Biological

Link to episode: https://www.buzzsprout.com/1402771/8763556-the-biology-of-hiv.mp3?download=true

Things I link in the episode:

Intro

This is A Viral Podcast, and I am its viral host. I preface this episode by saying that I am not a professional, and the resources that I am using are in the description.

So, what did I decide to talk about today? HIV and AIDS. Kind of, I guess I’ll say ambitious, to assume that anyone that does listen to this has already decided they like this show. Why would you? I have no idea. This is just fun for me and I learn a lot about fields that I’m interested in. Instead of some attempts at jokes, while telling you about some Roman physician, you get to listen to me talk about HIV.

This is the first of three parts I am releasing on HIV and AIDS. For some really lighthearted fun. This part will address the science behind the virus and disease. The next will be a discussion on the social and political impacts of AIDS. And the third will be my opinions on some of the AIDS documentaries I have watched, there are quite a few.

I want to give a content warning that this part will discuss how HIV can be spread and the symptoms of infection, which are slightly graphic.

Part Zero: HIV

HIV, or the Human Immunodeficiency Virus, is a human retrovirus, that’s a bit redundant the human immunodeficiency virus is a human retrovirus. It causes AIDS, Acquired Immunodeficiency Syndrome.

Part One: Retroviruses

Retroviruses are single-stranded RNA viruses that use the process of reverse transcription to create a single-stranded DNA version of themselves, which then makes a double-stranded DNA version. The process that quickly makes single-stranded RNA into double-stranded DNA has many typos, which creates many mutations. Because at some point, evolutionarily, it was more advantageous to perform this quickly than effectively. And, even now, this has given HIV the benefit of making vaccine attempts much more difficult. In doing this, retroviruses fail to follow the Central Dogma, a sequence that all life follows: DNA create RNA, which create proteins. As retroviruses use RNA instead of DNA, they create a DNA version using reverse transcription, this is then inserted into the DNA genome of the host. This uses the enzyme reverse transcriptase to synthesize a DNA intermediary, which is integrated into the host genome. This was suggested by Howard Temin and led to he and David Baltimore receiving the 1975 Nobel Prize in Medicine. The more radical part of this hypothesis was actually the idea that RNA could form DNA and not its insertion into the host DNA, as that had been seen in studying bacteriophages into the genomes of viruses.

Basically, retroviruses made of RNA make DNA, which is inserted into a host’s DNA using the enzyme integrase, which make RNA which make proteins. Non-retroviruses make RNA into proteins, without having a DNA version.

We have known about retroviruses since 1976 when they were reported about by Robert Gallo. They were confirmed in 1981 by Yorio Hinuma. Also in 1981, as I will talk about later, AIDS was reported on, under other names. We will talk about Gallo later too.

I’m getting ahead of myself, HIV is a human retrovirus that infects by creating a version of it capable of entering its host’s genome to create more of itself. What’s next, you know post-reverse transcription.

Part Two: How Does HIV work?

How is HIV Spread?

HIV spreads from person-to-person through the following fluids: blood, semen, pre-seminal fluids, rectal fluids, vaginal fluids, and breast milk. To spread, these fluids need to come into contact with mucous membranes or the bloodstream. HIV is not spread through contact with air, insects, or touching that doesn't involve the exchange of body fluids mentioned above. Someone with an undetectable viral load has nearly no risk of sexually transmitting HIV. The lower the viral load, the less likely it is for an HIV-positive person to spread HIV. Examples of how HIV can be spread: vaginal or anal sex without a condom or HIV preventative medicines and sharing injection drug equipment like needles. These are with someone that is HIV-positive, I think we disproved spontaneous generation in the 19th century. We did, it was in 1859 by Louis Pasteur in a competition by the French Academy of Sciences. But, it is best to be safe in these practices to avoid spreading sexually transmitted diseases.

HIV can also be spread during pregnancy, birth, and breastfeeding. It is uncommon for HIV to be spread during oral sex, blood trasnfusions, biting, and contact of wounds. HIV is most infectious in the first few weeks after infection, when many people are unaware that they are infected.

