Abstract
Background
We aimed to assess the kinetics of drug-resistant viral variants (DRVs) harboring the M184V mutation in proviral DNA of long-term virally suppressed patients, and factors ...associated with DRV persistence.
Methods
Human immunodeficiency virus (HIV) DNA from blood cells stored in 2016 and 2019 was sequenced using Sanger and ultradeep sequencing (SS and UDS; detection threshold 1%) in antiretroviral therapy (ART)-treated patients with HIV RNA < 50 copies/mL for at least 5 years, with past M184V mutation documented in HIV RNA.
Results
Among 79 patients, by combining SS and UDS, M184V was found to be absent in 26/79 (33%) patients and persistent in 53/79 (67%). M184V-positive patients had a longer history of ART, lower CD4 nadir, and higher pretherapeutic HIV RNA. Among 37 patients with viral sequences assessed by UDS, the proportion of M184V-positive DRVs significantly decreased between 2016 and 2019 (40% vs 14%, P = .005). The persistence of M184V was associated with duration and level of HIV RNA replication under lamivudine/emtricitabine (3TC/FTC; P = .0009 and P = .009, respectively).
Conclusions
While it decreased over time in HIV DNA, M184V mutation was more frequently persistent in HIV DNA of more treatment-experienced patients with longer past replication under 3TC/FTC.
An ultrasensitive sequencing technique showed that the M184V mutation progressively cleared in the HIV DNA reservoir over time in virally suppressed HIV patients. However, this mutation was likely to persist in patients with sustained past replication under lamivudine or emtricitabine.
OBJECTIVE:High hepatitis C virus (HCV) treatment uptake combined with effective direct-acting antiviral-based regimens resulted in a dramatic decline of HCV infection in French people living with HIV ...(PLWH). We assessed the yearly incidence of new HCV infection in PLWH enrolled in the large French Dat’AIDS cohort from 2012 to 2016 with a specific focus on MSM.
METHODS:The incidence of new HCV infection was determined yearly in HCV-negative PLWH with serological follow-up during 2012–2016. The incidence of HCV reinfection was determined in patients who were cured of a previous infection.
RESULTS:Among 40 714 PLWH, HCV status was available in 38 217 (94%). A total of 5557 PLWH (15%) were HCV infected at first time-point, 82% of whom were cured of HCV by the end of 2016. Among 21 519 HCV-negative PLWH with serological follow-up (63 449 patient-years), 219 first HCV infections occurred (MSM188, others31). Similarly, among 3406 patients who were cured of a previous infection (10 602 patient-years), 73 reinfections occurred (MSM51, others22). From 2012 to 2016, the incidence of a first infection in MSM rose from 0.5 to 0.92% patient-years, whereas the incidence or reinfection remained stable (2.52–2.90% patient-years).
CONCLUSION:Despite a high HCV treatment uptake and cure rate, the incidence of new HCV infection (first infection or reinfection) regularly increased in French HIV-positive MSM between 2012 and 2016. The incidence of reinfection fluctuated but remained constantly higher than the incidence of first infection, suggesting that a subgroup of MSM pursued high-risk practices following cure of a first infection.
Pill burden during antiretroviral treatment (ART) is associated with worse adherence and impaired virological suppression. We compared the effectiveness, tolerance, and persistence on treatment of ...single tablet regimens (STRs) with non-STR once-daily regimens in patients receiving first-line ART.
Retrospective analysis of naïve HIV-1 infected patients prospectively enrolled in the French Dat'AIDS cohort and initiating first-line ART with STRs or once-daily non-STRs from 2004 to 2013. The primary outcome was time to treatment discontinuation defined by any change in the treatment regimen. STR and non-STR groups were compared controlling for baseline risk factors by inverse probability weighted treatment Cox analysis (IPWT) and propensity-score matching (PSM).
Overall, 3212 patients (STR 499, non-STR 2713) were included. Median time to treatment discontinuation was shorter in non-STR patients than in STR patients, both in the IPWT (HR = 0.61, p<0.0001) and the PSM cohort (HR = 0.55, p<0.0001). This difference disappeared when censoring ART modification for simplification, both in the IPWT (HR = 0.97, p = 0.65) and the PSM cohort (HR = 0.91, p = 0.33). A lower rate of virological failure was observed with STRs than with non-STRs in both cohorts (HR = 0.23; p = 0.002 and HR = 0.22, p = 0.003, respectively). A lower rate of treatment modification for adverse event was observed with non-STRs in the IPWT cohort (HR = 1.46, p<0.0001), but not in the PSM cohort (HR = 1.22, p = 0.11).
First-line therapy with STRs was associated with a longer time to treatment discontinuation than with non-STRs. However, when ART modification for simplification was not considered as a failure, STRs and non-STRs were similar.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
To assess whether antiretroviral therapy (ART) prescriptions differ between naive and virally suppressed HIV patients born in France (PBFs) and in Sub-Saharan Africa (PBSSAs).
Observational ...single-center study.
We included all PBFs and PBSSAs who entered into care at Pitié-Salpêtrière Hospital, Paris, France, from 01/01/2000 to 31/12/2018, with plasma HIV-RNA>200 copies/mL. We first compared the initial ART in naive PBFs and PBSSAs. Second, we compared the last-prescribed ART (including drug-reduced ART: daily 2-drug regimens, daily 1-drug regimens and intermittent 3-drug regimens) in virally suppressed PBFs and PBSSAs, by focusing on patients in care in 2018 with HIV-RNA <50 copies for at least 24 months. A univariable and multivariable logistic regression model was used to assess the impact of geographical origin on ART prescriptions.
