CROI 2015 Program and Abstracts

Abstract Listing

Poster Abstracts

Conclusions: This study shows that children aged 2 to 5 years born to HIV-positive women have a 4-fold increased risk of M.tb infection compared to HIV-unexposed children. This increased risk may be even higher than measured as HIV-infected children may not react to TST. Further research is required to investigate whether observed increased risk in HIV-exposed children is due to increased susceptibility to M.tb and/or increased Mtb exposure. HIV and TB are family diseases and improved tuberculosis control in the long-term will only be achieved with better integration between HIV, TB, maternal and child health services in high-burden settings.

TUESDAY, FEBRUARY 24, 2015 Session P-T6 Poster Session

Poster Hall

2:30 pm– 4:00 pm ART Adherence, Adverse Effects, and Retention Among Pregnant Women and Infants 886 ARV Adherence Associated with Reduced Breastmilk HIV Viral Load and HIV Transmission Nicole L. Davis 4 ; William C. Miller 4 ; Michael G. Hudgens 4 ; Charles S. Chasela 1 ; Dorothy Sichali 2 ; Julie A. Nelson 4 ; Joseph Rigdon 4 ; Sascha R. Ellington 3 ; Athena P. Kourtis 3 ; Charles M. van der Horst 4 BAN study team 1 UniversityofWitswatersand,Johannesburg,SouthAfrica; 2 UNCProject-Malawi,Lilongwe,Malawi; 3 USCenters forDiseaseControlandPrevention(CDC),Atlantaq,GA,US; 4 UniversityofNorthCarolina,ChapelHill,NC,US Background: To prevent mother-to-child HIV transmission, antiretroviral (ARV) interventions have been used to reduce HIV viral replication in breastmilk and maternal blood. Achieving and maintaining viral suppression relies on adherence to ARV regimens. Methods: A case cohort study was conducted using data from the Breastfeeding, Antiretrovirals and Nutrition study to comprehensively assess the role of adherence on transmission. We included mothers randomized to 28 weeks of postpartummaternal ARV or infant nevirapine who had ≥ 1 plasma or breastmilk specimen available between 2-24 weeks postpartum. Among these, we included all mothers who transmitted HIV to their infants between 2-28 weeks and 15% of mothers who did not transmit HIV by 28 weeks (n=31 and 232, respectively). Adherence was measured using maternal ARV pill counts and categorized as poor (0-80%), partial (81-98%) and near perfect (>98%). Associations between maternal ARV adherence and breastmilk HIV RNA concentration were assessed using mixed effects models. Cox models were used to estimate associations between breastmilk HIV RNA concentration and breastmilk HIV transmission between 2-28 weeks. A Monte Carlo simulation was then conducted to estimate the number of transmissions that would have been averted between 2-28 weeks postpartum if all mothers randomized to maternal ARVs (n=848) had been 100% adherent. Results: Mean adherence was 88% [median 0.96, IQR 0.86-1.00] among mothers in the maternal ARV arm. Having at least partial maternal ARV adherence significantly reduced the odds of having detectable (>40 copies/ml) breastmilk HIV RNA (partial vs. poor OR 0.23, 95%CI 0.08-0.67; near perfect vs. poor OR 0.36, 95% CI 0.16-0.81). Detectable breastmilk HIV RNA was associated with 7.4 (95% CI 3.2-17.1) times the adjusted relative rate of breastmilk HIV transmission. Among mothers who transmitted HIV to their infant, all had at least one plasma viral load >100 copies/ml. Using Monte Carlo simulation, if all mothers randomized to maternal ARVs had been 100% adherent we estimated a 36% decrease in HIV transmissions between 2-28 weeks postpartum, compared to transmissions estimated under observed adherence [transmissions under perfect adherence: 14, 95% prediction interval (PI) 7-21; transmissions under observed adherence: 22, 95% PI 13-32]. Conclusions: Lower breastmilk RNA was associated with better adherence and lower risk of transmission. Maintaining plasma viral load <100 copies/ml may be effective at preventing breastmilk transmission. 887 PeripartumHair Levels of Antiretrovirals Predict Viral Suppression in UgandanWomen Catherine A. Koss 1 ; Peter Bacchetti 1 ; Deborah Cohan 1 ; Paul Natureeba 1 ; Howard Horng 1 ;Tamara Clark 1 ; Edwin Charlebois 1 ; Moses R. Kamya 2 ; Diane Havlir 1 ; Monica Gandhi 1 1 University of California San Francisco, San Francisco, CA, US; 2 Makerere University College of Health Sciences, Kampala, Uganda Background: Combination antiretroviral therapy (ART) is recommended for all HIV-infected pregnant womenworldwide. Adequate antiretroviral (ARV) exposure is critical tomaintain maternal health and reduce transmission to infants and partners. Hair concentrations are a non-invasivemeasure of cumulative ARV exposure that integrate adherence and pharmacokinetics and are the strongest predictor of viral suppression in large prospective cohorts. However, hair concentrations of ARVs have not yet been examined in the peripartumperiod. Methods: The PROMOTE trial (NCT00993031) enrolled HIV-infected, ART-naïve pregnant Ugandan women at 12-28 weeks gestation who were randomized to initiate lopinavir (LPV) or efavirenz (EFV)-based ART. Small hair samples were collected at 30-34 weeks gestation and 12 weeks postpartum. EFV and LPV hair concentrations were measured via liquid chromatography/tandemmass spectrometry. Multivariate logistic regression models examined predictors of viral suppression (HIV-1 RNA <400 c/ml) at delivery and 24 weeks postpartum in women on ART for ≥ 6 weeks. Potential predictors included log-transformed ARV hair concentration (interpolated for delivery), age, pretreatment HIV-1 RNA, self-reported adherence, and time on ART. Results: Among 325 women, mean age was 30 years (SD 5.4) and median CD4 cell count was 366 cells/mm 3 (IQR 270-488) at ART initiation. Median time on ART at delivery was 17 weeks (IQR 14-21). Mean self-reported adherence was >97% in each arm. Viral suppression was achieved by 98% (EFV) and 87% (LPV) at delivery and 93% (EFV) and 91% (LPV) at 24 weeks postpartum. In multivariate models including self-reported adherence and pretreatment HIV-1 RNA (Table), ARV hair concentrations were the strongest predictor of viral suppression at delivery (EFV: aOR 1.86 per doubling in concentration [95% CI: 1.14-3.1], p=0.01; LPV: aOR 1.90 [95% CI: 1.33-2.7], p=0.0004) and 24 weeks postpartum (EFV: aOR 1.81 [95% CI: 1.22-2.7], p= 0.003; LPV: aOR 1.53 [95% CI: 1.05-2.2], p=0.03).

Poster Abstracts

534

CROI 2015