A Timeline of HIV Infection

Someone is infected with HIV. The virus begins replicating in the first few days, and spreads throughout the body. Reservoirs of virus are hidden in blood cells, lymph nodes, brain cells, and the intestinal tract. At this point, the body is fighting the infection through seroconversion, the production of antibodies. Detectable antibodies can take three to twelve weeks to form, depending on the immune system. These antibodies are used to test for HIV. In this acute stage, many experience flu-like symptoms for about two to three weeks. As the CD4 count, which I will address in the next section, continues to drop. More severe symptoms like night sweats, fast heart rate, and extreme fatigue can be experienced.

Second, the latency period begins around six weeks after initial infection. CD4 cells are slowly reduced as the viral load increases. This stage lasts on average, for ten years. Many people that are HIV-positive do not pass the latent stage of infection as we have medications to decrease viral loads to undetectable levels.

Finally, there is AIDS. CD4 counts are incredibly low and there is an increase in the viral load. From here opportunistic infections and cancers can emerge easily.

What Does HIV Do?

HIV attacks the immune system, which is responsible for fighting the infections. It does this by attaching to CD4 cells, which are T-cells with a CD4 protein on them, T-cells being a type of white blood cell. CD4 cells make the body respond to infection. When they attach to the CD4 cells, they kill them and use them to spread the infection in the body.

To combat the loss of CD4 cells, the immune system produces more. When the body is unable to produce these faster than the HIV kills them, disease is developed and symptoms appear

This weakens the immune system, opening the body to opportunistic infections like Tuberculosis, which is the leading cause of death in people with HIV.

Part Three: Treatment

There is no cure for HIV. However, we have developed treatment regimens of various antiretrovirals. ARVs work by lowering the viral load, the amount of HIV in the bloodstream, allowing more CD4 cells to be produced.

These treatments must be continued, to maintain a suppressed viral load. In most cases, viral loads are suppressed within months and become undetectable.

There are three categories of ARVs. There are a lot of acronyms coming up.

ARVs are antiretrovirals, this is the name for the type of treatment used against retroviruses, specifically HIV.

First, there are Nucleoside reverse transcriptase Inhibitors NRTIs. These work by blocking reverse transcriptase, the enzyme that synthesizes a DNA version of HIV. Without this process of reverse transcription, HIV cannot replicate.

Next we have Non-nucleoside reverse transcriptase inhibitors NNRTIs. These actually work similarly to NRTIs, but work on a different part of reverse transcriptase.

Protease inhibitors or PIs, inhibit protease [did I explain the role of protease inhibitors well enough? hmm], another enzyme necessary for the replication of HIV.

We’re done with the acronyms, that wasn’t too bad. NRTIs, NNRTIs, and PIs.

Entry inhibitors work by stopping HIV from binding to the host cell. These are not the first choice to fight against HIV.

Finally, integrase inhibitors block integrase, which sends the genetic material of HIV to the cells it infects.

Part Four: AIDS

AIDS is the late and most severe stage of HIV infection. To be diagnosed with AIDS, one’s CD4 cell count has to drop below 200 cells per cubic millimeter of blood. The typical range is 5 to 16 hundred.

The first reported case of AIDS was in the CDC’s Morbidity and Mortality Weekly Report in June of 1981. This issue says that two young and previously healthy men died of pneumonia, typically seen almost exclusively in the immunosuppressed.

Part Five: A Brief History of the AIDS Epidemic

So, I’m going to talk more about the history of AIDS, which is ongoing, in the next episode. But I thought I would give a brief history on the advancement of knowledge and treatment of HIV and AIDS.

HIV-related deaths peaked from 2005 to 2006 where 1.96 million people died each year, but since then annual deaths have dropped.

