CROI 2016 Abstract eBook

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Poster Abstracts

433 A Comparison of the Pharmacokinetics of Efavirenz During Pregnancy and Postpartum

Stein Schalkwijk 1 ; Brookie M. Best 2 ; Angela Colbers 1 ; Alice Stek 3 ; JiajiaWang 4 ; David Hawkins 5 ; Mark Mirochnick 6 ; David M. Burger 1 ; for the International Maternal Pediatric Adolescent AIDS ClinicalTrials (IMPAACT) P1026s ProtocolTeam, and the Pharmacokinetics of Newly Developed Antiretroviral Agents in HIV-infected PregnantWomen (PANNA) Study Network 1 Radboud Univ Med Cntr, Nijmegen, Netherlands; 2 Univ of California San Diego, San Diego, CA, USA; 3 Univ of Southern California, Los Angeles, CA, USA; 4 Harvard Sch of PH, Boston, MA, USA; 5 Chelsea and Westminster Hosp NHS Fndn Trust, London, UK; 6 Boston Univ Sch of Med, Boston, MA, USA Background: Efavirenz (EFV) 600mg is currently recommended by WHO as a first-line antiretroviral agent in HIV infected adults. A dose reduction to 400mg EFV has been proposed because of concerns regarding toxicitity. EFV is widely used during pregnancy in those countries where HIV infection is most common. Pregnancy can reduce exposure to antiretroviral agents with a corresponding risk of poor maternal virologic control and PMTCT. Pharmacokinetics (PK) of EFV 600 mg have been previously studied in pregnancy with contradictory results. The aim of this multinetwork study was to further investigate the PK of EFV 600 mg in pregnant women. Methods: HIV-infected pregnant women treated with EFV 600 mg once daily were recruited by the P1026s network (N=10) and PANNA network (N=13). Intensive PK profiles were obtained during 2 nd (2T) and 3 rd trimester (3T) and at least two weeks postpartum (PP). 2T and 3T PK parameters were compared with PP. Where possible cord blood and maternal delivery blood samples were obtained. Results: Seven, 19 and 22 women completed 2T, 3T, and PP PK evaluations. Median (range) age was 33 (20-40) years. 21 subjects were Black, 2 mixed race. The geometric means (GM) (95% CI) for AUC 0-24h , C max and C min in 3T were 60 (49-74) mg*h/L, 4.6 (3.7-5.5) mg/L and 1.8 (1.4-2.3) mg/L, respectively. The GM during PP for AUC 0-24h , C max and C min were 63 (50-80) mg*h/L, 4.3 (3.4-5.3) mg/L and 1.9 (1.4-2.6) mg/L, respectively. When comparing 3T to PP (N=19), GM ratios (90% CI) were 1.01 (0.92-1.10), 1.11 (0.94- 1.29), and 0.97 (0.82-1.16) for AUC 0-24h , C max , and C min . Similar results were found when comparing 2T to PP (N=5). Two patients had a C min below the suggested threshold of 1.0 mg/L during 3T, but not PP. One patient had a C min below 1.0 mg/L only PP. Three patients used concomitant rifampicin, but no obvious deviations were observed and C min levels were >1.0 mg/L. Median (range) gestational age at delivery was 39 wks(33-42); birth weight was 3310 (1875-4150) gm. All of the children for whom HIV-infection status was available were not infected as of the last HIV test. The median (range) ratio of cord to maternal concentrations (n=4), was 0.81 (0.65-0.95). Conclusions: No significant effects of pregnancy on EFV PK parameters were observed and EFV 600mg led to adequate exposure during pregnancy. The absence of a significant pregnancy-related effect on EFV PK in this study suggests that a prospective evaluation in pregnant women of the proposed EFV dose reduction to 400mg is warranted. 434 Contamination of Herbal Medicines With ARVs andWidespread Use by PLWH in Nigeria Joshua Gini 1 ; Bala I. Harri 2 ; Elkanah D. Kabilis 3 ; Mark Stevens 4 ; Paul P. Pama 5 ; Alieu Amara 1 ; Dilly P. Sujan 1 ; Justin Chiong 1 ; Saye Khoo 1 ; for the Pharmacology Research Laboratories University of Liverpool 1 Univ of Liverpool, Liverpool, UK; 2 Dalhatu Araf Specialist Hosp, Lafia, Nassarawa State, Lafia, Nigeria; 3 Gombe State Specialist Hosp, Gombe, Nigeria; 4 Faith Alive Fndn, Jos Plateau State, Nigeria; 5 Fed Med Cntr Katsina, Katsina, Nigeria Background: Nigeria has an estimated 3.1 million people living with HIV (PLWH), accounting for nearly 10% of global HIV burden. Use of traditional medicines is high in the general population. Here, we sought to evaluate the use of herbal medicines amongst (PLWH), and undertake a country-wide analysis of herbal medicines used by PLWH for possible contamination with antiretrovirals (ARV). Methods: Part A) large questionnaire-based survey of patients attending health centres in mixed rural and urban centres across 4 states. Data were collated and analysed using SPSS. Part B) country-wide (Fig. 1) collection of herbal samples for drug analysis. Investigators followed a standard protocol i) street vendors from a mixture of urban and rural settings were approached ii) a request for herbals for treatment of general pains, hepatitis, UTI, and febrile ailments on a background of HIV iii) herbals sold as powders or liquids were purchased iv) instructions for use, date and site were recorded. Analysis for efavirenz, nevirapine, lopinavir, darunavir, ritonavir, atazanavir, emtricitabine, tenofovir and lamivudine using validated LC-MS/MS methods was performed at the University of Liverpool. Results: Of 742 PLWH aged 2-91y, prevalence of herbal medication use was 41.8% (310). Use of herbals was significantly associated with educational attainment (31.8% in patients with little or no education, vs 43.8% and 44.8% in patients with secondary and tertiary education respectively; P= 0.037) and with employment status (44.9% of the employed vs 36.7% of unemployed patients used herbals; P= 0.01). Of those who took herbals, 45% did so prior to commencement of ARVs, 53.9% did so to cure HIV (46%with little effect while 5.1% believed themselves cured); influence of family or friends contributed to herbal intake in 75%. Of 138 herbal samples collected across 8 States, 3 (2%; all from large cities) contained measurable antiretrovirals. One sample contained tenofovir (0.2ng/mg powder) and emtricitabine (0.0065ng/mg powder), while two samples contained tenofovir (0.2 and 1.6ng/mg powder) and emtricitabine (0.123 and 0.00049ng/mg powder), with one of these also containing lamivudine (0.25ng/mg powder) Conclusions: Herbal use amongst PLWH is widespread, poorly recorded and often precedes ARV therapy. Contamination with ARVs is worrying (particularly in untreated patients) given the potential for drug resistance.

Poster Abstracts

key

Survey

Herbal medicines

Fig 1:Map of Nigeria showing Regions where survey was conducted and herbal samples were collected

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CROI 2016