OBJECTIVES:Following an alert on neural tube defects and dolutegravir, we sought to evaluate if the exposure integrase strand transfer inhibitors (INSTIs) at conception was associated with birth ...defects or other adverse pregnancy outcomes.
METHODS:In the prospective national French Perinatal Cohort (EPF), we studied birth defects and other perinatal outcomes by matching each pregnant woman exposed to INSTIs with a pregnant woman exposed to darunavir/ritonavir receiving the same backbone of nucleoside reverse transcriptase inhibitors and matched for other characteristics such as age, geographic origin, center and year of delivery.
RESULTS:Among 808 women exposed to INSTIs during pregnancy (raltegravir=703, dolutegravir=57 and elvitegravir=48), we reported a slightly higher rate of birth defects in infants exposed at conception to raltegravir (6.7%) vs infants exposed to raltegravir later in pregnancy2.9% if initiated during pregnancy as first-line, and 2.5% as second-line treatment, p=0.04. When compared to matched controls, raltegravir exposure at conception was not significantly associated with birth defects6.4% vs 2.3%, p = 0.08. There was no cluster of birth defect type and no neural tube defects were observed. Other perinatal outcomes, such as preterm birth and stillbirths, did not differ significantly between raltegravir-exposed women and matched counterparts. No difference in any outcome was observed for elvitegravir/cobicistat or dolutegravir.
CONCLUSION:We found a non-significant trend for an association between exposure to raltegravir at conception and birth defects which needs to be evaluated by larger prospective surveillance data, as these drugs are increasingly prescribed in women living with HIV.
To identify factors associated with mother-to-child HIV-1 transmission (MTCT) from mothers receiving antenatal antiretroviral therapy.
The French Perinatal Cohort (EPF), a multicenter prospective ...cohort of HIV-infected pregnant women and their children.
Univariate analysis and logistic regression, with child HIV status as dependent variable, were conducted among 5271 mothers who received antiretroviral therapy during pregnancy, delivered between 1997 and 2004 and did not breastfeed.
The MTCT rate was 1.3% 67/5271; 95% confidence interval (CI), 1.0-1.6. It was as low as 0.4% (5/1338; 95% CI, 0.1-0.9) in term births with maternal HIV-1 RNA level at delivery below 50 copies/ml. MTCT increased with viral load, short duration of antiretroviral therapy, female gender and severe premature delivery: 6.6% before 33 weeks versus 1.2% at 37 weeks or more (P < 0.001). The type of antiretroviral therapy was not associated with transmission. Intrapartum therapy was associated with four-fold lower MTCT (P = 0.04) in case of virological failure (> 10 000 copies/ml). Elective cesarean section tended to be inversely associated with MTCT in the overall population, but not in mothers who delivered at term with viral load < 400 copies/ml odds ratio (OR), 0.83; 95% CI, 0.29-2.39; P = 0.37. Among them, only duration of antenatal therapy was associated with transmission (OR by week, 0.94; 95% CI, 0.90-0.99; P = 0.03).
Low maternal plasma viral load is the key factor for preventing MTCT. Benefits in terms of MTCT reduction may be expected from early antiretroviral prophylaxis. The potential toxicity of prolonged antiretroviral use in pregnancy should be evaluated.
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.
To assess humoral responses to SARS-CoV-2 Delta-variant in people with HIV (PWH) after BNT162b2-vaccination.
Multicenter cohort study of PWH with CD4 + cell count less than 500 cells/μl and viral ...load less than 50 copies/ml on stable antiretroviral therapy for at least 3 months.
Anti-SARS-CoV-2 receptor-binding-domain IgG antibodies (anti-RBD IgG) were quantified and neutralization capacity was evaluated by ELISA/GenScript and virus-neutralization-test against the D614G-strain, beta and delta variants before vaccination (day 0) and 1 month after complete schedule (M1).
