BACKGROUND:Assessing the potential increased risk of viral rebound (VR) in migrants requires adequate control for sex and acquisition risk groups. METHODS:People living with HIV1, enrolled in the ANRS CO4-French Hospital Database on HIV, who achieved virological suppression with antiretroviral therapy (ART) initiated between 2006 and 2016 were included. We first compared the risk of VR, with loss to follow-up and death considered as competing events, across origin among the HIV acquisition groups, then across acquisition groups among the different origins, and finally across modality of a variable combining sex, acquisition group, and origin. Models were adjusted for clinical and biological confounding factors. RESULTS:We included 21 571 French natives (FRA), 10 148 migrants from sub-Saharan Africa (SSA), 1137 migrants from the non-French West Indies (NFWI), and 4205 other migrants (OTHER). The 5-year probability of VR was 19% (95% confidence interval [CI] 19-20) overall, 15% in FRA, 21% in OTHER, 26% in SSA, and 34% in NFWI (p < 0.0001). It was 14% in men who have sex with men (MSM), 23% in heterosexual men, and 23% in women (p < 0.0001). After adjustment, all acquisition groups had a higher risk of VR than MSM from FRA, with men and women from NFWI having the highest risk (adjusted hazard ratio [aHR] 2.46; 95% CI 2.12-2.86 and aHR 2.59; 95% CI 2.20-3.04, respectively). Within each acquisition group, all groups of origin had a higher risk of VR than FRA. Within each region of origin, except the NFWI, heterosexual men had a higher risk of VR than MSM. CONCLUSIONS:After accounting for sex and acquisition group, migration, especially from NFWI, remains prognostic of VR.

L'étude nationale française ANRS EN20 a rapporté qu'en 2010, les décès des PVVIH survenaient en l'absence de contrôle virologique (CV≥ 50 cp/mL) chez 44% d'entre elles, avec un taux de CD4 à 243/mm3 en médiane, et 25% des décès étaient liées au SIDA. Depuis, les caractéristiques des décès chez les PVVIH n'ont pas été étudiées, malgré l'évolution attendue en lien avec l'introduction de plus en plus précoce des tARV et l'optimisation de leur efficacité. L'étude MORTIFO a eu pour objectif de décrire les caractéristiques des décès des PVVIH, survenus entre 2016 et 2020. Etude observationnelle ayant inclus les PVVIH suivies au sein de 12 centres hospitaliers et décédées entre 2016 et 2020. Parmi les 6754 PVVIH prises en charge entre 2016 et 2020, 293 (4%) PVVIH sont décédées et ont été incluses. Il s'agissait d'hommes pour n=206 (70%), ayant un âge médian de 58 ans (Q1-Q3, 52-66) et nées en France pour n=164 (55%). Le groupe à risque de transmission du VIH était les personnes déclarées « Hétérosexuelles » (n=135, 46%), « UDIV » (n=80, 27%), et « HSH » (n=56, 19%). L'infection VIH était connue depuis 22 ans (12-27), traitée depuis 17 ans (10-22), avec un nadir de CD4 à 109/mm3 (39-219). Au décès, 236 (82%) avaient une CV< 50 cp/mL, avec des CD4 à 388/mm3 (186-806) et un ratio CD4/CD8 à 0.6 (0.3-0.9). La coinfection VHC (Ig anti-VHC+) concernait 101 (35%) PVVIH dont 74/101 (73%) étaient guéries au décès; Par ailleurs 18 PVVIH (6%) étaient coinfectées par le VHB (Ag HBs+). Au dècès, 193 (62%) PVVIH étaient fumeurs actifs ou sevrés, 38 (14%) consommaient au moins 40g d'alcool par jour et 31 (10%) consommaient d'autres drogues. Enfin, 174 (59%) PVVIH sont décédées à l'hôpital et 62 (21%) n'avaient pas de logement personnel au moment du décès. Les décès liés au SIDA représentaient 29 (10%) des causes de décès. La première cause de décès était les cancers non classant SIDA (n=96, 33%) dont 32/96 (33%) cancers pulmonaires, 11/96 (11%) hémopathies, 9/96 (9%) cancers du sein et 7 (7%) cancers anaux. Concernant les autres causes, 40 (14%) PVVIH sont décédées de pathologies cardio-neurovasculaires, 22 (8%) d'hépatopathie (cirrhose ou CHC) et 9 (3%) sont décédées de la COVID en 2020. La part des décès liée au SIDA semble avoir nettement diminué par rapport aux données nationales de 2010, en lien avec un contrôle virologique plus fréquent et des CD4 plus élevés au décès. Les cancers non SIDA représentent la première cause de décès entre 2016 et 2020, en particulier les cancers pulmonaires. Le jeune âge au décès s'explique possiblement par l'exposition fréquente à divers facteurs de risque de comorbidités (tabac, alcool, drogues, coinfection VHC, précarité), et possiblement par l'activation immunitaire qui persiste à un niveau élevé, comme en témoigne le ratio CD4/CD8 bas au décès (< 0.9 chez 75% des PVVIH). Améliorer la prise en charge des PVVIH passe par le contrôle des facteurs de risque et le dépistage/traitement précoce des comorbidités telles que les cancers non classant SIDA. Aucun lien d'intérêt

