CROI 2018 Abstract eBook

Abstract eBook

Poster Abstracts

of this research was to investigate the effect of ART on maternal BM in the context of pregnancy and lactation. Methods: Two groups of pregnant women, 95 HIV+ (on TDF-3TC-EFV, previously ART naïve) and 96 HIV- were recruited in Kampala, Uganda and followed prospectively. Data were collected at 36 wks gestation (PG36), 2 (PP2) and 14 wks postpartum (PP14). Whole body (WB), lumbar spine (LS) and total hip (TH) BM density (BMD) was measured by DXA. Bone turnover markers (BTM), PTH and 25(OH)D were measured. The primary outcome was the difference between the groups in % change (± SE) in maternal LS BMD between PP2 and PP14. Results: Median age was 24.5 (IQR 21.1, 26.9) yrs. Body weight was 4-5% lower in HIV+ women. By PP14, mean duration on ART was 29.3±5.1 wks, adherence was >95% and median CD4 count was 403 (IQR 290-528). All women were breastfeeding (BF) at PP2 and PP14. More HIV+ women reported exclusive BF (PP2 82.9% v 58.7%; PP14 86.7% v 66.2%, both p<0.05). BMD decreased between PP2 and PP14 at all skeletal sites in HIV+ (WB -1.2±0.2%; LS 1.8±0.4%; TH 4.0±0.4%; all p<0.05) and HIV- women (WB -0.6±0.2%; LS 2.5±0.4%; TH 2.7±0.4%; all p<0.05). Reductions in LS BMD were not different between groups (p=0.3). However, HIV+ women had a greater reduction in TH BM which remained after size-adjustment (TH -3.7±0.3% v -2.7±0.3%, p=0.04). BTM increased in both groups between PG36 and PP14. HIV+ women had greater increases (CTX 74.6±5.9% v 56.2±5.9%; P1NP 100.3±5.0% v 72.6±5.0%; BAP 67.2±3.6% v 57.1±3.6%; all p<0.05). Changes in PTH and 25(OH)D were not different between groups (PTH +60.0±6.4% v +57.6±6.4%; 25(OH)D -13.9±4.1% v -11.1±3.1%; both p<0.05). HIV+ women had 33-35% higher PTH at PG36 and PP14 (p≤0.0001). Conclusion: These data show a significantly greater reduction in TH BMD in Ugandan HIV+mothers on option-B+ ART compared to HIV- mothers in the first 3 mo of lactation, consistent with changes in BTM. It is important to determine if these are temporary or have long-term consequences for bone health. 722 RATES OF BONE LOSS SLOW AFTER THE FIRST YEAR OF ART: START BMD SUBSTUDY FINAL RESULTS Andrew Carr 1 , Birgit Grund 2 , Ann V. Schwartz 3 , Anchalee Avihingsanon 4 , Sharlaa Badal-Faesen 5 , Jose I. Bernadino 6 , Patrick W. Mallon 7 , Vicente Estrada 8 , Alberto M. La Rosa 9 , Sanjay Pujari 10 , David White 11 , Nicole Wyman Engen 2 , Kristine E. Ensrud 2 , Jennifer Hoy 12 1 St. Vincent’s Hosp, Sydney, NSW, Australia, 2 University of Minnesota, Minneapolis, MN, USA, 3 University of California San Francisco, San Francisco, CA, USA, 4 Chulalongkorn University, Bangkok, Thailand, 5 University of the Witwatersrand, Johannesburg, South Africa, 6 Hospital La Paz Institute for Health Research, Madrid, Spain, 7 University College Dublin, Dublin, Ireland, 8 University Hospital Clinic of San Carlos, Madrid, Spain, 9 Asociacion Civil Impacta Salud y Educacion, Lima, Peru, 10 Institute of Infectious Diseases, Pune, India, 11 Heart of England NHS Foundation Trust, Birmingham, UK, 12 Monash University, Melbourne, VIC, Australia Background: Initial antiretroviral therapy (ART) in adults with normal CD4 counts accelerates loss of bone mineral density (BMD) over the first 1-2 years. Whether this loss continues with longer therapy is unclear. Methods: We compared the effects of immediate and deferred ART on BMD change in adults in the BMD substudy of START, which randomized ART-naïve adults with CD4>500 cells/µL to immediate or deferred (CD4<350) ART. Deferred group offered ART after May 2015. BMD was measured annually for up to 5 years at the total hip and lumbar spine (L1-L4) by dual-energy X-ray absorptiometry. Mean percent changes in BMD from baseline and annual percent changes were estimated and compared between treatment groups using longitudinal mixed models, by intention to treat (ITT) and by ART use (Immediate vs. no ART [Deferred group censored at ART start]). We also assessed predictors of BMD change within group. Results: 411 participants were included (Immediate=201; Deferred=210). Median baseline age was 32 years, with 80% non-white, 24%women and median CD4 count 643 cells/µL. Groups were well balanced at baseline. The most common initial drugs in the Immediate group were tenofovir disoproxil fumarate (TDF; 83%) and efavirenz (79%); a protease inhibitor was used by 13%. Mean follow-up was 4.5 years. In the Immediate group, 96%-97% of participants used ART throughout Years 1-5. In the Deferred group, 16%, 28%, 58%, and 85% used ART at the Year 1, 2, 3, and 4 visits, respectively. BMD changes by ITT and by ART use are shown in the Table. Averaged through follow-up, BMD decreased more in the Immediate versus the Deferred group (Table, first 2 rows), but groups converged by Year 3 at the spine (diff=-0.5,

