CROI 2019 Abstract eBook

Abstract eBook

Oral Abstracts

RG7356 neutralized more potently than the parental bnAb, PGDM1400, for 14/16 of HIV-1 strains tested. The mean level of neutralization enhancement (defined as IC 50 ratio of parental and bispecific Ab) was 8.6 (range 0.6 to 75.5). Mechanistically, the potency enhancement occurred irrespective of target cell CD44 expression but was critically dependent on presence of CD44 on the virion surface. Similar enhancement of virus neutralization was observed when PGDM1400 was replaced by other bnAbs (e.g., 10-074 and N6). Conclusion: Our data provide strong evidence that bnAbs neutralize most HIV-1 strains through predominantly monovalent binding and increasing avidity via binding to a host protein on the virion surface could substantially enhance virus neutralization. Nicole Salazar-Austin 1 , Sanjay Lala 2 , Ziyaad Waja 2 , Silvia Cohn 1 , Jennifer Hoffmann 3 , Fildah Mashabela 2 , Christopher Hoffmann 1 , Kelly E. Dooley 1 , Richard E. Chaisson 1 , Neil A. Martinson 2 , for the TSHEPISO Study Team 1 Johns Hopkins University School of Medicine, Baltimore, MD, USA, 2 University of the Witwatersrand, Soweto, South Africa, 3 University of Maryland, Baltimore, MD, USA Background: Pregnancy and HIV both increase the risk of tuberculosis (TB) disease which results in poor maternal and infant outcomes. IMPAACT study P1078 found that isoniazid preventive therapy (IPT) during pregnancy resulted in a higher risk of adverse maternal and neonatal outcomes compared to IPT post-delivery, questioning the safety of IPT in pregnant women living with HIV (PWLHIV). Methods: Tshepiso was a prospective cohort study evaluating maternal and infant outcomes among PWLHIV with and without active TB disease from January 2011 through January 2014 in Soweto, South Africa. Mother-infant pairs were followed through one year of life. Here we report the outcomes among PWLHIV without TB disease who reported initiating vs not initiating IPT during pregnancy. This was an observational study; IPT was initiated by public antenatal and HIV clinics and not by the study. Results: The Tshepiso study enrolled 155 PWLHIV without TB disease. This analysis includes 151 women with known pregnancy outcomes; 69 (46%) reported initiating IPT during pregnancy. The median age and CD4 T-cell count at enrollment was 30 years (IQR 27,31) and 364 cells/mm3 (IQR 252,464) for women on IPT vs 29 years (IQR 26,32) and 372 cells/mm3 (IQR 275,477) for women not on IPT. 63 (78%) and 43 (65%) women were on cART, 52 (83%) and 37 (86%) with EFV, respectively. Viral load during pregnancy was <400copies/ mL in 60 (75%) women on IPT and 35 (52%) women not on IPT (p=0.004). The proportion of neonates born prematurely was lower in those exposed to IPT during pregnancy compared to unexposed (10% vs 22%; p=0.06). There was no difference in fetal demise (1% vs 1%; p=1.0), low birth weight (9% vs 12%; p=0.51), or congenital anomalies (1% vs 2%; p=1.0). A composite of the four outcomes (16% vs 28%; p=0.08) showed fewer events among infants exposed to IPT. Stratified analyses by viral load suppression did not demonstrate differences in pregnancy outcomes. Conclusion: In this study, IPT use during pregnancy was not associated with a higher rate of poor maternal or infant outcomes. Though this study had well characterized exposures and outcomes, it was not designed to study the effect of IPT on pregnancy outcomes. IPT exposed and non-exposed PWLHIV may differ in factors associated with adverse outcomes in PWLHIV. More research is needed to evaluate the safety of IPT for PWLHIV given their high risk of TB disease and the poor maternal and infant outcomes associated with maternal TB/HIV co-infection, despite appropriate therapy.

77 IPT AND PREGNANCY OUTCOMES IN HIV-POSITIVE WOMEN: THE TSHEPISO COHORT

Oral Abstracts

78 POTENTIAL CONCERN FOR TIMING OF DMPA INJECTION AMONG WOMEN TREATED FOR HIV AND TB Rosie Mngqibisa 1 , Susan E. Cohn 2 , Michelle A. Kendall 3 , Xingye Wu 3 , Kelly E. Dooley 4 , Helen Mcilleron 5 , Jennifer A. Robinson 4 , Cindy Firnhaber 6 , Jhoanna C. Roa 7 , Sharlaa Badal-Faesen 8 , Francis Angira 9 , Mpho S. Raesi 10 , James G. Hakim 11 , Catherine Godfrey 12 , for the A5338 study team 1 Enhancing Care Foundation, Durban, South Africa, 2 Northwestern University, Chicago, IL, USA, 3 Harvard University, Boston, MA, USA, 4 Johns Hopkins University School of Medicine, Baltimore, MD, USA, 5 University of Cape Town, Cape Town, South Africa, 6 University of Colorado, Aurora, CO, USA, 7 Social & Scientific Systems, Silver Spring, MD, USA, 8 University of the Witwatersrand, Johannesburg, South Africa, 9 KEMRI-UCSF, Kisumu, Kenya, 10 Botswana Harvard AIDS Institute Partnership, Gabarone, Botswana, 11 University of Zimbabwe, Harare, Zimbabwe, 12 National Institute of Allergy and Infectious Diseases, Bethesda, MD, USA Background: Effective contraception is of upmost importance for young women with HIV-associated TB, as unintended pregnancy among such women is associated with increased maternal and infant morbidity and mortality. Rifampicin (RIF) and Efavirenz (EFV) are both inducers of metabolizing enzymes and can reduce concentrations of contraceptive medications. Effects of these drugs on the pharmacokinetics (PK) of depot medroxyprogesterone acetate (DMPA), the most commonly used contraceptive in sub-Saharan Africa (SSA) and globally, are unknown. Safety of concurrent use of these 3 drugs is also unknown. We hypothesized that clearance of MPA would be increased when given with RIF and EFV, potentially resulting in levels of MPA <0.1 ng/mL (levels associated with escape ovulation) prior to 12 weeks post-DMPA dose. Methods: ACTG A5338 was a multicentre, single arm, PK study among women in SSA stable on EFV-based antiretroviral therapy (ART) and RIF-based TB treatment. We determined plasma MPA concentrations pre-dose and 2, 4, 6, 8, 10 and 12 weeks after DMPA 150 mg injection and measured plasma progesterone levels fromweek 2 onwards. The primary outcome measure was the proportion of women with sub-therapeutic MPA levels (<0.1 ng/mL) at week 12. MPA PK parameters were calculated using non-compartmental methods and compared with historical ART-naïve controls without TB who received DMPA. Results: Baseline characteristics of the 42 evaluable participants are shown in Table 1. Five women [11.9% (95% CI 4.0-25.6%)] had MPA <0.1 ng/mL at week 12 with one of the five having MPA <0.1 ng/ml at week 10 compared to one of 16 (6,3%) at week 12 among the historical controls. No participant had progesterone levels >5 ng/mL (suggesting ovulation) throughout the study including at week 12. Compared to historical controls, median area under the concentration-time curve over 12 weeks (AUC0-12) was lower (7.63 vs. 12.38 ng*wk/mL, p=0.004) and apparent clearance was higher (19,681 vs. 12,117 L/

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CROI 2019