CROI 2018 Abstract eBook

Abstract eBook

Poster Abstracts

538 IMPACT OF FIRST-LINE ART CHOICE AND DURATION OF VIRAL FAILURE ON SECOND-LINE OPTIONS Seema T. Meloni 1 , Chika K. Onwuamah 2 , Oche Agbaji 3 , Beth Chaplin 1 , David O. Olaleye 4 , Rosemary Audu 2 , Ezechi C. Oliver 2 , Godwin Imade 3 , Adesola Z. Musa 2 , Georgina N. Odaibo 4 , Holly Rawizza 5 , Prosper Okonkwo 6 , Emmanuel O. Idigbe 2 , Phyllis J. Kanki 1 1 Harvard University, Boston, MA, USA, 2 Nigerian Institute of Medical Research, Lagos, Nigeria, 3 Jos University Teaching Hospital, Jos, Nigeria, 4 University of Ibadan, Ibadan, Nigeria, 5 Brigham and Women’s Hospital, Boston, MA, USA, 6 AIDS Prevention Initiative In Nigeria, Abuja, Nigeria Background: The WHO recommends a simplified approach to second-line (2L) nucleoside reverse transcriptase inhibitor (NRTI) options in resource-limited settings (RLS); if zidovudine (AZT) was used in first-line (1L), then tenofovir (TDF) should be prescribed for 2L and vice versa. As AZT is commonly used for 1L in many RLS and data regarding impact of regimen choice and duration of virologic failure (VF) on accumulation of mutations in the context of current viral load (VL) monitoring guidelines remain sparse, this study was designed to compare the patterns of drug resistance mutations (DRM) for patients failing AZT- versus TDF-containing 1L ART to examine the potential impact on 2L NRTI options. Methods: Paired samples from patients that met the criteria for VF and were switched from 1L to 2L ART at three medical institutions in the APIN/Harvard PEPFAR Nigeria Programwere retrospectively identified. Genotyping was performed on the first sample with VL≥1000 copies/mL (S1) and the second from time nearest switch to 2L (S2). For each sample, the HIV-1 polymerase gene was sequenced. DRM were analyzed and genotype susceptibility score (GSS) calculated using reports from Stanford University’s HIVdb Program. Results: In total, 191 patients were included, of whom 88 (46%) were on a TDF- and 103 (54%) on an AZT-containing 1L regimen. At S1, there was no difference in percentage of patients that were resistant to 2L NRTI option (p=0.6), but at S2, we found that 28.2% of patients with 1L AZT versus 6.8% of patients with TDF had DRM compromising the recommended 2L NRTI backbone (p<0.001). Controlling for time between the paired samples, patients with <6 months between S1 and S2 had no difference in proportion with compromised 2L, whereas for those with 6-12 months between S1 and S2, 4.8% of those on 1L TDF versus 36.8% of patients on AZT were compromised to their 2L NRTI option (p=0.02). The median rate of decrease of GSS from S1 to S2 for those on TDF was 0.00 (IQR: 0.00-0.45) drug/year as compared to 0.50 (IQR: 0.00-1.00) drug/year for the AZT group. In a multivariate analysis, patients on 1L AZT had 9.90 times higher odds of having a compromised 2L NRTI option than patients on 1L TDF. Conclusion: This study revealed differences in the accumulation of DRM by 1L ART regimen resulting in compromised recommended 2L NRTI options in a time-dependent manner. Our findings have implications for regimen-specific recommendations on VL monitoring scheduling for people with elevated VL following initiation of ART.

Poster Abstracts

539 GENOTYPIC RESISTANCE PROFILES IN HIV-INFECTED CHILDREN WITH TREATMENT FAILURE Birkneh T. Tadesse 1 , Byron A. Foster 2 , Degu Jerene 3 , Kyle Cobarrubias 4 , Bemuluyigza Baraki 4 , Natalie Kinloch 4 , Mark Brockman 4 , Eyasu Makonnen 3 , Eleni Aklillu 5 , Zabrina Brumme 4 1 Hawassa University, Hawassa, Ethiopia, 2 Oregon Health and Sciences University, Portland, OR, USA, 3 Addis Ababa University, Addis Ababa, Ethiopia, 4 Simon Fraser University, Burnaby, BC, Canada, 5 Karolinska Institute, Stockholm, Sweden Background: Due to the lifelong nature of cART, treatment failure remains a major concern, particularly for pediatric patients in settings where cART options are limited. Access to drug resistance genotyping is limited in Southern Ethiopia and international shipping of frozen plasma is not feasible. We characterized HIV drug resistance among children experiencing virologic treatment failure on first-line cART in Hawassa, Ethiopia, using proviral DNA amplified from dried blood spots. Methods: EPHIC is a prospective pediatric HIV first-line treatment cohort with 788 children currently enrolled, with pVL and CD4 counts monitored semiannually. Dried blood spots were collected from 94 EPHIC participants experiencing WHO-defined virologic treatment failure with pVL ≥ 2500 copies/ ml. HIV DNA was extracted using commercial spin-column kits and protease, and a minimum of codons 1-240 of RT were amplified by nested PCR and sequenced using subtype C-optimized primers. Four primer sets (1 primary, 3 backup) were used to maximize PCR success. Resistance interpretation was performed using the Stanford HIV drug resistance database. Results: Participants were a mean of 11.4 (standard deviation [SD] 3.3) years old and had been on first line cART for a mean of 3.8 (SD 2.8) years. Eighty six (91.5%) children had WHO stage 1 or 2 disease; the remaining 8 (8.5%) had WHO stage 3 or 4 disease. Only 4(4.2%) participants had taken ART for prevention of mother to child transmission. Genotyping was successful for 93/94 (98.9%) participants, though 6 sequences were hypermutated and one contained a 23-base deletion, consistent with high proportions of defective proviruses in chronic HIV infection. All sequences were subtype C. Of the 86 intact sequences,

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