icon-    folder.gif   Conference Reports for NATAP  
  22nd Conference on Retroviruses and
Opportunistic Infections
Seattle Washington Feb 23 - 26, 2015
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Little or no DNA reservoir draining with
chemo plus autologous stem-cell transplant
  CROI 2015, February 23-26, 2015, Seattle, Washington
Mark Mascolini
High-dose chemotherapy plus autologous hematopoietic stem cell transplantation (HSCT) for lymphoma had little or no impact on HIV DNA in the peripheral blood mononuclear cell (PBMC) reservoir through 18 months, according to results of a 13-person study in France [1]. HIV DNA levels in HSCT patients after transplant were similar to those seen in nontransplant patients on suppressive antiretroviral therapy.
Researchers at Saint-Louis Hospital in Paris and at other institutions conducted this study to assess the impact of high-dose chemotherapy followed by autologous HSCT on the cellular HIV DNA reservoir in lymphoma patients. They noted that HIV DNA integrates into long-lived cells such as CD4 cells in blood and lymphoid tissue and macrophages in tissue. The researchers suggested that three factors may have contributed to the sole cure of HIV infection in the Berlin patient: myeloablative chemotherapy, graft-versus-host disease, and an allogeneic transplant with cells from a donor homozygous for the CCR5-delta 32 mutation, which protects against infection with CCR5-using HIV.
High-dose chemotherapy and autologous HSCT have failed to cure HIV infection. But use of those intense procedures allows researchers to study their impact on the HIV DNA reservoir. Together the two therapies massively deplete circulating CD4 cells, the French team noted, but what happens to the HIV DNA reservoir in PBMCs afterwards remains unclear.
The investigators tracked HIV DNA in 13 patients who received high-dose chemotherapy plus autologous HSCT for non-Hodgkin lymphoma or Hodgkin lymphoma at Saint-Louis Hospital from January 2012 to June 2014. All patients were taking antiretroviral therapy at the time of HSCT. Median follow-up from lymphoma diagnosis measured 3.4 years (interquartile range [IQR] 2.1 to 6.0) and from HSCT 19.3 months (IQR 14.6 to 19.9).
Eleven study participants were men and 2 women. Median age at HSCT stood at 46 (IQR 43 to 51), median HIV infection duration at 7.7 years (IQR 2.6 to 16.9), and median antiretroviral therapy duration at 7.6 years (IQR 1.4 to 13.4). Median time from lymphoma diagnosis to HSCT was 22.8 months (IQR 7.6 to 43.9). CD4 count at lymphoma diagnosis measured 386 (IQR 230 to 590). At the time of HSCT 8 people had a plasma viral load below 50 copies; viral load in the remaining 5 ranged from 55 to 434 copies. During follow-up through January 2015, 2 people died, 1 from lymphoma progression.
Median total HIV DNA in blood stood at 2.97 log copies/mL before HSCT, 1.68 log at HSCT, 2.80 log 0.5 to 6 months after HSCT, and 2.60 log more than 6 months after HSCT. Median HIV DNA levels in PBMCs did not change substantially from before HSCT (2.87 log per million PBMCs) to after HSCT (2.62 log). Median HIV DNA levels measured 2.88 log per million PBMCs more than 6 months before HSCT, 2.85 log within 6 months before HSCT, 2.65 log in the 6 months after HSCT, and 2.56 log more than 6 months after HSCT (change not significant).
The HIV DNA reservoir correlated positively with plasma HIV RNA (r = 0.45, P = 0.0001) and with total blood HIV DNA (r = 0.87, P < 0.0001).
The Paris team observed that HIV DNA levels in PBMCs before and after HSCT in these people resemble those previously reported in nontransplant patients on antiretroviral therapy (2.3 to 2.7 log per million PBMCs). They concluded that peripheral blood HIV DNA reservoirs persist and total HIV DNA in PBMCs remains stable after high-dose chemotherapy plus autologous HSCT. The researchers proposed that the slight decrease in number of HIV-infected PBMCs more than 6 months after HSCT probably reflects long-term control of plasma viral load with antiretroviral therapy, not a benefit of chemotherapy plus transplant.
1. Delagreverie H, Gerard L, Chaix ML, et al. Impact of combination of chemotherapy and autologous hematopoietic stem-cell transplantation for lymphoma on HIV reservoir persistence. CROI 2015. February 23-26, 2015. Seattle, Washington. Abstract 429.