroviral therapy regimen.

In this study, the dynamics of CD4 cell depletion during tenofovir/didanosine co-administration were analysed. Ninety-five HIV-positive patients were followed for 562 days, and 37 lost at least 50 CD4 cells, with a median delay of 274 days. Cox analysis showed that the CD4 cell decrease was associated with a duration of treatment by didanosine of more than 853 days and a didanosine dose of more than 5.50 mg/kg.

Adenine↗
PubMed2005

Long-term hepatitis B virus dynamics in HIV-hepatitis B virus-co-infected patients treated with tenofovir disoproxil fumarate.

BACKGROUND: The long-term impact of tenofovir disoproxil fumarate (TDF) on hepatitis B virus (HBV) replication has not yet been studied in HIV-HBV-co-infected patients. METHODS: We conducted a prospective study of HBV-DNA decay kinetics in 28 HIV-HBV-co-infected patients treated by TDF. HBV dynamics were studied using mixed linear models, and baseline factors affecting them were analysed using Cox models. RESULTS: The HBV-DNA load declined by a mean of 4.6 log copies/ml during follow-up (mean 71 weeks), and fell below the detection limit (200 copies/ml) in 21 patients. Inhibition of viral replication by TDF was associated with a decrease in alanine aminotransferase levels (125 versus 68 IU, P < 0.05). HBV-DNA decay was biphasic, with an rapid fall followed by a gradual decline. Baseline factors associated with a steeper first slope in the HBV-DNA decrease were high HBV load, positive hepatitis B e antigen (HBeAg) and YMDD mutations. Baseline factors increasing the time to reach an HBV-DNA level less than 200 copies/ml were high HBV load (150 days when HBV-DNA < 10 log, 316 days when HBV-DNA > 10 log) and positive HBeAg. Previous exposure to lamivudine or TDF-lamivudine did not modify HBV-DNA decrease under therapy in this population with a high prevalence of YMDD mutations. CONCLUSION: The long-term decline in HBV DNA under TDF is biphasic and is primarily influenced by the initial HBV load. However, the clinical significance of such an association remains moderate, and TDF can be efficiently included in the highly active antiretroviral therapy regimen of HIV-HBV-co-infected patients, regardless of HBV strains and their degree of replication.

Adenine↗
PubMed2005

Antiretroviral therapy in resource-poor countries: illusions and realities.

The prospects for antiretroviral therapy in resource-poor settings have changed recently and considerably with the availability of generic drugs, the drastic price reduction of brand-name drugs, and the simplification of treatment. However, such cost reductions, although allowing the implementation of large-scale donor programs, have yet to render treatment accessible and possible in the general population. Successfully providing HIV treatment in high-prevalence/high-caseload countries may require that we redefine the problem as a public health mass therapy program rather than a multiplication of clinical situations. The public health goal cannot simply be the reduction of morbidity and mortality for those treated but must be the reduction in morbidity and mortality for the many, that is, at a population level.

Anti-Retroviral Agents↗