A complete cure for HIV/AIDS remains elusive, but recent amazing progress in therapy is bringing new hope. This article describes recent breakthroughs in HIV therapy, including the development of a “Zombie Virus,” advances in blocking infection through bone marrow transplantation, and a new drug for pre-exposure prophylaxis.
Zombie Virus
An engineered HIV virus has been developed that infects and replicates in host cells, competing with the wild-type virus for coat components. Being a minimal virus, lacking many of the wild-type genes, it also outgrows the wild-type virus. A proof of concept was conducted in a related monkey model using Simian Immunodeficiency Virus (SIV) with the gene for the HIV surface protein, termed HSIV. After 30 weeks of coinfection, five out of six zombie-treated monkeys were healthy, and their levels of SHIV had dropped by a factor of 10⁵—from a peak of 100,000,000 copies/mL blood to 10,000/mL. In contrast, three out of four control animals were so sick at 16 weeks that they had to be euthanized (Science 385:586 and 622, 2024).
Blocking Infection
Bone marrow transplantation (BMT) is a complete replacement of a patient’s blood cells with donor cells and has been an effective therapeutic regime for patients with leukemia or lymphoma. This approach was applied to an HIV patient with cancer using bone marrow cells from a donor with a mutation in both alleles of CCR5, an HIV receptor on the surface of T lymphocytes. As first reported in Nature (vol 632, pg 235, 2024), this resulted in complete elimination of infection, as the mutation prevents infections. Infected cells died out, and new infections could not take place. Since then, five more patients have been apparently cured by BMT using homozygous mutant CCR5 cells.
Now, a seventh HIV patient has been reported “cured” for six years after stopping antiretroviral therapy, but using donor cells that had only one allele of mutant CCR5. A single copy of the CCR5 protein lowers the infectivity of HIV, and the chemotherapy required before bone marrow transplant may combine to clear the virus from the patient. BMT requires matching transplantation HLA types of donor and recipient, so the availability of donors with one mutant CCR5 allele greatly expands the pool of potential donors for HIV patients.
New Drug, Lenacapavir for Pre-Exposure
Antiviral medicines have been generally missing from our medical cabinet until very recently. Idoxuridine was approved for some herpes virus infections in 1962, and acyclovir was approved for chickenpox and herpes zoster in 1981. Gilead Sciences has been especially active in getting drugs approved for hepatitis and HIV.
In August 2024, Gilead announced that a twice-yearly injection of their drug lenacapavir as pre-exposure prophylaxis resulted in no infections in 2,000 at-risk women over one year, with similar results in men (review article by K. Kupferschmidt, Science 385:478, 2024). The therapy is seen as a great improvement in protection due to reduced stigma and better compliance compared to daily pill regimens.
