A study of the second HIV patient to undergo successful stem cell transplantation from donors with an HIV-resistant gene found that there was no active viral infection in the patient’s blood 30 months after they stopped antiretroviral therapy, according to a case report published in The Lancet HIV journal.1

Using ultrasensitive viral load assays of plasma, semen, and cerebrospinal fluid (CSF) samples, the researchers were able to detect HIV-1 RNA. Cell-copy number and total HIV-1 DNA levels were quantified in multiple replicates of gut biopsy samples and lymph-node tissue using droplet digital PCR (ddPCR) and quantitative real-time PCR.2

The researchers were also able to analyze the presence of intact proviral DNA using multiplex ddPCR targeting the packaging signal (ψ) and envelope (env). To measure HIV-1-specific T-cell responses, intracellular cytokine staining was conducted. To measure humoral response to HIV-1, low sensitive and low-avidity antibody assets were used.2

The results showed that the HIV-1 viral load in plasma remained undetectable in the patient up to 30 months using an assay with a detection limit of 1 copy per mL. The patient’s CD4 count was 430 cells per μL at 28 months, in addition to a very low-level positive signal for HIV-1 DNA was recorded in peripheral CD4 memory cells. At 21 months, the viral load in semen was undetectable in both plasma and cells; at 25 months, CSF was within normal parameters, with HIV-1 RNA below the detection limit.2

HIV-1 DNA by ddPCR was negative in rectum, caecum, and sigmoid colon and terminal ileum tissue samples at 22 months. Further, lymph-node tissue from axilla was positive for the long-terminal repeat and env, negative for ψ and integrase, and negative by the intact proviral DNA assay at 27 months. The HIV-1-specific CD4 and CD8 T-cell responses have also remained absent at 27 months.2

Low-avidity env antibodies have continued to decline, and mathematical modeling suggests that the probability of remission for life is 98% in the context of 80% donor chimerism in total HIV target cells and greater than 99% probability of remission for life with 90% donor chimerism.2

The researchers concluded that the patient has been in HIV-1 remission for 30 months with no detectable replication-competent virus in blood, CSF, intestinal tissue, or lymphoid tissue. In addition, donor chimerism has been maintained at 99% in peripheral T cells, which leads the researchers to suggest that these findings represent an HIV-1 cure.2

Although this is a monumental moment in HIV research, professor Ravindra Kumar Gupta, PhD, lead author of the study, said health care providers should still be careful with how this treatment is used. "We propose that these results represent the second ever case of a patient to be cured of HIV,” Gupta said in a press release. “Our findings show that the success of stem cell transplantation as a cure for HIV, first reported nine years ago in the Berlin patient, can be replicated. It is important to note that this curative treatment is high-risk, and only used as a last resort for patients with HIV who also have life-threatening haematological malignancies. Therefore, this is not a treatment that would be offered widely to patients with HIV who are on successful antiretroviral treatment.” 1


REFERENCES
  1. Second patient has been cured of HIV, study suggests. ScienceDaily. https://www.sciencedaily.com/releases/2020/03/200310164741.htm. Published March 10, 2020. Accessed March 18, 2020.
  2. Gupta RK, Peppa D, Hill AL, et al. Evidence for HIV-1 cure after CCR5Δ32/Δ32 allogeneic haemopoietic stem-cell transplantation 30 months post analytical treatment interruption: a case report. The Lancet HIV. 2020; doi: https://doi.org/10.1016/S2352-3018(20)30069-2.