Human immunodeficiency virus (HIV) pre-exposure prophylaxis (PrEP) refers to a strategy involving the use of antiretroviral (ARV) drugs to decrease the risk of HIV infection in uninfected individuals whose behavior would combine with local HIV prevalence to place them at high risk of infection. In 2012, the use of tenofovir disoproxil fumarate and emtricitabine (TDF/FTC) in combination was approved by the US Food and Drug Administration for use as PrEP, based on the results of the iPrEx 1-3 study and Partners PrEP, 4 with the former showing a 44% reduction in the incidence of HIV transmission in men who have sex with men as compared with placebo treatment, when combined with a comprehensive package of prevention. Partners PrEP showed a 67-75% relative reduction in the incidence of HIV infection using TDF/FTC among heterosexual couples in sexual partnerships containing one seronegative partner.Although there is conceptual proof of PrEP in these specific contexts, recent negative results of two studies in women, FEMPrEP 5 and VOICE, 6 showed no evidence of benefit of daily oral TDF/FTC. These negative outcomes were later ascribed to suboptimal adherence to the dosing regimen, thus indicating the need for high motivation in order to attain prevention success. Therefore, durable adherence is critical for a successful long-term prevention strategy. 2,4,6 In addition, the potential for side effects and toxicities associated with the use of TDF/ FTC 2,7 remains a concern due to its widespread administration as HIV PrEP.An optimal PrEP therapy should be safe to administer and be readily distributed to the relevant target tissues in concentrations that are sufficient to provide protection against HIV infection. Ideally, PrEP agents should be characterized by convenient dosing and by routes of administration that do not depend on the recipient maintaining daily adherence to dosing.The nonnucleoside reverse-transcriptase inhibitor RPV is a diarylpyrimidine derivative that was approved by the Food and Drug Administration in 2011 for oral administration for the treatment of HIV infection in combination with other ARV drugs. 1,3 A parenteral formulation of rilpivirine (RPV-LA) with prolonged pharmacokinetic (PK) exposure is being developed, enabling improved adherence to ARV treatment over prolonged periods and having potential as an agent for HIV PrEP. 2,8,9 The potential advantages of a long-acting formulation include infrequent parenteral administration and a low potential for gastrointestinal side effects associated with lifelong oral ARV intake. Rilpivirine long-acting (RPV-LA) is a parenteral formulation enabling prolonged plasma exposure. We explored its multiple-compartment pharmacokinetics (PK) after a single dose, for pre-exposure prophylaxis. Sixty-six HIV-negative volunteers were enrolled: women received an intramuscular dose of 300, 600, or 1,200 mg, with plasma and genital levels measured to 84 days postdose; men receiving 600 mg had similar PK determined in plasma and rectum. Ex vivo antiviral activity of cervi...

These data fully characterize the PK of TFV and TFV-DP, FTC and FTC-TP, and EFV after stopping the drug combination. Although decay in concentrations can be related to a target for EFV, this is more difficult for the IC phosphates. Consensus on 'target' triphosphate/diphosphate concentrations will further our understanding of missed/delayed doses in treatment and prevention strategies.

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Patients prefer fewer pills and once-daily (qd) dosing without food restrictions. We assessed the impact on adherence [by Medication Event Monitoring System (MEMS) cap monitoring] of switching from abacavir (ABC) and lamivudine (3TC) twice daily (bid) to ABC/3TC fixed-dose formulation (FDC, Kivexa s ) qd to achieve a qd regimen. MethodsA randomized, open-label, 8-week study comparing adherence, efficacy and safety of immediate vs. delayed switching from ABC/3TC to FDC qd. ResultsNinety-four patients were dosed. Significantly improved adherence was observed at week 4 with qd ABC/3TC across all three adherence variables: taking compliance 99.2% (90.7-100%) vs. 96.6% (60.0-100%) (P 5 0.017); dosing compliance 97.1% (64.3-100%) vs. 91.9% (33.3-100%) (P 5 0.016); and timing compliance 95.5% (53.8-100%) vs. 86.3% (4.3-100%) (P 5 0.006). Treatment satisfaction increased significantly at week 4 with ABC/3TC qd [92% (82-99%) vs. 85% (75-93%) (P 5 0.004)]. Two patients were withdrawn from the study because of intolerance to ABC/3TC. ConclusionsSwitching from ABC and 3TC bid to ABC/3TC FDC qd significantly improved adherence by MEMS cap monitoring at week 4 and improved patient satisfaction with therapy. The results remain to be confirmed over a longer follow-up. Use of qd regimens supports adherence and improves treatment satisfaction relative to bid regimens.Keywords: abacavir, adherence, HIV, lamivudine, once daily, treatment satisfaction IntroductionSignificant improvements have been observed in HIVassociated mortality and morbidity since the introduction of highly active antiretroviral therapy (HAART) [1]. Therapeutic success with any medication is dependent not only on the intrinsic properties of that medication but also on the individual's ability to reliably take the medication. This is particularly true in HIV infection, where the consequence of failing to achieve durable full viral suppression with antiretroviral therapy (ART) is the evolution of resistant virus and a reduction in treatment options [2]. Factors consistently associated with treatment success include the individual's belief systems regarding medication [3], education regarding HIV disease and its management [4], active substance abuse [5] and the social, emotional and financial status of the individual [6]. Factors relating specifically to ART include medication tolerability [7] and regimen characteristics such as the frequency of dosing and the number of pills per intake [8].A systematic review of studies across a range of medical specialties in which adherence was assessed by electronic recording devices indicated that once-daily (qd) therapy improves adherence to therapy relative to more frequent DOI: 10.1111DOI: 10. /j.1468DOI: 10. -1293DOI: 10. .2008 (2008), 9, 667-672 667 dosing, although statistical significance was not demonstrated relative to twice-daily (bid) regimens [9]. A large survey of HIV-positive persons has indicated that they would prefer therapy involving few pills, qd dosing and no food restrictions [10]. An increasing num...

TDF use for 2 weeks does not affect insulin sensitivity, as assessed by the hyperinsulinaemic euglycaemic clamp in HIV-negative male volunteers. TDF use resulted in modest, but statistically significant, reductions in total and LDL cholesterol.