Bone loss slows, but continues long-term in HIV-positive people on antiretroviral therapy

People with HIV experienced a decrease in bone density at the hip and spine during their first two years after starting antiretroviral therapy (ART). While bone loss slowed after 96 weeks, it continued to decline more rapidly among HIV-positive people compared with the usual age-related bone loss seen in HIV-negative people over seven years, researchers reported at the recent 8^th International AIDS Society Conference on HIV Pathogenesis, Treatment and Prevention in Vancouver.

Research over the course of the epidemic has found that people living with HIV typically have lower bone density and higher risk of fractures than HIV-negative people, but whether this is attributable to HIV infection itself, associated metabolic or immunological changes, antiretroviral drug toxicity or a combination of factors is not fully understood.

Studies have shown that people on ART – especially regimens containing tenofovir (Viread, also in the Truvada, Atripla, Eviplera, and Stribild combinations) or HIV protease inhibitors – experience bone loss during the first couple of years after starting treatment, but less is known about longer-term effects on bone health.

Philip Grant of Stanford University and fellow investigators with ACTG study A5318 performed long-term follow-up bone density tests using dual-energy X-ray absorptiometry (DEXA) on HIV-positive people who had received baseline and earlier follow-up DEXA scans during the A5202/A5224s trial.

In A5202 treatment-naive participants were randomly assigned to start ART using either efavirenz (Sustiva) or ritonavir-boosted atazanavir (Reyataz), combined with either tenofovir/emtricitabine (the drugs in Truvada) or abacavir/lamivudine (the drugs in Kivexa or Epzicom). A5224s was a sub-study looking at metabolic changes including body fat distribution and bone loss.

The researchers compared bone mineral density (BMD) changes between these HIV-positive participants and HIV-negative control subjects from the Boston Area Community Health BACH/Bone study and the Women's Interagency HIV Study (WIHS), adjusting for age, sex, race/ethnicity and body mass index (BMI).

This analysis included 97 HIV-positive participants and 614 HIV-negative control subjects. In both groups most participants were men and about a third were black. The HIV-positive group was younger on average (40 vs 46 years), less likely to be Hispanic (14% vs 31%) and had lower BMI at the time of their first DEXA (24 vs 28). About a third in both groups were current smokers, but the HIV-negative participants were more likely to have never smoked.

Among the HIV-positive participants the median CD4 T-cell counts at the time of the first and last DEXA were 247 and 598 cells/mm³, respectively. At the last DEXA 86% had HIV RNA <200 copies/ml. They had used tenofovir for a median of 5.8 years and protease inhibitors for 3.7 years.

Each participant received a single long-term follow-up DEXA, done a median of 7.5 years after the first scan for the HIV-positive group, 7 years for the HIV-negative men in BACH/Bone and 5 years for the HIV-negative women in WIHS.

Over the entire follow-up period – from first to last DEXA – BMD fell by a mean -1.01% at the lumbar spine and -1.56% at the hip per year in the HIV-positive group, while rising by a mean +0.04% at the spine and falling by -0.31% at the hip in the HIV-negative group.

During the first 96 weeks on ART, HIV-positive participants had significantly higher annual rates of BMD decline at the lumbar spine and the total hip compared to HIV-negative controls (difference of -1.05% at spine and -1.25% at hip).

Long-term follow-up DEXAs showed that people with HIV had significantly greater BMD decline at the lumbar spine (difference of -0.31% per year), but not at the hip.

In the HIV-positive group, the rate of BMD decline slowed significantly between weeks 0-96 and the later period (-0.75% per year at the spine and -1.29% per year at the hip).

During the first 96 weeks, higher pre-ART CD4 count was associated with increased spine BMD (+0.20% per additional 50 cells/mm³), while higher baseline viral load was associated with decreased spine and hip BMD in a multivariate analysis. Use of tenofovir/emtricitabine vs abacavir/lamivudine was associated with significantly lower spine and hip BMD during the first 96 weeks (both -0.87%), but there was no difference between people taking efavirenz vs atazanavir.

During the later period, no HIV-related characteristics – including CD4 count, viral load and treatment regimen – were significantly associated with spine or hip bone loss. Lower total lean body mass, but not BMI, was associated with greater BMD decline at both the spine and hip after 96 weeks (+0.05% at spine and +0.06% at hip per 1 kg).

"In [people with] HIV, BMD continues to decline with time at both the lumbar spine and total hip, but at significantly slower rate, after the first 96 weeks of ART," the researchers summarised. "Compared to HIV-uninfected controls, HIV-infected persons on ART for 7 years have a faster decline in lumbar spine, but not hip, bone mineral density."

"Starting ART at a higher T-cell count may be protective for preservation of bone health," they suggested, adding that "modification of additional risk factors through weight-bearing exercise may prevent further loss, although prospective studies are needed."

Grant P et al. Long-term bone mineral density changes in antiretroviral-treated HIV-infected individuals. 8^th International AIDS Society Conference on HIV Pathogenesis, Treatment, and Prevention (IAS 2015), Vancouver, abstract TUPDB0103, 2015.