CROI 2015 Program and Abstracts

Abstract Listing

Poster Abstracts

recommended lopinavir (LPV) trough concentration (C trough

) of 1mg/L for predicting virologic failure (VF) and intermediate-to-high level LPV resistance in Asian children in a

resistance monitoring study of second-line antiretroviral therapy (ART). Methods: Data from study participants in Indonesia, Thailand, and Vietnam receiving second-line LPV-based ART and followed for ≥ 24 weeks were analyzed. All had random or trough LPV concentrations and viral load assessments at 24 weeks after enrollment. Those with VF (HIV RNA >1000 copies/mL) had genotypic resistance testing; 46MLI, 47V, 54V, 76V, 82AS, 88S, and 90M were considered major PI mutations. For VF and resistance, we calculated sensitivity, specificity, and area under the receiver operating characteristics curve (AROC) as a measure of correctly predicting outcomes, versus the target LPV level. Results: The 223 children on LPV had a median age of 10.4 (IQR 7.9-13.4) years; 61%were male. At study enrollment, mean CD4 was 842 ± 438 cells/mm 3 , mean HIV RNA was 2.3 ± 0.9 log 10 copies/mL, median LPV duration was 2.5 (IQR1.3-4.2) years, and ≥ 95% adherence was reported by visual analogue scale (VAS) in 200 (90%) and by pill count in 192 (86%). In 84 children with a LPV C trough at week 24, a cut-off at 1 mg/L gave an AROC of 0.82 in predicting VF with sensitivity of 67% and specificity of 96% (Table 1). Of 21 children with VF at study week 24, 7 had major PI mutations (5 with intermediate/high level resistance) but only 1/7 had low LPV C trough . After week 24,14 children had VF and LPV C trough available: 5 (35%) had LPV C trough <1 mg/L, and only 2 with C trough >1mg/L had major PI mutations. Multivariate logistic regression found LPV concentrations <1 mg/L vs. ≥ 1mg/L (OR 6.47; 95%CI 2.15-19.50, P=0.001) and CD4 ≤ 20% (OR 2.83; 95%CI 1.01-7.89, P=0.05) were associated with VF; age, duration on LPV, WHO staging, and adherence assessed by pill count or VAS were not. No factors predicted major LPV resistance mutations.

Conclusions: LPV C

trough of 1 mg/L predicted VF, but not the risk of major LPV mutations. Children with LPV concentrations <1mg/L and CD4 ≤ 20%were at greater risk for VF.

WEDNESDAY, FEBRUARY 25, 2015 Session P-V1 Poster Session

Poster Hall

2:30 pm– 4:00 pm Postexposure Prophylaxis (PEP) 957 Significant Intolerability of Efavirenz in HIV Occupational Postexposure Prophylaxis SurasakWiboonchutikul 1 ;VarapornThientong 1 ; Patama Sutha 1 ; Boonchai Kowadisaiburana 2 ;Weerawat Manosuthi 1 1 Bamrasnaradura Infectious Diseases Institute, Nonthaburi, Thailand; 2 Bangkok Hospital, Bangkok, Thailand

Background: Postexposure prophylaxis (PEP) has been used to decrease a risk of HIV transmission after occupational exposure. Regimen completion is one of the most important factors in successful prophylaxis. Limited data are available on tolerability of PEP regimens in healthcare workers (HCWs) in resource-limited settings. We aimed to describe the characteristics of occupational exposure, and sought to determine factors associated with incompletion of the 4-week HIV prophylactic course. Methods: A retrospective study was conducted among HCWs who accidentally exposed to blood or body fluid of patients at Bamrasnaradura Infectious Diseases Institute, Thailand, between March 1996 and June 2014. The characteristics of exposure were described, and logistic regression analysis was used to determine factors associated with incompletion of the 4-week prophylactic course. Results: A total of 225 exposure episodes were reported (163 percutaneous injury, 43 mucosal exposure, 6 non-intact skin exposure, and 13 intact skin exposure). The mean (SD) age was 33.1 (9.9) years and 189 (84%) were females. The most frequently exposed groups were nurses (43%), patient or nurse assistants (18%), and medical technicians (15%). The HIV status of the source was defined in 149 (66%) episodes which were positive in 101 (68%). Of 225 exposures, PEP was prescribed in 155 (69%) episodes but was subsequently intentionally discontinued in 26 episodes (HIV source was negative in 19, refusal to continue in 7). PEP courses should have completed in 129 episodes. Of 129 prescribed regimens, 38%were 2 NRTIs, 37%were 2 NRTIs + PIs, 12%were Zidovudine alone, 9%were 2 NRTIs + Efavirenz (EFV), and 4%were 2 NRTIs + Raltegravir. Only 91 of 129 (71%) HCWs were able to complete the 4-week regimen. Multivariate analysis showed that 2 NRTIs + EFV was the only significant factor associated with incompletion of the 4 week-course (OR 33.3; 95% CI 4.2-100; p < 0.01). Other factors including age, gender, staff position, status of the source, and other PEP regimens were not associated with incompletion of the 4-week course ( p > 0.05). The reason for premature discontinuation of 2 NRTIs + EFV was intolerability in all HCWs. None of the HCWs was reported to have HIV seroconversion. Conclusions: Two NRTIs + EFV regimen was significantly associated with premature discontinuation of occupational PEP. This regimen should not be further used for HIV prophylaxis following occupational exposure in the resource-limited settings. 958 Rilpivirine-Emtricitabine-Tenofovir for HIV Nonoccupational Postexposure Prophylaxis Rosalind Foster 1 ; John McAllister 2 ;Tim R. Read 3 ; Anna Pierce 4 ; Robyn Richardson 2 ; Anna McNulty 1 ; Andrew Carr 2 On behalf of the EPEP Study Researchers 1 Sydney Sexual Health Centre, Sydney, Australia; 2 St Vincent’s Centre for Applied Medical Research, Sydney, Australia; 3 Melbourne Sexual Health Centre, Melbourne, Australia; 4 The Alfred Hospital, Melbourne, Australia Background: CDC recommends 3-drug post-exposure prophylaxis (PEP) with emtricitabine-tenofovir disoproxil fumarate (FTC-TDF) plus raltegravir (RAL) for 28 days. But in one non-occupational (N)PEP study, FTC-TDF-RAL adherence was imperfect (only 52% took all 3 pills/day) and RAL was associated with acute muscle adverse effects (9%). FTC-TDF coformulated with rilpivirine (RPV) as a single-tablet regimen (STR) is a well-tolerated, once-daily NPEP candidate. A plasma tenofovir (TFV) level >40ng/mL is thought to reflect recent full adherence, whereas a level <10ng/mL suggests no dose for ≥ 7 days. NPEP studies to date have neither evaluated STRs nor measured TFV levels. We hypothesized FTC/ RPV/TDF as an STR NPEP would be safe, well-tolerated, and result in high adherence. Methods: We evaluated NPEP with STR FTC/RPV/TDF for 28 days in gay men after high-risk, sexual exposure, in an open-label, single-arm study. We assessed adherence (pill count; patient report; and plasma TFV levels at Week 4 in a subset by HPLC), adverse events (AEs) and HIV status through Week 12. Final intention-to-treat (ITT) analyses are reported.

Poster Abstracts

570

CROI 2015