In the first years of AIDS, in the 80s, the life expectancy was one year after diagnosis. In 1996, this increased to thirty-nine years if infected at twenty. And in 2011, became seventy years. The last two values come from a study by Kaiser Permanente that compared life expectancy in HIV+ and HIV- individuals with the average age of participants being 41 years for people with HIV and 40 for HIV- people. This study measures the average additional years that newly infected twenty 20-year-olds could expect.

Why did the numbers change when they did?

First, we should identify where the data changed.

The study includes a graph, I will have a link to the study in the description. The steepest region in the graph, representing the time period with the greatest change in fatality, is between 1996 and 1998. In 1996, the use of a combination of antiretrovirals began. These were successful and allowed CD4 counts to raise enough to make HIV a chronic condition rather than a terminal one.

Medicine

So, great! There’s this medication regimen that can be used and it helps people with AIDS reach a manageable HIV status. This is great, right? Well, for those that can access this medication, yes. They can lower their viral load, increase CD4 counts to undetectable levels, and live relatively normal lives. But for those that can’t afford the thousands of dollars per year that these medications have costed? I’ll address this issue, and many more social and political issues related to AIDS, in my next episode of this season.

But before I end this episode, I wanted to include the experience of someone that is HIV+ to detail the physical impact that HIV has on the body.

Part Six: First-Hand Accounts

I have included two first-hand accounts anonymously posted on Avert. I have shortened them, but you can find the full accounts linked in the description as well as others.

One: Born with HIV

I was born with HIV. I was diagnosed at birth in 1990. My chances of survival were incredibly slim. I lived in hospitals the first several years of my life. I’ve been on most HIV treatment regimens.

I was constantly educated about HIV, but trying to understand it was so hard. Before I was eight, I’d lost both parents to AIDS. I resented the doctors, HIV and AIDS, my parents, even God.

I didn’t understand my body; I was really skinny but with a bloated stomach, and thin cheeks, almost skeletal-like. I had other side effects from having this type of immune system and from taking treatment. I always felt different.

I had hepatitis C for a while, but I’ve been undetectable since high school. I graduated in 2009 and lived a ‘normal’ life.

I’m resilient. I don’t have to go through what my parents went through. I recall vivid images of their last days and think if only antiretroviral treatment was as advanced then as it is now, they may have lived.

Two:

I was diagnosed with advanced HIV/Kaposi's Sarcoma In December last year.

I also had to deal with the lifetime medication that was giving me mood swings, lightheadedness, body rashes, and insomnia. It’s depressing but on the bright side, the antiretrovirals suppressed the virus inside me from multiplying. Also, the skin lesions on my body from Kaposi’s Sarcoma slowly but surely decreased in size and hopefully will fade away with patience.

For now, chemotherapy has been put on hold - I am so glad. Advances in modern medicine help as they give me hope that I will live a full life and not go back to asking ‘Am I going to die soon?’

Part Seven: A Brief Biography

Okay, so, this has been a lot, or at least I think it has been. I want to conclude this episode, and maybe other episodes if you think I should, with a brief biography of a scientist that has contributed to the fight against this disease. For HIV, I have chosen Dr. Don Francis.

On a personal note, reading an interview he did with FRONTLINE inspired me to become interested in Epidemiology. I will link to the transcript in the description. Francis worked at the Center for Disease and Prevention for twenty-one years. He coordinated with the World Health Organization for the Smallpox Eradication Program and investigated the first Ebola outbreak. He directed the CDC AIDS laboratory and worked with the Institut Pasteur to find the virus that causes AIDS, which we now know is HIV. He joined Genentech and found or co-founded the International Vaccine Initiate, VaxGen, and Globa Solutions for Infectious Diseases. Dedicated to forming HIV vaccines. GSID is now also used to track variants of the SARS-CoV-2.

Outro

So, first, thank you to my friends Sanjana (Nihalani) and Sim (De Jesus) for recording the first-hand accounts.

The next two episodes on HIV and AIDS should be out one each week. So, I’m reading through my script, and that is a very generous assessment of the speed of me writing these scripts. So expect it to be less than a month? I’ll try to get another shorter one, like the Galen episode, out before then. Thank you very much for listening!