By: Elizabeth Kopec, PharmD Candidate c/o 2014, South University School of Pharmacy at Columbia, SC

–

Human immunodeficiency virus (HIV) is a global pandemic, with approximately 35.3 million people infected in 2012. The United States currently has 1.3 million people living with HIV, with 20,000 deaths occurring every year due to acquired immune deficiency syndrome (AIDS).¹ In 2012, 1.7 million people died worldwide of AIDS-related illnesses.²

HIV destroys CD4 cells, which secrete cytokines to activate immune responses as part of the body’s immune system. A normal CD4 count in a healthy person ranges from 500 cells/mm³ to 1,000 cells/mm³. However, as the HIV spreads, CD4 counts decrease to levels low enough to prevent the body from effectively fighting off infections, which eventually leads to AIDS. A CD4 count of 200 cells/mm³ or less is diagnostic of AIDS, but a CD4 count of 350 cells/mm³ is when opportunistic infections become communicable and antiretroviral therapy is initiated. Currently, the World Health Organization recommends beginning antiretroviral therapy when the CD4 count falls to 500 cells/mm³ to help those with HIV live longer and stay healthier by acting earlier in the progression and lowering the amount of virus in the blood.³

AIDS-related illnesses remain a problem among those with uncontrolled or untreated AIDS, and are linked to increasing rates of morbidity and mortality.⁴ There are multiple AIDS-related illnesses, but some of the most common opportunistic infections include pneumocystis jirovecii pneumonia, toxoplasma gondii, candidiasis, cytomegalovirus, and mycobacterium avium complex. Other complications include cancers, anemia, high cholesterol, depression, and lactic acidosis. HIV-associated nephropathy and chronic kidney disease are significant complications of HIV infection due to the high mortality rate (50%) in the first year of dialysis in this population, and are becoming a major concern due to the growing prevalence (30%) of abnormal renal function in HIV-infected patients.^5,6

Patients with HIV are at a higher risk of kidney damage due to the nephrotoxic side effects associated with antiretroviral drugs, such as indinavir and tenofovir.⁷ Because nephrotoxicity is such a common and severe adverse event, renal function tests are preformed at the time of diagnosis and are repeated annually.⁸ Risk factors for renal disease in HIV-infected patients include old age, female gender, diabetes, hypertension, and hepatitis B and C infections.⁹

It has been postulated that HIV infection is associated with an increased risk of early kidney injury in females,and several studies have been conducted to research early renal damage in HIV-infected women. ¹⁰ A study performed between 1999 and 2000 compared urine injury markers between HIV-infected and HIV-uninfected women. A total of 908 women were infected with HIV, whereas 289 women were not infected. Tubular injury markers were determined to be the best factor to research the decline and progression of kidney structure and function over time. Particularly, interleukin-18 (IL-18) and kidney injury molecule-1 (KIM-1) were measured due to their specificity to the proximal tubule of the nephron.¹¹ Both biomarkers were found in very low concentrations in healthy individuals and in high concentrations in critically ill patients. It was found that the HIV-infected women had more extensive tubulointerstitial and glomerular injury than uninfected women, proving that KIM-1 and IL-18 are good predictors of ensuing decline in renal function.¹²

Predictors of Proteinuria and Renal Failure Among Women with HIV Infection is another clinically relevant study that researched the variables associated with renal failure in HIV-infected women. A total of 2,057 women were evaluated twice a year for four to five years by urine analysis, CD4 lymphocyte count, HIV RNA level, and serum creatinine level. The study found that proteinuria is associated with elevated HIV RNA level, CD4 lymphocyte counts of lass than 200 cells/mm3, African American race, and the presence of the hepatitis C antibody. There is currently no information, however, to suggest differences in the clinical course of HIV-associated renal disease based on gender.¹³

