CROI 2015 Program and Abstracts

Abstract Listing

Poster Abstracts

TUESDAY, FEBRUARY 24, 2015 Session P-T11 Poster Session

Poster Hall

2:30 pm– 4:00 pm PMTCT-Associated Drug Resistance inWomen and Infants 907 ART Failure and Resistance Among Pregnant and Post-PartumWomen in South Africa Christopher J. Hoffmann 1 ; Silvia Cohn 1 ; Fildah Mashabela 2 ; Jennifer Hoffmann 1 ; Kelly E. Dooley 1 ; Richard E. Chaisson 1 ; Neil Martinson 2 theTSHEPISO StudyTeam 1 Johns Hopkins University School of Medicine, Baltimore, MD, US; 2 Perinatal HIV Research Unit (PHRU), Johannesburg, South Africa

Background: In South Africa, 30% of pregnant women presenting for antenatal care are HIV-infected, many of whom are started on antiretroviral therapy (ART). Postpartum adherence and retention may be compromised by system limitations and patient-level factors. Increased loss from care, failed transitions in care, treatment failure, and acquired drug resistance may result when adherence to medications or visits diminishes. Methods: Tshepiso is a prospective study of HIV-infected pregnant women with and without active TB disease in Soweto, South Africa. Women are enrolled prenatally, and mother-infant pairs are followed for 12 months postpartum. CD4 count and viral load are evaluated at all study visits. HIV drug resistance was performed on 12-month postpartum specimens with an HIV RNA >1000c/mL. We compared pre and post-partum virologic suppression (defined as HIV RNA <400 c/mL) and CD4 count change among 103 women who were in care and receiving ART both pre-partum and postpartum. Results: At enrollment for the 103 women, the median age was 29 years, gestational age 29 weeks, CD4 count was 317 cells/mm 3 ; 43 (42%) women were co-infected with TB, and 23 (22%) were on ART prior to pregnancy. During pregnancy, 93 (87%) women had an HIV RNA <400 c/mL compared to 73 (71%) at 12 months postpartum (McNemar’s, p<0.001). From delivery to one year post-partum, women with a suppressed HIV RNA had an increase in CD4 count to a median of 480 cells/mm 3 (IQR: 374, 625) while women without suppression at 12 months had a decline to a median of 278 cells/mm 3 (IQR: 224, 330) (Kruskal Wallis, p<0.001); both groups started with a pre-partummedian CD4 count of 300 cells/mm 3 . Plasma samples for 28 of the 30 women with viral load >1000 copies/mL at 12 months were tested for HIV drug resistance; 25 were amplified. 12 (48%) had major resistance mutations: all 12 had NNRTI resistance, 4 (16%) had an M184V mutation. Among the 25 women, resistance at 12 months was associated with pre-partum HIV RNA >400 c/mL (p=0.003) but was not associated with TB treatment or timing of ART initiation. Conclusions: The proportion of women with HIV virologic suppression dropped substantially from delivery to 12 months post-partum and was associated with HIV drug resistance and lower CD4 counts. Regimen selection for future PMTCT and re-engagement in care must take this into account. Improved strategies to support post-partum adherence, especially among those without complete virologic suppression during pregnancy, are needed. 908 High Prevalence of HIV-1 Drug-Resistance Mutations in Subtype C Transmitting Mothers Detected Using 454 Ultra-Deep Sequencing Johanna Ledwaba 1 ; Anna Salimo 1 ; KarlTechnau 4 ; SimonTravers 3 ; Lynn Morris 1 ; Gillian Hunt 1 ; Louise Kuhn 2 1 National Institute for Communicable Diseases, National Health Laboratory Service, Sandringham, South Africa; 2 Columbia University, New York, NY, US; 3 University of the Western Cape, Modderdam, South Africa; 4 University of the Witwatersrand, Johannesburg, South Africa Background: In 2010, new PMTCT guidelines were implemented in South Africa wherein pregnant women with CD4 count <350 cells/ml received HAART (Option B) and women with CD4 count >350 cells/ml received antenatal and intrapartum prophylaxis (Option A). In this study we performed 454 ultra deep pyrosequencing to determine the prevalence of maternal drug resistance variants in HIV-1-transmitting mothers after guideline changes were implemented. Methods: The Finding Infants with HIV Disease: