1. Chapter 5: The Medical Side of Living with HIV/AIDS

2. The Medical Side of Living with HIV/AIDS HIV+ people are living longer, healthier lives, in large part because of advances in anti- HIV drug therapies Despite these therapies, people living with HIV/AIDS face many medical, psychological, and social challenges

3. History of HIV/AIDS Treatment In the early years of the epidemic, an AIDS diagnosis meant a rapid decline in health and imminent death In 1987, the first antiretroviral drug, AZT, slowed the progress of HIV In 1996, scientists created tests that measured viral load in plasma of HIV+ people, enabling measurement of disease progression In the late 1990’s it was believed that high doses of HAART right after HIV was diagnosed would be most effective at slowing disease progression

4. History of HIV/AIDS Treatment (continued) Now physicians wait until the more advanced stages of HIV disease to prescribe HAART as HAART is accompanied by many negative side effects Many ways to treat the opportunistic infections that often accompany HIV/AIDS have been developed The federal Department of Health and Human Services and the Henry J. Kaiser Family Foundation developed and regularly update guidelines for the management of HIV infection in adults and adolescents

5. Antiretroviral Drugs Slow HIV Replication Antiretroviral drugs work by keeping HIV from multiplying. There are four kinds of antiretroviral drugs: Nucleoside Reverse Transcriptase Inhibitors (NRTI’s) HIV uses a reverse transcriptase to convert RNA to DNA in order to reproduce itself. NRTI’s are faulty versions of reverse transcriptase that prevent DNA from creating new viruses. Non-Nucleoside Reverse Transcriptase Inhibitors (NNRTI’s) NNRTI’s also interfere with reverse transcriptase. NNRTI’s chemically bind to reverse transcriptase and make it unable to do its job.

6. Antiretroviral Drugs Slow HIV Replication (continued) Protease Inhibitors (PI’s) After HIV hijacks a cell’s nucleus to make copies of itself, it needs an enzyme called protease to chop its long chains of proteins into infectious bits. Protease inhibitors chemically bind to protease so that it cannot cleave the HIV proteins into mature viral particles. Fusion Inhibitors To make copies of itself, HIV first uses its spikes to fuse with the host cell’s membrane, and then thrusts its contents inside. Fusion inhibitors work by attaching themselves to one of the proteins on HIV spikes, which makes the HIV spike unable to fuse with the host cell.

7. New Antiretroviral Medications New antiretroviral medications that are currently being developed could include the following improvements:  Drugs that are easier for the body to absorb and circulate  Drugs that last longer in the body  Drugs with fewer negative side effects  Drugs that interfere with different stages of HIV replication, such as integrase inhibitors (which would keep HIV’s newly-formed DNA from implicating itself in the host cell’s DNA) HIV coreceptor blockers (which would keep HIV from binding with the host cell membrane)

8. Goals of Antiretroviral Therapy The goals of antiretroviral therapy are:  reduce a person’s viral load as much as possible, for as long as possible  restore the number of CD4+ cells to within the normal range  strengthen the immune system so that it responds to pathogens  halt disease progression  prevent or reduce resistant variants of HIV  conserve the number of non-HIV-resistant drugs available to the patient in the future  minimize side effects  maximize patient adherence (that is, make sure the patient takes all the right drugs in the right amounts at the right times) Antiretroviral therapy (sometimes called Highly Active Antiretroviral Therapy, or HAART) typically combines three or more antiretroviral drugs that work together to keep HIV from multiplying

9. Initiating Antiretroviral Therapy  willingness and readiness to begin therapy  risk of progression to AIDS (as measured by the patient’s viral load and CD4+ cell count)  level of immunodeficiency (as measured by the patient’s CD4+ cell count)  assessment risks versus benefits of initiating therapy  likelihood of adhering to the medication regimen Some people choose to put off therapy for as long as it is safely possible. Others decide to begin therapy earlier. Both strategies have merit, and both are supported by research. The decision to initiate therapy should be made by patient and physician, taking into account the patient’s

10. Critical Factors for Successful HIV/AIDS Treatment Provider’s level of experience  An HIV specialist should supervise treatment  Patients who have an experienced provider live longer and are healthier than those who do not Patient’s level of adherence  Patients must take all of the right pills at the right times, or levels of the drugs in their bodies drops, allowing the HIV in their bodies to multiply  The more the HIV multiply, the more likely they are to mutate into a drug resistant form of the disease  Since there are only about 20 anti-HIV drugs – some of which many people cannot take, because of their side effects – people quickly run out of drugs that work against their HIV disease

11. Adherence to Antiretroviral Treatment May Be Difficult Many people have difficulty taking the medications, because:  They cannot afford it  Remembering to take the right drugs in the right doses at the right times is difficult  Having the time and the place to take the drugs is difficult for some people  HAART has many negative side effects Side effects of HAART include: fatigue diabetes nausea high cholesterol abdominal pain diarrhea skin rashes vomiting wasting

12. Opportunistic Infections As HIV damages the immune system, many different bacteria, viruses, fungi, and protozoa invade and infect the body. HIV+ people first develop mild symptoms of opportunistic infections 7-8 years (on average) after exposure to HIV. Their symptoms include:  Swollen lymph nodes that persist for more than 3 months  Fatigue  Weight loss  Frequent fevers and sweats  Persistent or frequent yeast infections  Persistent skin rashes & flaky skin  Pelvic inflammatory disease that does not respond to treatment  Short-term memory loss  Frequent or severe herpes infections  Shingles

13. Opportunistic Infections (continued) Pneumocystis Carinii Pneumonia (PCP) (a kind of pneumonia) Kaposi's sarcoma (KS) (a kind of cancer) HIV wasting syndrome (extreme weight loss) Non-Hodgkin's lymphoma (a kind of cancer) HIV encephalopathy (AIDS Dementia) Candidiasis (Yeast Infection) of the esophagus, trachea, bronchi, or lungs Cryptosporidiosis, chronic intestinal (a bacterial infection of the intestines) Cytomegalovirus disease (CMV) (a kind of eye infection) Tuberculosis (outside of the lungs) Herpes simplex virus infection Progressive Multifocal Leukoencephalopathy (PML) (a nervous system disorder) Primary lymphoma of the brain (a kind of cancer) Toxoplasmosis of the brain (a parasitic infection of the brain) Coccidioidomycosis (a fungal infection) Salmonella septicemia (a bacterial infection) Bacterial infections, recurrent Pulmonary tuberculosis Recurrent bacterial pneumonia (two or more episodes in 1 year) Invasive cervical cancer The 26 opportunistic infections, that, accompanied by a positive HIV test, indicate AIDS include the following:

14. Treating HIV-Related Symptoms and Opportunistic Infections Symptom or Infection Treatments Weight loss eat more calories (take appetite stimulants) eat a balanced diet and/or nutritional supplements exercise moderately treat diarrhea and opportunistic infections of the stomach and intestines Yeast infections use antifungal creams, suppositories, and lozenges use antifungal pills Herpes shorten outbreaks with antiviral medications Shingles take anti-herpes drugs use pain-relief therapies, including nerve-blockers and skin treatments Pulmonary Tuberculosis if the disease is not active, take isoniazid for 6 months if the disease is active, then take a combination of antibiotics for 6 months