10/02/2026
TDF, in particular, has been associated with renal toxicity, including declines in kidney function and electrolyte imbalances, as well as reductions in bone mineral density (BMD), increasing the risk of osteomalacia and fractures over time. While 3TC is generally well tolerated, its combination with TDF may exacerbate renal and bone issues. DTG, on the other hand, has been linked to neuropsychiatric side effects such as insomnia and anxiety, and emerging evidence suggests it may contribute to weight gain and neurological effects like gait disturbances or paralysis, potentially due to neurotoxicity or mitochondrial dysfunction with prolonged use. Additionally, long-term therapy raises concerns about mitochondrial toxicity, which can lead to lactic acidosis, myopathy, and neuropathy, further affecting patient health.
HIV-positive individuals are particularly vulnerable to low BMD due to a combination of factors related to the infection itself and the effects of antiretroviral drugs like TDF. Chronic inflammation, immune activation, and cytokine release promote bone resorption, while TDF impairs renal phosphate handling and calcium absorption, disrupting bone metabolism. These factors, combined with common co-morbidities such as malnutrition, vitamin D deficiency, smoking, and alcohol use, significantly increase the risk of osteopenia, osteoporosis, and fractures. Such bone health issues can severely impact morbidity and quality of life by causing pain, disability, and reduced mobility, emphasizing the need for proactive management strategies.
To mitigate long-term risks, regular screening through dual-energy X-ray absorptiometry (DEXA) scans is recommended to monitor BMD, enabling early detection and intervention. Optimizing antiretroviral regimens by switching from TDF to safer alternatives like TAF can help preserve renal and bone health. Nutritional support, including adequate calcium and vitamin D intake, and lifestyle modifications such as weight-bearing exercises and smoking cessation, are vital for maintaining bone strength. Pharmacological therapies like bisphosphonates may be prescribed for high-risk individuals, and managing other health conditions that contribute to bone loss is essential. Additionally, routine neurological assessments are crucial to detect early signs of neurotoxicity, ensuring prompt management to prevent permanent deficits. Overall, a comprehensive, multidisciplinary approach is necessary to address these long-term risks and improve outcomes for HIV-positive patients on TDF/3TC/DTG therapy.
