HIV THERAPY (BRIEF REVIEW)

Highly active antiretroviral therapy: initiated when patients present with AIDS-defining illness, low CD4 cell count < 350 cell/mm³, or high viral load. Regimen consists of tree drugs to prevent resistance: 2 nucleoside reverse transcriptase inhibitors (NRTIs) + one protease inhibitor, or two NRTIs + 1 non NRTIs. (Le, Bhushan, & Tolles, 2011).

In January 2011, the Department of Health and Human Services (DHHS) Panel on Antiretroviral Guidelines for Adults and Adolescents issued updated guidelines on initiation of antiretroviral therapy (2011) as fallow.

•Antiretroviral therapy should be initiated in all patients with a history of an AIDS-defining illness or with a CD4 count below 350 cells/µL

•Antiretroviral therapy should be initiated regardless of CD4 count in pregnant patients, patients with HIV-associated nephropathy, and those with hepatitis B virus coinfection when treatment of hepatitis B virus infection is indicated

•The panel was divided on the initiation of antiretroviral therapy in patients with CD4 counts between 350 and 500 cells/µL: 55% of panel members considered this a strong recommendation, while 45% considered it a moderate recommendation

•The panel was also divided on initiation of antiretroviral therapy in patients with CD4 counts above 500 cells/µL: half of the panel members favored initiation in this setting, while the other half considered treatment initiation as optional.

Protease inhibitors: Saquinavir-Ritonavir-Inclinavir-Nelfinavir-Amprenavir.

            Assembly of virions depends on HIV-1 protease (pol gene), which cleaves the polypeptide products of HIV mRNA into their functional parts. Thus, protease inhibitors prevent maturation of new viruses.

Toxicity: hyperglycemia, GI intolerance, lipodystrophy, and thrombocytopenia.

Nucleoside Reverse Transcriptase Inhibitors (NRTIs): Ziclovudine (ZDV, formerly AZT) - Didanosine (ddI) - Zalcitabine (ddC) - Stavudine (d4T).

Competitively inhibit nucleotide binding to reverse transcriptase and terminate the DNA chain (lack a 3’-OH group), must be phosphorylated by thymidine kinase to be active. ZDV is used for general prophylaxis and during pregnancy to reduce risk of fetal transmission.

Toxicity: Bone marrow suppression, peripheral neuropathy, lactic acidosis, rash, and megaloblastic anemia.

Non-Nucleoside Transcriptase Inhibitors (NNTIs): Neviparine – Efavirenz – Declaviridine.

            Bind to reverse transcriptase al site different from NRTIs. Do not require phosphorylation to be active or compete with nucleotides.

Toxicity: Same as NRTIs.

Enfuvirtide: Fusion inhibitors bind viral gp4 subunit; inhibit conformational change required for fusion with CD4 cells, blocking entry and replication; used in patients with persistent viral replication despite antiretroviral therapy.

Toxicity: hypersensitivity reaction, reaction at subcutaneous injection site, increase risk of bacterial pneumonia.

The January 2011 DHHS guidelines list the following regimens as preferred in treatment-naive patients:

•Efavirenz/tenofovir/emtricitabine (EFV/TDF/FTC)

•Ritonavir-boosted atazanavir + tenofovir/emtricitabine (ATV/r + TDF/FTC)

•Ritonavir-boosted darunavir + tenofovir/emtricitabine (DRV/r + TDF/FTC)

•Raltegravir + tenofovir/emtricitabine

The guidelines consider lopinavir/ritonavir–based regimens as alternative rather than preferred, except in pregnant women, in whom twice-daily lopinavir/ritonavir plus zidovudine/lamivudine remains preferred (Bennett, 2011).

 Bibliography

2011, D. (n.d.). Panel on Antiretroviral Guidelines for Adults and Adolescent. Guigelines for the use of antiretroviral agentes in HIV-1 infected adults and adolescents. Retrieved from Department of Health and Human service.: http://aidsinfo.nih.gov/contentfiles/AdultandAdolescentGL.pdf

Bennett, N. J. (2011, Nov 9). Medscape.com. Retrieved from HIV disease Treatment & Management: http://emedicine.medscape.com/article/211316-treatment#aw2aab6b6b2

Le, T., Bhushan, V., & Tolles, J. (2011). First AID for the USMLE step 1. usa: McGraw Hill.

Panel on Antiretroviral Guidelines for Adults and Adolescent. Guidelines for the use of antiretroviral agents.. (n.d.). Department od Health and human services, January 10, 2011;1-174. Accessed June 16, 2011.