HIV treatment reduces risk of fractures

Treatment with antiretroviral drugs reduces the risk of low-impact fractures, according to a case-controlled study published in the on-line edition of AIDS. Investigators compared fracture incidence between patients taking HIV therapy and non-treated individuals.

Despite the overall beneficial effect of treatment, the investigators found a complex relationship between drug class and duration of therapy and fracture risk.

Although there are concerns that tenofovir (Viread, also in the combination pills Truvada and Atripla) causes reductions in bone mineral density, the investigators found no robust evidence that the drug was associated with an increased risk of fracture.

“Our study identified an overall reduced risk for fracture in persons treated versus not treated with antiretroviral drugs for HIV infection,” write the authors.

With the right treatment and care, the prognosis of many HIV-positive patients is excellent. However, there is an increased prevalence of low bone mineral density in patients with HIV. The exact causes are uncertain, but may include HIV infection itself, the ageing of the HIV-infected population, and the side-effects of antiretroviral therapy. Nor are the clinical consequences clear. Some studies have shown that patients taking HIV treatment have an increased risk of fragility fractures, but such findings have been contradicted by other research.

Because of this continuing uncertainty, investigators in the US designed a case-controlled study involving patients who received HIV care between 1997 and 2008. The incidence of  low impact fragility fractures was compared between patients who received HIV therapy lasting at least twelve months and individuals with no history of antiretroviral treatment. The relationship between specific classes of antiretrovirals, individual drugs and duration of therapy and fracture risk was also examined. Finally, because of tenofovir’s association with low bone mineral density, the investigators compared fracture incidence between patients taking this drug and that seen among individuals taking abacavir (Ziagen, also in the combination pills Kivexa and Trizivir).

Cases were matched with four controls of exactly the same gender who were exactly the same age.

The study included 2411 cases and 9144 controls. An increased risk of fracture was associated with behavioural characteristics such as excess alcohol intake and low levels physical activity (both p < 0.0001). Some health-related factors were also associated with a significant increase in fracture risk. These included low body weight and a prior history of fractures (both p < 0.0001). More advanced HIV infection was also revealed as an important risk fracture for fractures (p < 0.0001).

Overall, HIV treatment reduced the risk of fractures (p < 0.0001). Nucleoside reverse transcriptase inhibitors (NRTIs), non-NRTIs (NNRTIs) and protease inhibitors were also associated with a reduction in fracture risk (p < 0.0001; p < 0.0001 and p = 0.0001 respectively). A significant reduction in the incidence of fracture was seen with both shorter and longer duration of therapy.

However, a more complex picture emerged when the investigators examined fracture risk according to the use of specific antiretroviral drugs.

For instance, therapy with the protease inhibitors darunavir (Prezista) and saquinavir (Invirase) was associated with an increased risk of fracture (p = 0.043 and p = 0.002 respectively). This increase in risk was regardless of the duration of exposure.

Treatment with several antiretroviral drugs, including nevirapine (Viramune), ddI (Videx) and ritonavir (Norvir) was initially associated with an increased risk of fracture, but this association disappeared with longer duration of treatment.

A number of widely-used agents had a consistent relationship with a reduced risk of fracture. These included efavirenz (Sustiva, also in the combination pill Atripla), 3TC (lamivudine, Epivir, also in the combination pills Kivexa, Combivir and Trizivir), FTC (emtricitabine, most widely taken in the combination pills Truvada and Atripla), tenofovir and AZT (Retrovir, also combined in Combivir and Trizivir).

Atazanavir (Reyataz), fosamprenavir, and lopinavir (Kaletra) neither increased nor decreased the risk of fracture. This neutral association was also found for a number of older agents which are now rarely used or discontinued.

Combinations containing abacavir were associated with a 25% reduction in fracture risk (OR = 0.75; 95% CI, 0.64-0.88). This was comparable to the reduction in risk seen for non-abacavir regimens (OR = 0.61; 95% CI, 0.54-0.69).

Tenofovir-containing regimens were associated with a 37% reduction in the risk of fracture (OR = 0.63; 95% CI, 0.55-0.72). The reduction in risk as similar for non-tenofovir regimens (OR = 0.68; 95% CI, 0.59-0.78).

The investigators believe their results indicate an overall benefit of antiretroviral treatment for bone health.

They conclude: “Our findings contribute evidence to and support for future robust analysis of observational cohort data to assess and identify modifiable risk factors associated with aging and drug exposure–response relationships. Such comparative research efforts will be integral to optimizing incremental net health benefits and antiretroviral treatment in years to come.