BackgroundIt is cost-effective to perform an HIV test in people with specific indicator conditions (IC) with an undiagnosed HIV prevalence of at least 0.1%. Our aim was to determine the HIV prevalence for 14 different conditions across 20 European countries.MethodsIndividuals aged 18-65 years presenting for care with one of 14 ICs between January 2012 and June 2014 were included and routinely offered an HIV test. Logistic regression assessed factors associated with testing HIV positive. Patients presenting with infectious mononucleosis-like syndrome (IMS) were recruited up until September 2015.ResultsOf 10,877 patients presenting with an IC and included in the analysis, 303 tested positive (2.8%; 95% CI 2.5-3.1%). People presenting with an IC in Southern and Eastern Europe were more likely to test HIV positive as were people presenting with IMS, lymphadenopathy and leukocytopenia/ thrombocytopenia. One third of people diagnosed with HIV after presenting with IMS reported a negative HIV test in the preceding 12 months. Of patients newly diagnosed with HIV where data was available, 92.6% were promptly linked to care; of these 10.4% were reported lost to follow up or dead 12 months after diagnosis.ConclusionThe study showed that 10 conditions had HIV prevalences > 0.1%. These 10 ICs should be adopted into HIV testing and IC specialty guidelines. As IMS presentation can mimic acute HIV sero-conversion and has the highest positivity rate, this IC in particular affords opportunities for earlier diagnosis and public health benefit.

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.

OBJECTIVESTo analyse the frequency and causes of treatment discontinuation in patients who were treated with an integrase strand transfer inhibitor (INSTI), with a focus on neuropsychiatric adverse events (NPAEs).METHODSPatients in 18 HIV reference centres in France were prospectively included in the Dat'AIDS cohort. Data were collected from all patients starting an INSTI-containing regimen between 1 January 2006 and 31 December 2016. All causes of INSTI-containing regimen discontinuations were analysed, and patients' characteristics related to discontinuation due to NPAEs were sought.RESULTSINSTIs were prescribed to 21315 patients: 6274 received dolutegravir, 3421 received elvitegravir boosted by cobicistat, and 11620 received raltegravir. Discontinuation was observed in 12.5%, 20.2% and 50.9% of the dolutegravir-, elvitegravir- and raltegravir-treated patients, respectively (P < 0.001). Discontinuation for NPAEs occurred in 2.7%, 1.3% and 1.7% of the dolutegravir-, elvitegravir-, and raltegravir-treated patients, respectively (P < 0.001). In the multivariate analysis, discontinuation for NPAEs was related to dolutegravir versus elvitegravir (HR = 2.27; 95% CI 1.63-3.17; P < 0.0001) and versus raltegravir (HR = 2.46; 95% CI 2.00-3.40; P < 0.0001), but neither gender (HR for women = 1.19; 95% CI 0.97-1.46; P = 0.09) nor age (P = 0.12) was related. The association with abacavir was not retained in the final model.CONCLUSIONSAlthough discontinuation for side effects was less frequent with dolutegravir than with boosted elvitegravir, discontinuation for NPAEs, although rare (2.7%), was more frequent with dolutegravir. No patient characteristic was found to be associated with these side effects in this very large population.