We enrolled 97 PWH, 85 received two vaccine shots. The seroconversion rate for anti-RBD IgG was 97% 95% confidence interval (CI) 90-100% at M1. Median (IQR) anti-RBD IgG titer was 0.97 (0.97-5.3) BAU/ml at D0 and 1219 (602-1929) at M1. Neutralization capacity improved between D0 (15%; 50% CI 8-23%) and M1 (94%; 95% CI 87-98%) ( P < 0.0001). At M1, NAbs against the D614G strain, beta and delta variants were present in 82, 77, and 84% PWH, respectively. The seroconversion rate and median anti-RBD-IgG level were 91% and 852 BAU/ml, respectively, in PWH with CD4 + cell count less than 250 ( n = 13) and 98% and 1270 BAU/ml for CD4 + greater than 250 ( n = 64) ( P = 0.3994). NAbs were present in 73% of PWH with CD4 + less than 250 and 97% of those with CD4 + cell count greater than 250 ( P = 0.0130). NAbs against beta variant were elicited in 50% in PWH with CD4 + cell count less than 250 and in 81% of those with CD4 + cell count greater than 250 ( P = 0.0292). CD4 + and CD8 + T-cell counts were unchanged, whereas CD19 + B-cell counts decreased after vaccination(208 ± 124 at D0 vs. 188 ± 112 at M1, P < 0.01). No notable adverse effects or COVID-19 cases were reported.
Seroconversion rates were high, with delta-neutralization rates similar to those for the D61G strain, after a two-dose BNT162b2 vaccination in PWH.
Abstract
Background
Several studies have shown that NNRTI/PI-based triple therapy could be safely administered as a 4 days (4D) or 5 days (5D) a week maintenance strategy. We report here our ...experience of using an integrase inhibitor (INSTI)-based 4D/5D regimen in virologically suppressed HIV patients.
Methods
This cohort study enrolled adult patients on ART with viral load (VL) <50 copies/mL for >1 year, who switched to an INSTI-based triple regimen given 4D/5D a week. The primary endpoint was the virological efficacy rate at Week (W) 48, with virological failure defined as confirmed VL ≥50 copies/mL.
Results
A total of 73 patients were included (n = 28 for 4D, n = 45 for 5D): 54 men (74%), median (IQR) age 51 (45–57) years, ART duration 10 (6–18) years and duration of viral suppression 5 (2–9) years at baseline. As of 25 March 2019, the median follow-up was 21 (14–35) months, with a total of 161 patient-years of follow-up; all patients had reached the W24 visit, 66 (90%) W48 and 34 (47%) W96. Four patients discontinued the strategy: virological failure (n = 2) at W60 and W67, respectively, switch for renal toxicity (n = 1) at W28 and switch to rilpivirine/dolutegravir (n = 1) at W65. Overall the rate of virological success (95% CI) was 100% (94%–100%) at W24 and W48 and 93.7% (79.8%–98.2%) at W96.
Conclusions
While waiting for the final results of the large randomized QUATUOR ANRS-170 study, our real-life results suggest that the use of an intermittent maintenance triple-drug regimen given as a weekend (2 or 3 days) off is as effective with an INSTI-based regimen as with a PI or an NNRTI.
We retrospectively studied outcomes for patients infected with human immunodeficiency virus who received highly active antiretroviral therapy (HAART) and had stopped receiving secondary prophylaxis ...against toxoplasmic encephalitis (TE) or disseminated Mycobacterium avium complex (MAC) infection. Nineteen patients had a history of TE, and 26 had a history of disseminated MAC infection. The median duration of secondary prophylaxis was 27 months, and the median duration of HAART before discontinuation of secondary prophylaxis was 22 months. Median CD4+ cell counts at the time of cessation of secondary prophylaxis against TE or disseminated MAC infection were 404 and 105 cells/mm3, respectively. Plasma virus load was undetectable in 68% of the patients who had a history of TE and in 31% of patients who had a history of disseminated MAC infection. Patients were followed up for a median of 29 months after discontinuation of secondary prophylaxis; no relapses occurred in patients with a history of TE, and 3 relapses occurred in patients with a history of disseminated MAC infection (incidence, 4 relapses per 100 person-years).
Target-detected (TD) results or low-level viraemia (LLV) can be observed in HIV-1 patients on ART, which regularly raises questions.
We describe here the impact on HIV-1 RNA quantification of ...switching from the COBAS AmpliPrep/COBAS TaqMan (CAP/CTM) to the Cobas 6800 system (C6800), based on analyses of viraemia close to the lower limit of quantification (LLoQ).
We retrospectively selected two groups of patients: 200 individuals whose viral loads (VLs) were consistently <50 copies/mL with CAP/CTM for at least 3 years before switching to C6800 (group 1), and 35 other patients with confirmed LLV when C6800 was in use (group 2). In both groups, we compared several consecutive VL results performed before and after the change of quantification assay. Analyses were performed with McNemar's paired tests or Fisher's exact tests.
