Direct-acting antivirals (DAA) lead to high sustained virological response (SVR) rates and decrease the risk of disease progression. We compared SVR rates and all-cause, liver- and non-liver-related ...deaths, liver-related events, and non-liver-related cancers in HIV/HCV-coinfected and HCV-monoinfected participants from 2 French cohort studies after initiation of DAA treatment.
Up to 4 HCV-monoinfected participants from the ANRS CO22 HEPATHER cohort were matched by age and sex to each HIV/HCV-coinfected patient from the ANRS CO13 HEPAVIH cohort; both are nationwide, prospective, multicentre, and observational. Participants were initiated on DAAs between March 2014 and December 2017. Cox proportional hazards models adjusted by age, sex, duration since HCV diagnosis, HCV transmission routes, HCV genotypes, cirrhosis, tobacco, alcohol consumption, and SVR (time dependent) were used.
A total of 592 HIV/HCV-coinfected and 2,049 HCV-monoinfected participants were included; median age was 53.3 years (inter-quartile range: 49.6–56.9) and 52.9 years (49.6; 56.7), 1,498 (73.1%) and 436 (73.6%) were men, and 159 (28.8%) and 793 (41.2%) had cirrhosis, respectively. SVR was observed in 92.9% and 94.6%, respectively. HIV coinfection was associated with higher risk of all-cause death (hazard ratio HR 1.93; 95% CI 1.01–3.69), non-liver-related death (HR 2.84; 95% CI 1.27–6.36), and non-liver-related cancer (HR 3.26; 95% CI 1.50–7.08), but not with liver-related-death (HR 1.04; 95% CI 0.34–3.15) or liver-related events (HR 0.66; 95% CI 0.31–1.44).
After DAA treatment, HIV-coinfected individuals had similar SVR rates and risk of liver-related deaths and events compared with HCV-monoinfected individuals, but had a higher risk of all-cause and non-liver-related deaths and non-liver-related cancers.
We compared the risk of several clinical events in participants infected by human immunodeficiency virus and hepatitis C virus with those infected with hepatitis C virus alone, matched on age and sex, after treatment with contemporary direct-acting antivirals. We found a higher risk of all-cause deaths, non-liver-related deaths, and non-liver-related cancers in participants coinfected with the human immunodeficiency virus and hepatitis C virus, and no differences for the risk of liver-related deaths or events.
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•Similar rates of SVR exist between HIV/HCV co-infected and HCV mono-infected participants.•There is a higher risk of all-cause deaths, non-liver-related deaths, and cancers in HIV/HCV co-infected participants.•There is a similar risk of liver-related deaths and liver-related events in both populations.
In this placebo-controlled phase II randomized clinical trial, 103 human immunodeficiency virus type 1 (HIV-1)-infected patients under cART (combined antiretroviral treatment) were randomized 2:1 to ...receive either 3 doses of DNA GTU-MultiHIV B (coding for Rev, Nef, Tat, Gag, and gp160) at week 0 (W0), W4, and W12, followed by 2 doses of LIPO-5 vaccine containing long peptides from Gag, Pol, and Nef at W20 and W24, or placebo. Analytical treatment interruption (ATI) was performed between W36 to W48. At W28, vaccinees experienced an increase in functional CD4
T-cell responses (
< 0.001 for each cytokine compared to W0) measured, predominantly against Gag and Pol/Env, and an increase in HIV-specific CD8
T cells producing interleukin 2 (IL-2) and tumor necrosis factor alpha (TNF-α) (
= 0.001 and 0.013, respectively), predominantly against Pol/Env and Nef. However, analysis of T-cell subsets by mass cytometry in a subpopulation showed an increase in the W28/W0 ratio for memory CD8
T cells coexpressing exhaustion and senescence markers such as PD-1/TIGIT (
= 0.004) and CD27/CD57 (
= 0.044) in vaccinees compared to the placebo group. During ATI, all patients experienced viral rebound, with the maximum observed HIV RNA level at W42 (median, 4.63 log
copies cp/ml; interquartile range IQR, 4.00 to 5.09), without any difference between arms. No patient resumed cART for CD4 cell count drop. Globally, the vaccine strategy was safe. However, a secondary HIV transmission during ATI was observed. These data show that the prime-boost combination of DNA and LIPO-5 vaccines elicited broad and polyfunctional T cells. The contrast between the quality of immune responses and the lack of potent viral control underscores the need for combined immunomodulatory strategies. (This study has been registered at ClinicalTrials.gov under registration no. NCT01492985.)
In this placebo-controlled phase II randomized clinical trial, we evaluated the safety and immunogenicity of a therapeutic prime-boost vaccine strategy using a recombinant DNA vaccine (GTU-MultiHIV B clade) followed by a boost vaccination with a lipopeptide vaccine (HIV-LIPO-5) in HIV-infected patients on combined antiretroviral therapy. We show here that this prime-boost strategy is well tolerated, consistently with previous studies in HIV-1-infected individuals and healthy volunteers who received each vaccine component individually. Compared to the placebo group, vaccinees elicited strong and polyfunctional HIV-specific CD4
and CD8
T-cell responses. However, these immune responses presented some qualitative defects and were not able to control viremia following antiretroviral treatment interruption, as no difference in HIV viral rebound was observed in the vaccine and placebo groups. Several lessons were learned from these results, pointing out the urgent need to combine vaccine strategies with other immune-based interventions.