ObjectivesGiven the effectiveness of treatment of HIV, hepatitis B virus (HBV) and hepatitis C virus (HCV) infections, there are considerable benefits associated with determining HIV/HBV/HCV status. We evaluated the feasibility and acceptability of systematic screening and subsequent care in an oral and maxillofacial surgery department.MethodsThe anaesthesiologists proposed screening for HIV, HBV and HCV to all individuals of unknown infection status undergoing surgery between 19 April 2016 and 19 April 2017. The endpoints were the rates of test offer, acceptance/refusal and new diagnoses. Seropositive individuals were referred to infectious disease specialists. Associations between age, sex or surgery type and test offer (eligible individuals) or acceptance/refusal (those offered testing) were investigated.ResultsOf the 1407 individuals attending the department, 1322 were eligible for inclusion in the study. Testing was proposed to 899 individuals [68%; 95% confidence interval (CI) 65–71%], 831 of whom accepted the offer (92.4%; 95% CI 90.5–94.1%). Results were obtained for 787 individuals (41 samples were uncollected and three were invalid). Age was the only factor associated with test offer in multivariable analysis [odds ratio (OR) 0.90; 95% CI 0.84–0.97, per additional 10 years], and no factor was associated with acceptance. Of the five, three and eight individuals testing positive for HIV, HBV and HCV, four, two and one patient, respectively, reported prior knowledge of seropositivity. The new diagnosis rate was 0.13% (95% CI 0–0.7%) for HIV and HBV, and 0.89% (95% CI 0.36–1.82%) for HCV [three positive polymerase chain reaction (PCR) tests]. All individuals newly diagnosed with HIV or HCV infection received specific antiviral treatment.ConclusionsRates of screening offer and acceptance were high. Substantial screening resources are required to decrease the impact of the hidden epidemics of HIV, HBV and HCV infections.

L’incidence des maladies sexuellement transmissibles (MST) ne cesse d’augmenter, representant un enjeu mondial de sante publique. Le voyage joue un role majeur dans leur diffusion. Peu d’etudes se sont interessees aux MST des voyageurs. L’objectif de ce travail etait de decrire le spectre des MST chez les voyageurs, infectes ou non par le VIH, diagnostiquees entre 2008 et 2016 dans le service de Maladies Infectieuses et Tropicales de l’hopital Pitie-Salpetriere. Nous avons inclus retrospectivement les patients ayant consulte pour une MST acquise en voyage dans la periode d’etude via une recherche dans 2 bases de donnees cliniques puis l’analyse systematique de leur dossier. 140 episodes de MST au retour de voyage ont ete retenus. Ils concernaient principalement des hommes (89%), notamment ayant des rapports sexuels avec des hommes (HSH, 54%) et infectes par le VIH (40%). Chez les voyageurs VIH-, les principales MST etaient les primoinfections VIH (38%), les infections a Neisseria gonorrhoeae (NG, 17%) et les primoinfections herpetiques (14%). Chez les VIH+, il s’agissait des syphilis (43%), des infections a Chlamydiae trachomatis (CT, 22%), des infections a NG (13%) et des hepatites C aigues (12%). Chez les VIH+, les formes anales predominaient pour les infections a CT et NG, refletant la proportion elevee d’HSH. Les VIH contractaient principalement les MST en Afrique subsaharienne et les VIH+ en Amerique latine/Caraibes et en Europe de l’ouest. Ce travail fournit une description et une analyse precises de 140 episodes de MST en lien avec le voyage, avec un large spectre de diagnostics et de formes cliniques, et fournit des donnees nouvelles sur les voyageurs VIH+.

