CROI 2015 Program and Abstracts

Abstract Listing

Poster Abstracts

894-A Pharmacokinetics of Rifampin in TB/HIV-CoinfectedWomen: Does Pregnancy Matter? Paolo Denti 1 , Helen McIlleron 1 , Neil Martinson 2 , Silvia Cohn 2 , Jennifer Hoffmann 2 , Richard Chaisson 2 , Kelly Dooley 2 , Fildah Mashabela 3 , Regina Msandiwa 3 On behalf of theTSHEPISO StudyTeam 1 Division of Clinical Pharmacology, University of Cape Town, Cape Town, South Africa; 2 Johns Hopkins University School of Medicine, Baltimore, Maryland, United States; 3 Perinatal HIV Research Unit, University of the Witwatersrand, Soweto, South Africa Background: Pregnant women are at high risk of progression from latent to active TB. They are typically treated with the same regimen as non-pregnant adults. Pregnancy, though, induces physiological changes that impact drug exposures. The effects of pregnancy on the pharmacokinetics (PK) of rifampin, the key sterilizing drug in anti-TB treatment, are unknown. Methods: Prospective cohort of pregnant, HIV-infected women with tuberculosis in Soweto, South Africa. Women taking standard first-line TB treatment had PK sampling at around 37 weeks’ gestation or delivery, then at around 6 weeks postpartum. Blood samples were generally collected pre-dose, then 2, 4, and 6-8 hours post-dose. Cord blood was also collected. Rifampin was quantified using LC-MS/MS, with lower limit of quantification 0.117 mg/L. A population PK model was developed using nonlinear mixed-effects modeling. Treatment outcomes and transmission events were collected. Results: PK information was available from 33 pregnant women with HIV receiving standard TB treatment, median age and weight were 29 years and 64 kg, respectively. A population PK analysis using 48 PK profiles and 183 samples was performed. A one-compartment model with first-order elimination and transit compartment absorption described the data well. Allometric scaling based on total body weight was applied to clearance and volume. Pregnancy reduced rifampin clearance by 14% (p<0.026). No other covariates influenced PK. Based on individual post-hoc estimates, median (IQR) rifampin AUC0-24h and Cmax during pregnancy were 40.8 mg.h/L (27.1-54.2) and 8.4 mg/L (7.1- 10.0), compared to 37.4 (26.8-50.3) and 9.0 (6.6-11.9) post-partum. Of the twenty-two available cord blood samples, rifampicin was detectable (>0.117 mg/L) in eight samples. Cord blood concentrations were generally lower than maternal peri-partum concentrations (when available) and detectable only if delivery occurred within 8 hours after maternal dose intake. Conclusions: Rifampin exposures were increased modestly during the last trimester of pregnancy, seemingly due to decreased clearance. This suggests that no dose adjustment is necessary in pregnancy. Rifampin was detected in cord blood samples. The clinical relevance of exposures to this potent inducer of metabolizing enzymes among HIV-exposed infants is unclear.

infants is unclear.

Prediction-corrected visual predictive check of the final model, stratified by pregnancy status. The solid and dashed lines are the 5th, 50th, and 95th percentiles of the observed data, while the shaded areas represent the 95% confidence intervals for the same percentiles as predicted by the model. An appropriate model is expected to have all observed percentiles within the simulated confidence intervals.

Poster Abstracts

TUESDAY, FEBRUARY 24, 2015 Session P-T8 Poster Session

Poster Hall

2:30 pm– 4:00 pm Planning and Preventing Pregnancy 895 Safer Conception Delayed by Lack of HIV Viral Suppression Sheree R. Schwartz 1 ; Rebecca Phofa 2 ; NompumeleloYende 2 ; Jean Bassett 2 ; NoraWest 2 ; Ian Sanne 3 ; AnneliesVan Rie 1 1 University of North Carolina, Chapel Hill, NC, US; 2 Witkoppen Health and Welfare Centre, Johannesburg, South Africa; 3 University of the Witwatersrand, Johannesburg, South Africa Background: Safer conception strategies can reduce transmission risks among couples and infants when one or both partners are HIV-infected. Data on safer conception from Sub-Saharan Africa are not available. We report outcomes from a safer conception clinic in South Africa. Methods: From July 2013-September 2014, 129 women and 70 men enrolled in Sakh’umndeni , a safer conception clinic at the primary care Witkoppen Health and Welfare Centre in Johannesburg. Services offered are antiretroviral therapy (ART) independent of CD4 count, pre-exposure prophylaxis, education on importance of viral load suppression, timed unprotected sex, and self-insemination when the male partner is HIV-uninfected. We estimate time-to-clinical readiness to safely conceive (TTRC), time-to-pregnancy (TTP), and describe viral suppression at pregnancy diagnosis. TTCR is defined as time from enrollment to viral suppression in both partners, HIV negative status confirmation in serodiscordant partner, and absence of contraindications for safe conception. Results: At enrollment, most women (122/129, 95%) were HIV-infected, of which 85% (104/122) were on ART, and 48% (59/122) virally suppressed. While encouraged to attend as a couples, only 54% (70/129) of male partners ever attended. At presentation 67% of men were HIV-infected, 74% (35/47) were on ART and 19% (9/47) were virally suppressed. To date, less than half of 129 women achieved clinical readiness to safely conceive (Figure 1). Common reasons for not being ready were lack of viral suppression (63.5%) and awaiting partner clinic attendance (17.6%). Median TTCR among the 36 women ever ready to safely attempt conception was 3.2 months [IQR 1.3-6.2] and 17% (6/36) became pregnant. While only 9% of couples were clinically ready to conceive by 6 months of follow-up, 26% of women had conceived by then (Figure 1). We observed 20 pregnancies, 17 among HIV positive women. All women safely conceiving were virally suppressed at pregnancy diagnosis (n=4) or had repeat HIV-negative test results (n=2). All (4/17) HIV positive women not virally suppressed at pregnancy diagnosis had viral loads <1000. No partner or infant infections have been observed.

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CROI 2015