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Although the risk of developing lymphoma has decreased in the highly active antiretroviral therapy era, this cancer remains the major cause of mortality in HIV-infected patients. Autologous hematopoietic stem cell transplantation (ASCT) outcome does not differ for HIV-infected versus HIV-uninfected patients. We propose to develop a new treatment for HIV-associated high-risk lymphoma based on autologous transplantation of two genetically modified products: CD4 + T lymphocytes and CD34 + hematopoietic stem cells (HSPCs). The cells will be transduced ex vivo with the Cal-1 lentiviral vector encoding for both a short hairpin RNA (shRNA) against CCR5 (sh5) and the HIV-1 fusion inhibitor C46. The transduced cells will be resistant to HIV infection by two complementary mechanisms: impaired binding of the virus to the cellular CCR5 co-receptor and decreased fusion of the virus as C46 interacts with gp41 and inhibits HIV infection. This phase I/II pilot study, also entitled GENHIV, will involve two French participating centers: Saint Louis Hospital and Necker Hospital in Paris. We plan to enroll five HIV-1-infected patients presenting with high-risk lymphoma and require a treatment with ASCT. The primary objective of this study is to evaluate the safety, feasibility, and success of engraftment of Cal-1 gene-transduced CD4 + T lymphocytes and CD34 + HSPCs.

We report the first case of mother-to-infant transmission and follow-up for an HIV-1 group O virus from Cameroon. Isolates were obtained from the mother at delivery and from the child at birth and when 16 and 30 months old. We analyzed the viral evolution within mother and child by examining 51 sequences spanning C2V3 regions of the viral envelope gene. The mother carried two genotypes, v1 and v2. The genotype v1 was dominant in the child at birth, and persisted as a minor genotype at age 30 months. The genotype v2 was absent in the child sequences. The variability of the nucleotide sequences of the isolates from the child increased with age from 0.8 to 6%, and a novel genotype (v3) appeared at age 30 months. The nonsynonymous-to-synonymous mutation ratio increased with the age of the child, from 0.75 at birth to 1.86 at 30 months, indicating a high rate of fixation of amino acid changes in the child. The overall pattern was similar to that reported by Ganeshan et al. (J Virol 1997;71:663-677) for group M viruses infecting child with a slow-developing form of the disease.