In group 1, the frequency of TD results (below or above the LLoQ) increased significantly after the switch to C6800 for patients with <25% of results being TD for VLs performed with CAP/CTM (P < 0.0001). Significantly more patients had at least one VL ≥20 or ≥50 copies/mL with C6800, in both group 1 (37.0% versus 18.5%; P < 0.0001 and 6.5% versus 0%; P = 0.0009, respectively) and group 2 (100% versus 66%; P = 0.0015 and 97% versus 40%; P < 0.0001, respectively).
C6800 revealed residual or low-level HIV-1 RNA that was not detected with CAP/CTM, resulting in twice as many patients being found to have a VL ≥20 copies/mL. Physicians and patients should be aware of possible differences in results between assays, and it is crucial to specify the quantitative assay used in studies.
Background. The rate of mother-to-child transmission (MTCT) of human immunodeficiency virus (HIV) type 1 is as low as 0.5% in non–breast-feeding mothers who delivered at term while receiving ...antiretroviral therapy with a plasma viral load <500 copies/mL. This situation accounted for 20% of the infected children born during the period 1997–2006 in the French Perinatal Cohort. We aimed to identify factors associated with such residual transmission risk. Methods. We performed a case-control study nested in the aforementioned subpopulation of the French Perinatal Cohort. Results. Nineteen case patients (transmitters) and 60 control subjects (nontransmitters) were included. Case patients and control subjects did not differ by geographical origin, gestational age at HIV diagnosis, type of antiretroviral therapy received, or elective Cesarean delivery. Case patients were less often receiving treatment at the time that they conceived pregnancy than control subjects (16% vs 45%; P=.017). A lower proportion of case patients had a viral load <500 copies/mL, compared with control subjects, at 14 weeks (0% vs 38.1%; P=.02), 28 weeks (7.7% vs 62.1%; P=.005), and 32 weeks: (21.4% vs 71.1%; P=.004). The difference remained significant when we restricted analysis to the 10 of 16 intrapartum transmission cases. In a multivariate analysis at 30±4 weeks adjusted for viral load, CD4+ T cell count, and time at antiretroviral therapy initiation, viral load was the only factor independently associated with MTCT of HIV (adjusted odds ratio, 23.2; 95% confidence interval, 3.5–553; P<.001). Conclusions. Early and sustained control of viral load is associated with a decreasing residual risk of MTCT of HIV-1. Guidelines should take into account not only CD4+ T cell count and risk of preterm delivery, but also baseline HIV-1 load for deciding when to start antiretroviral therapy during pregnancy.
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.
Background Silent cerebral small-vessel disease (CSVD) is defined as white matter hyperintensities, silent brain infarction, or microbleeds. CSVD is responsible for future vascular events, cognitive ...impairment, frailty, and shorter survival. CSVD prevalence among middle-aged people living with well-controlled human immunodeficiency virus (HIV) infection (PLHIV) is unknown. Methods The French National Agency for Research on AIDS and Viral Hepatitis (ANRS) EP51 Microvascular Brain Retina and Kidney Study (MicroBREAK; NCT02082574) is a cross-sectional study with prospective enrollment of treated PLHIV, ≥50 years old with viral load controlled for ≥12 months, and frequency age- and sex-matched HIV-uninfected controls (HUCs). It was designed to estimate CSVD prevalence on 3T magnetic resonance imaging (3D fluid-attenuated inversion recovery, transversal T2-weighted gradient-echo imaging and diffusion-weighted imaging), as diagnosed by 2 blinded neuroradiologists. A logistic regression model was used to assess the impact of HIV on CSVD after adjustment for traditional risk factors. Results Between June 2013 and May 2016, 456 PLHIV and 154 HUCs were recruited. Median age was 56 and 58 years, respectively (P = .001), among whom 84.9% and 77.3%, respectively (P = .030), were men. CSVD was detected in 51.5% of PLHIV and 36.4% of HUCs with an adjusted odds ratio (aOR) of 2.3. The HIV impact differed according to age, with aOR values of 5.3, 3.7, and 1.0 for age groups <54, 54–60, and >60 years, respectively (P = .022). Older age, hypertension, and lower CD4 cell count nadir were independently associated with a higher risk of CSVD among PLHIV. Conclusions HIV is an independent risk factor for CSVD. Despite sustained immunovirological control, the CSVD prevalence was twice as high among middle-aged PLHIV than HUCs.
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