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.

Ventricular coupling of electrical and mechanical dyssynchronization in heart failure patients.

We studied the relationships of electrical and mechanical synchronization in patients with heart failure (CHF) and various degree of ventricular conduction delays. Ninety-two CHF patients (60 +/- 13 years old, LVEF < 45%), NYHA II-III-IV, and 35 age-matched control subjects were studied with angioscintigraphic phase analysis. We measured ejection fractions (LVEF, RVEF) and calculated the total activation time for the left (TtLV) and right ventricle (TtRV), and the synchronization time between right and left ventricle (TRVLV), and between LV apex and base (Tab). Patients were divided into three groups according to QRS duration: group 1 < 120 ms (n = 28), group 2 < 150 ms (n = 23), group 3 > or = 150 ms (n = 41). In group 1: LVEF = 31.1 +/- 10.9%, RVEF = 30.1 +/- 12.6%, TtLV = 204 +/- 70 ms, TtRV = 183 +/- 61 ms, TRVLV = 7 +/- 33 ms, Tab = 29 +/- 23 ms. In group 2, these were: 27.8 +/- 9.1%, 27.8 +/- 8.8%, 227 +/- 95 ms, 248 +/- 137 ms, 35 +/- 42 ms*, and 39 +/- 53 ms respectively. In group 3: LVEF = 20.5 +/- 9.5%t, RVEF = 28.4 +/- 16.1%, TtLV = 304 +/- 155 mst, TtRV = 234 +/- 106 mst, TRVLV = 64 +/- 42 mst, and Tab = 67 +/- 48 ms*, all P < 0.001 versus controls *P < 0.05 versus G1, tP < or = 0.01 versus G1. A significant relation links QRS to both inter- and intraventricular asynchrony (TRVLV: r = 0.65; TtLL: r = 0.70, Tab: r = 0.60), and to LV function (r = 0.72); while LVEF relates more closely to intraventricular asynchrony: TtLV (r = 0.52), TtLL (r = 0.67), than to interventricular asynchrony: TRVLV (r = 0.48); P < 0.01, P < or = 0.001. In CHF patients, electromechanical and contractile alterations are coupled; regional activation may be an early parameter allowing the detection of ventricular dyssynchronization.