Genital Human Immunodeficiency Virus-1 RNA and DNA Shedding in Virologically Suppressed Individuals Switching From Triple- to Dual- or Monotherapy: Pooled Results From 2 Randomized, Controlled Trials.

BACKGROUND: Increasingly, people living with human immunodeficiency virus (HIV) benefit from lower drug regimens (LDRs). Exploring viral genital shedding during LDRs is crucial to ensure their safety. METHODS: We pooled genital sub-studies from 2 clinical trials in this area. Patients were randomized 1:1 to continue abacavir/lamivudine/dolutegravir or switch to dolutegravir (MONCAY trial), or to continue tenofovir/emtricitabine + a third agent or switch to tenofovir/emtricitabine (TRULIGHT trial). Participants whose plasma HIV-RNA remained <50 copies/mL had sperm or cervicovaginal lavage collected between Weeks 24 and 48. HIV-RNA and HIV-DNA were amplified by ultrasensitive polymerase chain reaction. The main objective was to measure the proportion of participants who had no detectable HIV in genital fluids, both according to each strategy and then in an aggregated analysis (LDR versus triple therapies). RESULTS: There were 64 participants (35 males, 29 females) included: 16 received dual therapies and 16 received triple therapies in TRULIGHT; and 16 received monotherapies and 16 received triple therapies in MONCAY. In TRULIGHT, 13/15 (87%) of evaluable participants on dual therapy had no detectable HIV in their genital fluid, versus 14/15 (93%) under triple therapy (P = 1.0). In MONCAY, these figures were 12/15 (80%) on monotherapy versus 13/16 (81%) on triple therapy (P = 1.0). In the pooled analysis, a similar proportion of participants in the LDR and triple therapy groups had no detectable HIV: 25/30 (83%) and 27/31 (87%), respectively (P = .73). CONCLUSIONS: There was no evidence of increased HIV-RNA and/or -DNA shedding in the genital fluids of people who maintained undetectable plasma HIV-RNA during LDRs. CLINICAL TRIALS REGISTRATION: NCT02302547 and NCT02596334.

Dolutegravir-based monotherapy or dual therapy maintains a high proportion of viral suppression even in highly experienced HIV-1-infected patients.

BACKGROUND: Dolutegravir is a powerful, well-tolerated integrase inhibitor with a high genetic barrier to resistance and may thus constitute the backbone of lightened regimens. METHODS: This was a monocentric, retrospective study. HIV-1-infected patients receiving dolutegravir as monotherapy (mDGV) or dual therapy (dDGV) were systematically identified. The primary outcome was the proportion of patients who maintained undetectable (<50 copies/mL) plasma HIV RNA [plasma viral load (PVL)]. RESULTS: We identified 21 patients on mDGV (50 mg/day) and 31 on dDGV (50 or 100 mg/day, with atazanavir  ±  ritonavir, n = 12; rilpivirine, n = 11; maraviroc, n = 3; lamivudine, n = 3; darunavir/ritonavir, n = 1; or abacavir, n = 1). All of the patients were treatment experienced and 48% had experienced at least one virological failure. The baseline characteristics were as follows (for the mDGV/dDGV patients, respectively): 5%/29% had a history of AIDS; the median (IQR) highest PVL was 4.5 (4.3-5.5)/5.3 (4.7-5.6) log copies/mL; the median (IQR) nadir CD4+ count was 310 (280-468)/199 (134-281) cells/mm(3); 100% had undetectable PVL before the mDGV for a median (IQR) duration of 5.9 (3.5-9.9) years/81% had undetectable PVL before the dDGV for a median (IQR) duration of 3.7 (1.4-8.3) years; and the median (IQR) HIV DNA level was 2.7 (2.1-3.1)/2.9 (2.7-3) log copies/10(6) PBMCs. At the last follow-up visit, 100% and 97% of patients showed undetectable PVL following mDGV and dDGV, respectively [median (IQR) follow-up of 32 (29-45) and 50 (30-74) weeks, respectively]. CONCLUSIONS: In our experience, dolutegravir-based lightened regimens provided a high proportion of viral suppression, even in highly treatment-experienced patients.

Long-term antiretroviral therapy initiated during primary HIV-1 infection is key to achieving both low HIV reservoirs and normal T cell counts.

