This Week in HIV Research: Bone Concerns Aren’t Just for Older Folks

In Journal of Acquired Immune Deficiency Syndromes, the authors of a meta-analysis of 84 papers on fracture risk and bone mineral density (BMD) called for a greater focus on bone health in younger people living with HIV (PLWH). They suggested that HIV and antiretroviral therapy should be considered risk factors for osteoporosis, similar to other factors, such as smoking or low vitamin D levels.

Their analysis found a rapid decline in BMD after HIV treatment starts, with density stabilizing after one year on antretrovirals in most cases. The exception to this occurred among people taking tenofovir disoproxil fumarate (TDF), in whom the decline continued.

The observed higher fracture risk in PLWH compared to controls was not entirely explained by lower BMD. One reason may be higher levels of hepatitis B or C coinfections among PLWH, which further increase fracture risk. Study authors advised providers to consider this fact, especially as this population ages.

The authors also proposed guidelines for osteoporosis screening and management in PLWH. These include screening PLWH ≥ 40 years old for osteoporosis using dual-energy X-ray absorptiometry, and starting those with T-scores below 1.5 who have other risk factors on anti-osteoporosis treatment with alendronate or zoledronic acid. T-scores could also be used to determine whether a medication switch from TDF is warranted.

Adjusting the dosage for darunavir (Prezista), dolutegravir (Tivicay), or lamivudine (Epivir) in older PLWH is currently not necessary, a small study published in AIDS showed.

As people age, their livers and kidneys clear drugs and other substances more slowly, potentially causing greater drug concentrations to remain in the body. To assess the extent to which this may be relevant to antiretroviral usage among older people living with HIV, study participants older than 55 were drawn from the Swiss HIV Cohort. While single-point pharmacokinetic data was available for 804 people, a full investigation could only be performed in 19 participants, 17 of whom were men.

Medication clearance and exposure were compared between those older than 65 years of age and those younger than 65. Study authors noted that these parameters can vary significantly independent of age. Thus, the observed 40% lower boosted darunavir clearance and the 11% higher lamivudine exposure in the older group compared to the younger one were not clinically significant.

Pharmacokinetic values were similar to previously reported variations, study authors noted. The 18-hour t_½ clearance time for dolutegravir in the older group (compared to 12 hours in 56- to 65-year-olds) also should make little difference, since that drug is usually taken once a day, they wrote.

“Advanced age does not affect boosted darunavir, dolutegravir, and lamivudine pharmacokinetics to a clinically significant extent,” study authors concluded. That said, they called for additional studies on antiretrovirals in older PLWH.

More evidence that undetectable = untransmittable—i.e., that a fully suppressed viral load translates to no risk of onward sexual HIV transmission—comes from a study of 332 virally suppressed participants in the Women’s Interagency HIV Study that was published in AIDS.

While HIV was found in 47% of 38 cervicovaginal lavage samples collected before starting antiretroviral therapy, only one of the 38 samples collected after one year of HIV treatment contained the virus. No HIV was found in 294 vaginal samples from women who had been virally suppressed in plasma for a median of 7 years.

The results held even among those who had signs of genital inflammation when the samples were collected. However, the group was small (n=38). Other studies had found some viral shedding among women with markers of genital inflammation, but participants in these studies had been virally suppressed for shorter periods than in the current analysis.

“The duration of HIV-1 suppression may be an important factor in the relationship between viral suppression and absence of transmission,” study authors concluded, noting that their data strengthens providers’ U=U message for women.

Among PLWH, full viral suppression is associated with better executive function compared to participants with a detectable viral load, an analysis of 15-year data from the University of California-San Diego’s HIV Neurobehavioral Research Program found.

The study, which was published in AIDS, included 1,943 participants (more than 80% of whom were men) for a total of 5,555 study visits spanning the years 2000 to 2015. Everyone reported recent adherence to their HIV treatment regimen. At baseline, 69% of participants were virally suppressed (viral load ≤ 50 copies/ml). As measured by T-score, non-impaired executive function was significantly associated with a suppressed viral load (odds ratio 1.57; P < .001). No association between viral suppression and global neuropsychological performance—or any domains other than executive function, for that matter—was observed.

Study authors found this result somewhat surprising but noted that evidence suggests HIV affects executive function more than other domains. The observed better executive functioning is likely the result of viral suppression, rather than its cause, they wrote. They cautioned that their results may not be generalizable to women, or to settings where almost everyone is virally suppressed. “Going forward, further research on the clinical implications of both neurocognitive impairment and lack of virologic suppression are needed in studies of [PLWH],” they concluded.