Background/Purpose: For almost two decades, bone alterations have been observed in the course of HIV infection, characterized by a marked decrease in bone mineral density (BMD) and an increase in the frequency of fractures as a result of fragility. It is not clear if it is HIV infection per se that contributes to the decrease in BMD, osteoporosis and bone fagility, or if the risk factors associated with the disease (malnutrition, low body weight, high smoking rate and alcohol consumption or low vitamin D levels). In adults, the decrease in BMD has also been associated with prolonged treatment with antiretrovirals and more specifically therapy with tenofovir. The aim of this study was to evaluate the deleterious effects in bone metabolism, produced by tenofovir vs other HIV treatment in naïve patients.

Methods: A cohort of 114 HIV-naïve patients were included in the study. Patients were separated by treatment: 1) Tenofovir Disoproxil Fumarate (TDF), 2) Tenofovir Alafenamide (TAF), 3) Abacavir/Dolutegravir/Lamivudin combo (ADL), 4) Protease Inhibitors (PI). Epidemiological, immunological, and metabolic parameters, as well as BMD were evaluated. Bone markers, proinflammatory and anti-inflammatory cytokines were analyzed in serum at basal and 12 months post-treatment by MILLIPLEX® MAP Luminex® Technology. The diagnosis of osteopenia/osteoporosis was made according to the WHO criteria.

Results: The mean age was 34.7 years (range 19-50 years). 91% was on CDC stage A. The median CD4 was 481 cell/µL (IQR=339.5), 10% had CD4 under 200 cell/µl, and 42% had CD4/CD8 under 0.4. 71% (71/143 p) had low Vitamin D levels, 4% low BMI (< 18.5). Osteopenia or osteoporosis was found in 53% and 11% respectively. In the serum/plasma we found differences at molecular level among different treatments (Table 1). We observed that both TDF and TAF presented a more aggressive resorptive profile than other antiretroviral drugs. We observed that there are no significant differences between the TDF and TAF group at 12 months. However, we have observed an increase in CTX, P1NP and DKK1 for TDF being greater than for TAF and the other treatments. All antiviral presented a pro-inflammatory profile with no significant differences among groups (Table 2).

Conclusion: HIV-naïve patients under 50 years have a high prevalence of bone fragility and osteoporosis, and patients treated with tenofovir (both TDF and also TAF) had greater bone deterioration and proinflammatory state than other patients at 12 months of treatment.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/first-line-antiretroviral-therapy-with-tenofovir-produces-deleterious-effects-on-bone-and-an-increase-in-proinflammatory-cytokines-expression-after-12-months-of-treatment-in-naive-hiv-patients/