Recent Advancements in HIV/AIDS Treatment
Kutzer, Dolores; Hicks, Megan; Hlebik, Erin; Infantino, Jeremy, Drug Topics
This article titled "Recent advancements in HIV/AIDS treatment" includes review of the pathogenesis and clinical presentation of an HIV infection, review of methods of detection and diagnosis, and latest medications approved for the treatment of HIV/AIDS such as: tipranavir, fosamprenavir, darunavir, atazanavir, enfuvirtide, raltegravir, emtricitabine, and maraviroc. Discussion includes indications, pharmacokinetics, precautions, adverse effects, drug interactions, dosage and availability, and patient counseling.
Since the first reported case in 1982, HIV infections have been noted in staggering numbers. There are an estimated one million individuals currendy living with HIV/AIDS in the United States, with approximately 40,000 new infections occurring each year. Most new infections are attributed to men who have sex with men (MSM). However, the numbers of heterosexual transmission and those occurring in young adults and adolescents are also on the rise.
The most common methods of transmission is through contact between infected bodily fluids and the mucosal surfaces lining the intestinal tract and the genitalia and the sharing of needles for intravenous drug abuse. Factors that increase the risk of transmission include having a high viral load or an advanced infection (AIDS), if vaginal or rectal bleeding occurs during sexual intercourse, if a male is uncircumcised, co-infection with other sexually transmitted infections (STIs), menstruation, and hormonal imbalances.
Pathogenesis: HIV is a positive sense, single stranded RNA retrovirus. It possesses an indolent and complicated infectious cycle. Infections result in a destruction of CD4 lymphocytes and cell-mediated immunity.
After the virus gains entry into the body, it binds to host CD4 cells and chemokine co-receptors by utilizing a glycoprotein located on its outer surface (gpI60). The gp!60 is comprised of two smaller units (gp4l and gp!20). Gp 120 has a higher affinity for the CD4 cell receptors, playing a significant role in the initial internalization of the virus. Chemokines (CCR5 and CXCR4) help to further promote internalization.
Since HIV is a RNA virus, it must convert its RNA into viral DNA. To do this, the virus carries an essential RNA-dependent DNA polymerase enzyme called reverse transcriptase (RT). RT is rather inaccurate, creating many errors which promote viral mutation. The new viral DNA enters the nucleus to incorporate into the host DNA using the enzyme DNA integrase. Integration is random, creating cell abnormalities that lead to apoptosis. After integration is complete, the virus utilizes the host cell to duplicate its newly formed DNA and produce viral proteins, RNA, and surface glycoproteins.
Viral RNA, proteins, and other necessities are packaged together under the host cell membrane. This package then buds off from the host cell, using the membrane to form its own and take on host characteristics. Once free from the host cell, the new viron uses HIV protease to create mature proteins and an infectious virus.
Clinical Presentation: Most patients present with acute mononucleosis-like signs and symptoms two to six weeks after exposure including: fever, weight loss, night sweats, aseptic meningitis, nausea, vomiting, diarrhea, fatigue, sore throat, and myalgias. Symptoms usually resolve after two weeks.
Resolution of the initial signs and symptoms marks die start of the clinically latent period. However, viral replication is never fully suppressed or eliminated and the immune system over time slowly declines. Steady decline in CD4 levels is the most clinically measurable component of immune system decline. The viral load will reach a set-point after a drop in plasma viral counts, which may remain relatively constant for years. High viral loads constitute a poor prognosis and more rapid development of AIDS.
During the clinically latent period, patients experience mild and nonspecific symptoms that come and go over the course of several months or years. …