A total of 1944 naive patients were included (915 PBSSAs and 1029 PBFs). PBSSAs were more frequently women, hepatitis B coinfected, with a lower pretherapeutic CD4 T-cell count, and most had tuberculosis at HIV diagnosis. After adjustment for confounders, PBSSAs were more likely to receive a first-line protease inhibitor-based regimen (OR 1.61, 95% CI: 1.31 to 1.98), and less likely to receive an integrase inhibitor-based regimen (OR 0.61, 95% CI: 0.42 to 0.88). Of the 968 virally suppressed patients (431 PBSSAs and 537 PBFs), PBSSAs were less likely to receive drug-reduced ART, including 2-drug regimens and intermittent three-drug regimens (OR 0.48, 95% CI: 0.36 to 0.65).
Differences in ART prescriptions between PBSSAs and PBFs were not only explained by different clinical and virologic situations. Personal motivations of doctors in choosing ART according to country of birth need to be explored.
Liver damage associated with chronic unexplained high serum transaminases in human immunodeficiency virus (HIV)‐infected patients under combined antiretroviral therapy is unknown. Liver histology was ...prospectively investigated in patients presenting serum transaminase elevation for more than 6 months, after exclusion of alcohol abuse, hepatitis C virus (HCV) or hepatitis B virus (HBV) infection, autoimmune, and genetic liver diseases. In a subgroup of patients, liver mitochondrial activities were measured by spectrophotometry and mitochondrial DNA (mtDNA) by real‐time polymerase chain reaction (PCR). Thirty patients were included with median values of alanine aminotransferase (ALT) levels: 80 U/L, age: 46 years, body mass index: 23 kg/m2, HIV RNA: 200 copies/mL, CD4 count: 365/mm3, duration of HIV infection: 13 years, and duration of treatment exposure: 118, 41, and 53 months for nucleoside reverse transcriptase inhibitors, non‐nucleoside reverse transcriptase inhibitors, and protease inhibitors, respectively. Histological anomalies were found in 22 of 30 patients. Steatosis was present in 18 patients, severe in nine patients, and associated with inflammation in 16 patients with a diagnosis of non‐alcoholic steatohepatitis (NASH). Fibrosis was found in 18 patients, severe in six patients and associated with steatosis in 13 patients. Significant liver respiratory complex I defect, contrasting with high complex IV activity and normal mitochondrial DNA content, was observed in the group of patients compared with controls. The presence of NASH was correlated with high fasting glycemia and insulin levels, not with liver mitochondrial function or mitochondrial DNA content. Conclusions: HIV‐infected patients on combined antiretroviral therapy with chronic transaminase elevation of unknown origin have a high rate of liver lesions, mostly consistent with NASH related to insulin resistance. (HEPATOLOGY 2008.)
Abstract
Background
Data from nonrandomized studies have suggested that hydroxychloroquine could be an effective therapeutic agent against coronavirus disease 2019 (COVID-19).
Methods
We conducted an ...observational, retrospective cohort study involving hospitalized adult patients with confirmed, mild to severe COVID-19 in a French university hospital. Patients who received hydroxychloroquine (200 mg 3 times daily dosage for 10 days) on a compassionate basis in addition to standard of care (SOC) were compared with patients without contraindications to hydroxychloroquine who received SOC alone. A propensity score-weighted analysis was performed to control for confounders: age, sex, time between symptom onset and admission ≤ 7 days, Charlson comorbidity index, medical history of arterial hypertension, obesity, National Early Warning Score 2 (NEWS2) score at admission, and pneumonia severity. The primary endpoint was time to unfavorable outcome, defined as: death, admission to an intensive care unit, or decision to withdraw or withhold life-sustaining treatments, whichever came first.
Results
Data from 89 patients with laboratory-confirmed COVID-19 were analyzed, 84 of whom were considered in the primary analysis; 38 patients treated with hydroxychloroquine and 46 patients treated with SOC alone. At admission, the mean age of patients was 66 years, the median Charlson comorbidity index was 3, and the median NEWS2 severity score was 3. After propensity score weighting, treatment with hydroxychloroquine was not associated with a significantly reduced risk of unfavorable outcome (hazard ratio, 0.90 95% confidence interval, .38–2.1, P = .81). Overall survival was not significantly different between the 2 groups (hazard ratio, 0.89 0.23; 3.47, P = 1).
Conclusion
In hospitalized adults with COVID-19, no significant reduction of the risk of unfavorable outcomes was observed with hydroxychloroquine in comparison to SOC. Unmeasured confounders may have persisted however, despite careful propensity-weighted analysis and the study might be underpowered. Ongoing controlled trials in patients with varying degrees of initial severity on a larger scale will help determine whether there is a place for hydroxychloroquine in the treatment of COVID-19. In hospitalized adults with COVID-19, no significant reduction of the risk of unfavorable outcomes was observed with hydroxychloroquine in comparison to SOC.
In hospitalized adults with Covid-19, no significant reduction of the risk of unfavorable outcomes was observed with hydroxychloroquine in comparison to standard of care.
PDF