OBJECTIVES:We assessed virological outcomes of darunavir use in France from 2012 to 2016, in three groups of people living with HIV (PLHIV): (i) antiretroviral (ARV)-naive PLHIV; (ii) ARV-experienced PLHIV switching to darunavir while failing therapy; and (iii) ARV-experienced PLHIV switching to darunavir while virologically controlled. METHODS:Virological success (VS) was defined as a plasma HIV-1 viral load (VL) <50 copies/mL and virological failure (VF) as two consecutive VL >50 copies/mL or one VL >50 copies/mL followed by a treatment switch prior to the next VL measurement. The cumulative incidence of VS was assessed considering darunavir discontinuation, loss to follow-up and death as competing risks, while estimates of cumulative incidence of VF accounted for loss to follow-up and death. RESULTS:Among the 3235 ARV-naive PLHIV initiating darunavir, the 4 year cumulative incidence of VS was 80.9% and was associated with lower VL and higher CD4 cell counts. Among the 3485 ARV-experienced PLHIV switching to darunavir while failing therapy, the 4 year cumulative incidence of VS was 82.2% and was associated with lower VL. Among the 3005 ARV-experienced PLHIV switching to darunavir while virologically controlled, the 4 year cumulative incidence of VF was 12.6%. The risk of VF was higher with darunavir monotherapy [subdistribution hazard ratio (sHR)=1.67, 95% CI 1.15-2.42] while no difference was observed with dual therapy (sHR = 1.00, 95% CI 0.71-1.42) relative to triple therapy or more. CONCLUSIONS:Darunavir-containing regimens yielded similarly high rates of viral suppression in PLHIV whether they were ARV naive or ARV experienced switching to darunavir while failing therapy, or of maintaining VS in ARV-experienced PLHIV switching to darunavir while virologically controlled.

Background:Darunavir/ritonavir is a potent PI with a high genetic barrier and pharmacological robustness favourably investigated as monotherapy. Whether darunavir could be dose reduced in the context of monotherapy deserves investigation.Methods:Patients with HIV suppressed viraemia (plasma viral load <50 copies/mL for 12 months) under ART who had switched to darunavir/ritonavir monotherapy at 600/100 mg/day between 2013 and 2015 were included in this observational 48 week single-centre study. The primary outcome was the proportion of patients with virological success (defined as plasma viral load <50 copies/mL) at week 24. Secondary outcomes included treatment strategy success and resistance.Results:Thirty-one patients were included with the following baseline characteristics [median (IQR)]: age 52 years (47-57), CD4+ 649 cells/mm3 (463-813), ART duration 16.3 years (9.2-22.3), nadir CD4+ 195 cells/mm3 (144-261) and duration of HIV suppression 7.8 years (4.8-9.7). Prior to switch, ART consisted of PI monotherapy for 28 of 31 patients [darunavir/ritonavir 800/100 mg/day (n = 26), lopinavir/ritonavir (n = 1) and atazanavir/ritonavir (n = 1)] and a triple drug regimen for 3 of 31 patients. Within the 48 weeks of follow-up, no virological failure occurred and two patients discontinued 600/100 mg of darunavir/ritonavir due to side effects at week 16 and 40, leading to a virological suppression rate of 100% (95% CI = 89-100) at weeks 24 and 48. Strategy success rates were 96.8% (95% CI = 83.3-99.9) at week 24 and 93.5% (95% CI = 78.6-99.2) at week 48. Median (IQR) Ctrough values of 800/100 mg of darunavir/ritonavir and 600/100 mg of darunavir/ritonavir were 1537 ng/mL (1286-1724) and 1255 ng/mL (873-2161), respectively.Conclusions:A lower dose of darunavir/ritonavir used as monotherapy (600/100 mg/day) was highly effective in virologically suppressed HIV-infected patients. Further studies are needed to confirm these data.

