Abstract
There are limited data regarding long-term BMD changes over time among treatment-naïve people living with HIV (PLHIV) after initiating combined antiretroviral therapy (cART) in Asia. We aimed to study bone mineral density (BMD) changes among treatment-naïve PLHIV started treatment with tenofovir disoproxil fumarate (TDF)- or non-TDF-containing regimen and HIV-uninfected controls in an Asian setting. The study was a five-year prospective study. BMD at lumbar spine (LS) (L1 to L4), total hip (TH), and femoral neck (FN) were measured by dual energy X-ray absorptiometry (DEXA) scans at baseline, months 12, 24 and 60. Multivariate logistic regression models were used to explore factors associated with mean BMD ≥5% reduction after 5 years of cART. A total of 106 PLHIV (75 and 31 started TDF- and non-TDF-containing regimen, respectively) and 66 HIV-uninfected individuals were enrolled. The mean percent changes of BMD were significantly different longitudinally between TDF and non-TDF users (p<0.001 for LS, p = 0.006 for TH and p = 0.02 for FN). HIV-positive status and on TDF-containing regimen was independently associated with BMD loss ≥5% at month 60 (adjusted odds ratio [aOR] 7.0, 95% confidence interval [95%CI] 2.3–21.0, P = 0.001 for LS; aOR 4.9, 95%CI 1.7–14.3, P = 0.003 for TH and aOR 4.3, 95%CI 1.6–11.2, P = 0.003 for FN) compared to HIV-uninfected individuals. In a multivariate model for PLHIV only, TDF use (vs. non-TDF, P = 0.005) and pre-treatment CD4+ count <350 cells/mm3 (vs. ≥350 cells/mm3, P = 0.02) were independently associated with ≥5% BMD loss in TH at month 60. Treatment-naïve PLHIV initiating treatment with TDF-containing regimen have higher BMD loss in a Thai cohort. TDF use and low pre-treatment CD4 count were independently associated with BMD loss at month 60 at TH. Earlier treatment initiation and interventions to prevent bone loss could improve skeletal health among PLHIV.Clinicaltrials.gov: NCT01634607
Highlights
People living with HIV (PLHIV) have higher risks for decreased bone mineral density (BMD) and bone-related morbidities such as osteoporosis and fragility fractures compared to HIVnegative individuals [1,2,3,4,5,6,7]
In the multivariate models, when we included both PLHIV and HIV-uninfected individuals, we found that the HIV-positive status and tenofovir disoproxil fumarate (TDF)-containing regimen were independently associated with 5% decrease in BMD at month 60 for all sites compared to HIV-uninfected individuals after adjusting for age, sex and body mass index (BMI) (Table 3)
In separate multivariate models for PLHIV only, we found that TDF use and baseline CD4+ cell count < 350 cells/mm3 were independently associated with 5% BMD loss (Table 3) at total hip (TH) but not at the other sites at month 60 after adjusting for age, BMI, baseline CD4 count, HIV RNA level and other significant cofounders from the univariate model
Summary
People living with HIV (PLHIV) have higher risks for decreased bone mineral density (BMD) and bone-related morbidities such as osteoporosis and fragility fractures compared to HIVnegative individuals [1,2,3,4,5,6,7]. Despite virological suppression with combination antiretroviral therapy (cART), treatment-associated adverse effects are still common among PLHIV in low-middle income settings where treatment options are limited. Certain antiretroviral drugs such as tenofovir disoproxil fumarate (TDF) and some protease inhibitors (PI) have been shown to be associated with reduced bone mineral density (BMD) in both treatment-naïve and treatment-experienced PLHIV [18,19,20]. We aimed to study the long-term BMD changes prospectively using dual X-ray absorptiometry (DEXA) scan among treatment-naïve PLHIV who started their treatment with either TDF-containing or non-TDF-containing regimen and HIV-uninfected individuals
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