Publications

30

Dec, 2015

Darunavir population pharmacokinetics in pregnancy

 

Authors: Moltò J, Valle M, Colbers A, Clotet V, Burger D.

Published: 16th edition of the International Workshop on Clinical Pharmacology of HIV & Hepatitis Therapy, May 26th – 28th 2015, Westin Alexandria

 

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18

Sep, 2015

HIV-1 Drug Resistance and Second-line Treatment in Children Randomized to Switch at Low versus Higher RNA Thresholds

 

Authors: Harrison L, Melvin A, Fiscus S, et al. For PENPACT-1 (PENTA 9PACTG 390) Study Team.

Published in: JAIDS 2015;70(1):42-53

Background The PENPACT-1 trial compared virologic thresholds to determine when to switch to second-line antiretroviral therapy (ART). Using PENPACT-1 data, we aimed to describe HIV-1 drug resistance accumulation on first-line ART by virologic threshold.

Methods PENPACT-1 had a 2 × 2 factorial design, randomizing HIV-infected children to start protease inhibitor (PI) versus nonnucleoside reverse transcriptase inhibitor (NNRTI)-based ART, and switch at a 1000 copies/mL versus 30,000 copies/mL threshold. Switch criteria were not achieving the threshold by week 24, confirmed rebound above the threshold thereafter, or Center for Disease Control and Prevention stage C event. Resistance tests were performed on samples ≥1000 copies/mL before switch, resuppression, and at 4-years/trial end.

Results Sixty-seven children started PI-based ART and were randomized to switch at 1000 copies/mL (PI-1000), 64 PIs and 30,000 copies/mL (PI-30,000), 67 NNRTIs and 1000 copies/mL (NNRTI-1000), and 65 NNRTI and 30,000 copies/mL (NNRTI-30,000). Ninety-four (36%) children reached the 1000 copies/mL switch criteria during 5-year follow-up. In 30,000 copies/mL threshold arms, median time from 1000 to 30,000 copies/mL switch criteria was 58 (PI) versus 80 (NNRTI) weeks (P = 0.81). In NNRTI-30,000, more nucleoside reverse transcriptase inhibitor (NRTI) resistance mutations accumulated than other groups. NNRTI mutations were selected before switching at 1000 copies/mL (23% NNRTI-1000, 27% NNRTI-30,000). Sixty-two children started abacavir + lamivudine, 166 lamivudine + zidovudine or stavudine, and 35 other NRTIs. The abacavir + lamivudine group acquired fewest NRTI mutations. Of 60 switched to second-line, 79% PI-1000, 63% PI-30,000, 64% NNRTI-1000, and 100% NNRTI-30,000 were <400 copies/mL 24 weeks later.

Conclusions Children on first-line NNRTI-based ART who were randomized to switch at a higher virologic threshold developed the most resistance, yet resuppressed on second-line. An abacavir + lamivudine NRTI combination seemed protective against development of NRTI resistance.

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11

Sep, 2015

I was like, oh my God, what happens if it doesn’t work’? Young people living with HIV, clinical trial participation and the truth economy

 

Authors: Bernays S, Seeley J, Paparini S, Rhodes T

Published: BSA Medical Sociology Conference, York, 9-11 September 2015 (Paper ID No: W0012148)

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1

Sep, 2015

Raltegravir in HIV-1 Infected Pregnant Women: Pharmacokinetics, Safety, and Efficacy

 

Authors: Blonk MI, Colbers AP, Hidalgo-Tenorio C, et al. Pharmacokinetics of Newly Developed Antiretroviral Agents in HIV-Infected Pregnant Women PANNA Network; PANNA Network.

Published in: Clin Infect Dis. 2015; 61(5):809-816. 

BackgroundThe use of raltegravir in human immunodeficiency virus (HIV)–infected pregnant women is important in the prevention of mother-to-child HIV transmission, especially in circumstances when a rapid decline of HIV RNA load is warranted or when preferred antiretroviral agents cannot be used. Physiological changes during pregnancy can reduce antiretroviral drug exposure. We studied the effect of pregnancy on the pharmacokinetics of raltegravir and its safety and efficacy in HIV-infected pregnant women.

Methods An open-label, multicenter, phase 4 study in HIV-infected pregnant women receiving raltegravir 400 mg twice daily was performed (Pharmacokinetics of Newly Developed Antiretroviral Agents in HIV-Infected Pregnant Women Network). Steady-state pharmacokinetic profiles were obtained in the third trimester and postpartum along with cord and maternal delivery concentrations. Safety and virologic efficacy were evaluated.

