Abstract
Highly active antiretroviral therapy (HAART) is used in HIV-infected patients. Alongside the prolongation of patients' life, adverse side effects associated with long-term therapy are becoming an increasing problem. Therefore, optimizing of HAART is extremely important. The study is aimed at evaluating the toxicity of abacavir and etravirine in monotherapy on the reproductive system, liver, kidneys, and bones in young, sexually mature, male rats. Thirty-six 8-week-old male Wistar rats randomized into three 12-animal groups received either normal saline (control), abacavir 60 mg/kg (AB group), or etravirine 40 mg/kg (ET group) once daily for 16 weeks. Semen morphology, oxide–redox state parameters (MDA, SOD, catalase, GPx, glutathione, GSH/GSSG ratio) in tissue homogenates (testes, liver, kidneys), and serum samples were studied. In bones, microcomputed tomography and a four-point bending test were performed. Total sperm count, sperm concentration, motility, and sperm morphology did not differ significantly in AB or ET groups compared to the control. In the flow cytometry of semen, an increased percentage of cells with denatured DNA was noticed for both tested drugs. However, no significant changes of oxide–redox state in testicular homogenates were found, except of increased SOD activity in the AB-receiving group. Additionally, ET significantly altered catalase and GPx in the liver and SOD activity in kidneys. Abacavir decreased catalase in the liver and GSH levels in kidneys. AB caused significant changes to bone microarchitecture (bone volume fraction, trabecular number, connectivity density, total porosity) and increased Young's modulus. Etravirine had a greater impact on macrometric parameters of bones (tibial index, mid-tibial diameter, femur length). After 4 weeks in the ET group, a lower 1,25-dihydroxyvitamin D3 serum concentration was found. The results showed that abacavir and etravirine disturb oxidative stress. An increase in the percentage of sperms with chromatin damage suggests decreased fertility in rats receiving the studied drugs. Both drugs affected bone formation in growing rats. Additionally, etravirine disturbed vitamin D metabolism.
Highlights
According to the World Health Organization (WHO) statistics, there are about 37.9 million people infected with the human immunodeficiency virus (HIV)
No differences in body weight were observed between the groups during the entire study period (Figure 5)
The present study did not demonstrate any effect of etravirine on bone microarchitecture in neither in bone histomorphometry nor bone microcomputed tomography (mCT) examination. These findings are consistent with the results presented by other authors [103, 104], who found no negative impact of the therapy with raltegravir plus etravirine and ritonavir-boosted darunavir plus etravirine on bones
Summary
According to the World Health Organization (WHO) statistics, there are about 37.9 million people infected with the human immunodeficiency virus (HIV). Many awareness-raising campaigns, and better health education, there are about 1.7 million new HIV cases every year [1]. Antiretroviral therapy made it possible to decrease the viral load below the sensitivity limit of diagnostic tests, caused an increase in the level of CD4 lymphocytes, and reduced the incidence of opportunistic infections and the development of full-blown acquired immunodeficiency syndrome (AIDS). HIV therapy involves highly active antiretroviral therapy (HAART), meaning that patients are treated with drug combinations. The identification of the numerous adverse effects of a single drug becomes problematic
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