Patient May Have Naturally Achieved a Sterilizing Cure for HIV Infection

A patient may have naturally achieved a sterilizing cure for HIV infection after 7 years of no detectable genome-intact or replication-competent HIV-1 proviruses, suggesting that a sterilizing cure may be a rare but possible outcome. These findings were published in Annals of Internal Medicine.

The patient was a 30-year-old woman who was diagnosed with HIV infection in 2013. At the time of her diagnosis, the patient’s partner, who also had HIV infection, had a detectable plasma viral load of 186,000 copies/mL. Four years later, the patient’s partner died of AIDS.

Between 2013 and 2020, the researchers collected and analyzed multiple blood plasma and tissue samples from the patient. The presence of HIV-1 was assessed via near-full-length individual proviral sequencing, quantitative viral outgrowth assays, analyses of cell-associated HIV-1 RNA and DNA, plasma viral load, intracellular cytokine staining, and an in vitro infection assay.

During an 8-year follow-up period, the researchers noted that results from 10 commercially available viral load tests indicated the patient’s HIV viral load was below detection thresholds. In addition, results of laboratory studies showed no clinical signs of an HIV-associated disease. In 2019, blood plasma analysis showed that the patient was negative for 18 commonly used antiretroviral (ART) agents.

The patient did not begin ART therapy until she became pregnant in September 2019. After delivering a healthy baby who was negative for HIV infection in March 2020, the patient stopped ART therapy. After discontinuing ART, the patient’s HIV viral load remained undetectable on polymerase chain reaction testing. In addition, serologic testing showed that the patient was negative for both hepatitis C and hepatitis B viral infections; the patient had no history of any other sexually transmitted infection.

The researchers used near-full-length individual proviral sequencing for single-genome amplification of HIV DNA to evaluate the patient’ persistent HIV reservoir cells. Peripheral blood mononuclear cells (PBMC) collected in 2017 (n=1.188 billion), 2019 (n=265 million), and 2020 (n=923); mononuclear cells (n=503) from the placenta also were assessed for HIV. A total of 7 defective proviral HIV-1 DNA species were found, none of which were from the placenta. Of note, the presence of these DNA products indicated the patient previously had HIV infection, including active cycles of viral replication.

On subsequent analysis of a total of 150 million resting CD4+ T cells via viral outgrowth assays, the researchers found no replication-competent viral particles. In addition, the patient had no detectable viral RNA copies on ultrasensitive analysis of HIV-1 RNA from 4.5 mL of blood plasma.

On analysis of immunologic assays, the researchers found that the patient had HIV-1-specific memory CD4⁺ and CD8⁺ T-cell responses.

This study was limited by the fact that a sterilizing cure for HIV infection cannot be empirically confirmed. In addition, the researchers noted that the absence of evidence is not evidence of absence.

According to the researchers, these findings “raise the possibility that a sterilizing cure for HIV-1 infection, defined by the absence of detectable intact HIV-1 proviruses, is an extremely rare but possible clinical outcome.”

Disclosure: Some author(s) declared affiliations with industry. Please see the original reference for a full list of disclosures.

Reference

Turk G, Seiger K, Lian X, et al. A possible sterilizing cure of HIV-1 infection without stem cell transplantation. Ann Intern Med. Published online November 16, 2021. doi:10.7326/L21-0297