icon-    folder.gif   Conference Reports for NATAP  
18th International Workshop
on Comorbidities and Adverse
Drug Reactions in HIV,
September 12-13, 2016, New York
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BMD and Bone Markers Improve Over 18 Years in Perinatally HIV Infected
  18th International Workshop on Comorbidities and Adverse Drug Reactions in HIV, September 12-13, 2016, New York
Mark Mascolini
Young adults infected with HIV at birth or early in life had lower bone mineral density (BMD) and worse blood and urine markers of bone health than matched controls in an 86-person US study [1]. But longitudinal data in 33 of these people with HIV showed that BMD and biomarker results improved through an average 4.4 years of follow-up.
HIV infection and antiretroviral therapy are associated with bone loss and other bone abnormalities. The impact of HIV and its treatment on bone health is particularly concerning in people infected at birth or early in life as they try to control their infection through decades of life, aiming to maximize bone growth in their first decades. Normally, humans reach peak bone mass around age 30.
This study aimed to determine how HIV infection and therapy affect BMD, bone Z scores, and bone markers in young adults infected with HIV perinatally or early in life as they approach the age when bone mass should peak. A National Institute of Allergy and Infectious Disease (NIAID) team recruited 65 HIV-positive people infected early in life and older than 18 at their last follow-up visit. They matched the HIV group to 21 healthy controls. All participants had whole-body and spine DXA scans and gave yearly blood and urine samples.
For the cross-sectional comparison, median age measured 23 years in the HIV group and 25 in controls, a nonsignificant difference. A nonsignificantly lower proportion of people with HIV were men (38% versus 48%). Racial/ethnic proportions for HIV cases and healthy controls were 37% and 52% Caucasian, 51% and 43% African American, and 14% and 19% Hispanic. Median body mass index was 25 kg/m2 in both groups, and the HIV group had a nonsignificantly higher proportion of smokers (28% versus 19%). Among people with HIV, median CD4 count stood at 542 and viral load at 5038 copies. While 86% of these people were currently taking antiretrovirals, only 57% had a viral load below 40 copies.
Whole-body BMD was significantly lower in the 65 people with HIV than in the 21 controls (median 1.148 versus 1.212 g/cm2, P = 0.008), and the whole-body bone Z score was significantly lower (worse) in the HIV group (-0.1 versus +0.4, P = 0.01). Spine BMD and Z score did not differ significantly between people with and without HIV.
NTX-telopeptide, a marker of bone resorption, was significantly higher (worse) in the HIV group (median 52 versus 33 nmol/mm, P = 0.03). The HIV group also had significantly higher levels of three other bone turnover markers--alkaline phosphatase (P = 0.02), osteocalcin (P = 0.007), and parathyroid hormone (P = 0.02).
People with HIV had taken tenofovir for an average 4 years, stavudine (d4T) for 4, and didanosine (ddI) for 4. Very few people were still taking d4T or ddI, while 54% currently took tenofovir. Longer use of ddI or d4T correlated with lower whole-body BMD (ddI r = -0.3, P = 0.02; d4T r = -0.27, P = 0.03) and with lower whole-body Z scores (ddI r = -0.29, P = 0.03; d4T r = -0.29, P = 0.02). The same analysis found no association between use of tenofovir or any other antiretroviral and whole-body BMD or Z scores. And no antiretrovirals were linked to spine BMD or Z scores.
[from Jules: in speaking the study investigators they suggested the reason why TDF was not associated with whole body BMD or Z-score but did find an association with ddI or d4T was because perhaps that dci & d4T were used first by patients & perhaps their affects overcame any affects by later taking TDF.]
The NIAID team had data for 33 HIV-positive people through an average 4.4-year follow-up. Comparing baseline values with those at the latest follow-up visit showed significant average increases in whole-body BMD (+0.08, P < 0.0001), spine BMD (+0.06, P = 0.0001), and whole-body Z score (+0.3, P = 0.0014). Although alkaline phosphatase, NTX-telopeptide, and osteocalcin decreased significantly in people with HIV over time, levels remained higher in them than in healthy controls.
The researchers concluded that BMD and biomarker results "indicate abnormal bone health and increased bone turnover" in people with HIV. Because of the improvement in age-adjusted Z score, the investigators suggested that "with time, the HIV-infected patients are approximating a normal bone density for their age."
1. Mattingly AS, Jones SE, Unsal AB, et al. Decreased bone density among perinatally infected HIV+ adults is related to thymidine analogue exposure: longitudinal evaluation suggests bone density improves over time. 18th International Workshop on Comorbidities and Adverse Drug Reactions in HIV, September 12-13, 2016, New York. Abstract 003.






Overall, bone mineral density and bone turnover measures improved for the patients over the duration of follow up as evidenced by the fact that alk phos, osteocalcin and NTX telopeptides decreased over time
In particular, it is important to note that the improvement in z-score is age adjusted, suggesting that with time, the HIV infected patients are approximating a more normal bone density for their age