Abracadabra: Magic Johnson and Anti-HIV Treatments

Although Magic Johnson tested positive for HIV in 1991, his routine HIV tests show that his virus load is currently at undetectable levels and does not show AIDS-related symptoms. Thus, Johnson is considered a non-progressor. Many people who are non-progressors live with HIV without major health complications and their immune system seems to keep the virus under control. Progressors are people who have uncontrollably high virus load levels and advance to AIDS quickly, usually within five years after infection.

What keeps Magic Johnson alive and symptom free? In order to answer this, it's important to understand the several steps that occur during the life cycle of HIV.

HIV Life Cycle:

(1) Entry: HIV uses a receptor on its surface called gp160 (glycoprotein 160, aka envelope protein) to bind to T cells. The receptors on T cells that gp160 interacts with are CD4 and one of two chemokine co-receptors, CXCR4 or CCR5. Once bound to the cell surface, a conformational change in the receptors allows the virus to enter the cell.

(2) Enzyme 1—Reverse Transcriptase (RT): Once the HIV is in the host cell, the virus protective covering (nucleocapsid) degrades and releases the 2 RNA strands that comprise the HIV genome. The HIV genome is converted from RNA to dsDNA by the enzymatic action of Reverse Transcriptase (RT).

(3) Enzyme 2—Integrase (IN): The copy of the HIV genome in DNA form is inserted into the host's genome by the enzymatic action of integrase. Once inserted into the host genome, HIV is called a provirus. The HIV genome, which encodes for HIV proteins, is translated by host cell machinery into immature or nascent polypeptides that have no function until cleaved into smaller polypeptides. Where in the host genome would be ideal places for the provirus to be inserted?

(4) Enzyme 3—Protease (PR): The nascent polypeptides are cleaved into mature, functional HIV proteins by the enzymatic actions of protease.

(5) Exit: Once the newly synthesized HIV proteins are synthesized in the host cell, the HIV virions assemble with all the necessary components and bud out of the host cell to produce new virus particles. The virion acquires the envelope proteins gp41 and gp120 as they bud. Hundreds or thousands of virions may be produced within a single cell.

Magic Johnson has worked with Dr. Michael Mellman, his personal physician for the past 20 years, to try to keep the virus under control using a combination of antiretroviral drugs. This combination therapy is termed HAART or Highly Active Anti-Retroviral Therapy. The "drug cocktails" that make up a HAART regimen combine the power of multiple drugs to block multiple targets in the HIV life cycle. Central to Magic's therapy regimen is a drug called Combivir®, a combination of two drugs: lamivudine and zidovudine, which are nucleoside reverse transcriptase inhibitors. You may be familiar with zidovudine by another name, AZT. HAART regimens can cost an average of $1,000 per month or more depending on the source and type of drugs administered.

Johnson was recently hired as a spokesperson for GlaxoSmithKline, the company that produces Combivir®. The medication Magic Johnson takes is not a top secret magic bullet but rather a commercially available antiretroviral treatment. Thus, the same medication that Magic Johnson takes to control his HIV infection is available to everyone who is HIV-positive.

Part II—"A Magic Bullet or Magic Medicine?"

HIV Life Cycle:

Questions