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Dominique Salmon

Publications and source records attributed to Dominique Salmon.

At least 19 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↗
PubMed2006

Risk factors for osteonecrosis in HIV-infected patients: impact of treatment with combination antiretroviral therapy.

BACKGROUND: Osteonecrosis was increasingly associated with HIV infection in the 1990s. It is unclear whether its risk increases with the duration of HIV infection, the duration of combination antiretroviral therapy (cART) or both. OBJECTIVE: To analyse factors associated with the rate of symptomatic osteonecrosis, particularly the relative impacts of the duration of HIV infection and the duration of cART, using the French Hospital Database on HIV, which comprises a large number of subjects with substantial follow-up. METHODS: Poisson regression model was used to identify factors associated with the rate of osteonecrosis among patients enrolled in 1996-2002. RESULTS: The study involved 56,393 subjects with a total follow-up of 229,031 person-years. Symptomatic osteonecrosis was diagnosed in 104 subjects with an incidence rate of 4.5/10,000 person-years. Multivariate analysis identified three factors associated with the rate of osteonecrosis: prior AIDS-defining illnesses [adjusted relative rate (RR), 3.1; 95% confidence interval (CI), 2.0-4.9], the CD4 cell nadir [RR, 1.6 (95% CI, 0.9-2.9) for CD4 cell count 50-199 cells/microl; RR, 1.8 (95% CI, 1.0-3.3) for CD4 cell count < 50 cells/microl; both relative to CD4 cell count > or = 200 cells/microl] and exposure to cART. Compared with unexposed patients, the RR of osteonecrosis ranged from 2.6 (95% CI, 1.2-5.9) in patients treated with cART for < 12 months to 5.1 (95% CI, 2.1-12.6) in patients treated for > or = 60 months. CONCLUSIONS: Osteonecrosis appears to be a complication of both HIV infection and cART.

Adult↗
PubMed2006

Clinical safety of HIV lipopeptides used as vaccines in healthy volunteers and HIV-infected adults.

BACKGROUND: HIV-1 lipopeptides have been developed by the French National Agency for AIDS Research (ANRS) for use as candidate vaccine against HIV since 1994. Between 1996 and 2005, four different lipopeptide constructs were tested alone or in combination with recombinant canarypox HIV vaccines in 10 trials conducted in France. The aim of this study was to review clinical safety of HIV lipopeptides. METHODS: A meta-analysis based on individual subject data examined clinical safety data collected in eight preventive trials and two therapeutic trials enrolling 200 HIV-1-uninfected healthy volunteers and 48 HIV-1-infected patients. RESULTS: Of 248 trial participants, eight (3.2%) did not complete follow-up: seven among the 200 healthy volunteers, and one among the 48 HIV-1 infected patients. During the 354 person-years of follow-up, 860 lipopeptides injections were administered. Local reactions were common. However, in trials where lipopeptides were tested without adjuvant and appropriate diluents, none of the vaccinees experienced severe local response. Systemic reactions were generally mild and transient. No grade 4 reaction was reported; 18 subjects experienced grade 3 systemic events related to the vaccination, mainly asthenia, fever, headache and arthralgia. Multivariate analysis showed that female sex, number of injections and diluent (more reactions in 5% glucose alone than in combination with Tris-HCl buffer) significantly increased systemic reactions related to the vaccination. CONCLUSION: These data demonstrate that reactogenicity and systemic safety of HIV lipopeptides vaccine are acceptable both in healthy volunteers and HIV-infected adults.

AIDS Vaccines↗
PubMed2006

A cohort study of enfuvirtide immunological and virological efficacy in clinical practice.

The aim of the study was to evaluate, under routine circumstances, the immunological and virological efficacy of antiretroviral regimens containing enfuvirtide in multi-class experienced HIV-1 infected patients. This retrospective monocentric study analyzed the clinical, immunological, and virological data of 18 HIV-1 infected patients who started enfuvirtide and completed at least 3 months of therapy. Following 3 months of enfuvirtide therapy, 11 (61%) patients had HIV-1 RNA below 400 copies/ml, among whom 8 (44%) patients below 50 copies/ml. In the ten patients still receiving enfuvirtide after 12 months, the median increase in CD4 cell count was 159 cells/microl (range, -25 to +301) and the mean decrease in HIV-1 RNA was 2.5 +/- 1.4 log(10) copies/ml; in six of these patients, viral load remained below 50 copies/ml. Five patients discontinued enfuvirtide for virological failure but none as a consequence of adverse event. Mutations located within the 36-45 amino acid domain of HR1 region of gp41 and associated to enfuvirtide resistance were found in all seven patients with persistent viral replication. In addition, a new mutation, A50V, emerged in one patient with late viral rebound. Its disappearance after treatment discontinuation suggests that it could play a role in resistance to enfuvirtide. In conclusion, enfuvirtide may be a good therapeutic option as rescue therapy in treatment-experienced patients. However, the mutations conferring resistance to enfuvirtide develop rapidly when viral load is not controlled confirming that enfuvirtide should be prescribed in association with an active background regimen.

