Plasma Tenofovir Levels to Support Adherence to TDF/FTC Preexposure Prophylaxis for HIV Prevention in MSM in Los Angeles, California.

BACKGROUND: Tenofovir disoproxil fumarate/emtricitabine preexposure prophylaxis (PrEP) is effective against HIV acquisition when taken as prescribed. Strategies that identify and intervene with those challenged by adherence to daily medication are needed. SETTING: PATH-PrEP was an open-label single-arm interventional cohort study conducted at 2 community-based clinical sites in Los Angeles, CA. METHODS: We enrolled self-identified men who have sex with men and transgender women ≥18 years of age at an elevated risk of HIV acquisition. Participants received a postexposure prophylaxis (PEP)-based or PrEP-based HIV prevention package for at least 48 weeks. Plasma tenofovir levels from each PrEP visit assessed as below the limit of quantitation (<10 ng/mL) triggered increased adherence support. RESULTS: Three hundred one participants enrolled. Forty-eight-week retention in the PrEP cohort was 75.1%. Biomarker evidence of PrEP adherence consistent with ≥4 doses per week at weeks 4, 12, 24, 36, and 48 was found in 83.1%, 83.4%, 75.7%, 71.6%, and 65.5% of participants, respectively; younger and African American participants were less likely to have protective drug levels. Most of those with suboptimal adherence had adherence improvement after brief intervention. One seroconversion occurred in a participant who discontinued PrEP. Nearly half (46.4%) of participants were diagnosed with at least 1 incident sexually transmitted infection during 48 weeks of study follow-up. CONCLUSIONS AND RELEVANCE: PrEP was acceptable and well tolerated in a diverse population of men who have sex with men in Los Angeles. A brief intervention triggered from biomarkers of poor adherence was associated with improved adherence. Drug level monitoring has the potential to allow targeting of additional adherence support to those struggling with daily tablet adherence.

Evaluation of the Lipid Concentrations after Switching from Antiretroviral Drug Tenofovir Disoproxil Fumarate/Emtricitabine to Abacavir Sulfate/Lamivudine in Virologically-suppressed Human Immunodeficiency Virus-infected Patients.

Objective Recently, tenofovir disoproxil fumatate (TDF)-related side effects, such as renal nephrotoxicity and reduction of bone mineral density, have been reported. Consequently, increased switching from fixed-dose tablet TDF and emtricitabine (TDF/FTC) to abacavir and lamivudine (ABC/3TC) has occurred. Interestingly, while TDF has a lipid-lowering property, one of the ABC-related side effects is hyperlipidemia. Therefore, such switching could cause lipid elevation. To evaluate the change in lipid levels associated with switching from TDF/FTC to ABC/3TC in virologically-suppressed human immunodeficiency virus (HIV)-infected patients. Methods This is a retrospective, single-center study. We included the HIV-infected patients whose therapy included a drug switch from TDF/FTC to ABC/3TC between September 2009 and December 2012 at Ryukyu University Hospital. The exclusion criteria were HIV-RNA >40 copies/mL on the switching day, and a documented therapy change to a lipid-lowering agent or any other antiretroviral agents within 3 months before or after switching. We compared the low-density lipoprotein (LDL), high-density lipoprotein (HDL), total cholesterol (TC), and triglyceride (TG) levels before switching to three months after. Results A total of 18 patients met the inclusion criteria. The LDL, HDL, and TC levels significantly increased three months following the switch (p<0.05), with median (interquartile range) values of 17 (7, 32), 6 (2, 13), and 27 (10, 45) mg/dL, respectively. The TG values did not markedly change. Conclusion Switching from TDF/FTC to ABC/3TC resulted in significantly increased LDL, HDL, and TC levels.

Impact of combination antiretroviral therapy in the NOD.c3c4 mouse model of autoimmune biliary disease.

BACKGROUND & AIMS: The NOD.c3c4 mouse model develops autoimmune biliary disease characterized by spontaneous granulomatous cholangitis, antimitochondrial antibodies and liver failure. This model for primary biliary cirrhosis (PBC) has evidence of biliary infection with mouse mammary tumour virus (MMTV), suggesting that the virus may have a role in cholangitis development and progression of liver disease in this mouse model. We tested the hypothesis that MMTV infection is associated with cholangitis in the NOD.c3c4 mouse model by investigating whether antiretroviral therapy impacts on viral levels and liver disease. METHODS: NOD.c3c4 mice were treated with combination antiretroviral therapy. Response to treatment was studied by measuring MMTV RNA in the liver, liver enzyme levels in serum and liver histology using a modified Ishak score. RESULTS: Combination therapy with the reverse transcriptase inhibitors, tenofovir and emtricitabine, resulted in a significant reduction in serum liver enzyme levels, attenuation of cholangitis and decreased MMTV levels in the livers of NOD.c3c4 mice. Furthermore, treatment with the retroviral protease inhibitors, lopinavir and ritonavir, in addition to the reverse transcriptase inhibitors, resulted in further decrease in MMTV levels and attenuation of liver disease in this model. CONCLUSIONS: The attenuation of cholangitis with regimens containing the reverse transcriptase inhibitors, tenofovir and emtricitabine, and the protease inhibitors, lopinavir and ritonavir, suggests that retroviral infection may play a role in the development of cholangitis in this model.