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Objectives: The aim of this study was to assess the impact of hepatitis B virus (HBV) infection on non‐liver malignancies in people living with HIV (PLWH). Methods: All persons aged ≥ 18 years with known hepatitis B virus (HBV) surface antigen (HBsAg) status after the latest of 1 January 2001 and enrolment in the EuroSIDA cohort (baseline) were included in the study; persons were categorized as HBV positive or negative using the latest HBsAg test and followed to their first diagnosis of nonliver malignancy or their last visit. Results: Of 17 485 PLWH included in the study, 1269 (7.2%) were HBV positive at baseline. During 151 766 person‐years of follow‐up (PYFU), there were 1298 nonliver malignancies, 1199 in those currently HBV negative [incidence rate (IR) 8.42/1000 PYFU; 95% confidence interval (CI) 7.94–8.90/1000 PYFU] and 99 in those HBV positive (IR 10.54/1000 PYFU; 95% CI 8.47–12.62/1000 PYFU). After adjustment for baseline confounders, there was a significantly increased incidence of nonliver malignancies in HBV‐positive versus HBV‐negative individuals [adjusted incidence rate ratio (aIRR) 1.23; 95% CI 1.00–1.51]. Compared to HBV‐negative individuals, HBsAg‐positive/HBV‐DNA‐positive individuals had significantly increased incidences of nonliver malignancies (aIRR 1.37; 95% CI 1.00–1.89) and NHL (aIRR 2.57; 95% CI 1.16–5.68). There was no significant association between HBV and lung or anal cancer. Conclusions: We found increased rates of nonliver malignancies in HBsAg‐positive participants, the increases being most pronounced in those who were HBV DNA positive and for NHL. If confirmed, these results may have implications for increased cancer screening in HIV‐positive subjects with chronic HBV infection. [ABSTRACT FROM AUTHOR]

Objectives: Low HIV reservoirs may be associated with viral suppression under a lower number of antiretroviral drugs. We investigated tenofovir disoproxil fumarate/emtricitabine as a maintenance strategy in people living with HIV (PLHIV) with low HIV-DNA.Methods: TRULIGHT (NCT02302547) was a multicentre, open-label, randomized trial comparing a simplification to tenofovir disoproxil fumarate/emtricitabine versus a triple regimen continuation (tenofovir disoproxil fumarate/emtricitabine with a third agent, control arm) in virologically suppressed adults with HIV-DNA <2.7 log10 copies/106 PBMCs and no prior virological failure (VF). The primary endpoint (non-inferiority margin 12%) was the percentage of participants with a plasma viral load (pVL) <50 copies/mL in ITT (Snapshot approach) and PP analyses at Week 48 (W48).Results: Of the 326 participants screened, 223 (68%) were randomized to the tenofovir disoproxil fumarate/emtricitabine arm (n = 113) or control arm (n = 110). At W48, the tenofovir disoproxil fumarate/emtricitabine and control arms maintained a pVL < 50 copies/mL in 100/113 (88.5%) and 100/110 (90.9%) participants, respectively (ITT difference 2.4%, 95% CI -5.9 to 10.7; PP difference 3.4%, 95% CI -4.2 to 11.0). Six VFs occurred in the tenofovir disoproxil fumarate/emtricitabine arm (two with emerging mutations M184V and K65R) versus two in the control arm (ITT difference 3.5%, 95% CI -1.9 to 9.4). All VFs were resuppressed after treatment modification.Conclusions: Although non-inferiority was shown, simplification to tenofovir disoproxil fumarate/emtricitabine should not be used for most PLHIV because of a low risk of VF with resistance. [ABSTRACT FROM AUTHOR]

Résumé: L'archivage du VIH dans ses cellules cibles à demi-vie longue est responsable de la constitution de ce que l'on appelle ses réservoirs. La quantification de l'ADN VIH total dans les cellules mononucléées sanguines, qui ne représente sans doute qu'une approximation de l'ensemble des réservoirs anatomiques et cellulaires, a cependant fait l'objet de nombreuses études qui ont montré des corrélations fortes avec d'autres méthodes de quantification des réservoirs, avec l'histoire naturelle de l'infection, son évolution virologique, immunologique et clinique sous traitement, ainsi que sa valeur prédictive du succès de certaines stratégies d'allègement ou d'interruption thérapeutique. Cette technique est facilement accessible en routine et, même s'il n'existe pas encore de seuils quantitatifs validés pour les prises de décision, il peut être utile d'y recourir pour éclairer certaines situations clinico-virologiques ou pour conforter certains choix thérapeutiques (en particulier lors d'allègement). Archiving HIV in its long half-life target cells is responsible for building what are called its reservoirs. The quantification of total HIV DNA in blood mononuclear cells, which probably represents only an approximation of all anatomical and cellular reservoirs, has, however, been the subject of numerous studies which showed strong correlations with other methods of quantification of reservoirs, with the natural history of the infection, its virological, immunological and clinical evolution under treatment, as well as its predictive value of the success of specific strategies (i.e. therapeutic de-escalation or interruption). This technique is easily accessible routinely and, although there are still no quantitative thresholds validated for decision-making, it may be useful to use it to clarify certain clinical or virological situations or to reinforce specific therapeutic choices (especially during therapeutic de-escalation). [ABSTRACT FROM AUTHOR]

