December 1 will mark World AIDS Day, a time to spotlight the ongoing fight against HIV/AIDS. HIV doesn’t directly kill people—it’s the opportunistic infections that come with a weakened immune system that are deadly. What’s fascinating is how the virus explicitly targets CD4 T-cells, the very immune cells that coordinate your body’s defense system. HIV essentially leaves the immune system leaderless. Today’s Primer showcases the therapies stopping HIV from hijacking the body.

Why It Matters

HIV used to be a death sentence. Today, thanks to anti-retroviral therapies (ART), it’s a manageable chronic disease—if you have access. But barriers to treatment for an estimated 10 million and rising infections in 28 countries mean the fight is far from over.

HIV 101: How It Hijacks the Body

HIV is a retrovirus, a master hacker of human cells. Here’s how it works:

1. HIV invades CD4 T-cells, the immune system’s frontline defenders.
2. HIV converts its single-stranded RNA into double-stranded DNA using reverse transcriptase.
3. HIV integrates its viral DNA into human DNA—turning the CD4 T-cell into a virus factory.
4. The infected CD4 T-cell produces viral proteins that assemble into new HIV particles.
5. HIV destroys CD4 T-cells, leaving the body vulnerable to other infections.

The Science of Stopping HIV

Modern HIV drugs block the virus at every turn. Here’s how:

• Integrase Inhibitors: Dolutegravir, Bictegravir, and Cabotegravir stop HIV from integrating its DNA into human cells, freezing replication.
• Nucleotide Reverse Transcriptase Inhibitors: Tenofovir Alafenamide and Emtricitabine block the enzyme that converts HIV’s RNA into DNA, cutting replication off at the knees.
• Non-Nucleoside Reverse Transcriptase Inhibitors: Efavirenz disrupts reverse transcriptase by jamming its structure.
• Protease Inhibitors: Ritonavir and Darunavir prevent the assembly of mature viral particles by blocking protease, the enzyme that processes viral proteins.
• Fusion Inhibitors: Maraviroc and Enfuvirtide keep HIV out of cells by blocking its entry pathways.

Cocktail Strategy

HIV is a shape-shifter. Its sloppy reverse transcriptase enzyme makes constant mistakes when copying its genome, leading to frequent mutations. This is why ART regimens combine multiple drugs to target the virus from different angles and reduce the risk of resistance. The fight against HIV is a race between innovation and evolution.

Cocktail Fodder

Some people are naturally resistant to HIV. They have a rare genetic mutation called CCR5-Δ32, which prevents HIV from entering their cells. This mutation inspired Maraviroc, a drug that mimics this natural resistance by blocking the same pathway. These discoveries underline how understanding rare cases can lead to breakthrough treatments!

Bottom Line

With science on our side, biopharma has turned HIV into a manageable disease—but rising infections and treatment gaps demand urgent global action.