p=0.26) and Year 4 at the hip (diff=-0.2, p=0.68) as most Deferred group participants started ART. In the Immediate group, BMD declined by 2.1% at the spine and 2.0% at the hip during Year 1; afterwards, BMD was stable at the spine and continued to decline at the hip by 0.5% per year. The annual rates of BMD change after Year 1 were similar in the Immediate group and those who remained ART-naïve in the Deferred group. No clinical, HIV-related or ART characteristic consistently predicted greater BMD loss with immediate ART (including use of TDF), or while ART-naïve in the Deferred group. Conclusion: BMD declined at both hip and spine after ART initiation. After Year 1, BMD change was comparable between the Immediate group and those who remained ART-naive, suggesting that bone loss slows after the first year of ART.

Poster Abstracts

723 GREATER BONE TURNOVER MARKER DECLINE WITH ZOLEDRONIC ACID THAN WITH TDF-SWITCHING Andrew Carr 1 , Robyn Richardson 1 , Stephen J. Kerr 2 , Peter R. Ebeling 3 , Nicholas Pocock 1 , Jhon Rojas 4 , Esteban Martinez 4 , Jennifer Hoy 3 1 St. Vincent’s Hosp, Sydney, NSW, Australia, 2 HIV–NAT, Thai Red Cross AIDS Research Centre, Bangkok, Thailand, 3 Monash University, Melbourne, VIC, Australia, 4 Hospital Clinic of Barcelona, Barcelona, Spain Background: Zoledronic acid (ZOL) 5mg annually was more effective than switching tenofovir disoproxil fumarate (TDF) at increasing bone mineral density (BMD) over 24 months in HIV-infected, osteopenic adults. The relative effects of ZOL vs. TDF-switching on plasma bone turnover markers (BTMs) are unknown. Further, it is not clear if TDF causes bone loss by reducing bone formation or increasing bone resorption. Methods: We measured plasma levels of C-terminal telopeptide of type 1 collagen (CTX; a marker of bone resorption) and procollagen type 1 N propeptide (P1NP; a marker of bone formation) in participants in the randomised trial comparing annual ZOL 5mg with TDF switching over 24 months. Percent changes in CTX and P1NP were compared in the per-protocol population at Months 1, 3, 6, 12 and 24 with a Wilcoxon test and over all follow-up with Generalised Estimating Equations (GEE). We also determined whether BTM changes at Month 3 predicted hip and spine BMD changes (Pearson’s correlation coefficient). Results: Plasma samples were available for 42 of 44 participants (95%) in the TDF switch group and 41 of 42 participants (98%) in the ZOL group. Median percent decreases in both BTMs were significantly greater with ZOL than with TDF-switching through Month 24 by GEE and at each time point (all p<0.001; see Figure 1). For example, at Month 12 the median (IQR) changes for ZOL vs. TDF- switch groups for P1NP were -53.5% (IQR -40.5%, -63.3%) and -25.4% (-9.8%, -41.0%), respectively, and for CTX were -49.7% (-30.7%, -62.7%) and -19.1% (+13.4%, -41.6%), respectively. Combining both groups, decreases in P1NP at M3 were more strongly correlated with decreases in BMD at M24 at the spine (r2=-0.44; p<0.001) and hip (r2=-0.45; p<0.001) than were the respective decreases in CTX (spine r2=-0.36; p=0.001, and hip r2=-0.23; p=0.051). In patients who switched TDF, the decrease at Month 1 in CTX was -19.7% (IQR -39.2%, +6.1%) whereas the change for P1NP was only -4.0% (–15.4%, +7.1%). Conclusion: ZOL resulted in larger decreases in bone turnover than did TDF- switching. The decrease in bone turnover in the TDF-switch group suggests that TDF reduces BMD by increasing bone turnover. Early changes in P1NP predicted BMD changes at 24 months with both ZOL and TDF-switching.

CROI 2018 269