Objectives: The objective of this study was to address the dynamics of archived resistant quasispecies in cell-associated HIV-1 DNA over time in heavily ART-experienced patients with currently suppressed plasma HIV-1 RNA.Methods: Longitudinal ultra-deep sequencing (UDS) analysis of reverse transcriptase, protease and V3 Env regions was performed on blood-cell-associated HIV-1 DNA samples. Drug-resistance-associated mutations (DRAMs) and tropism were interpreted using the ANRS and Geno2Pheno algorithms. We analysed frozen blood cells from patients enrolled in the INNOVE and ANRS 123 ETOILE studies who achieved sustained viral suppression after salvage optimized ART (SOT).Results: Samples were available at baseline and 6 and ≥12 months after SOT initiation in 10 patients. V3 loop sequences displayed wide intra-individual dynamics over time. Viral variants harbouring DRAMs exhibited three non-exclusive scenarios. First, when SOT exerted the same selective pressure as previous failing regimens, some viral quasispecies still harboured the same DRAMs at the same level as at the time of virological failure. Thus, as DRAMs were mostly associated with the same viral variant, variants with a complete resistance pattern remained archived. Second, some viral variants harbouring DRAMs were no longer detected over time when SOT consisted of new antiretroviral classes or had resistance profiles distinct from those of previous failing regimens. Third, variants with new DRAMs associated with SOT emerged in blood cells during follow-up despite sustained virological control.Conclusions: Using longitudinal UDS analysis and focusing on DRAMs and tropism as markers, we demonstrated that, despite sustained virological control, archived HIV-1 DNA quasispecies continued to evolve. [ABSTRACT FROM AUTHOR]

The Kaposi sarcoma-associated herpesvirus (KSHV)-DNA level was determined in samples from 71 patients with Kaposi sarcoma (KS), 28 patients with multicentric Castleman disease (MCD), and 8 patients with primary effusion lymphoma (PEL). KSHV-DNA levels were higher in patients with active KS or MCD than in those with KS or MCD in remission. Among patients with active disease, the highest KSHV-DNA levels were observed in effusion fluid samples from patients with PEL (7.2 log10 copies/150,000 cells), followed by blood samples from patients with MCD and PEL (4.86 and 3.83 log10 copies/150,000 cells, respectively), and the lowest levels were observed in blood samples from patients with KS (2.63 log10 copies/150,000 cells). Determining the KSHV-DNA level may be useful in diagnosing KSHV-associated disease and for following up patients with KS when the development of MCD or PEL is suspected. [ABSTRACT FROM AUTHOR]

Background. The objective of this work was to assess the role of human immunodeficiency virus (HIV) reservoirs in the risk of disease progression, by studying the relationship between HIV DNA level in peripheral blood mononuclear cells (PBMCs) and progression toward acquired immunodeficiency syndrome (AIDS). Methods. HIV-1 DNA levels in PBMCs were determined by quantitative polymerase chain reaction for 383 patients enrolled in the SEROCO Cohort Study who had experienced seroconversion and had been followed up for >8 years. We compared the predictive values of HIV DNA level, HIV RNA level, and CD4+ cell count. Results. Between 6 and 24 months after seroconversion, HIV DNA level was a major predictor of progression to AIDS independently of HIV RNA level and CD4+ T cell count (adjusted relative risk [RR] for a 1-log10 increase, 3.20 [95% confidence interval {CI}, 1.70-6.00]). HIV DNA level was also a major predictor of disease progression during the first 6 months after seroconversion (adjusted RR, 4.16 [95% CI, 1.70-10.21]), when HIV RNA level and CD4+ T cell count were less predictive. Thus, a combination of these 3 markers provides the best estimate of the risk of disease progression for each patient. Conclusions. Our results suggest that HIV DNA level could be a useful additional marker in clinical practice and could aid in helping to define the best time to initiate treatment for each patient. [ABSTRACT FROM AUTHOR]

Objective: To describe HIV-1 DNA levels from baseline (W0) to week 52 (W52) among patients receiving either interleukin-2 (IL-2) + optimized background therapy (OBT) or OBT as salvage treatment. [ABSTRACT FROM PUBLISHER]