The Challenge of HIV-1 Subtype Diversity-NEJM

This is a summary report of "The Challenge of HIV-1 Subtype Diversity" from The New England Journal of Medicine.

The scariest nightmare. A sickness that cannot be cured. Inherited or acquired by mistake, the HIV virus is a Kevlar-covered chameleon with rabbit-like reproduction that takes over the body's T-cells. Cells that are not killed by the virus are infected permanently. HIV integrates itself into the host's genome. As a retrovirus, HIV releases its viral RNA into the cell. A strand of DNA is made from the RNA template. HIV does not have proofreading ability during reverse transcriptase to ensure exact replication of the virus. Therefore, the virus is frequently mutated. The newly formed viral DNA is now a provirus and is incorporated into the cell's genes. The proviral genes will be part of the host's genome through future generations of RNA and passed along to infect other cells.

Many subtypes of the HIV-1 virus exist and new strains are constantly emerging. It is possible for one person to carry two strains of HIV. This makes it very difficult to find a cure. A cure would have to attack all of the strains and recombinant forms of HIV.

The origin of HIV-1 has been traced. Chimpanzees in several isolated communities in southern Cameroon (located in Africa near Nigeria) carried a simian virus called SIVcpz. This virus was likely passed blood borne to human hunters. The virus is suspected to have spread along the Congo River into Zaire where the earliest traceable documentation of the HIV-1 virus. The sample is from 1959.

There are four different groups of HIV-1. The most common circulating type is HIV-1, Group M. Group M has thirteen known subgroups called "subtypes". The subtypes are denoted with letters. The sub-subtypes are denoted with numbers. Most often, subtypes stay endemic but their recombinant forms can be found elsewhere. By the time the particular virus is passed on enough to reach a different geographic location, it has usually morphed into a recombinant form of the original subtype. Some of the virus's forms can be traced by following drug trafficking routes. Tracing the virus is important to understanding for a possible cure, but recombinant forms of the virus make finding a cure difficult.

The virus's resistance to antiretroviral therapy can be primary or secondary. Primary resistance due to a drug-resistant strain is found in newly infected persons. Secondary resistance is categorized by an infected person's acquired resistance to the therapy over time. The article continues on to explain the differences between B subtype and Non-B subtype patients' resistance to antiretroviral therapy. After reading it over and over again, my brain cannot wrap around it to make sense of it. I will leave antiretroviral therapy here.

In order to silence HIV-1 virus strains, for good, a preventative vaccine must be found. The problem scientists are having exists in the diversity of HIV-1 in all of its subtypes, sub-subtypes, recombination and evolution of the virus. Scientists have found and administered "multisubtype consensus sequences", but patients showed limited response to them. Researchers believe that finding a successful HIV-1 vaccine will require further understanding of the genetic diversity of HIV-1, "create neutralizing antibodies and generate strong CD4+ and CD8+ T-cell responses."

Merck Research Laboratories developed a T-cell vaccine using "recombinant adenovirus type 5 vector containing gag, pol and nef genes from subtype B." The trial was stopped in September 2007 since the statistical data proved the research to be futile. A different study (2B) used the same vaccine, partially, in South Africa. The data received from this study raised questions about whether or not the vaccinated persons were more likely to acquire HIV-1 if they had a preexisting resistance to the adenovirus type 5 used in the vaccine.

HIV replicates and mutates sporadically lending to misunderstanding and elusion of a cure. Further understanding of HIV-1 subtype diversity is key to controlling and stopping this pandemic. With the death of the infected and vaccines for everyone, we will be able to put an end to HIV worldwide. Hopefully, a cure will come soon. HIV has overstayed its "welcome", if it was ever welcomed, and it is time for an end. HIV is undeniably the worst sickness ever to appear second only to the Black Plague. We need funding. We need a cure.