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BICTEGRAVIR DISTRIBUTION AND BICTEGRAVIR/FTC/TAF ACTIVITY IN GENITAL TRACT AND RECTUM
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CROI 2020 March 8-11
Reported by Jules Levin
![0316201](../images/031620/031620-15/0316201.gif)
Arkaitz Imaz1, Juan M. Tiraboschi1, Jordi Niubo1, Javier Martinez-Picado2, Mackenzie L. Cottrell3, Pere Domingo4, Ivan Chivite5, Eugènia Negredo6, Sandra Morenilla
1.HIV and STI Unit, Infectious Diseases Department, Bellvitge University Hospital--IDIBELL, University of Barcelona, L'Hospitalet de Llobregat, Barcelona, Spain;; 2. Microbiology Department, Bellvitge University Hospital--IDIBELL, University of Barcelona, L'Hospitalet de Llobregat, Barcelona, Spain;; 3. IrsiCaixa AIDS Research Institute, Badalona, Spain;; 4. ICREA, Barcelona, Spain;; 5. UNC Eshelman School of
Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA;; 6. Infectious Diseases Department, Santa Creu i Sant Pau Hospital, Barcelona, Spain;; 7. Internal Medicine Department, Sant Joan Desp. Mois.s Broggi Hospital, Sant Joan Desp., Barcelona, Spain;; 8. Lluita Contra la Sida Foundation, Germans Trias i Pujol University Hospital, Badalona, Barcelona, Spain
Program Abstract
Antiretroviral distribution in the genital tract (GT) and rectum is required to suppress HIV replication within these compartments. Pharmacokinetics and HIV decay in the GT and rectum have not yet been described for the new integrase inhibitor bictegravir (BIC).
Prospective study of HIV-1–infected, ART–naive males (n=15) and females (n=8) initiating BIC/F/TAF 50/200/25 mg. HIV-1 RNA was measured (Abbott RealTime HIV-1; quantification limit 40 c/mL) in blood plasma(BP) as well as in seminal plasma (SP) and rectal fluid (RF) in men, and cervicovaginal fluid (CVF) in women, at baseline (BL), days 3, 7, 14 and 28, and weeks 12 and 24. HIV-1 RNA decline between timepoints in SF and RF were compared to BP. Total BIC concentrations were quantified in BP, SP, RF, rectal tissue (RT) and CVF at 24 hours post dose (C24h) on day 28 and week 12 using a validated LC-MS/MS assay.
Median (range) BL characteristics were: age 30 (20-57) yrs; CD4 419 (9-1165) cells/ BP HIV-1 RNA 4.89 (3.17-6.10) log10 c/mL. HIV-1 RNA was >40 c/mL at BL in SP, RF and CVF in 12/15, 13/15 and 4/8 individuals, with a median(range) of 3.74 (2.29-4.74), 4.29 (2.75-5.22) and 2.56 (1.61-3.56) log10 c/mL. HIV-1 RNA decrease was significantly lower in SP compared to BP up to day 14 with no statistically significant differences thereafter, whereas no differences were observed between RF and BP. Of those with HIV-1 RNA >40 c/mL in SP, RF and CVF at BL, 42%, 77% and 100% had undetectable HIV-1 RNA at day 14, and 92%, 92% and 100%, respectively, at day 28, whereas 47% of men and 37% of women had HIV-1 RNA >40 c/mL in BP at day 28. In men, median(range) BIC C24h in BP, SP, RF and RT were 2640 (424-10300) ng/mL; 65.5 (20.1-923) ng/mL; 23.4 (4.5-336.9) ng/swab; and 74.1 (6.0-478.5) ng/g, respectively. In women, BIC C24h in BP and CFV were 2320 (834-5770) ng/mL and 61.6 (14.4-1760.2) ng/mL. On average BIC C24h in SP,CVF and RT (assuming tissue density=1g/ml) were 2.7%, 2.8% and 2.6% of BP C24h. Total BIC concentrations exceeded the EC50 for wild type HIV-1 (1.1 ng/mL) in all compartments.
