Today we'll be talking about a virus that's had an enormous impact on the world in which we live, both because of the incurable disease that it causes, and also because around the globe, the stigma associated with this disease has fueled widespread discrimination. This 38 year old lawyer named Anthony contracted the virus from a sexual partner, and on the other side of the world, six month old Tembesa may have contracted the same virus while inside her mother's womb, during her delivery, or while breastfeeding. Anthony had been in a long term relationship for almost eight years when the relationship ended unexpectedly. A week later, he spent the night with a man he'd met at a jazz bar and they had unprotected sexual intercourse. It was a decision he would regret for the rest of his life. Three weeks later, he developed flu-like symptoms including a fever, swollen, tender lymph nodes and a rash on his chest and back. Fearing that he may have contracted a sexually transmitted infection, Anthony went to see his physician, who performed several blood tests including an HIV antibody test and an HIV RNA PCR test. Tembesa's mother lives in a South African township where approximately 30% of the pregnant women are HIV positive. She didn't receive any prenatal care, traveling to the nearest maternity clinic only when her labor pains began. After she gave birth to Tembesa, her HIV positive status was confirmed, and she was started on antiretroviral treatments. Tembesa's HIV status remains unknown. In very young babies, HIV antibody tests are inaccurate because of the ability of maternal HIV antibodies to cross the placenta and persist in the baby for many months. In many under-resourced areas, testing isn't done on babies of HIV positive mothers until 18 months of age or until symptoms of the disease first appear. HIV is a blood borne virus that's typically transmitted via sexual intercourse, via intravenous drug needles or blood transfusions, or through mother to child transmission. Infection with HIV usually occurs in three phases. The first phase, called seroconversion or acute infection, occurs after the virus enters the body. Langerhans cells, which are specialized dendritic cells, are the first targets of the HIV virus, and these then fuse with CD4 positive T cells to spread the virus deeper into body tissues. Including lymphoid tissues, where much of the viral replication takes place. The virus also replicates inside the blood stream, and the serum viral load is a useful marker for the viral replication occurring in the reservoirs. During the seroconversion phase, a variety of immune cells become infected with the virus, including macrophages which steadily release the virus into the bloodstream acting as a pro-viral reservoir as well as a source of active infection. At this point, the viral load is typically very high and the host immune system detects the virus and begins deploying alternate pathways, including CD8 positive T cells and antibody producing B cells in an attempt to eliminate the virus. These immune responses are only partially successful, and the viral load typically drops to a steady state with CD4 positive T cell counts returning almost to the normal range. This marks the beginning of the asymptomatic, or clinically latent infection phase. Like Tembesa's mother, patients in this stage often don't show signs of infection and this phase can last anywhere from three to ten years, or even longer. During this phase, viral replication is ongoing, but the host's immune response successfully keeps the infection at bay. Functional CD4 positive T cell counts are steadily declining through this phase, even though the patient may be asymptomatic. As functional CD4 positive T cells are lost, antibody production by B cells becomes disregulated, and the resulting immune deficiency allows for opportunistic infections to develop. This marks the onset of the third phase of infection, acquired immune deficiency syndrome, or AIDS. In the United States, a CD4 positive T cell count less than 200 per microliter is used to define this phase. Infections associated with AIDS differ in different parts of the world, with diseases like Candidiasis and Pneumocystis pneumonia more commonly seen in developed settings, while infections like TB are more common complications of HIV infection in the developing world. The loss of immune function can also facilitate the development of cancers, like Kaposi Sarcoma or Lymphoma. Both Anthony and Tembesa's mother received antiviral therapy to treat their HIV infections. In Anthony's case, he was able to adhere regularly to a multi-component drug regimen, and the therapy was initiated early enough to significantly reverse the loss of T cells associated with his HIV infection. In the case of Tembesa's mother, the efficacy of the treatment was decreased because therapy was initiated relatively late In the infection, when her CD4 counts were approaching the 200 per microliter threshold. She also found it difficult to adhere to the challenging drug regimen available in her setting that required her to travel regularly to the nearest clinic to receive her medications. This was exacerbated by the fact that she afraid of the stigma associated with the disease and didn’t want her friends and neighbors to know about her diagnosis. Her health declined progressively as Tembesa grew, but this mother took great joy in the fact that her little girl appeared healthy and happy. In Anthony’s part of the world, antiretroviral therapy has been very effective in improving the prognosis and increasing survival rates associated with HIV infection. Public health interventions have raised awareness, increasing the number of people being tested and preventing the spread of infection. Both of these interventions are more difficult in countries with large under-resourced populations. In some developing countries, political denial of the seriousness of the HIV crisis, as well as reduced access to life-saving antiretroviral therapy, has led to high infection rates and widespread misinformation about the disease. In recent years, despite the loss of millions of lives to the HIV epidemic since its onset, access to antiretroviral therapy has improved and the global health community is focused on expanding this access even further.
