Publications

BACKGROUND

The impact of antiretroviral therapy (ART) on sexual risk behavior and HIV transmission among HIV-infected persons in Africa is unknown.

OBJECTIVE

To assess changes in risky sexual behavior and estimated HIV transmission from HIV-infected adults after 6 months of ART.

DESIGN AND METHODS

A prospective cohort study was performed in rural Uganda. Between May 2003 and December 2004 a total of 926 HIV-infected adults were enrolled and followed in a home-based ART program that included prevention counselling, voluntary counseling and testing (VCT) for cohabitating partners and condom provision. At baseline and follow-up, participants' HIV plasma viral load and partner-specific sexual behaviors were assessed. Risky sex was defined as inconsistent or no condom use with partners of HIV-negative or unknown serostatus in the previous 3 months. The rates of risky sex were compared using a Poisson regression model and transmission risk per partner was estimated, based on established viral load-specific transmission rates.

RESULTS

Six months after initiating ART, risky sexual behavior reduced by 70% [adjusted risk ratio, 0.3; 95% confidence interval (CI), 0.2-0.7; P = 0.0017]. Over 85% of risky sexual acts occurred within married couples. At baseline, median viral load among those reporting risky sex was 122 500 copies/ml, and at follow-up, < 50 copies/ml. Estimated risk of HIV transmission from cohort members declined by 98%, from 45.7 to 0.9 per 1000 person years.

CONCLUSIONS

Providing ART, prevention counseling, and partner VCT was associated with reduced sexual risk behavior and estimated risk of HIV transmission among HIV-infected Ugandan adults during the first 6 months of therapy. Integrated ART and prevention programs may reduce HIV transmission in Africa.

Graft-versus-host disease (GVHD) remains a source of significant morbidity and mortality in the setting of allogeneic stem cell transplantation. Improving outcomes in stem cell transplant recipients will require additional therapeutic modalities for GVHD, especially for those patients who fail to respond to initial therapy with steroids. This article provides an introduction to accompanying articles in this issue of Biology of Blood and Marrow Transplantation concerning the current state of GVHD management with an emphasis on the role of extracorporeal photopheresis as a therapeutic modality. Topics discussed include challenges associated with the design of clinical studies of GVHD therapies, the efficacy of and proposed mechanisms of photopheresis in the setting of GVHD, and our emerging understanding of regulatory T cell biology as it relates to allogeneic stem cell transplantation.

BACKGROUND

Umbilical cord blood (CB) is a promising source of hematopoietic stem cells for allogeneic transplantation. However, delayed engraftment and impaired immune reconstitution remain major limitations. Enrichment of donor grafts with CB T cells expanded ex vivo might facilitate improved T-cell immune reconstitution post-transplant. We hypothesized that CB T cells could be expanded using paramagnetic microbeads covalently linked to anti-CD3 and anti-CD28 Ab.

METHODS

CB units were divided into three fractions: (1) cells cultured without beads, (2) cells cultured with beads and (3) cells cultured with beads following CD3+ magnetic enrichment. All fractions were cultured for 14 days in the presence of IL-2 (200 IU/mL).

RESULTS

A mean 100-fold expansion (range 49-154) of total nucleated cells was observed in the CD3+ magnetically enriched fraction. Following expansion, CB T cells retained a naive and/or central memory phenotype and contained a polyclonal TCR diversity demonstrated by spectratyping.

DISCUSSION

Our data provide evidence that naive and diverse CB T cells may be expanded ex vivo and warrant additional studies in the setting of human CB transplantation.

BACKGROUND

The generation of AML-specific T-lymphocyte responses by leukemia-derived DC has been documented by multiple investigators and is being pursued clinically. An obstacle to widespread use of this strategy is that it has not been possible to generate leukemic DC from all patients, and an alternative approach is needed if the majority of leukemia patients are to receive therapeutic vaccination in conjunction with other treatment protocols.

METHODS

In the present study, we generated DC from CD14-selected monocytes isolated from healthy donor PBPC and loaded them with a total cell lysate from AML patient blasts.

RESULTS

Immature in vitro-derived DC exhibited robust phagocytic activity, and mature DC demonstrated high expression of CD80, CD83, CD86 and the chemokine receptor CCR7, important for DC migration to local lymph nodes. Mature, Ag-loaded DC were used as APC for leukemia-specific cytotoxic T-lymphocyte (CTL) induction and demonstrated cytotoxic activity against leukemic targets. CTL lysis was Ag-specific, with killing of both allogeneic leukemic blasts and autologous DC loaded with allogeneic AML lysate. HLA-matched controls were not lysed in our system.

DISCUSSION

These data support further research into the use of this strategy as an alternative approach to leukemia-derived DC vaccination.