Internal medicine is a medical specialty that is often poorly understood by the general public and sometimes misidentified. In an era of increasing subspecialization and high technicality, it is ...characterized by a comprehensive approach centered on clinical evaluation. Unlike what is observed in most developed countries, where systemic autoimmune diseases are managed by organ specialists based on their mode of presentation, French internists are at the forefront for diagnosing and managing these diseases. Their multidisciplinary training gives them legitimacy to justify this role. Internists also play a crucial role in the management of patients requiring unplanned hospitalizations downstream from emergency departments and in connection with primary care. Internists primarily practice in a hospital setting, with a specific position in the French healthcare system aligned with the training frameworks of all medical specialties. To better define internal medicine, its role in care activities, as well as in education and research, internists organized a General Assembly of internal medicine that took place on September 28, 2023, in Paris. Structured around think tanks focusing on care, education, and research activities, the general assembly aimed to improve visibility on internal medicine and internists. This article recounts the discussions that animated this meeting and highlights the main ideas that emerged. These general assemblies constitute a foundational step and will be followed by a Consultation Conference in order to better identify and promote internal medicine and internists, regardless of their types and places of practice.
Background. Treatment initiation at the time of primary human immunodeficiency virus (HIV) type 1 (HIV-1) infection has become less frequent in recent years. Methods. In the French prospective PRIMO ...Cohort, in which patients are enrolled at the time of primary HIV-1 infection, 30% of the 552 patients recruited during 1996–2004 did not start receiving antiretroviral treatment during the first 3 months after diagnosis. We analyzed the patients' clinical and immunological outcomes and examined potential predictors of disease progression. Progression was defined as the occurrence of an acquired immunodeficiency syndrome (AIDS)—related clinical event or a CD4 cell count <350 cells/mm3. Results. Fifty-six (34%) of the untreated patients experienced immunological progression during a median duration of follow-up of 24 months, and 1 of these patients had an AIDS-related event. The estimated risks of progression were 25%, 34%, and 42% at 1, 2, and 3 years after enrollment, respectively. Compared with patients who did not have progression, those with progression had significantly lower CD4 cell counts at diagnosis (455 vs. 738 cells/mm3), higher plasma HIV RNA levels (4.9 vs. 4.5 log10 copies/mL), and higher HIV DNA levels (3.3 vs. 3.0 log10 copies/106 peripheral blood mononuclear cells PBMCs). All 3 parameters were significantly associated with progression in univariate analysis. In multivariate analysis, only the CD4 cell count and HIV DNA level were independently predictive of disease progression (relative hazard for CD4 cell count, 1.84 per decrease of 100 cells/mm3; relative hazard for HIV DNA level, 2.73 per increase of 1 log10 copies/106 PBMCs). Conclusions. Both a low initial CD4 cell count and a high HIV DNA level are predictive of rapid progression of untreated primary HIV-1 infection. Affected patients may therefore benefit from close clinical and laboratory monitoring and/or early administration of treatment.
Objectives
Single nucleotide polymorphisms in the cytochrome P450 (CYP) 2B6 gene have been associated with high interindividual variation in efavirenz pharmacokinetics. However, clinical data on the ...relationship of CYP2B6 polymorphisms with the occurrence of efavirenz‐induced central nervous system (CNS) symptoms are limited.
Methods
We analysed four polymorphisms in the CYP2B6 (516 G>T), CYP3A5 (6986 A>G) and ATP‐binding cassette, sub‐family B, member 1 (ABCB1) (2677 G>T/A and 3435 C>T) genes in HIV‐infected adults virologically suppressed on a protease inhibitor‐based regimen who switched to a regimen containing emtricitabine, didanosine and efavirenz in the setting of the ANRS ALIZE trial. Kaplan−Meier methods and Cox regression analysis were used to investigate their association with efavirenz plasma levels and CNS events up to 48 months after switching.
Results
In total, 191 patients with a median age of 41 years, who were 87% male and 85% Caucasian, were enrolled in the study. Variant allelic frequencies were 0.49, 0.93, 0.59 and 0.63 for CYP2B6 516, CYP3A5 392, ABCB1 2677 and ABCB1 3435, respectively. The median efavirenz plasma concentration (MEPC) was 2.2 mg/L interquartile range (IQR) 1.7–2.8 mg/L and was significantly higher in patients with the deficient CYP2B6 516T. Overall, 242 CNS events were reported in 104 individuals (54%). No correlation was found between MEPC and CNS events. The occurrence of a first CNS event was lower in patients with the CYP2B6 516 G/G genotype vs. CYP2B6 516 T genotypes 50% (IQR: 40–60%) vs. 66% (IQR: 56–75%), respectively; P = 0.02. In an adjusted Cox regression model, there was a tendency towards a higher risk of a first CNS event among carriers of the variant CYP2B6 516 T allele (relative risk 1.4 95% CI, 0.99–2.1; P?=?.06), compared with noncarriers.