La persistance d'une réplication VIH de bas niveau (RéBaN) est observée dans la littérature chez 4–8 % des patients sous traitement antirétroviral (TAR), et pose de nombreuses questions – observance, résistance et stratégies ultérieures. Notre objectif était d'analyser la prévalence et de décrire les caractéristiques cliniques, virologiques et pharmacologiques associées aux RéBaN confirmées. Étude transversale, monocentrique incluant les patients sous TAR sans interruption depuis au moins 24 mois, avec une RéBaN définie par les deux dernières charges virales plasmatiques (CVp) entre 21 et 400 cp/mL (RéBaN « low » [RéBaNL] si deux CVp entre 21 et 50 cp/mL, et RéBaN « high » [RéBaNH] si au moins une des deux CVp entre 51 et 400 cp/mL). Les CVp étaient toutes mesurées par la technique Roche/Cobas 6800. L'analyse portait sur le sous-groupe des patients sous trithérapie avec une RéBaNH : – analyse des caractéristiques clinico-biologiques ; – calcul du genotypic sensitivity score (GSS) pour le TAR en cours à partir des génotypes cumulés ; – analyse des dosages pharmacologiques (DP) réalisés dans les 12 derniers mois (classés « satisfaisants » quand les concentrations plasmatiques mesurées des trois molécules étaient suffisantes). Au 1er janvier 2017, 224/3971 (5,6 %) patients sous TAR depuis plus de 24 mois présentaient une RéBaN, dont 161/224 (72 %) étaient sous trithérapie, 44/224 (20 %) sous bithérapie et 8/224 (4 %) sous monothérapie. Parmi les patients sous trithérapie, 92/161 (57 %) présentaient une RéBaNL et 69/161 (43 %) une RéBaNH. Ces 69 patients présentaient en médiane un âge de 53 ans (IQR 45–59), un nadir de CD4 à 178/mm3 (IQR 108–313), des CD4 actuels à 648/mm3 (IQR 449–609), une durée totale de TAR de 11 ans (IQR 6–18) et une durée sous le TAR actuel de 12 mois (IQR 5–32). Le score GSS a pu être calculé chez 52/69 de ces patients (197 génotypes sur ARN-VIH et 17 sur ADN-VIH analysés) : il était de 3 dans 83 % des cas (43/52 patients) et de 2 ou 2,5 dans les 17 % restants (9/52 patients). Des DP sous le TAR en cours étaient disponibles pour 28/69 de ces mêmes patients (42 DP analysés) : 23/28 patients (82 %) avaient un ou plusieurs dosages « satisfaisants » sous le TAR en cours, avec une virémie concomitante détectable. La majorité des patients présentant une RéBaN confirmée sont infectés par un virus sensible au TAR, sous trithérapie, avec des concentrations antirétrovirales plasmatiques adéquates. La signification et l'origine de la persistance des RéBaN, en dépit d'un TAR théoriquement efficace, ne sont pas connues. Une étude en cours devrait nous permettre d'explorer leur physiopathologie.

