Caspershire Meta

HIV research

I remember back in fall semester 2014, I took an introductory course in microbiology. It was the first time I learned streaking bacteria on plates and watching them grow, later to be identified and characterized. The course had a heavy emphasis on bacteria, although we were also exposed to materials related to viruses and bacteriophages.

I remember that one fine day, we watched a movie during the class time about the emergence of the HIV infection and the AIDS epidemic in the United States. The movie was “And The Band Played On”, an adaptation of a book written by Randy Shilts (that was his second book, FYI). Fast forward a few years later, in fall semester 2016 I took the human immunology course and I bumped into HIV/AIDS again. The instructor told us that no one should die because of HIV/AIDS in 2016 in developed nations because we have ways to suppress it.

HIV is a particularly interesting virus. It is not that it has an impregnable capsid that resists all insults, but rather it hides within our genome, piggy-backing on us while occasionally producing virions to continue its survival. It infects and killer T cells, an important immune cell type. When the number of T cells dropping, an infected individual would be severely weakened. Opportunistic pathogens see an opening and waste no time.

I don’t intend to write a very long article about this. On Caspershire Vault, I have an entry on HIV vaccine trials that have been going around. We haven’t had yet a dramatic success with our vaccine strategy, but we are slowly getting there. I am hopeful about this as our knowledge grows over the time. This entry on Caspershire Meta will serve as a reference pointer to materials related to this disease. I will be updated from time to time to reflect changes.

  • HIV was clinically observed in 1981 in the US. Before HIV was identified as the causal agent, diseases caused by opportunistic pathogens appeared such as PCP and Kaposi’s sarcoma. Those diseases only happen in people with a severely compromised immune system.
  • GaĆ«tan Dugas (Canadian) was incorrectly designated as the patient zero (index case). Because of that, Dugas was thought as the person who brought HIV into the US, specifically in California around March 1984. Later in 2016, a study published in Nature exonerated him from the title after a group of researchers made an announcement that HIV existed in the US since the 1970s (1978-1979 samples), probably coming from the Caribbean. A paper by Worobey et al., DOI: 10.1038/nature1982. STAT also has a somewhat similar story.
  • Genetically, HIV is closely related to the simian immunodeficiency virus (SIV). Researchers suggest that HIV evolved from SIV around the 1920s in Kinshasa (present-day DR Congo). It became the source of pre-1960s HIV pandemic (Faria et al., 2014, DOI: 10.1126/science.1256739). Per BBC article, HIV arrived in the US around the 1970s, just about the time where gay men were concentrated in big cities like New York and San Francisco.
  • The anti-retroviral drug azidothymidine (AZT, NRTI-class drug) was approved as the treatment for HIV infection in 1986, the first one prescribed for treating HIV. Its mode of action is by selectively inhibiting the HIV’s reverse transcriptase, therefore preventing the virus from integrating its genetic information into our genome.
  • In 1983, two research groups independently published that a novel retrovirus may be the causal agent for AIDS patients. Both published their findings in the same journal, the Science. In fact, it was the same issue and back-to-back (Gallo et al., Barre-Sinoussi et al.). Both named it differently; Gallo named it HTLV-III, while Barre-Sinoussi named it LAV. Later they figured out that both were the same, renamed it as HIV.

Primer initiated on October 15th, 2017. Expecting more updates.

More updates!

  • Since HIV break all hell loose, we need an “all hell breaks loose” way to counter it. Till date, there is no effective vaccine against HIV but we have several vaccines in the pipeline. I have a special research collection on HIV vaccine trials on Caspershire Vault. Thus, here it comes HAART (highly active anti-retroviral therapy), to which nowadays we just call it ART.
  • Since 1996, a number of publications appeared in The New England Journal of Medicine (NEJM) demonstrating that more drugs were better than just one. Later, some physicians coined the term cART to better reflect the nature of the therapy. Today, there are 6 classes of drugs that are working in tandem to inhibit HIV proliferation. They are entry inhibitors (e.g. maraviroc), nucleoside reverse-transcriptase inhibitors (e.g. zidovudine), non-nucleoside reverse transcriptase inhibitors (e.g. nevirapine), integrase inhibitors (e.g. raltegravir), and protease inhibitors (e.g. lopinavir).
  • It is hard to develop a vaccine against HIV. The problem here is that we want to induce the activity of both cytotoxic T-cells and neutralizing antibody production by the B cells. Thus, the current strategy is to employ the heterologous prime-boost vaccination. But still, we are quite far from reaching > 90% success rate.
  • Although it looks pretty grim, we do have prophylactic measure against the HIV infection. Known as the pre-exposure prophylaxis (PrEP, the brand name is Truvada), a combination of drugs tenofovir and emtricitabine can effectively block HIV from incorporating its genetic materials into the host’s genome. Problem is, you need to take this drug every day.
  • Ever since HAART was introduced in 1995, deaths (due to AIDS) have declined. Since we don’t have a good vaccine against HIV, we are still seeing the increase in HIV cases. Here’s the chart.
  • In Malaysia (my country), the source of HIV infection is from sharing needles by drug users. Dr. Adeeba Kamarulzaman and her like-minded colleagues had set up the needle-exchange programs. Doing this in Malaysia, a conservative Islamic country (that’s more like its facade), she received backlashes from the public. It is unfortunate that she was denounced because the policy she proposed, which was misconstrued as helping the addicts, but all she thought was to reduce harm. Here’s a special issue on strategies against HIV/AIDS curated by Science AAAS.
  • Even a new, hot technology like CRISPR/Cas failed to fight against HIV.

updated on October 21st, 2017