HIV 2022 – The Battle Continues

In 1982, the Centers for Disease Control (CDC) coined the term Acquired Immunodeficiency Syndrome (AIDS) to describe a new disease that had appeared in the United States. Initially mysterious in its cause, AIDS was quickly shown to result from infection with a newly discovered virus (a discovery that eventually earned Dr. Luc Montagnier the 2008 Nobel Prize in Physiology or Medicine). The virus was named the human immunodeficiency virus (HIV), and analysis of the virus showed that it belonged to a family of viruses known as retroviruses. Retroviruses are unique among the viral world for their novel life cycle that involves inserting their genetic information into the DNA of the host cell. Retroviruses actually have RNA as their genetic material, but once inside an infected cell the virus uses its reverse transcriptase enzyme to convert its RNA into DNA. The viral DNA then travels to the cell nucleus and uses another viral enzyme called integrase to insert the viral DNA into the host cell DNA. From this integrated viral DNA (called a provirus), the virus makes new copies of itself, and these progeny viruses are released from the cell to infect other cells. This insertion is a permanent event, so the infected cell continues to crank out new virus until it dies naturally or is destroyed by the immune system. Unfortunately, our immune system is unable to eliminate HIV which results in infected patients having chronic, permanent infections. Over time, the virus wreaks havoc with the immune system, and patients slowly become immunodeficient which makes them highly susceptible to other infections and cancers. Importantly, such chronically infected individuals have viruses in their blood and bodily fluids and can transmit the virus to others via blood contact, breast feeding, or sexual activity (see HIV.gov).

In the early years of the HIV epidemic, the disease was usually fatal as there were no effective treatments. Likewise, there was no protective vaccine so sexual partners of infected individuals were at risk for acquiring the virus, even if practicing safe sex. While a vaccine is still lacking, great strides have been made in anti-HIV drugs. There are now 7 classes of drugs available, with each class blocking a different step in the life cycle of the virus. The most commonly used classes are the reverse transcriptase inhibitors (block the conversion of the viral RNA into DNA), the protease inhibitors (block the processing of the viral proteins), and the integrase inhibitors (block the insertion of the viral DNA into the host DNA so no provirus forms). These drugs can control the infection by inhibiting viral reproduction and/or infection of new cells. This results in greatly reduced virus production (lower viral loads) which helps prevent immune system damage in the patient and also lowers the risk of transmitting the virus to a partner. While none of the drugs completely cures anyone, continuous drug therapy keeps the individual healthy and able to live a fairly normal life.

Another important element in fighting HIV is to reduce new infections in the population. In the absence of an HIV vaccine, prophylactic drug therapy has been developed to help prevent at-risk individuals from contracting HIV. Currently, there are two oral medications available for HIV prevention, Truvada and Descovy. Both drugs contain a combination of different reverse transcriptase inhibitors and each is taken as a daily pill. When taken as prescribed, each drug reduces the risk of acquiring HIV from sexual activity by 99%. However, maintaining a daily pill regimen can be challenging, and even missing one day can reduce the drug’s effectiveness at preventing HIV infection. To overcome the compliance challenge, in December of 2021 the Federal Drug Administration (FDA) approved a new injectable HIV prophylactic called Apretude for use by HIV-negative individuals. Apretude is a long-acting integrase inhibitor that when tested against Truvada was even more effective at preventing HIV infections. Importantly, Apretude has a much easier administration schedule than the daily oral medications. The initial Apretude injection is followed by a second injection one month later with subsequent injections required every two months. A prevention schedule only requiring 6 shots per year rather than 365 daily pills should reduce compliance lapses and help ensure greater safety for at-risk individuals. Apretude should be available to the public sometime in early 2022 and hopefully will become another significant weapon against an insidious virus.

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