BACKGROUND:Reducing drug burden is a key challenge for achieving lifelong suppressive HIV therapy. Dolutegravir, with a high potency, long half-life and high genetic barrier, offers potential for monotherapy. METHODS:This observational single-centre study enrolled all patients with HIV RNA (viral load) <50 copies/mL for at least 12 months, with CD4 >350 cells/mm(3) and with no failure under integrase inhibitor therapy who had switched from suppressive ART to dolutegravir monotherapy (50 mg/day). Primary outcome was proportion of patients with viral load <50 copies/mL at week 24. RESULTS:Twenty-eight patients treated for a median ART duration of 17 years (IQR 11-20), virally suppressed for a median of 79 months (IQR 42-95) and with a median CD4 count of 624 cells/mm(3) (IQR 524-761), were enrolled. Baseline ART consisted of a three-drug (n = 10), two-drug (n = 10) or single-drug (n = 8) regimen with integrase inhibitor exposure in 13 patients. The proportion of patients maintaining viral load <50 copies/mL was 96% (95% CI 79%-100%) at week 4, 100% (95% CI = 85%-100%) at week 8, 93% (95% CI 76%-99%) at week 12 and 92% (75-99) at week 24. Three patients (3.70%; 95% CI 3.4%-10.8%) with prior integrase inhibitor experience had HIV RNA rebound with the presence of resistance mutations. Genotyping of HIV DNA using the Sanger method or ultradeep sequencing showed no integrase inhibitor resistance-associated mutations (RAMs) except for the mutation 74I in a patient on a suppressive elvitegravir regimen. The median within- and between-subject variability of dolutegravir C24 was 25% and 34%, respectively. Nine patients with a year of follow-up remained virally suppressed. CONCLUSIONS:Dolutegravir has the potency to be further investigated as a single ART in randomized studies, particularly in patients with no prior exposure to integrase inhibitors.

ObjectivesThe aim of the study was to assess the impact of rapid and sustained viral control produced by combination antiretroviral therapy (cART) on HIV‐associated immune activation and inflammation.MethodsIn this longitudinal observational study, we examined changes in interleukin‐6 (IL‐6), interferon‐γ‐inducible protein‐10 (IP‐10), monokine induced by interferon‐γ (MIG) and soluble CD14 (sCD14) levels during 2 years of effective first‐line cART. Biomarker levels before and after cART were compared with those observed in healthy subjects, using the Wilcoxon signed rank test. Elevated biomarker levels were defined with respect to values for healthy subject (mean + 2 standard deviations). Factors associated with persistently elevated biomarker levels after 2 years of cART were identified by logistic regression.ResultsWe included in the study 139 patients with a median HIV‐1 RNA level of 4.8 log10 HIV‐1 RNA copies/mL and a median CD4 cell count of 294 cells/μL at cART initiation [day 0 (D0)]. At D0, all biomarker levels were higher than in healthy subjects (P < 0.05). After 2 years of cART, IL‐6, IP‐10 and MIG levels fell significantly, by a median of 0.54, 420 and 1107 pg/mL, respectively (all P < 0.001), and were no longer elevated in > 75% of patients. In contrast, sCD14 levels did not change significantly (0.18 × 106 pg/mL; P = 0.102) and remained elevated. Older age was associated with elevated levels of IP‐10 [odds ratio (OR) 1.60 per 10 years older; P = 0.047] and MIG (OR 1.92 per 10 years older; P = 0.007) after 2 years of cART.ConclusionsThe rapid and sustained viral suppression produced by first‐line cART reduced IL‐6, IP‐10 and MIG to normal levels, while sCD14, a marker of monocyte activation, remained elevated. High levels of IP‐10 and MIG tended to persist in older patients.

