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Dominique Salmon

Publications and source records attributed to Dominique Salmon.

10 recordsLinked to original sources
PubMed2025

Targeting the SARS-CoV-2 reservoir in long COVID.

There are no approved treatments for post-COVID-19 condition (also known as long COVID), a debilitating disease state following SARS-CoV-2 infection that is estimated to affect tens of millions of people. A growing body of evidence shows that SARS-CoV-2 can persist for months or years following COVID-19 in a subset of individuals, with this reservoir potentially driving long-COVID symptoms or sequelae. There is, therefore, an urgent need for clinical trials targeting persistent SARS-CoV-2, and several trials of antivirals or monoclonal antibodies for long COVID are underway. However, because mechanisms of SARS-CoV-2 persistence are not yet fully understood, such studies require important considerations related to the mechanism of action of candidate therapeutics, participant selection, duration of treatment, standardisation of reservoir-associated biomarkers and measurables, optimal outcome assessments, and potential combination approaches. In addition, patient subgroups might respond to some interventions or combinations of interventions, making post-hoc analyses crucial. Here, we outline these and other key considerations, with the goal of informing the design, implementation, and interpretation of trials in this rapidly growing field. Our recommendations are informed by knowledge gained from trials targeting the HIV reservoir, hepatitis C, and other RNA viruses, as well as precision oncology, which share many of the same hurdles facing long-COVID trials.

Humans↗
PubMed2004

Malignancy-related causes of death in human immunodeficiency virus-infected patients in the era of highly active antiretroviral therapy.

BACKGROUND: Before the introduction of highly active antiretroviral therapy (HAART), malignancies accounted for less than 10% of all deaths among human immunodeficiency virus (HIV)-infected patients. This figure may have increased, and the observed types of malignant disease may have been modified, as a result of decreased occurrence of opportunistic infections, the chronicity of HIV infection, the possible oncogenic role of HIV itself, and the aging of the HIV-infected population. METHODS: All French hospital wards involved in the management of HIV infection were asked to prospectively document the deaths of HIV-infected patients in the year 2000. Underlying causes of death were defined using a standardized questionnaire. RESULTS: Of a total of 964 deaths, 269 (28%) were attributable to malignancies. Acquired immunodeficiency virus (AIDS)-related malignancies were the underlying cause of 149 deaths (15%); among these malignancies were non-Hodgkin lymphoma (n = 105 [11%]), noncerebral lymphoma (n = 78 [median CD4 count, 86 x 10(6) per liter; interquartile range [IQR], 35-231 x 10(6) per liter), and primary cerebral lymphoma (n = 27 [median CD4 count, 20 x 10(6) per liter; IQR, 4-109 x 10(6) per liter). Kaposi sarcoma was associated with 40 deaths (4%), and cervical carcinoma was associated with 5 (0.5%). Non-AIDS-related malignancies were the underlying cause of 120 deaths (13%); these non-AIDS-related malignancies included 103 solid tumors (50 respiratory tumors, 19 hepatocarcinomas, 9 digestive tumors, and 6 anal tumors; median CD4 count, 218 x 10(6) per liter; IQR, 108-380 x 10(6) per liter) and 17 hemopathies (12 Hodgkin lymphomas, 4 myeloid leukemias, and 1 myeloma; median CD4 count, 113 x 10(6) per liter; IQR, 56-286 x 10(6) per liter). Compared with patients who died of other causes, patients who died of solid tumors were more likely to be male, to smoke, to be older, and to have higher CD4 counts. CONCLUSIONS: Malignant disease has been a major cause of death among HIV-infected patients in industrialized nations since the introduction of HAART. Whereas lethal hemopathies and Kaposi sarcoma are associated with advanced immunosuppression, lethal solid tumors can occur in patients with controlled HIV infection.

Acquired Immunodeficiency Syndrome↗
PubMed2004

Evidence of genotypic resistance diversity of archived and circulating viral strains in blood and semen of pre-treated HIV-infected men.

OBJECTIVE: To study the genetic diversity of drug-resistant HIV strains present in blood and in semen, especially those archived in peripheral blood mononuclear cells (PBMC) and non-sperm cells (NSC). METHODS: Paired blood and semen samples were collected from twenty heavily pre-treated HIV-infected men. HIV RNA in blood plasma (BP) and seminal plasma (SP), as well as proviral DNA in PBMC and NSC were quantified and used for resistance genotyping. Phylogenetic analysis of protease gene clones was used to explore the diversity of the viral quasi-species. RESULTS: Median BP HIV RNA, PBMC proviral DNA, SP HIV RNA and non-sperm cell proviral DNA loads were respectively: 4.77, 3.65, 3.16 and 1.77 log10 copies per ml or per 10 cells. Resistant HIV strains were found in the BP and PBMC of all the patients, in the SP of 14 patients, and in the NSC of five patients. Overall, the blood and genital compartments exhibited different genotypic resistance patterns in six patients (30%), with additional resistance mutations in the semen of four patients. Phylogenetic analysis of clones of HIV protease gene showed that viral strains in SP originated not only from passive diffusion from BP, but also from local production in semen. The storage of archived proviruses differed according to the anatomic reservoir. CONCLUSION: HIV resistant strains are frequent (70%) in the semen of heavily pre-treated men, and the diversity of genotypic resistance pattern confirms HIV compartmentalization. Thus, the risk of sexual transmission of resistant strains can only be partly predicted by standard tests applied to BP.

Adult↗
PubMed2004

Use of well-defined HIV-derived epitopes to evaluate CD4(+) and CD8(+) T cell responses in patients with chronic HIV-1 infection treated with HAART.

