Background and Objectives Few studies have evaluated the effects of anti-retroviral therapy (ART) on skeletal metabolism in Asian populations. We examined the impact of tenofovir plus lopinavir/ritonavir (TDF + LPVr) on bone turnover in Chinese HIV patients over 2 years by comparing a group treated with first-line zidovudine plus nevirapine (AZT + NVP) therapy, to a group of treatment-failure patients switched to TDF + LPVr, and hypothesised that bone turnover marker (BTM) levels at 2 years would be greater in the TDF + LPVr group.
Materials and Methods We performed a secondary analysis of bone turnover markers (BTM) at baseline and two years in stored plasma samples collected from 2/2009 – 1/2013 as part of a multi-center trial. Two groups were compared: 1) treatment-naïve patients initiated on zidovudine (AZT)/lamivudine (3TC) plus nevirapine (NVP) at enrollment, and 2) patients who failed first-line ART and were switched to tenofovir (TDF)/3TC plus lopinavir/ritonavir (LPVr). Laboratory tests included the resorption marker, C-terminal cross-linking telopeptide of type-1 collagen (CTX) and the formation marker procollagen type 1 N-terminal propeptide (P1NP).
Results In the TDF + LPVr group, plasma samples were available from 59 subjects at baseline and 56 subjects at two years. Of these subjects, 36 had samples available from both time points. In the AZT + NVP group, plasma samples were analysed from 82 subjects at baseline and 61 samples at two-years. All 61 subjects with two-year samples also had baseline samples available. Sex, body mass index (BMI), alcohol use, smoking history, HIV viral load, or CD4+ count were similar at baseline, however the TDF + LPVr group was older (42.2 ± 8.0 v. 38.0 ± 9.8 years, p = 0.003) and reported longer median time since HIV diagnosis [61 mo., interquartile range (IQR) 56-72 v. 1 mo., IQR 0-11; p<0.001]. Median change in CTX over two years was + 0.24 ng/mL (IQR 0.10–0.43; + 59.6%) in the TDF + LPVr group and + 0.09 ng/mL (IQR -0.03 to 0.18; + 31.3%) in the AZT + NVP group (p = 0.001), whereas median changes in P1NP were + 25.5ng/mL (IQR 2.4-51.3; + 42.4%) and + 7.11 ng/mL (IQR -4.3 to 21.6; + 15.3%), respectively (p = 0.012). Differences remained after adjusting for age, sex, and BMI. CTX correlated to P1NP at baseline and two years in both treatment groups. 25OHD levels remained stable in patients receiving TDF + LPVr (p = 0.568), but decreased in the AZT + NVP group (p = 0.007). Correspondingly, iPTH did not change in the TDF + LPVr group, but increased in the AZT + NVP group (p<0.001).
Conclusions Switching to a TDF/3TC + LPVr regimen after treatment failure resulted in greater increases in BTMs than initiation with an AZT + NVP containing regimen in Chinese HIV patients. Following this change, bone resorption increased by nearly 60%, which is much greater than the 20-35% increase from baseline described previously in non-Chinese populations. Further studies are warranted to elucidate these findings.