CROI 2017 Abstract e-Book

Abstract eBook

Poster and Themed Discussion Abstracts

1 Brigham and Women’s Hosp, Boston, MA, USA, 2 Respiratory and Meningeal Pathogens Rsr Unit, Soweto, South Africa, 3 Botswana Harvard AIDS Inst Partnership, Gaborone, Botswana, 4 Boston Children’s Hosp, Boston, MA, USA, 5 Goodtables Consulting, Norman, OK, USA, 6 Harvard Univ, Boston, MA, USA, 7 Botswana Ministry of Hlth, Gaborone, Botswana Background: Transplacental transfer of pathogen-specific IgG antibodies is deficient in HIV-exposed uninfected (HEU) infants and may contribute to observed 2 to 5-fold increase in early infant mortality. We sought to determine whether maternal ART improves this deficit. Methods: We utilized paired mother-infant serum specimens drawn within 7 days of birth from an observational study of HIV-infected pregnant women during transition from Option A to Option B+ in Botswana. Levels of IgG specific to pertussis, diphtheria, and tetanus toxoids, hepatitis B surface antigen, and capsular polysaccharides of H. influenzae type b and 13 types of S. pneumoniae (1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, and 23F) were measured by multiplex immune assay. Multivariable linear and Poisson models included adjustment for maternal CD4, age, and socioeconomic factors. Results: Of 439 enrolled mothers receiving either zidovudine or ART in pregnancy, specimens were analyzable from 157 mother-infant pairs (49 ART-exposed) and an additional 34 infants (16 ART-exposed). There were no significant differences in specimen availability by ART exposure (p=0.60). Mothers received median of 2.4 months of zidovudine (IQR 2.0 to 2.8 months) or 22.3 months of ART (IQR 3.3 to 47.3 months) prior to delivery. CD4 cell count was higher for women receiving zidovudine than ART- median 448 and 421 cells/μL, respectively (p=0.023). Maternal ART was not associated with higher pathogen-specific IgG titers in maternal sera. However, in adjusted analyses, maternal ART was associated with 53% (95%CI 30 to 75%, p<0.001) improvement in the placental transfer ratio (infant/maternal pathogen-specific IgG titer) and 35% (95%CI 15 to 67%, p=0.016) increase in infant pathogen-specific IgG concentrations compared with zidovudine. The effect of ART placental transfer was similar in mothers initiating ART prior to or during pregnancy (p=0.35 for interaction). In adjusted individual IgG analyses, ART was associated with improved placental transfer for all antibodies except H. influenzae type b (Figure). Maternal ART had a greater effect on transplacental transfer of antibodies to S. pneumoniae types (61% increase, p=0.003 for interaction). Conclusion: Maternal ART, whether started during or prior to pregnancy, is associated with improved transplacental transfer and higher concentrations of pathogen-specific antibodies in HEU infants. In addition to reduction in HIV transmission risk, maternal ART may enhance humoral immunity of vulnerable HEU infants. 788 EVALUATION OF MATERNAL AND INFANT HIV POINT-OF-CARE DIAGNOSTICS AT BIRTH IN TANZANIA Issa Sabi 1 , Hellen Mahiga 1 , Jimson Mgaya 1 , Otto Geisenberger 2 , John France 3 , Michael Hoelscher 2 , Arne Kroidl 2 1 NIMR–Mbeya Med Rsr Cntr (MMRC), Mbeya, Tanzania, 2 Univ of Munich, Munich, Germany, 3 Mbeya Referral Hosp, Mbeya, Tanzania Background: Point-of-Care (PoC) HIV testing for early infant diagnostics (EID) enables nurse-based, decentralized testing with the potential to replace centralized laboratory EID procedures which are complicated by linkage. Additionally, PoC maternal viral load (VL) monitoring around delivery can immediately identify high VL as a risk factor for mother-to- child transmission. In our study we investigated the operational feasibility and accuracy of a novel PoC technology for EID and maternal VL monitoring in primary obstetric health centers in Mbeya, Tanzania. Methods: In this prospective cohort study we included HIV-infected pregnant women and their exposed infants during delivery. Maternal plasma HIV-RNA monitoring was performed by quantitative HIV PoC testing (Cepheid Xpert HIV-1 Quant) during delivery. Nurse based qualitative HIV EID PoC testing (Cepheid Xpert HIV-1 Qual) was performed at birth, and after 1, 2, 3 and 6 weeks postpartum. Maternal viral loads and positive EID PoC test results were confirmed from plasma and infants dry blood spots (DBS) using the Roche COBAS TaqMan system. HIV negativity in infants was confirmed from DBS at the last study visit. Results: Between July 2015 and August 2016, 600 mother-child pairs were included, and 15 (2.5%) infants were diagnosed HIV positive. Of those 11 (73%) were diagnosed at birth suggesting intra-uterine infection, and 4 were either detected at week 1, 2 or 3 suggesting peripartal transmission. The Xpert HIV-1 Qual PoC test correctly identified all HIV infected and non-infected infants (no false positive or negative test results). In mothers we found a good agreement between the quantitative Xpert HIV-1 Quant PoC test and the TaqMan plasma HIV-RNA, however, the Xpert HIV-1 Quant HIV-RNA results indicated slightly higher viral loads as compared to the TaqMan with a mean difference of 0.34 log10 (range -0.46 to 1.14). PoC test procedures were well accepted by nurses/midwives and mothers. Conclusion: We could demonstrate an excellent Xpert HIV-1 PoC test performance and operational feasibility for EID at birth up to week 6 and maternal viral load monitoring at delivery. Both tests have the potential to facilitate rapid infant antiretroviral treatment initiation or use of enhanced postnatal infant prophylaxis. 