Bone disease in HIV-infected individuals and the effects of antiretroviral therapy

Bone loss and fractures are more common in HIV‐infected than HIV-uninfected adults. This thesis examined bone disease measures and related factors among HIV-infected adults who participated in two clinical trials of combination antiretroviral therapy.Three sub-studies in the STEAL trial investigated different aspects of bone health in virologically-suppressed adults randomised to either tenofovir/emtricitabine (TDF/FTC) or abacavir/lamivudine (ABC/3TC). The first study compared bone metabolism between arms and identified predictors of bone loss over 96 weeks. The second study evaluated bone structural parameters. The third study explored possible links between human leukocyte antigens (HLA) and BMD. Bone loss over 96 weeks was also examined in a sub-study of Second-Line, a study in adults from middle-income countries virologically failing standard first-line therapy, randomised to raltegravir+lopinavir/ritonavir or conventional 2-3 nucleoside/nucleotide reverse transcriptase inhibitor (N(t)RTIs)+lopinavir/ritonavir therapy.STEAL participants randomised to TDF/FTC experienced significantly greater BMD decrease compared to ABC/3TC. Bone markers also increased with TDF/FTC, but early changes in markers did not predict bone loss. Independent predictors of reduced BMD included randomisation to TDF/FTC, lower fat mass, lower bone formation, and PI use. Tenofovir use at the time of randomisation was associated with reduced bone structure measures, but no structural parameter changed significantly over 96 weeks. A possible association was found between BMD and HLA supertypes, particularly HLA-DQ3. In Second-Line, there were greater BMD decreases among N(t)RTI-recipients compared with raltegravir. Most of the BMD decrease occurred in the first 48 weeks of treatment with little change thereafter. Independent predictors for BMD decrease included lower baseline body mass index, longer tenofovir exposure, greater change in CD4+ from baseline to week 12, and higher baseline plasma HIV-RNA.Taken together, these studies contribute additional evidence regarding the complex relationship between HIV-infection, traditional risk factors, viral and immune mediators, antiretroviral therapy (particularly tenofovir) and bone quality. Further research might allow for more effective clinical management of HIV-infected patients at risk of bone disease and fractures