Highly active antiretroviral therapy (HAART) is associated with a dramatic clinical benefit to HIV-infected patients through significant plasma viremia reduction and CD4(+) T cells increase. In previous reports, HIV-specific CD4(+) and/or CD8(+) T cell responses have been studied separately during HAART; therefore the relationship between these two virus-specific populations is currently not well understood. In this study, both HIV-specific CD4(+) and CD8(+) T cell responses were investigated using a large panel of well-defined T cell epitope peptides in 24 HIV-1-infected patients undergoing HAART, with undetectable viral load and CD4(+) T cell count >/= 350/mm(3). One-third of the patients had CD4(+) T cells able to proliferate when exposed to HIV-1 protein fragments but only two patients displayed polyclonal responses. In addition the majority (78%) of HAART-treated patients displayed no or monospecific CD8(+) T cell responses and the phenotypic analysis of these HIV-specific CD8(+) T cells demonstrated the absence of terminally differentiated effectors. In conclusion, the experimental approach used in this study shows that CD4(+) T cell responses may persist during HAART but are not associated with strong CD8(+) T cell responses

Antiretroviral Therapy, Highly Active↗
PubMed2003

Quantitation of cytomegalovirus (CMV) DNA by real-time PCR for occurrence of CMV disease in HIV-infected patients receiving highly active antiretroviral therapy.

In HIV-infected patients treated with highly active antiretroviral therapy (HAART) included in the Predivir cohort, we have evaluated the usefulness of CMV DNA quantitation by a TaqMan PCR assay from peripheral blood leukocytes (PBLs) to predict CMV disease occurrence. In parallel with the immune restoration after treatment by HAART, the percentage of positive samples decreased progressively from 7.3% at Day 0 to 3.5% at Month 12. Among the CMV markers, the smallest concordance with PBL CMV TaqMan PCR, as evaluated by kappa, was observed with pp65 antigenemia, whereas concordance with all other CMV markers was high. Among the 16 patients with CMV DNA copies at least once >100/150,000 cells, CMV disease occurred in six during follow-up, whereas among the 159 patients with CMV DNA copies always <10/150,000 cells, CMV disease occurred in three and among the seven patients with CMV DNA copies >10 and <100 occurred in only one. In univariate Cox models, all the CMV markers including PBL CMV TaqMan PCR >10/150,000 cells (RR: 27.6, IC95: 7.1-107.2), the CD4 cell count <75 cells/mm(3) and the HIV viral load >100,000 copies/ml were predictive for CMV disease. In a stepwise multivariate analysis, which should be interpreted with caution due to the small number of events (n = 10), three covariates were associated independently with CMV disease: pp65 antigenemia >100 nuclei/200,000, PBL CMV TaqMan PCR >10 copies/150,000 cells and HIV viral load remaining or increasing >100,000 copies/ml.

Adult↗
PubMed2002

Assisted reproduction in HIV-1-serodifferent couples: the need for viral validation of processed semen.

BACKGROUND: Many HIV-infected men and women have a strong desire for a child. Assisted reproductive technologies (ART) are an option for HIV-serodifferent couples to reduce the risk of HIV transmission from an infected man to the woman. Potential HIV contamination of selected spermatozoa after semen processing is an important issue in this context. METHODS: HIV in processed semen obtained in our laboratory since 1995 were analysed. HIV RNA and DNA detection was performed in the selected spermatozoa of 125 men. HIV RNA was analysed in blood and semen plasma as well as HIV DNA in non-sperm cells. RESULTS: HIV RNA and DNA were detected in the selected spermatozoa of eight and two men (6.4% and 1.6%), respectively. HIV RNA was detected with a median load of 5 copies/10(6) spermatozoa. Six of the eight men were untreated, one was taking nucleoside analogue therapy and one was on highly active antiretroviral treatment (HAART). HIV RNA detection was more likely to be positive in selected spermatozoa of men with high seminal plasma viral load. HIV RNA was detected in 26% and 11% of selected spermatozoa fractions when the seminal plasma load was > 10,000 copies/ml and 20-10,000 copies/ml, respectively, but in none when the seminal plasma tested negative. CONCLUSION: Selected spermatozoa may be positive for HIV RNA detection even in treated patients. Viral validation of processed semen is necessary in ART programmes for serodifferent couples, particularly in men with only partially or poorly controlled HIV infection.

Anti-HIV Agents↗
PubMed2002

[Causes of death in HIV-infected French drug users, 1995-2000].

Since the decline in mortality among HIV-infected persons after introduction of highly active antiretroviral therapy, concerns related to co-morbidities have increased as they may impair vital prognosis, particularly in intravenous (IV) drug users. We describe firstly the changes in the distribution of the causes of death between 1995 and 2000 among IV drug users in the "Aquitaine Cohort" based on hospital information system, and secondly the distribution of the causes of death among IV drug users in the French national survey "Mortalité 2000" specifically set up in 2000 for optimal exhaustiveness. The total number of deaths declined between 1995 and 2000 and 1/3 were IV drug users. Deceased IV drug users were younger than other deceased patients, had longer median time from diagnosis of HIV infection and higher median CD4 cell count. Poor socio-economic conditions were notified in 55%. Among IV drug users, the proportion of AIDS-related deaths was above 75% in 1995 and below 30% in 2000. In 2000, 25% of deaths were HCV-related, 12% of deaths were due to accident, overdose or suicide, and 8% were due to non-AIDS non-HCV related cancer. Among IV drug users, improvement in vital prognosis requires to improve management of HCV infection and to take into account socio-economic conditions and other addictive behaviours like alcohol consumption and smoking.

Adult↗