789 EVALUATION OF THE CEPHEID HIV-1 QUAL POINT-OF-CARE TEST FOR HIV DIAGNOSIS AT BIRTH Maryanne R. Ibrahim 1 , Sikhulile Moyo 2 , Terence Mohammed 3 , Kenneth Maswabi 2 , Gbolahan Ajibola 2 , Rebecca Gelman 2 , Chloe Auletta-Young 1 , Shahin Lockman 1 , Joseph Makhema 2 , Roger L. Shapiro 1 1 Doris Duke Intl Clinical Rsr Fellowship, Los Angeles, CA, USA, 2 Botswana Harvard AIDs Rsr Inst Partnership, Gaborone, Botswana, 2 Dana–Farber Cancer Inst, Boston, MA, USA Background: HIV point-of-care (POC) testing may facilitate early infant diagnosis, but the accuracy of POC testing in the first week of life and in the setting of antiretroviral prophylaxis for the prevention of mother-to-child HIV transmission (MTCT) is unknown. This study aimed to evaluate the sensitivity and specificity of the Cepheid Xpert® HIV-1 Qual POC test compared with the Roche Taqman HIV DNA PCR platform to diagnose infant HIV infection in the first 96 hours of life. Methods: As part of an early infant treatment study, infants < 96 hours of life were screened for HIV at 5 hospital maternity wards in Botswana. Infants received post-exposure antiretroviral prophylaxis (PEP) with single-dose nevirapine and zidovudine, and most mothers received 3-drug antiretroviral therapy in pregnancy and at delivery. Dried blot spot screening samples were initially tested using the Roche Taqman HIV DNA PCR platform. To evaluate sensitivity of POC testing, remaining dried blood spots from the PCR-positive screening samples were tested using the Cepheid Xpert® HIV-1 Qual test. Seventy-five HIV-exposed, PCR negative infants were also selected for testing by Cepheid to evaluate POC assay specificity. The study was powered to have a lower 95% confidence limit of 82% sensitivity with 15 true-positive samples. Results: Fourteen of 15 PCR positive samples tested positive by Cepheid POC, yielding a sensitivity of 93.3% (95% CI: 68.1 – 99.8%). Among the 15 PCR positive infants, baseline viral load ranged from<40 copies/ml to >10,000,000 copies/ml, with a median of 2,403 copies/ml (Table 1). Twelve (80%) of the 15 infants were exposed to maternal 3-drug antiretroviral therapy near delivery, and all but one received PEP prior to screening. The HIV RNA for the infant with false negative POC testing was 1661 copies/mL. Of note, two infants with low HIV RNA (< 40 copies/mL and 272 copies/ml) were correctly identified as HIV positive by Cepheid POC. All of the 75 PCR-negative samples tested negative by Cepheid POC, yielding a specificity of 100% (95% CI: 96.1 –100%). Conclusion: Our study demonstrates high sensitivity and specificity for the Cepheid POC assay in the first week of life despite lowmedian infant HIV RNA and extensive PEP. The Cepheid POC testing platformmay be a useful approach for adding early infant HIV diagnosis in Botswana. 790 TARGETED HIV SCREENING AT BIRTH CAN IDENTIFY THE MAJORITY OF IN UTERO TRANSMISSIONS Maryanne R. Ibrahim 1 , Kenneth Maswabi 2 , Gbolahan Ajibola 2 , Sikhulile Moyo 2 , Michael D. Hughes 3 , Chloe Auletta-Young 3 , Daniel R. Kuritzkes 4 , Mathias Lichterfeld 5 , Joseph Makhema 2 , Roger L. Shapiro 3 1 Doris Duke Intl Clinical Rsr Fellowship, Los Angeles, CA, USA, 2 Botswana Harvard AIDS Inst Partnership, Gaborone, Botswana, 3 Harvard Univ, Boston, MA, USA, 4 Brigham and Women’s Hosp, Boston, MA, USA, 5 Massachusetts General Hosp, Boston, MA, USA Background: Botswana tests for in utero and intrapartummother-to-child HIV transmission (MTCT) by infant HIV PCR at age 6 weeks. Limitations to this strategy include early mortality, loss-to-follow-up, and delayed treatment initiation for infected infants. In 2015, the Botswana-Harvard Partnership launched the Early Infant Treatment Study to identify HIV-infected infants at birth and offer immediate antiretroviral therapy. To determine the feasibility of targeted birth testing for infants at high-risk of HIV infection, we evaluated risk factors for in utero MTCT that were identifiable at delivery. Methods: HIV-exposed infants were screened at 5 hospital maternity wards by trained research assistants in the Gaborone and Francistown regions of Botswana. Screened infants met the following inclusion criteria: mother/guardian ≥ 18 years of age, gestational age at birth ≥ 35 weeks, birth weight ≥ 2000 grams, age < 96 hours, and eligible

Poster and Themed Discussion Abstracts

CROI 2017 342