Adult↗
PubMed2006

New CD4+ and CD8+ T cell responses induced in chronically HIV type-1-infected patients after immunizations with an HIV type 1 lipopeptide vaccine.

We showed that an anti-HIV lipopeptide vaccine injected to HIV-uninfected volunteers was well tolerated and able to induce a specific CD4(+) and CD8(+) T cell responses. The same vaccine was injected in HIV-1 chronically infected patients controlled by HAART to evaluate its immunogenicity. In this trial, 24 patients were immunized three times with a mixture of six lipopeptides (Nef 66-97, Nef 117-147, Nef 182-205, Gag 183-214, Gag 253-284, and Env 303-335) at 0, 3, and 6 weeks. We studied the HIV-1-specific CD4(+) T cell proliferative responses. The IFN-gamma secretion by activated CD8(+) T cells was evaluated, using an ex vivo ELISpot assay and 60 CD8(+) T cell epitopes derived from the vaccine. Before immunization (W0), anti-HIV CD4(+) T cell responses to Gag, Nef, and Env large peptides were detected in 7/23 (30%) analyzable patients. After three injections, 17/23 (74%) patients had a proliferative response and 16 of them induced new specific CD4(+) T cell responses. At W0, CD8(+) T cell responses to HIV-1 epitopes were detected in 6/23 (26%) patients. After vaccination, 16/23 (70%) patients showed CD8(+) T cell responses and 13 of these patients induced new T cell responses to 25 different HIV-1 epitopes. These HIV-1 epitopes were detected in patients with various HLA class I molecules (HLA-A2, -A3/A11, -A24, -B7 superfamily, -B8), as found in the majority of the white population. Lipopeptides induce new anti-HIV T cell responses in vaccinated infected patients and could be used as a new immunotherapy strategy. The majority of these responders induced specific new CD4(+) and CD8(+) T cell responses.

AIDS Vaccines↗
PubMed2006

Inhibition of anti-tuberculosis T-lymphocyte function with tumour necrosis factor antagonists.

Reactivation of latent Mycobacterium tuberculosis (Mtb) infection is a major complication of anti-tumour necrosis factor (TNF)-alpha treatment, but its mechanism is not fully understood. We evaluated the effect of the TNF antagonists infliximab (Ifx), adalimumab (Ada) and etanercept (Eta) on anti-mycobacterial immune responses in two conditions: with ex vivo studies from patients treated with TNF antagonists and with the in vitro addition of TNF antagonists to cells stimulated with mycobacterial antigens. In both cases, we analysed the response of CD4+ T lymphocytes to purified protein derivative (PPD) and to culture filtrate protein (CFP)-10, an antigen restricted to Mtb. The tests performed were lymphoproliferation and immediate production of interferon (IFN)-gamma. In the 68 patients with inflammatory diseases (rheumatoid arthritis, spondylarthropathy or Crohn's disease), including 31 patients with a previous or latent tuberculosis (TB), 14 weeks of anti-TNF-alpha treatment had no effect on the proliferation of CD4+ T lymphocytes. In contrast, the number of IFN-gamma-releasing CD4+ T lymphocytes decreased for PPD (p < 0.005) and CFP-10 (p < 0.01) in patients with previous TB and for PPD (p < 0.05) in other patients (all vaccinated with Bacille Calmette-Guérin). Treatments with Ifx and with Eta affected IFN-gamma release to a similar extent. In vitro addition of TNF antagonists to CD4+ T lymphocytes stimulated with mycobacterial antigens inhibited their proliferation and their expression of membrane-bound TNF (mTNF). These effects occurred late in cultures, suggesting a direct effect of TNF antagonists on activated mTNF+ CD4+ T lymphocytes, and Ifx and Ada were more efficient than Eta. Therefore, TNF antagonists have a dual action on anti-mycobacterial CD4+ T lymphocytes. Administered in vivo, they decrease the frequency of the subpopulation of memory CD4+ T lymphocytes rapidly releasing IFN-gamma upon challenge with mycobacterial antigens. Added in vitro, they inhibit the activation of CD4+ T lymphocytes by mycobacterial antigens. Such a dual effect may explain the increased incidence of TB in patients treated with TNF antagonists as well as possible differences between TNF antagonists for the incidence and the clinical presentation of TB reactivation.