BACKGROUND AND PURPOSE:The lack of antiretroviral (ARV) backbone activity associated with raltegravir has been proposed as the main explanation for virological relapse observed in patients with undetectable viraemia who are switched from a ritonavir-boosted protease inhibitor (PI) to raltegravir. However ARV activity remains difficult to assess in this context. The aim of our study was to precisely assess the ARV backbone activity in patients with undetectable viraemia who underwent raltegravir switching strategies and to evaluate the efficacy of such switching strategies based on the genotypic sensitivity score (GSS). METHODS:Patients with a plasma human immunodeficiency virus type 1 (HIV-1) RNA level of <50 copies/mL on a stable two ARV-class regimen were enrolled if they switched one of their ARV drugs to raltegravir 400 mg twice daily. The GSS was calculated using a genotyping test performed on the HIV-1 RNA of the last plasma measurement with a HIV-1 RNA level of >50 copies/mL before the switch and on the results of all previous genotyping tests. The primary endpoint was the proportion of patients with a plasma HIV-1 RNA level of <50 copies/mL at week 24. RESULTS:Fifty-six patients were enrolled in this study. The proportion of patients with a plasma HIV-1 RNA level of <50 copies/mL at week 24 was 92.9 % (range 83.0-97.2 %) in the intent-to-treat analysis and 98.1 % (90.0-99.7 %) in per-protocol analysis. When the backbone was fully active, the proportion was 100.0 % (86.7-100.0 %) at week 24 and week 48 in the per-protocol analysis. We observed a decrease in plasma total cholesterol and triglycerides of -12.7 % (p = 0.005) and -26.5 % (p = 0.001), respectively. CONCLUSIONS:Raltegravir switching strategies are effective when the associated backbone is fully active according to the GSS. In the context of undetectable viraemia, where ARV activity remains difficult to assess, the determination of the GSS requires the entire ARV history of the patient and all previous HIV-RNA genotyping test results.

OBJECTIVESTo evaluate whether a dual nucleoside reverse transcriptase inhibitor (NRTI) strategy can control HIV replication in antiviral therapy (ART)-naive HIV-infected patients with a high CD4 cell count and a low viral load (VL).METHODSThis observational study included all HIV-infected treatment-naive patients with a CD4 cell count >300 cells/mm(3), a plasma HIV RNA between 1000 copies/mL and 30,000 copies/mL and wild-type virus who initiated dual NRTI ART between January 2008 and December 2012. HIV RNA and CD4 cell count were assessed at Day 0, Week (W) 4, W12, W24 and W48. The primary endpoint was the proportion of patients with a plasma VL (pVL) <50 copies/mL at W24.RESULTSTwenty patients were included. The median (IQR) baseline characteristics were: time since HIV diagnosis, 25 months (8-66 months); CD4 cell count, 592 cells/mm(3) (405-798 cells/mm(3)); HIV RNA, 10,395 copies/mL (4106-16,566 copies/mL); and HIV DNA, 464 copies/10(6) peripheral blood mononuclear cells (195-1168 copies/10(6) PBMC). Nineteen patients received tenofovir/emtricitabine and one patient received abacavir/lamivudine. At W12, 88% of the patients with available data (n = 16/18, 95% CI 0.65-0.99) had a pVL <50 copies/mL. Overall, the proportion of patients with a pVL <50 copies/mL was 100% (n = 20/20, 95% CI 0.83-1.0) at W24 and 95% (n = 18/19, 95% CI 0.74-0.99) at W48 (with one patient lost to follow-up and one patient with poor treatment compliance). The median increase in CD4 cells was 83 cells/mm(3) (40-310 cells/mm(3)). There was no discontinuation of antiretroviral therapy for any reason such as lack of efficacy or toxicity.CONCLUSIONSThis pilot study suggests that, in patients with a high CD4 cell count and a low VL, a dual NRTI strategy may represent a potentially effective treatment strategy to control HIV replication. This needs to be confirmed in larger controlled clinical studies.