BIC/F/TAF resulted in rapid HIV-1 RNA decay in GT and rectum. Total BIC concentrations in these compartments exceed the EC50 for wild-type HIV-1.
Arkaitz Imaz1, Juan M. Tiraboschi1, Jordi Niubo1, Javier Martinez-Picado2, Mackenzie L. Cottrell3, Pere Domingo4, Ivan Chivite5, Eugènia Negredo6, Sandra Morenilla
1.HIV and STI Unit, Infectious Diseases Department, Bellvitge University Hospital--IDIBELL, University of Barcelona, L'Hospitalet de Llobregat, Barcelona, Spain;; 2. Microbiology Department, Bellvitge University Hospital--IDIBELL, University of Barcelona, L'Hospitalet de Llobregat, Barcelona, Spain;; 3. IrsiCaixa AIDS Research Institute, Badalona, Spain;; 4. ICREA, Barcelona, Spain;; 5. UNC Eshelman School of
Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA;; 6. Infectious Diseases Department, Santa Creu i Sant Pau Hospital, Barcelona, Spain;; 7. Internal Medicine Department, Sant Joan Desp. Mois.s Broggi Hospital, Sant Joan Desp., Barcelona, Spain;; 8. Lluita Contra la Sida Foundation, Germans Trias i Pujol University Hospital, Badalona, Barcelona, Spain
Program Abstract
Antiretroviral distribution in the genital tract (GT) and rectum is required to suppress HIV replication within these compartments. Pharmacokinetics and HIV decay in the GT and rectum have not yet been described for the new integrase inhibitor bictegravir (BIC).
Prospective study of HIV-1–infected, ART–naive males (n=15) and females (n=8) initiating BIC/F/TAF 50/200/25 mg. HIV-1 RNA was measured (Abbott RealTime HIV-1; quantification limit 40 c/mL) in blood plasma(BP) as well as in seminal plasma (SP) and rectal fluid (RF) in men, and cervicovaginal fluid (CVF) in women, at baseline (BL), days 3, 7, 14 and 28, and weeks 12 and 24. HIV-1 RNA decline between timepoints in SF and RF were compared to BP. Total BIC concentrations were quantified in BP, SP, RF, rectal tissue (RT) and CVF at 24 hours post dose (C24h) on day 28 and week 12 using a validated LC-MS/MS assay.
Median (range) BL characteristics were: age 30 (20-57) yrs; CD4 419 (9-1165) cells/ BP HIV-1 RNA 4.89 (3.17-6.10) log10 c/mL. HIV-1 RNA was >40 c/mL at BL in SP, RF and CVF in 12/15, 13/15 and 4/8 individuals, with a median(range) of 3.74 (2.29-4.74), 4.29 (2.75-5.22) and 2.56 (1.61-3.56) log10 c/mL. HIV-1 RNA decrease was significantly lower in SP compared to BP up to day 14 with no statistically significant differences thereafter, whereas no differences were observed between RF and BP. Of those with HIV-1 RNA >40 c/mL in SP, RF and CVF at BL, 42%, 77% and 100% had undetectable HIV-1 RNA at day 14, and 92%, 92% and 100%, respectively, at day 28, whereas 47% of men and 37% of women had HIV-1 RNA >40 c/mL in BP at day 28. In men, median(range) BIC C24h in BP, SP, RF and RT were 2640 (424-10300) ng/mL; 65.5 (20.1-923) ng/mL; 23.4 (4.5-336.9) ng/swab; and 74.1 (6.0-478.5) ng/g, respectively. In women, BIC C24h in BP and CFV were 2320 (834-5770) ng/mL and 61.6 (14.4-1760.2) ng/mL. On average BIC C24h in SP,CVF and RT (assuming tissue density=1g/ml) were 2.7%, 2.8% and 2.6% of BP C24h. Total BIC concentrations exceeded the EC50 for wild type HIV-1 (1.1 ng/mL) in all compartments.
BIC/F/TAF resulted in rapid HIV-1 RNA decay in GT and rectum. Total BIC concentrations in these compartments exceed the EC50 for wild-type HIV-1.
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