Adalimumab↗
PubMed2005

Therapeutic management of hepatitis and HIV infection in co-infected patients: results of a survey performed before the 2005 Consensus Conference.

The First European Consensus Conference on the Treatment of Chronic Hepatitis B and C in HIV Co-infected Patients aimed to produce recommendations that could be applied across Europe. However, some important differences exist around Europe, in terms of access to treatment and tests for monitoring. This short survey of 24 European countries showed that access to anti-HCV treatment is low (approximately 10%) in patients with HCV/HIV co-infection--generally access is higher in Western Europe than in Eastern or Northern Europe. This low use of anti-HCV therapy is not a result of poor availability (of drugs or virological tests), which are available in all countries surveyed. Recently published trials in co-infected patients and the outcome from this Consensus Conference will hopefully lead to wider access to anti-HCV therapy and better management of co-infected patients across Europe.

Antiviral Agents↗
PubMed2005

Repertoire, diversity, and differentiation of specific CD8 T cells are associated with immune protection against human cytomegalovirus disease.

To determine the correlates of immune recovery from active human CMV (HCMV) disease, we compared the antigenic repertoire, diversity, magnitude, and differentiation of HCMV-specific CD8+ T cells in HIV-HCMV coinfected subjects with no, cured, or active HCMV disease and in healthy HIV-negative HCMV-positive controls. ELISPOT-IFN-gamma assays using peptide pools spanning the pp65 and immediate early 1 (IE1) HCMV proteins showed that HCMV-specific CD8+ T cells had a significantly broader antigenic repertoire and greater diversity in HIV-positive patients controlling HCMV replication than in those with active HCMV disease, but the magnitude of the CD8 T cell response did not differ between the different groups. HCMV-specific T cells mainly were focused against IE1 during the short-term recovery from retinitis, and switched toward pp65 during long-term recovery. HCMV-specific T cells displaying an "early" (CD8+CD27+CD28+) and "intermediate" (CD8+CD27-CD28+) differentiation phenotype were increased significantly during long-term recovery compared with other HIV-positive patients and were nearly undetectable during active HCMV disease. HCMV-specific T cells with a "late" (CD8+CD27-28-) differentiation phenotype predominated in all cases. Therefore, restoration of immune protection against HCMV after active HCMV disease in immunodeficient individuals is associated with enlarged repertoire and diversity, and with early differentiation of virus-specific CD8+ T cells, thus defining immune correlates of protection against diseases caused by persistent viruses.

Acquired Immunodeficiency Syndrome↗
PubMed2005

Fulminant inflammatory leukoencephalopathy associated with HAART-induced immune restoration in AIDS-related progressive multifocal leukoencephalopathy.

HAART-induced immune restoration is beneficial for patients with AIDS-related progressive multifocal leukoencephalopathy (PML). However, in rare instances, an immune-reconstitution inflammatory syndrome (IRIS) may cause paradoxical clinical deterioration. We report the neuropathological study of an AIDS patient who presented with progressive cognitive deterioration; CD4(+) count was 117 and the HIV viral load >10(4); imaging showed non-enhancing lesions consistent with PML. Following initiation of HAART, CD4(+) was 300 and HIV viral load <10(3), but his neurological symptoms continued to deteriorate. Imaging revealed an increase in the size and number of lesions and enhancement of all the lesions. A stereotactic biopsy showed severe inflammatory and demyelinating lesions with marked infiltration by macrophages and T lymphocytes in the absence of a detectable infectious agent. Despite high doses of steroids, the patient died 3 months after admission. Autopsy showed two types of lesions: (1) active inflammatory PML changes with abundant JC virus, and intraparenchymal and perivascular infiltration by T lymphocytes, and (2) acute perivenous leukoencephalitis devoid of JC virus. Most lymphocytes were CD8(+) lymphocytes; CD4(+) lymphocytes were virtually absent. Two pathological reactions were associated with the paradoxical clinical deterioration related to dysregulation of the immune response characteristic of IRIS in PML: (1) an accentuation of JCV infection, and (2) a nonspecific acute perivenous leukoencephalitis. We suggest that both these types of lesions are due to an imbalance of CD8(+)/CD4(+) T cells, with massive infiltration of the cerebral parenchyma by CD8(+) cytotoxic T lymphocytes in the absence of sufficient CD4(+) response. Better understanding of the mechanisms of the IRIS may enable prevention or cure of this severe, sometimes fatal complication of HAART.