Abstract Background: Etravirine (ETR) is recommended as twice-daily dosing in pretreated patients. There are no data regarding the use of ETR once daily in HIV-experienced patients with prior resistance to first-generation non-nucleoside reverse transcripase inhibitors (NNRTIs).Objectives: To evaluate the capacity of once-daily ETR to maintain suppressed viremia over 48 weeks after switching from ETR twice daily in NNRTI-experienced patients.Methods: In this pilot open-label study, patients with plasma viral load (pVL) <50 copies/mL on a stable ETR 200 mg bid regimen were enrolled to switch to ETR 400 mg qd and followed up over 48 weeks. The primary endpoint was the proportion of patients with pVL <50 copies/mL at week 24. Secondary endpoints included the rate of pVL< 50 copies/mL at week 48, ETR pharmacokinetic parameters, and tolerability and resistance profile.Results: Twenty-four patients were included. They had extensive antiretroviral treatment for a median of 14 years (range, 1-19). All except for 2 had prior resistance to NNRTIs. Seven patients discontinued ETR once daily prior to week 48 for virological failure (3), protocol deviation (3), and side effects (1). At week 24, 95% of patients maintained pVL< 50 copies/mL (95% CI, 78.4-99.7) and 85% at week 48 (95%CI, 65.6-95.8). Two of the 3 patients with virological failure had ETR resistance mutations prior to initiation. The median ETR Ctrough level remained stable after switching from twice daily 515 ng/mL (340-758) to once daily 422 ng/mL (264-655).Conclusion: These results suggest that ETR is effective as a once-daily regimen in patients with prior NNRTI experience when HIV is sensitive to ETR. The stability of Ctrough concentrations on a once-daily regimen confirms the once-daily profile of the drug in experienced patients.

Purpose of the studyPerinatal transmission of HIV has fallen dramatically in countries where access to antiretrovirals is available, placing the focus of research on safety. The aim of this study is to assess whether in naïve or pretreated HIV‐1 women, a dual, zidovudine sparing regimen (3TC+ PI) initiated during pregnancy can control maternal viral load while preventing maternal and infant toxicities related to in utero exposure to zidovudine.MethodsWe performed a retrospective, descriptive study between January 2006 and 2012. Seventeen naïve and 28 pretreated women who received dual therapy (3TC + PI) during pregnancy were included in the studied group and compared to 49 women on standard triple therapy (3TC/ ZDV+ PI), who delivered in the same time interval, at the same hospital. The primary endpoint was the% of women with viral loads (VL) ≤ 50 cp/ml at delivery. Secondary endpoints included% of women with VL ≤ 400 cp/ml after one month of dual therapy and of women who remained under dual therapy until delivery and achieved a VL ≤ 50 cp/ml at delivery. We also compared safety outcomes during pregnancy and until 18 months in children.Summary of resultsGroups had indistinguishable median VL at day zero (200 vs. 1680, p = 0.29) and gestational ages at initiation of therapy (19.6 vs 18 weeks, p = 0.18). At initiation of dual therapy (in 80% of cases: 3TC + LPV/r; ATV/r or ATV), the median VL was 21,692 cp/ml (6589 to 31,269) for naïve women and 43 cp/ml (20 to 200) for pretreated women. In intent‐to‐treat analysis of the dual therapy group, 41/45 women (91.11%, 95% CI 78.7 to 97.5%) achieved their primary endpoint. The table presents proportions of viral success at primary and secondary endpoints in the dual (N = 45) and control (N = 49) groups. Groups had similar proportions of cesarean section (28.8% vs 34.7%, p = 0.65) and of prematurity and changes in ART due to intolerance. There was one case of MTCT for the controls and none in the dual therapy group. Newborns with prenatal ZDV exposure had higher proportions of clinical syndromes at birth (50% vs 25%, p = 0.02) and SAE in the first 18 months of life (90.3% vs 68.2%, p = 0.05) and worse haematological values at birth, with lower levels of haemoglobin (15.6 vs 17.5 g/dl, p = 0.05). ITT 3TC+PI 3TC/ZDV+PI p VL at delivery <50 91.1% 88.5% 0.72 VL at M1 <400 91.1% 73.4% 0.03 Virological success and maintained therapy p VL at delivery <50 82.2% 85.7% 0.76 ConclusionsThe 3TC+ PI dual therapy strategy in naïve or pretreated women achieved a satisfactory virologic effectiveness and resulted in less SAE in the first 18 months of life and better haematological parameters at birth for children.