CROI 2019 Abstract eBook

Abstract eBook

Poster Abstracts

therapy and CYP2B6 516G>T genotype status were joint predictors of NVP PK. Among children with CYP2B6 516GG genotype, NVP exposure was significantly lower in the TB co-infected compared to HIV-infected group; this difference was not seen in children with GT or TT genotypes. The proportion of children with NVP Cmin <3 mg/L was 61% in the co-infected group and 30% in the HIV group (P = 0.03). Among the TB/HIV co-infected children with paired samples, geometric mean ratio (90% CI) PK1/PK2 of NVP Cmax, Cmin and AUC0-12h were 0.68 (0.55–0.85), 0.84 (0.51–1.38) and 0.71 (0.56–0.91). Nine (41%) of 22 children with viral load data at 6 months had HIV RNA >200 copies/mL. Conclusion: First-line TB therapy reduced NVP plasma exposure in young HIV-infected children, especially those with CYP2B6 516GG genotype. Given that NVP dose optimization with TB therapy may require a genotype-guided approach, evaluation of more compatible alternatives to NVP is needed in young children with TB coinfection.

1 National AIDS and STD Control Programme, Nairobi, Kenya, 2 US CDC Nairobi, Nairobi, Kenya, 3 University of Washington, Seattle, WA, USA, 4 Kenya Medical Research Institute, Nairobi, Kenya Background: Access to life saving antiretroviral therapy (ART) in many resource-limited settings has increased, yet more than 30% of children on ART do not achieve viral suppression. Infants and children require continuous medication dose adjustments in response to changing pharmacodynamics, and inappropriate dosing may contribute to viral non-suppression. This study sought to determine the magnitude of prescription dosing errors and associated factors. Methods: We conducted a cross sectional study among HIV Infected children aged ≤11 years in four public health facilities in Nairobi, Kenya. Demographic, clinical and prescription data for the last clinical visit were abstracted from the medical charts of children receiving ART at the time of study. Descriptive statistics were used to summarize participant characteristics and prescription errors. Logistic regression was conducted to determine factors associated with dosing errors. Results: A total of 196 children were included in the study; among these, 53%were male and the median age was 7.9 years (Interquartile range [IQR] 4.8, 10.0). The most commonly used ART regimens were abacavir/lamivudine/ lopinavir/ritonavir taken by 61 (31%) children, followed by zidovudine / lamudivine /nevirapine with 43 (22%) children, and abacavir/ lamivudine/ nevirapine taken by 36 (18%) children. Overall, 85 (44%), 90 (46%) and 92 (47%) children lacked data on the antiretroviral (ARV) drug formulation, dosage, and frequency of dosing respectively, translating into almost half of children having prescription errors from the outset. Among 104 (53%) children with complete formulation, dosage and frequency of dosing prescription information, 38 (37%) had at least one prescription dosing error. In a multivariable model, being on non-nucleoside reverse transcriptase inhibitors was independently associated with an increased likelihood of a dosing error (adjusted odds ratio 8.8; 95% confidence interval 2.1-36.3). Conclusion: Almost half of children receiving antiretroviral therapy had inadequate prescription information and among those with adequate information, one third had prescription dosing errors. These findings call for urgent measures to address health care workers prescribing practices and knowledge, particularly on documentation and appropriate dosing including weight based dose adjustments. In addition, further evaluation should be conducted to determine association of prescription errors with viral suppression. Awewura Kwara 1 , Anthony Enimil 2 , Hongmei Yang 3 , Fizza S. Gillani 4 , Wael A. Alghamdi 1 , Antoinette Ortsin 5 , Albert Dompreh 5 , Lubbe Wiesner 6 , Charles A. Peloquin 1 , Sampson Antwi 2 1 University of Florida, Gainesville, FL, USA, 2 Kwame Nkrumah University of Science and Technology, Kumasi, Ghana, 3 University of Rochester, Rochester, NY, USA, 4 The Miriam Hospital, Providence, RI, USA, 5 Komfo Anokye Teaching Hospital, Kumasi, Ghana, 6 University of Cape Town, Cape Town, South Africa Background: Nevirapine (NVP)-based antiretroviral therapy (ART) is one of the limited options in children younger than 3 years old with TB/HIV coinfection. Given the scarce data, we examined the effect of first-line TB therapy on NVP pharmacokinetics (PK) in Ghanaian children. Methods: ART-naïve HIV-infected children aged 3–35 months with and without TB were treated with NVP 200 mg/m2 twice daily plus two NRTIs. The newWHO recommended higher dosages of rifampin and isoniazid were used. After 4 weeks of ART, PK samples were collected at 0, 2, 6, and 12 hours post- dose to measure NVP plasma concentrations, using a validated LC/MS/MS assay. In the co-infected patients, sampling was repeated after 4 weeks off TB therapy. PK parameters were calculated using noncompartmental analysis and were compared between groups using Wilcoxon Rank-sum test and within group using Signed-rank test. Results: Of the 53 patients, 23 (43%) had TB coinfection, of whom 15 completed PK sampling on (PK1) and off (PK2) anti-TB therapy. Baseline characteristics were similar in the two groups except co-infected children had lower median height-for-age-Z-score. Median NVP concentrations were lowest in the children with TB/HIV coinfection on TB therapy, followed by HIV infection only and highest in the co-infected off TB therapy (Figure). Median NVP Cmax, Cmin and AUC0-12h were not significantly different between children with HIV and those with TB/HIV on or off anti-TB therapy. In multivariate analysis, TB