Conclusions
The deficient CYP2B6 516 T allele is associated with higher efavirenz plasma drug levels and more frequent CNS‐related symptoms.
Introduction
Despite the advent of HIV cure‐related clinical trials (HCRCT) for people living with HIV (PLWH), the risks and uncertainty involved raise ethical issues. Although research has provided ...insights into the levers and barriers to PLWH and physicians' participation in these trials, no information exists about stakeholders' preferences for HCRCT attributes, about the different ways PLWH and physicians value future HCRCT, or about how personal characteristics affect these preferences. The results from the present study will inform researchers' decisions about the most suitable HCRCT strategies to implement, and help them ensure ethical recruitment and well‐designed informed consent.
Methods
Between October 2016 and March 2017, a discrete choice experiment was conducted among 195 virally controlled PLWH and 160 physicians from 24 French HIV centres. Profiles within each group, based on individual characteristics, were obtained using hierarchical clustering. Trade‐offs between five HCRCT attributes (trial duration, consultation frequency, moderate (digestive disorders, flu‐type syndrome, fatigue) and severe (allergy, infections, risk of cancer) side effects (SE), outcomes) and utilities associated with four HCRCT candidates (latency reactivation, immunotherapy, gene therapy and a combination of latency reactivation and immunotherapy), were estimated using a mixed logit model.
Results
Apart from severe SE – the most decisive attribute in both groups – PLWH and physicians made different trade‐offs between HCRCT attributes, the latter being more concerned about outcomes, the former about the burden of participation (consultation frequency and moderate SE). These different trades‐offs resulted in differences in preferences regarding the four candidate HCRCT. PLWH significantly preferred immunotherapy, whereas physicians preferred immunotherapy and combined therapy. Despite the heterogeneity of characteristics within the PLWH and physician profiles, results show some homogeneity in trade‐offs and utilities regarding HCRCT.
Conclusions
Severe SE, not outcomes, was the most decisive attribute determining future HCRCT participation. Particular attention should be paid to providing clear information, in particular on severe SE, to potential participants. Immunotherapy would appear to be the best HCRCT candidate for both PLWH and physicians. However, if the risk of cancer could be avoided, gene therapy would become the preferred strategy for the latter and the second choice for the former.
Assessing disease activity in patients suffering from autoimmune diseases is complex. Symptoms are multiple, often subjective and there are no reliable biomarkers. Many activity scores have been ...implemented to compare treatment efficacy in clinical trials. Their use in clinical practice is largely unknown. We performed a practical survey to analyze the use of activity scores in clinical practice to consider treatment response and to assess the determinants of their use.
A sample of French internists answered a questionnaire about activity scores of systemic lupus erythematosus, Sjögren's syndrome, autoimmune myositis and necrotizing vasculitis of small vessels. The frequency of use of these tools, the causes of their non-use, and the general opinion of practitioners about the place of theses scores in current practice were described.
The form was completed by 92 internists. Seventy percent of them supported the use of activity scores in consultations, but actually used them in less than 25% of patient visits. The reasons for the low use of these scores are mainly the ignorance of their existence (42%) and their length or complexity (28%).
The discrepancy between the ratio of practitioners who believe that scores have a place in daily practice and their actual use shows that the current scores do not meet the needs. The implementation of easily usable activity scores in inflammatory diseases remains a challenge for the internists.
Background. High grade non-Hodgkin lymphoma (NHL) remains the most common Acquired Immune Deficiency Syndrome (AIDS)—associated neoplasia and an important cause of mortality in people living with ...human immunodeficiency virus (HIV) infection in industrialized countries in the era of highly active antiretroviral therapy (HAART). Method. A case-control study was implemented in a large cohort of HIV-infected patients. Case patients had newly diagnosed NHL, and control subjects were matched for CD4+ cell count, calendar period, sex, and length of follow-up. Results. Variables associated with a decreased risk of NHL were the use of HAART during follow-up for at least 6 months (odds ratio OR, 0.46; 95% confidence interval CI, 0.21–0.98), receipt of a diagnosis of AIDS before the censoring date (OR, 0.37; 95% CI, 0.18–0.76), and undetectable level of HIV RNA during follow-up (OR, 0.34; 95% CI, 0.15–0.77). The use of antiherpetic drug for at least 6 months was associated with a nonsignificant decreased risk of NHL (OR, 0.40; 95% CI, 0.11–1.44; P = .16). In multivariate analysis, variables significantly associated with a decreased risk of NHL were the use of HAART for at least 6 months during follow-up (OR, 0.37; 95% CI, 0.16–0.87) and receipt of an AIDS-related diagnosis before the censoring date (OR, 0.44; 95% CI, 0.21–0.93). Age, transmission group, hepatitis B and C coinfections, CD4+ and CD8+ cell count nadir, and previous history of herpes virus infection were not associated with an increased risk for NHL. Conclusion. The use of HAART for at least 6 months was associated with a decreased risk of NHL, whereas uncontrolled HIV RNA load may be associated with an increased risk. The role of antiherpetic drugs needs further investigation.
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