Metabolic Complications of HIV Infection

• Which medications have been shown to be effective in treatment of osteoporosis in the HIV population?

Bisphosphonates are the mainstay of therapy for osteoporosis in the HIV-infected population. Only alendronate and zoledronate have substantial evidence of safety and effectiveness in the HIV-infected population, but these studies have been small and of limited duration.

Bisphosphonates are pyrophosphate analogues that inhibit bone resorption by binding to the hydroxyapatite crystals in the bone. Several prospective studies have shown alendronate to increase bone density compared to calcium and vitamin D alone in the HIV infected patients with reduced bone density [109,110], with significant reduction in markers of bone resorption [111].

Zoledronic acid (ZA), an amino-bisphosphonate which is infused intravenously, has also been used in smaller studies in HIV-infected persons. In a prospective study evaluating yearly ZA infusion to biennial ZA infusion in subjects with HIV and low bone density [112], biennial ZA infusions were found to be effective in improving and maintaining bone density in the HIV population. In another prospective study evaluating the effects of ZA in HIV-positive men, ZA infusion was given at baseline and at 12 months. Compared to placebo, treatment group had significantly higher bone density and lower bone turnover markers till 5 years after the last infusion [113].

In a meta-analysis evaluating the effect of bisphosphonates on bone mineral density in 328 adults with HIV infection from 8 randomized controlled trials (5 with alendronate and 3 with ZA as the intervention), a significant increase in BMD at the lumbar spine and hip was observed in the treatment groups at 48 and 96 weeks. However, these studies were not long enough to detect the impact of bisphosphonates on fracture risk [114]. ZA has also been shown to be effective in preventing ARV induced bone loss after a single infusion [115].

These studies confirm that both alendronate and ZA are effective in improving BMD in the HIV-infected population, with early studies showing a beneficial effect of ZA in mitigating ARV-induced bone loss as well. DXA may be repeated 1 to 2 years after initiation of osteoporosis therapy and less often subsequently if BMD is stable to improved [116].

Although these studies show significant improvement in bone density with treatment, longitudinal data on fracture reduction with these medications in the HIV-infected population are not available. Additionally, these patients have onset of osteoporosis at a younger age and the need for osteoporosis treatment needs to be assessed carefully before initiating treatment. There are other medications available for the treatment of osteoporosis in the non-HIV population such as raloxifene, teriparatide and denosumab, but no randomized controlled studies of these agents are available in the HIV-infected population.

Summary

The advent of highly potent antiretroviral therapy capable of early and prolonged viral suppression in HIV-infected patients has resulted in significant increases in life span. As we have already seen, this will likely lead to a rising incidence of various metabolic complications of HIV and ARV, including hyperlipidemia and diabetes with associated cardiovascular disease risk. A keen awareness of these potential complications, drug interactions, and possible toxicities will be paramount to their successful management. Appropriate care of HIV-infected individuals going forward will likely require multidisciplinary collaboration as the epidemic evolves to allow our patients to live not only longer, but healthier lives.

Corresponding author: Lisa M. Chirch, MD, UCONN Health, Farmington, CT 06030, chirch@uchc.edu.

Financial disclosures: None

Author contributions: All authors contributed equally to this article