Poster Abstracts

826 SAFETY AND EFFICACY OF STARTING ANTIRETROVIRAL THERAPY IN THE FIRST WEEK OF LIFE Roger L. Shapiro 1 , Kara Bennett 2 , Michael D. Hughes 1 , Kenneth Maswabi 3 , Gbolahan Ajibola 3 , Sikhulile Moyo 3 , Patrick Jean-Philippe 4 , Edmund V. Capparelli 5 , Terence Mohammed 3 , Oganne Batlang 3 , Shahin Lockman 6 , Max Essex 1 , Joseph Makhema 3 , Mathias Lichterfeld 6 , Daniel R. Kuritzkes 6 1 Harvard University, Boston, MA, USA, 2 Bennett Statistical Consulting, Inc, New York, NY, USA, 3 Botswana Harvard AIDS Institute Partnership, Gabarone, Botswana, 4 National Institute of Allergy and Infectious Diseases, Bethesda, MD, USA, 5 University of California San Diego, La Jolla, CA, USA, 6 Brigham and Women’s Hospital, Boston, MA, USA Background: Antiretroviral treatment (ART) started in the first week of life may limit HIV viral reservoir and improve treatment outcomes, but little information is available about safety, viral efficacy, and pharmacokinetics (PK) of ART in early infancy. Methods: HIV+ infants <7 days of age, >35 weeks gestation, and >2000g were offered enrollment in the Early Infant Treatment Study (EIT) in Botswana and started on treatment doses of NVP (6mg/kg BID), ZDV, and 3TC as initial ART, and changed to LPV/r, ZDV, 3TC after 2-5 weeks (when >2 weeks of life and >40 weeks gestational age equivalent). Study visits and HIV RNA testing occurred at weeks 0, 1, 2, 4, 8, 12. PK testing of NVP trough values occurred at weeks 1 and 2. Comparisons were by Wilcoxon rank sum testing and Spearman correlations. Results: From April 2015-July 2018, 40 HIV+ infants were enrolled; 37 (93%) had reached 12 wks on ART as of 20 September 2018. Median age at screening was 1 day after birth (range 0, 4), and median age at ART initiation was 2 days after birth (range 1, 5). Median change from NVP-based to LPV/r-based ART was after 2.7 wks (range 2.3, 4.4 wks). No deaths or loss to follow-up occurred in the first 12 wks, and no modification of ART for toxicity occurred. Only 1 grade 3/4 neutropenia and no grade 3/4 anemias were reported through 12 wks. HIV RNA declined from a median of 4.05 log copies/mL at baseline (IQR 2.79, 4.86 log copies/mL) to 2.54 log copies/mL at 2 wks (IQR 1.86, 3.21) and <1.60 log copies/ mL at 12 wks (IQR <1.60, 1.89 log copies/mL) (Figure 1), and did not differ by infant HIV RNA at baseline (p=0.10). At 12 wks of ART, 21 (57%) of 37 had HIV RNA < 40 copies/mL, and only 3 (8%) were > 400 copies/mL. However, 9 (22.5%) infants had transient increases in HIV RNA in the 4-wk period following

825 EFFECT OF ANTITUBERCULOSIS THERAPY ON NEVIRAPINE PHARMACOKINETICS IN YOUNG CHILDREN

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