Acquired Immunodeficiency Syndrome↗
PubMed2005

Opportunistic infections as causes of death in HIV-infected patients in the HAART era in France.

The objective of the study was to describe the underlying causes of death of HIV-infected patients in the HAART era and to focus on those related to opportunistic infection (OI), in a national multicentre study ('Mortalité 2000'). A total of 964 deaths were recorded and 924 cases were available for analysis. Underlying cause of death were AIDS-related (47%), viral hepatitis (11%), non-AIDS cancers (11%), cardiovascular diseases (7%) and others (11%). Among patients who died of AIDS events, 262 (27%) died of at least one OI. OIs reported at the time of death were Cytomegalovirus infection 67 times, Pneumocystis jiroveci pneumonia 56, disseminated Mycobacterium avium intracellulare infection 53 and cerebral toxoplasmosis 48. Compared to patients who died of other causes, patients who died of OIs were younger and more likely to be infected through heterosexual contact, in poor socioeconomic conditions, migrants, more recently diagnosed for HIV infection, and naive of antiretroviral therapy and OI prophylaxis. OIs are still a major cause of death in HIV-infected patient in the HAART era, especially among patients recently diagnosed for HIV infection and who do not have access to care, as well as in long term infected patients where prophylaxis should be revisited.

AIDS-Related Opportunistic Infections↗
PubMed2005

Indinavir plasma concentration and adherence score are codeterminant of early virologic response in HIV-infected patients of the APROCO cohort.

To study the respective roles of indinavir concentrations and treatment adherence as predictors of early virologic response, we analyzed the patients of the APROCO cohort treated by indinavir 800 mg TID during the first 4 months. Minimum (Cmin), maximum (Cmax), and the ratio of the measured to expected concentrations (CR) were estimated for each patient at M4, from a population pharmacokinetic analysis of all data. The relationship among virologic success at M4 [plasma HIV RNA (VL) <500 copies/mL], baseline characteristics, estimated indinavir concentrations, and adherence score measured by a self-administered questionnaire, was analyzed by multivariate logistic regression. In the 216 studied patients, baseline median HIV RNA was 4.4 log10 copies/mL, and CD4 cell count was 309/mm. Virologic success was achieved in 195 (90%) patients; it was independently related to baseline viral load (OR = 0.524, CI 0.29-0.93; P = 0.03), antiretroviral treatment naive status (OR = 3.89, CI 1.29-11.76; P = 0.01), and indinavir Cmin (OR = 1.06, CI 1.02-1.10; P = 0.004) when adherence score was not included in the model, whereas full adherence was the only independent related factor when included in the model (OR = 8.8, 95% CI 2.85-27.3; P < 10). In the 168 fully adherent patients, virologic success was more frequent in patients with shorter duration of antiretrovirals at baseline (P = 0.03), lower baseline HIV RNA (P = 0.03), and higher indinavir CR (P < 10); the most discriminating Cmin cut-off was 194 ng/mL. Data on the relationship between indinavir plasma concentration and virologic success are therefore misleading without a concomitant assessment of adherence. These data suggest that any strategy of therapeutic drug monitoring must imply first a combined evaluation of plasma concentrations and adherence level and second an intervention target based on the results of both assessments.

Adult↗
PubMed2005

Population pharmacokinetics of tenofovir in human immunodeficiency virus-infected patients taking highly active antiretroviral therapy.