Evaluation of Resistance, pMTCT Failures and Linking Access to Care (FInHDER) Study, conducted in 5 clinics and hospitals in Johannesburg in 2011, set out to recruit treatment-naive HIV-infected infants and children >2 years of age presenting at routine PMTCT follow-up clinics and inpatient services. The study recruited mothers and infants who had full, partial or no access to PMTCT. As part of this study, 204 maternal plasma samples were collected and sequenced for HIV drug resistance mutations using ultra-deep pyrosequencing technology and 454 prototype plates containing lyophilized MID tagged primers. Sequence reads were analyzed using 454 AVA software and Seq2Res pipeline. Results: Of the 204 women, 116 had received PMTCT, 66 had received no PMTCT, 15 were receiving cART, and 10 had unknown exposure. Ultra deep sequencing by 454 was successful in 200 (98%) specimens. A total of 80 specimens (41.8%) had HIV-1 drug resistance detected by 454 UDPS: NNRTI mutations were detected in 68 (34%) specimens, NRTI mutations in 17 (9%), and dual-class resistance in 13 (7%). Single PI mutations were identified in 12 specimens. When stratified by age of child, NNRTI mutations were present in 17.2% (11.4 – 25.1%) of women in the exposed group whose time since childbirth was <6 months versus 6.1% (2.4 – 14.6%) in the unexposed group. Lower rates of NNRTI mutation were present between 6 months and 1 year [3.4% (1.3-8.5%)] and up to 2 years [2.6% (0.9-7.3%)] post exposure in the exposed group. However, in the unexposed group the NNRTI mutation rate remained constant [4.5% (1.6-12.5%)]. NNRTI resistance was driven by the K103N (n= 28, 24.3%) and Y181C (n=11, 9.5%) mutations in the exposed group, and by K103N (n=4, 5.4%) in the unexposed group. Conclusions: These data highlight the value of ultra-deep sequencing to reveal the presence of resistance mutations in transmitting mothers suggesting poor compliance and/or regimen failure during PMTCT exposure. 909 NVP Resistance in Infants Infected by HIV-1 via Breastfeeding in the BAN Study Julie A. Nelson 1 ; Ali Fokar 1 ; Michael G. Hudgens 1 ; Kara J. Compliment 1 ; GeraldTegha 2 ; Deborah Kamwendo 2 ; Athena P. Kourtis 3 ; Denise J. Jamieson 3 ; Charles M. van der Horst 1 ; Susan A. Fiscus 1 1 Univ of North Carolina at Chapel Hill, Chapel Hill, NC, US; 2 University of North Carolina Project–Malawi, Lilongwe, Malawi; 3 US Centers for Disease Control and Prevention (CDC), Atlanta, GA, US Background: The Breastfeeding, Antiretrovirals, and Nutrition (BAN) study showed that treatment of HIV-1-infected mothers (maternal antiretroviral (ART) arm) or prophylaxis of their infants (infant nevirapine (NVP) arm) for up to 28 weeks of breastfeeding were both effective in preventing HIV transmission via breastfeeding. In addition to the study interventions, all mothers and infants received single dose NVP during delivery and one week of AZT/3TC post-delivery to reduce NVP resistance. We assessed resistance in the infected infants from the 3 arms of the BAN study. Methods: The latest available plasma sample for each infant enrolled in BAN who was infected 2-48 weeks postpartumwas sequenced: 23 transmissions in the infant NVP arm [mean 24 weeks prophylaxis], 23 transmissions in the maternal ART arm [mean 26 weeks ART], and 34 transmissions in the control arm. Subtype C-specific primers were used for reverse transcription and nested PCR. Population sequencing was performed to identify resistance mutations in the RT gene. Available maternal plasma close to the time of each infant’s infection was sequenced for each case of infant NVP arm transmissions as well as for infants in the other arms with identified NVP resistance. Results: HIV-infected infants in the infant NVP armwere significantly more likely to have NVP resistance than infected infants in the other two arms of the trial, especially during breastfeeding through 28 weeks of age (50% in infant NVP arm vs. 6.3% in maternal ART arm and 10.7% in control arm, p=0.01). There was a nonsignificant trend toward higher

Poster Abstracts

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CROI 2015