Results Twenty-two patients were included, of which 68% started raltegravir during pregnancy. Approaching delivery, 86% of the patients had an undetectable viral load (<50 copies/mL). None of the children were HIV-infected. Exposure to raltegravir was highly variable. Overall area under the plasma concentration-time curve (AUC) and plasma concentration at 12 hours after intake (C12h) plasma concentrations in the third trimester were on average 29% and 36% lower, respectively, compared with postpartum: Geometric mean ratios (90% confidence interval) were 0.71 (.53–.96) for AUC0–12h and 0.64 (.34–1.22) for C12h. The median ratio of raltegravir cord to maternal blood was 1.21 (interquartile range, 1.02–2.17; n = 9).

Conclusions Raltegravir was well tolerated during pregnancy. The pharmacokinetics of raltegravir showed extensive variability. The observed mean decrease in exposure to raltegravir during third trimester compared to postpartum is not considered to be of clinical importance. Raltegravir can be used in standard dosages in HIV-infected pregnant women.

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30

Aug, 2015

Ritonavir pharmacokinetics in pregnancy

 

Authors: Colbers A, Clotet V, Burger D.

Published: 16th edition of the International Workshop on Clinical Pharmacology of HIV & Hepatitis Therapy, May 26th – 28th 2015, Westin Alexandria

 

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30

Aug, 2015

Etravirine pharmacokinetics during pregnancy and postpartum

 

Authors: Best B, Colbers A, Wang J, Taylor G, Stek A, van Kasteren M, Mirochnick M, Burger D.

Published: 24th Conference on Retroviruses and Opportunistic Infections, March 23rd-26th 2015, Seattle. P_892

 

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22

Jul, 2015

Maraviroc Pharmacokinetics in HIV-1-Infected Pregnant Women

 

Authors: Colbers A, Best B, Schalkwijk S, et al. PANNA Network and the IMPAACT 1026 Study Team.

Published in: Clin Infect Dis. 2015; 61(10):1582-1589.

Objective To describe the pharmacokinetics of maraviroc in human immunodeficiency virus (HIV)–infected women during pregnancy and post partum.

Methods HIV-infected pregnant women receiving maraviroc as part of clinical care had intensive steady-state 12-hour pharmacokinetic profiles performed during the third trimester and ≥2 weeks after delivery. Cord blood samples and matching maternal blood samples were taken at delivery. The data were collected in 2 studies: P1026 (United States) and PANNA (Europe). Pharmacokinetic parameters were calculated.

Results Eighteen women were included in the analysis. Most women (12; 67%) received 150 mg of maraviroc twice daily with a protease inhibitor, 2 (11%) received 300 mg twice daily without a protease inhibitor, and 4 (22%) had an alternative regimen. The geometric mean ratios for third-trimester versus postpartum maraviroc were 0.72 (90% confidence interval, .60–.88) for the area under the curve over a dosing interval (AUCtau) and 0.70 (0.58–0.85) for the maximum maraviroc concentration. Only 1 patient showed a trough concentration (Ctrough) below the suggested target of 50 ng/mL, both during pregnancy and post partum. The median ratio of maraviroc cord blood to maternal blood was 0.33 (range, 0.03–0.56). The viral load close to delivery was <50 copies/mL in 13 women (76%). All children were HIV negative at testing.

Conclusions Overall maraviroc exposure during pregnancy was decreased, with a reduction in AUCtau and maximum concentration of about 30%. Ctroughwas reduced by 15% but exceeded the minimum Ctrough target concentration. Therefore, the standard adult dose seems sufficient in pregnancy.

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18

Jul, 2015

I am scared of getting caught up in my lie’: challenges to self-reported adherence for young people living with HIV

 

Authors:  Bernays S, Seeley J, Paparini S, Rhodes T and the ARROW and BREATHER trial teams.

Published in: accepted for presentation at AIDS Impact, Amsterdam 28-31 July, 2015 (abstract 3435)

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18

Jul, 2015

Young people, clinical trials and ‘the HIV experience’: What can similarities across time and place tell us about growing up with HIV?

 

Authors:  Paparini S on behalf of Bernays S, Seeley S,  Rhodes T,  Namukwaya Kihika S,Kawuma-Kigawa R, Nakyambadde H, Kabajaasi O and the BREATHER Trial Team.

Published in: 3rd International ASSHH Conference, Stellenbosch, South Africa, 6-9 July 2015.

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18

Jul, 2015

“But it’s my story”: exploring the experience and effect of telling children how they have acquired HIV

 

Authors:  Seeley J on behalf of the Bernays S, Paparini S, Namukwaya Kihika S,  Rhodes T and the BREATHER Trial Team.

Published in: 3rd International ASSHH Conference, Stellenbosch, South Africa, 6-9 July 2015.

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