HIV/AIDS Biology 342

HIV Genus Lentivirus, Family Retroviridae Single stranded, enveloped RNA virus Long incubation period with long duration illness

HIV The HIV enters the host cell as a single stranded RNA Viral RNA is converted via a viral protein- reverse transcriptase into double-stranded DNA Next, this viral DNA is imported into the host cell nucleus and integrated into the cellular DNA Virus goes “latent” avoiding detection from host’s immune system. It can remain integrated for months to years – being replicated with the host cell’s DNA Eventually, the virus DNA cleaves from host DNA and is transcribed back into new viral RNA and viral proteins – then is packaged for released from the cell…

HIV Replication Cycle

Origin of HIV HIV originated from non-human primates from West-central Africa. The virus was transferred to humans sometime in the early 20th century HIV is most closely related to SIV which is endemic in chimpanzees and sooty mangabeys. (SIV smm) -> HIV – 2 (SIV cz) -> HIV - 1

History AIDS was first clinically observed in the US in 1981 – then called gay-related immunodeficiency disease – associated with Kaposi’s Sarcoma. The name was changed to AIDS – “Acquired Immunodeficiency Syndrome in 1982. It was initially thought to be caused by two viruses: LAV = Lymphadenopathy Associated Virus which caused severe swelling of lymph nodes and physical weakness, and HTLV = Human T- Lymphotropic Virus. In 1986 it was found that the two viruses were the same and given the name HIV = Human Immunodeficiency Virus.

Transmission of HIV Person to person within mucus membranes in specific body fluids including blood, semen, pre-seminal fluid, rectal fluids, vaginal fluids, and breast milk. HIV can be transmitted as both fee virus particles and/or virus within infected immune cells. HIV can not be transmitted in body fluids such as saliva, tears, or sweat. HIV is not transmitted through air, water, insects or ticks as vectors, skin contact, social kissing, or toilet seats.

Transmission Risk Hierarchy Anal sex Vaginal sex Multiple sex partners Sharing needles and syringes Birth and/or breast milk Blood transfusion Oral sex Broken skin contact Kissing with open wounds

HIV Infection Prevention Ask sex partners about test results Correct and consistent condom use Do not share needles, syringes, or other associated equipment Pre-exposure and post-exposure prophylaxis PrEP PEP

HIV Infection Symptoms 1st stage (acute - 2-6 wks. post exposure): flu-like fever, headache, diarrhea, nausea, vomiting, sore throat, aching muscles, fatigue, night sweats, and a red rash on torso that doesn’t itch. 2nd stage (Latent): asymptomatic for 10 + years – people are infective, their immune system is being destroyed (T-cell count slowly drops). 3rd stage (AIDS): dramatic weight loss, recurrent opportunistic infections, yeast infections in mouth, throat, vagina, easy bruising and bleeding, Kaposi sarcoma (skin cancer) and pneumocystis (Pneumonia), coma, and death.

AIDS Mortality HIV causes a slow but progressive failure of the host immune system which allows life- threatening infections by multiple opportunistic pathogens and also allows cancer to thrive.

HIV World Wide 2.1 million new infections per year 35 million people living with HIV infections 1.5 million people die each year Overall death toll from HIV = 39 million Sub-Saharan Africa with 70% of new HIV infections annually Followed by Asia, Pacific, Latin America, Caribbean, and Eastern Europe

HIV in United States New infections in the US: 47,500 per year. Living with infections in US: 1.2 million Percent who don’t know, est. ~ 13% up to 20%

Logistic Growth of AIDS in US

New Infections MSM = men who have sex with men

Infections by Ethnicity

World Wide Infections

AIDS today In 2014, reports estimate that 36.9 million people are living with the virus, some 70% of them in sub-Saharan Africa, and that number continues to increase because 15 million of them now are taking life prolonging antiretroviral drugs. South Africa alone has 6.8 million HIV-infected people—more than any other country.

Hidden HIV Researchers have developed a sophisticated new probe (DNA scope) that can find HIV in its hiding places. The new probe shows viral DNA to aid in the assessment of infection.

Longevity with HIV There is no cure for HIV infection and one is always a carrier of the virus, but… A healthy 20 year old infected today can expect to live an additional 40 years. Early detection today means a near normal life span. Antiretroviral Therapy (ART) must begin before the decline in function of the immune system.

ART: Antiretroviral Therapy ART stop/slows the progression of AIDS through a combination of at least 3 drugs. Each drug attacks HIV in a different way. A cocktail of drugs can block the virus from making DNA from its RNA, can inhibit assembly of viral proteins, prevent HIV from entering the host cell, and prevent HIV DNA insertion into the host DNA.

HIV Life Cycle and Inhibiting Drugs HIV starts as a free virus circulating in the blood stream until it attaches to an immune cell (usually a T- helper cell that destroys other infected cells) (2 drugs interfere here). HIV may enter other cells too, including brain cells. HIV RNA uses reverse transcriptase to build HIV DNA (16 drugs slow this) which it inserts (2 drugs block this) into the host cell chromosome – infection is established When the infected cell replicates so does HIV DNA. Eventually new viral proteins and RNA are assembled (10 drugs slow or inhibit this process) and new virus exits the cell through a process called “budding”.

cART: Combination Therapy A carefully monitored drug program is established early after diagnosis and lasts throughout the rest of life. 3 to 4 of the above drugs must be taken without interruption on a precise schedule. The drugs must be changed or rotated periodically to prevent drug resistance. The drugs reduce viral load – sometimes below detectable levels – but the virus is not gone and eventually will destroy the immune system.

Test & Treat Strategy There is no cure or vaccine for HIV infection but early detection and treatment can change HIV infection from a fatal disease to a manageable chronic disease. Education and treatment reduces transmission and slows the spread of HIV Problems Up to 20 % of infected people do not know - Rising health care costs inhibits treatments - New drugs are needed to fight drug resistance - Legislative battles over budget of health care coverage and HIV drug research continue -