The influence of renal function on tenofovir pharmacokinetics was investigated in 193 human immunodeficiency virus (HIV)-infected patients by the use of a population approach performed with the nonlinear mixed effects modeling program NONMEM. Tenofovir pharmacokinetics was well described by a two-compartment open model in which the absorption and the distribution rate constants are equal. Typical population estimates of apparent central distribution volume (V(c)/F), peripheral distribution volume (V(p)/F), intercompartmental clearance (Q/F), and plasma clearance (CL/F) were 297 +/- 28.5 [corrected] liters, 848 +/- 209 [corrected] liters, 80 +/- 15 [corrected] liters/h and 50.5 +/- 3.1 [corrected] liters/h, respectively. Apparent plasma clearance was related to body weight/serum creatinine ratio (BW/S(CR)) and to the existence of a tubular dysfunction. Concomitant treatment with lopinavir/ritonavir was found to decrease tenofovir clearance. Individual Bayesian estimates of CL/F were used to calculate the tenofovir area under the concentration-time curve from time zero to 24 h (AUC(0-24)). In patients without tubular dysfunction, AUC(0-24) values markedly decreased from 6.7 to 1.4 mg . h/liter for BW/S(CR) increasing from 0.44 to 1.73. The relevance of a dosage adjustment based on BW/S(CR) should be further evaluated.

Adenine↗
PubMed2005

Impact of newly available drugs on clinical progression in patients with virological failure after exposure to three classes of antiretrovirals.

OBJECTIVE: To study the prognosis of HIV-infected patients with virological failure after exposure to three classes of antiretroviral drugs (ARVs). DESIGN: Cohort study. SETTING: French Hospital Database on HIV. PATIENTS: Patients previously exposed to at least two nucleoside reverse transcriptase inhibitors (NRTIs), two protease inhibitors and one non-NRTI, with viral load (/L) values of > 5000 copies/ml after the exposure criteria were met and a new treatment initiated between 1998 and 2001 with VL > 5000 copies/ml. MAIN OUTCOME MEASURES: Risk of new AIDS-defining-events (ADEs) or death from first introduction of a drug never used before occurring between 1998 and 2001 defined as baseline. RESULTS: The main baseline characteristics of the 1092 patients were: previous ADE in 49% of cases, median CD4 cell count 181 microl, median VL 4.9 log10 copies/ml, median duration of ARV therapy 5.0 years and previous exposure to a median of nine ARVs. The crude progression rates were 20.1/100 patient-years among patients included in 1998, 15.1 in 1999, 11.1 in 2000 and 8.6 in 2001. After adjustment for baseline characteristics, the calendar year of inclusion was associated with the risk of clinical progression (P < 0.001). When the types of newly available drugs used at baseline or during follow-up were introduced into the model, year of inclusion was no longer associated with the risk of clinical progression (P = 0.42), while exposure to amprenavir/r, lopinavir/r, abacavir or tenofovir was associated with a lower risk. CONCLUSIONS: The clinical prognosis of heavily pretreated patients experiencing virological failure improved between 1998 and 2001, mainly thanks to the use of newly available drugs with more favourable resistance profiles.

Adult↗
PubMed2004

Causes of death among human immunodeficiency virus (HIV)-infected adults in the era of potent antiretroviral therapy: emerging role of hepatitis and cancers, persistent role of AIDS.

BACKGROUND: In the era of highly active antiretroviral therapy (HAART) mortality has decreased substantially among human immunodeficiency virus (HIV)-infected people with access to HAART, but there are concerns regarding co-morbidities and adverse effects of HAART, which may impair vital prognosis. The Mortality 2000 study examined the causes of death in HIV-infected adults at a national level in France in the year 2000. METHODS: All French hospital wards known to be involved in the management of HIV infection were asked to notify prospectively the deaths that occurred in 2000 among HIV-infected adults. The causes of death were documented using a standardized questionnaire. RESULTS: The 185 participating wards notified 964 deaths. The main underlying causes of death were AIDS-related (47%, non-Hodgkin's lymphoma: 23%), viral hepatitis (11%, hepatitis C: 9%, hepatitis B: 2%), cancer not related to AIDS or hepatitis (11%), cardiovascular disease (7%), bacterial infections (6%), suicide (4%), and adverse effect of antiretroviral treatments (1%). Among AIDS-related deaths, HIV infection had been diagnosed recently in 20%. Smoking was recorded in 72% of cancer-related deaths and alcohol consumption in 54% of hepatitis-related deaths. Among non-HIV related deaths between 25 and 64 years, the proportion of infectious diseases (including HCV and HBV-related deaths) was higher in HIV-infected adults than in the general population. CONCLUSIONS: Improved strategies for detecting HIV infection before AIDS-defining complications occur are needed in the era of HAART. The prevention of non-AIDS related cancers, especially lung cancer, the management of non-Hodgkin's lymphoma, and of viral hepatitis are also important priorities.

Acquired Immunodeficiency Syndrome↗
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↗