OBJECTIVES: To characterize viro-immunological outcomes following long-term combined antiretroviral therapy (cART) initiated during primary HIV infection (PHI) or chronic HIV infection (CHI) and to identify factors predictive of optimal viro-immunological responder (OVIR) status. METHODS: This was a prospective, single-centre cohort study of HIV-1-infected patients on effective cART. Total cell-associated HIV DNA levels and T cell counts before and during treatment were used to identify factors predictive of OVIR status {i.e. low HIV DNA level [<2.3 log10 copies/10(6) peripheral blood mononuclear cells (PBMCs)], together with normalization of the absolute/relative CD4+ T cell counts and CD4+/CD8+ ratio}. RESULTS: A total of 307 patients were enrolled, of whom 35 started cART during PHI (<4 months post-infection) and 272 during CHI. HIV DNA decay was modelled with a non-linear mixed-effects model that showed two phases of HIV DNA decay, both of which were significantly more pronounced in the PHI group. At the end of follow-up, after a median of 4 years of viral suppression (<50 copies/mL), HIV DNA levels were lower in the PHI group than in the CHI group (median = 2.15 versus 2.84 log10 copies/10(6) PBMCs; P< 0.0001). Immune reconstitution was more rapid and sustained in the PHI group (median = 883 versus 619 CD4+ cells/mm(3); 41% versus 31% CD4+; CD4+/CD8+ 1.31 versus 0.77; all P< 0.0001). Finally, OVIR status was obtained in 19/35 (54%) and 7/272 (3%) patients in the PHI and CHI groups (P< 0.0001), respectively. In a logistic regression analysis, cART initiation during PHI (OR = 16, 95% CI = 3.5-72.3) and HIV DNA level <3.3 log10 before treatment (OR = 4.8, 95% CI = 1.2-19.3) were independently predictive of OVIR status. CONCLUSIONS: Initiating cART during PHI represents a major opportunity to reduce HIV reservoirs and achieve optimal immune reconstitution.

Long-term HIV-1 virologic control in patients on a dual NRTI regimen.

BACKGROUND: Since the release of protease inhibitors, only 2 randomized trials in the late 1990s have re-assessed the potency of dual nucleoside reverse transcriptase inhibitor (NRTI) combination (2N) as a maintenance strategy for patients whose HIV RNA was suppressed by tri-therapy. The objective of this study was to describe the characteristics of patients who exhibited durable virologic suppression while receiving 2N. METHODS: A retrospective study was conducted in 2 French hospitals. Using electronic medical records, we identified all HIV-1-infected patients treated with tenofovir/emtricitabine or abacavir/lamivudine (without a third agent) between 2005 and 2012. RESULTS: Out of 1,255 patients, 37 (3%) received a 2N regimen and were included in this study. All received a fixed-dose combination of either tenofovir/emtricitabine (n = 31) or abacavir/lamivudine (n = 6). This regimen was a first-line (n = 8) or a simplification (n = 29) strategy. The total follow-up for patients receiving 2N was 123 patient-years (median, 3.2 years; interquartile range [IQR], 1.3-5.1). At the last visit, 33 of 37 patients were continuing with 2N and had HIV RNA <50 copies/mL (success rate of 89%, snapshot analysis). These patients had received early treatment (median CD4+ nadir, 340/mm3) and had a low HIV RNA zenith (median, 3.9 log/mL) and a low HIV DNA level (median, 2.5 log copies/106 peripheral blood mononuclear cells). Four patients, treated with tenofovir/emtricitabine in the simplify cation group, experienced viral failure. CONCLUSIONS: These results suggest that, in selected patients, a 2N fixed-dose combination is able to maintain viral suppression durably. Such a simple strategy could reduce both the constraints and side effects experienced by patients and the costs for the community.

Aortic prosthetic endocarditis with Neisseria elongata subspecies nitroreducens.

A case of Neisseria elongata subsp. nitroreducens endocarditis with a favourable course is presented. Dental foci were involved as the infective origin. Only conservative therapy was performed for 6 weeks; no complications were registered in 3 months of follow-up. The other 12 cases with similar aetiology communicated in the past 30 y were reviewed.