JURNALUL PEDIATRULUI – Year XIV, Vol. XIV, Nr. 53-54, january-june 2011 41 NEPHROTOXICITIES OF ANTI-RETROVIRAL TREATMENT Kundnani Nilima 1 , M Gafencu 1 , A Schiller 2 , Chintan N Thanki 3 , F Frunza 1 , Georgiana F Brad 1 , Margit Serban 1 Abstract Human immunodeficiency virus (HIV) infection is a global pandemic, with cases reported virtually from every country. HIV/AIDS being one of the world’s recent most devastating diseases, nearly 25 million people have died world over due to HIV infection since June 1981, when it was first diagnosed. According to the WHO, 33 million people worldwide are living with HIV. To provide access to highly active antiretroviral therapy (HAART), to the whole HIV suffering population remains a major goal to accomplish. Several studies have suggested that HAART improves renal function and prognosis for patients with HIV. Many individuals diagnosed are already with advanced renal disease and then due to lack of renal replacement therapies the mortality rate rises. HIV associated nephropathy (HIVAN) outcomes correlate with the clinical stage of the disease suggesting that early detection improves patient survival. On the other hand, with significant reductions in mortality and risk of progression to AIDS in the era of HAART, complications of long standing HIV infection and treatment should be dwelt with extreme importance. Most common nephrotoxic effects of antiretroviral include crystal-induced obstruction secondary to the use of protease inhibitors (indinavir and atanavir) and proximal tubule damage related to nucleoside reverse transcriptase inhibitors tenofovir. Acute kidney injury (AKI) can occur following tenofovir induced tubular dysfunction or because of mitochondrial dysfunction and lactic acidosis induced by nucleoside reverse transcriptase inhibitors. However looking to the benefits of HAART, fear of nephrotoxic effects can never be a valid reason for physicians to withhold antiretroviral therapy. Hence, identification of patients with pre-existing chronic kidney disease, who are at increased risk of renal damage, enables appropriate dose modifications, close monitoring and avoiding potential nephrotoxic drugs. Putting into practice some of the guidelines can further help save the renal complications. Key words: HIV, HAART, Kidney, Nephrotoxic Introduction Kidney proves to be the major excretory pathway for many drugs and their metabolites. Proximal tubule plays an important role due to its high rate of blood flow and the high level of toxins it has to process and hence this part of the kidney is always vulnerable to develop drug related damage. With the introduction of HAART, which has led to a dramatic decline in the mortality and morbidity of HIV infection, varieties of adverse renal effects have come up. Furthermore, improved survival among patients with HIV is anticipated to result in an increase in the risk of chronic HAART-associated metabolic complications, such as diabetes and dyslipidemia, which in turn can contribute to vascular damage and decreased renal function. Understanding the pathogenesis of HIV/AIDS, the HIV replication cycle and the mechanisms of HAART-related kidney disease is essential to adapt to future preventive measures such as dose adjustments, avoiding nephrotoxic drugs in patients at risk of developing kidney disease or having underlying renal diseases. Anti-retroviral for the treatment of HIV/AIDS Anti-retroviral drugs acting against the HIV are divided into 4 classes, which have received FDA approval: protease inhibitors (PIs), fusion inhibitors, non-nucleoside analog reverse transcriptase inhibitors (NNRTIs) and nucleoside/nucleotide analog reverse transcriptase inhibitors (NRTIs) (Table I). Of the 25 ARVs that have been approved, 3 are no longer being manufactured, either because of the development of improved formulations (i.e., amprenavir* replaced by fosamprenavir*) or because of limited use (i.e., delavirdine and zalcitabine). Currently, there are 22 antiretroviral agents available for clinical use. Several others are in various stages of basic and clinical development. As of February 2009, 17 of these have an approved pediatric treatment indication (noted with * below), and 16 are available as a pediatric formulation or capsule size. 1 “Louis Turcanu”Children Emergency Hospital, Timisoara 2 County Emergency Hospital, Timisoara 3 B.J. Medical College, India E-mail: aumnilu81@yahoo.co.in, mgafecu@umft.ro, t.schiller@yahoo.com, smartmedics@yahoo.com, florinifrunza@yahoo.com, giorgiana.brad@gmail.com, mserban@spitalcopiitm.ro