VIRAL BURDEN AND DISEASE PROGRESSION IN HIV-1-INFECTED PATIENTS WITH SICKLE-CELL-ANEMIA

The spleen and lymph nodes are major sites of human immunodeficiency v irus type 1 (HIV-I) replication, mutation, and genetic Variation in vi vo. If a major portion of the lymphatic tissue, such as the spleen, is removed or otherwise is unavailable for invasion by the HIV-1 virus, will the course of the infection be altered, resulting in a prolonged symptom-free interval or even increased survival? The spleen of most a dults with sickle cell anemia (SS) is nonfunctional due to recurrent e pisodes of microinfarction. If autosplenectomized SS patients are expo sed to HIV-1, they may be ideal candidates to examine the question of whether absence of splenic function at the time of infection will posi tively alter the course of HIV-l-related disease. All SS patients with a diagnosis of HIV-1 infection at five university sickle cell centers were included in the patient cohort. Patients in active treatment or in follow-up (group A, n = 11) underwent a series of quantitative vira l studies to determine their HIV-1 viral burden. The studies included the branched-DNA signal amplification assay, quantitative DNA-polymera se chain reaction (PCR), quantitative reverse transcription (RT)-initi ated-PCR, and in situ PCR. All patients who died of the complications of the acquired immunodeficiency syndrome (AIDS) or of SS, lost to fol low-up, or were otherwise unavailable for study (Group B: n = 7) were included in the total patient group. None of the patients in group B u nderwent quantitative viral studies. In addition, a control population (group C, n = 36) of HIV-1-infected African Americans without SS, of similar age and gender to the SS patients, were compared with the stud y population for outcomes, In eight of It active patients (group A), t he CD4+ T-lymphocyte counts were normal and viral burdens were low for an average of 10.25 years following diagnosis. These eight patients a ll from group A were the only long-term nonprogressors (44%) among a t otal of 18 SS patients (groups A and B). in group C (control), only fi ve patients of 36 were long-term nonprogressors (13.9%). Five patients (28%) of the total SS group (groups A and B) succumbed to AIDS. One o f the five was from Group A. The evaluation of a limited number of adu lt individuals suggests that a significant proportion of HIV-l-seropos itive SS patients (44%) may be asymptomatic long-term nonprogressors. In these patients, the CD4+ T-lymphocyte counts remained high and thei r viral burdens were remarkably lower than in non-SS HIV-1-seropositiv e individuals. Whereas this study does not prove an ''autosplenectomy' ' hypothesis, it suggests that in patients with both SS and HIV-1 infe ction, the retroviral disease may be ameliorated by host factors of wh ich absence of splenic function prior to HIV-1 infection may be one. ( C) 1998 Wiley-Liss, Inc.