The Microalbuminuria in HIV Infection study is another relevant clinical trial conducted to research if HIV infection is an independent risk factor for microalbuminuria. Albumin and creatinine concentrations and the albumin to creatinine ratio in patients were measured. Of the 967 subjects evaluated, 760 were infected with HIV. Researchers found that HIV infection was associated with a five-fold risk of microalbuminuria, and is a strong predictor of microalbuminuria. They also suggested that the severity of HIV might not be as important as other risk factors such as high systolic blood pressure and insulin resistance in predicting the presence of microalbuminuria.¹⁴

There are numerous HIV complications that patients need to be aware of and take precautions against. Some of these complications that may have more severe consequences include opportunistic infections, tuberculosis, and lymphomas. Other complications are becoming more prevalent among the HIV-infected population, with renal injury being the main complication due to its association with mortality. HIV-infected women are being recognized more as at risk population and early recognition and screening are crucial in detecting and deterring renal damage. Although crucial, it is not sufficient to be able to receive anti-viral therapy without as much social stigma as patients did years ago. Patients and healthcare professionals, as patient advocates, must be vigilant about preventing and treating other complications of the disease and anti-viral therapy that are now being recognized.

SOURCES:

1. World Health Organization. New Guidance on HIV. World Health Organization. http://www.who.int/hiv/en/. Updated October 2013. Accessed November 25, 2013.
2. US Department of Health and Human Services. CD4 Count. AIDS.gov. http://www.aids.gov/hiv-aids-basics/just-diagnosed-with-hiv-aids/understand-your-test-results/cd4-count/. Updated October 11, 2010. Accessed November 25, 2013.
3. Thomas G. WHO issues new HIV recommendations calling for earlier treatment . World Health Organization. June 30, 2013. Available at http://www.who.int/mediacentre/news/releases/2013/new_hiv_recommendations_20130630/en/. Accessed January 5, 2014
4. Antonia J, Melo M, Raimundo Mario, et al. Long-term Risk of Mortality for Acute Kidney Injury in HIV-Infected Patients: A Cohort Analysis. BMC Nephrology. 2013;14:1-7.
5. US Department of Veterans Affairs. Renal Disease. US Department of Veterans Affairs. http://www.hiv.va.gov/provider/manual-primary-care/renal-disease.asp. Published April 2009. Updated October 28, 2011. Accessed November 27, 2013.
6. Szczech LA, Gange SJ, Bartlett JA, et al. Predictors of Proteinuria and Renal Failure Among Women with HIV Infection. Kidney International. 2002;61:195–202
7. Shilpak MG, Scherzer R, Abraham A, et al. Urinary Markers of Kidney Injury and Kidney Function Decline in HIV-Infected Women. Journal of Acquired Immune Deficiency Syndromes. 2012;61:565-573.
8. Shilpak MG, Scherzer R, Abraham A, et al. Urinary Markers of Kidney Injury and Kidney Function Decline in HIV-Infected Women. Journal of Acquired Immune Deficiency Syndromes. 2012;61:565-573.
9. Flandre P, Pugliese P, Cuzin L, et al. Risk Factors of Chronic Kidney Disease in HIV-Infected Patients. Clinical journal of the American Society of Nephrology. 2011;6:1700-1707.
10. Jotwani V, Scherzer R, Abraham A, et al. Does HIV promote early kidney injury in women? Antiviral Therapy. 2013;21:38-45.
11. Salifu M, Misra N, et al. HIV-Associated Nephropathy. Medscape. http://emedicine.medscape.com/article/246031-overview. Updated June 7, 2013. Accessed November 26, 2013.
12. Jotwani V, Scherzer R, Abraham A, et al. Does HIV promote early kidney injury in women? Antiviral Therapy. 2013;2010:38-45.
13. Szczech LA, Gange SJ, Bartlett JA, et al. Predictors of Proteinuria and Renal Failure Among Women with HIV Infection. Kidney International. 2002;61:195–202
14. Szczech LA, Grunfeld C, Canchola JA, et al. Microalbuminuria in HIV Infection. AIDS. 2007;21:1003-1009.

Published by Rho Chi Post