HIV This Week

Harris M. Nephrotoxicity associated with antiretroviral therapy in HIV-infected patients. Expert Opin Drug Saf. 2008;7(4):389-400.

With the success of modern antiretroviral therapies in increasing longevity of patients with HIV infection, chronic conditions including renal disease have assumed a greater importance in patient management. Some antiretroviral therapies have themselves been identified to have clinically significant nephrotoxicity. Harris and colleagues aimed to review the risk factors and mechanisms for renal toxicity of antiretroviral drugs, and their impact on the clinical management of patients with HIV. Current literature and HIV treatment guidelines were reviewed. Background rates of renal disease and associated risk factors were significant in the HIV clinic population, and renal function should be assessed in all HIV-infected patients. Modern HIV treatment regimens have a relatively low but clinically significant nephrotoxic potential; therefore, renal function should be evaluated on an ongoing basis in patients receiving antiretroviral therapy.

Editors’ note: HIV can have direct effects on the kidney (HIV-associated nephropathy or HIVAN and thrombotic micro-blood vessel disease) and the body’s immune response can cause glomerulonephritis (local inflammation). HIVAN responds to antiretroviral therapy suppressing HIV but some antiretroviral drugs can have direct toxic effects on the kidney or can cause renal dysfunction indirectly. People living with HIV can also have other conditions affecting kidney function (hepatitis B or C, other liver disease, syphilis, diabetes, hypertension, recreational drug use, family history) and HIV-related renal disease tends to increase as CD4 count falls and viral load rises, therefore it is important to monitor kidney function regularly.

Chronic coinfection with herpes simplex virus type 2 (HSV-2) and human immunodeficiency virus (HIV) has been associated with an increased HIV viral load and more rapid disease progression, perhaps related to HSV-2-associated alterations in host immunity. Studies were nested within (1) a cross-sectional study of men coinfected with HIV and HSV-2 and (2) women not infected with HIV, both before and after HSV-2 acquisition. HSV-2 infection status was determined by ELISA. HIV-specific CD8(+) T cell epitopes were mapped, and proliferation of HIV-specific cells was also assessed. Systemic inflammatory and regulatory T cell populations were assayed by flow cytometry. The breadth of both the HIV-specific CD8(+) T cell interferon-gamma and proliferative responses was reduced in participants coinfected with HIV and HSV-2, independent of the HIV plasma viral load and CD4(+) T cell count, and the magnitude of the responses was also reduced. HSV-2 infection in this group was associated with increased T cell CD38 expression but not with differences in the proportion of CD4(+) FoxP3(+) regulatory T cells. However, in women not infected with HIV, acquisition of HSV-2 was associated with an increase in the proportion of regulatory T cells. In conclusion, HSV-2 coinfection was associated with reduced HIV-specific T cell responses and systemic inflammation. The immune effects of HSV-2 may underlie the negative impact that this coinfection has on the clinical course of HIV infection.

Editors’ note: Up to 80% of people living with HIV infection in sub-Saharan Africa have herpes simplex virus-2 (HSV-2) co-infection which appears to be associated with reduced HIV-specific T cell responses. Co-infection may be associated with a higher viral load, systemic inflammation due to activation of host Toll-like receptors, and HIV progression. Confirmation of research findings suggesting that HSV-2 treatment may delay HIV disease progression is urgently needed.