The Broad Benefits of AIDS Research

Absolutely, and some recent examples have been very dramatic. In 2012, a young girl with acute leukemia wasn’t responding to conventional treatments and was on the brink of death. But then she was given an experimental treatment using an anti-cancer gene that could only be delivered to her cells using disabled HIV as a carrier. Within weeks she was in remission and she remains cancer free.

An anti-cancer gene could only be delivered to her cells using disabled HIV as a carrier.

In 2014, a Utah man with the same type of aggressive leukemia received a similar treatment using disabled HIV (known as the SIN vector) and he, too, is now cancer free. Most recently, the SIN vector has been used in the cure of sickle cell anemia in young people with severe disease.

Additionally, six HIV-negative children with usually fatal genetic immune disorders (Wiskott Aldrich syndrome, severe combined immunodeficiency, and chronic granulomatous disease) were cured using similar targeted gene therapies, all of which employed inactivated HIV.

The rapid development of effective COVID-19 vaccines would not have been possible without HIV vaccine research.

All leading COVID-19 vaccines and vaccine candidates to date, including Pfizer and Moderna, rely on their ability to stimulate production of antibodies and T cells targeted to a COVID-19 virus coat protein known as S, or “spike.” S is required for the virus to infect a cell. But to ensure that a vaccine elicits an optimal response, its S protein component must be engineered to ensure that it is stabilized in the correct shape. This relies on insertion of an amino acid called proline into specific parts of S—a technique developed many years ago in the course of HIV vaccine research.

For the Pfizer and Moderna vaccines, delivery of the COVID-19 vaccine products starts with a genetic material, mRNA, encoding the optimized S protein. For over three decades, mRNAs have been tested as vaccine and therapeutic candidates, but with little success for two important reasons. First, when mRNA is delivered to cells, it induces a dangerous and potentially lethal immune response. To circumvent this problem, a technique for its modification was developed by Dr. Drew Weissman, a long-time amfAR grantee.

Once the mRNA is modified for safety, it must still be delivered to cells, and the second challenge is that mRNA is very fragile. Without specialized lipid shells, known as nanoparticles or “fat bubbles,” to protect it from being rapidly dissolved in tissue, and to facilitate its entry into immune cells, there would be no mRNA COVID-19 vaccine. Among their earliest therapeutic applications, these lipid nanoparticles were used for the evaluation of this mRNA/lipid strategy to produce anti-HIV antibodies in mice.

Experimental treatments for several types of cancer have grown directly out of AIDS research. Treating HIV involves blocking key receptors—proteins used by the virus to enter immune cells. One of these receptors, CXCR4, appears to be an important target in treating lung cancer. Researchers are now studying drugs originally designed to block CXCR4 in HIV patients to determine whether they might be used to fight this common form of cancer.

Several natural body hormones called growth factors promote the activity of HIV. Many of these hormones also accelerate the growth and spread of cancer cells. Blocking the activity of these hormones is a strategy first used experimentally to treat Kaposi’s sarcoma, a cancer found in patients with HIV/AIDS. Now it is also being tested in bladder, vulvar, and breast cancers, and has shown some exciting recent success in treating colon cancer.

Experimental treatments for several types of cancer have grown directly out of AIDS research.

In addition, small proteins and drugs that can block the growth of new blood vessels (which is critical to the survival of tumor cells) were originally developed to treat Kaposi’s sarcoma, but are now being tested in many other cancers as well. Finally, the protease inhibitor lopinavir, first developed to treat HIV, has been shown to be effective in attacking human papillomavirus, which can cause cervical cancer.

The profound immune suppression necessary for a bone marrow transplant to treat leukemia and other cancers often leads to devastating, even fatal, infections such as cytomegalovirus and Pneumocystis pneumonia, which also affect people with AIDS. New drugs to treat and prevent these infections in cancer patients have come directly from AIDS-targeted research.

Yes. HIV/AIDS therapies are critical in the treatment of other diseases. The HIV protease inhibitor, ritonavir, is one of the two main ingredients in Paxlovid, the primary antiviral drug used to treat COVID-19. Protease inhibitors, one of the first classes of anti-HIV drugs, revolutionized treatment for people living with HIV/AIDS in the mid-1990s and contributed to a rapid decline in AIDS-related deaths.

Three drugs developed to treat HIV—lamivudine, tenofovir, and entecavir—are now the mainstays of therapy for hepatitis B virus (HBV) infections. Another antiviral drug called adefovir, which failed as an HIV treatment, was found to suppress HBV at much lower dosages and has been approved for the treatment of chronic HBV disease. More recently, a drug called sofosbuvir that is modeled on HIV reverse transcriptase inhibitors, one of the main classes of anti-HIV drugs, is being used to treat and cure hepatitis C.

HIV-positive people may develop autoimmune problems, such as psoriasis or blood abnormalities associated with lupus. For these autoimmune diseases, treatments developed for HIV/AIDS should also apply when the same conditions occur spontaneously. A class of anti-HIV drug that blocks a protein known as CCR5, the key co-receptor for HIV’s entry into cells, is also being evaluated in inflammatory bowel disease and other autoimmune disorders.

One particle of HIV genetic material can be located among millions of other particles by using extraordinarily sensitive techniques known as PCR (polymerase chain reaction) and RT-PCR (reverse transcription PCR).

New PCR tests, developed for diagnosing HIV, are now routinely used to rapidly detect a number of other infectious diseases, including COVID-19, hepatitis C, tuberculosis, chlamydia, influenza, Lyme disease, and many fungal infections.

These techniques have also made it possible to measure otherwise undetectable levels of cancer cells in people who appear to have been cured. This detection allows doctors to initiate new therapy or to continue ongoing treatments that might otherwise have been discontinued.

Further, the discovery of HHV-8, a herpes virus linked to Kaposi’s sarcoma, was made possible by a new application of PCR. This technique is now being used worldwide to seek possible infectious causes for diseases of unknown origins.

New PCR tests, developed for diagnosing HIV, are now routinely used to rapidly detect a number of other infectious diseases.

Also, studying immune dysfunction associated with HIV has driven advances in affordable, automated, and portable point-of-care devices that could have a range of clinical applications in resource-limited settings.

Advocacy efforts by amfAR and other organizations were instrumental in getting the Food and Drug Administration to institute fast-track procedures to speed the review of new treatments for all life-threatening diseases. Fast-tracking has already been applied in the approval of treatments for conditions such as Alzheimer’s, AIDS, and cancer.