Increasing viral burden in CD4+ T cells from patients with human immunodeficiency virus (HIV) infection reflects rapidly progressive immunosuppression and clinical disease

Article Abstract:

Virtually overwhelming evidence has accumulated to implicate the human immunodeficiency virus type 1 (HIV-1) as the causative agent in AIDS. The virus infects cells expressing the CD4 cell-surface antigen, primary T cells, and cells of the monocyte-macrophage lineage. However, it has been observed that the number of infected CD4-positive T cells is actually quite small in patients with HIV infection. Among seropositive patients who have not yet developed AIDS, only between 1 in 100,000 and 1 in 100 cells in the blood are actually infected. This low rate of infection makes it difficult to account for the devastating effects of AIDS, and has prompted some investigators to postulate other mechanisms of the immunodeficiency. Such proposed mechanisms include suggestions that the presence of the virus may induce autoimmunity or that viral proteins shed from infected cells may induce immunosuppression. To more precisely observe changes in the viral infection of T cells during disease progression, a total of 27 HIV-positive subjects were monitored over period of at least one year. Fourteen patients were stable and 13 developed rapidly progressive disease. It was found that the proportion of infected T cells in the stable patients was lower than that observed at the outset in the patients who progressed. Even though the total number of CD4-positive cells were comparable, the patients who remained stable had infection rates of less than 1 in 10,000, while those who progressed had infection rates greater than 1 in 1,000 when the study began. Furthermore, the patients who progressed developed higher rates of infection, greater than 1 in 100, in the months prior to progression. Among the stable patients, none had an infection rate higher than 1 in 1,000 during the follow-up. These results suggest that the infection of T cells with HIV may play a direct role in the development of the immunosuppression associated with AIDS. Furthermore, measurement of the rate of viral infection of T cells may provide a useful warning for disease progression and may indicate that more aggressive therapy is warranted. (Consumer Summary produced by Reliance Medical Information, Inc.)

Infection, Physiological aspects, HIV (Viruses), HIV, T cells, Immunosuppression, Virus-induced immunosuppression

---

Trimetrexate-leucovorin dosage evaluation study for treatment of Pneumocystis carinii pneumonia

Article Abstract:

Pneumocystis carinii (Pc) pneumonia occurs in more than 80 percent of AIDS cases, and is one of the primary causes of death in patients with AIDS. The current therapy for Pc pneumonia consists of trimethoprim-sulfamethoxazole (T-S) or pentamidine isethionate (P-I), and produces significantly adverse side effects in as many as 80 percent of patients. Nonetheless, Pc pneumonia mortality ranges between 40 and 60 percent of cases. Trimetrexate (TX) is a new agent with promising effects. Its mode of action is the same as T-S, but it is 1,500 times more effective in binding to dihydrofolate reductase of pneumocystis. The addition of leucovorin (5-formyl tetrahydrofolate; LV) protects the patient's cells from the cytotoxic effects of TX. Used together, TX-LV should be a significant adjunct to the current formulary of AIDS patients with Pc pneumonia. A group of 54 AIDS patients with Pc pneumonia were enrolled in a dosage evaluation trial with TX-LV. Varying dosage schedules and combinations were administered, and the side effects, particularly hematologic (blood-related) in nature, were assessed. A full treatment course consisted of 21 full doses of TX. Therapeutically effective combination doses were achieved at 45 milligrams per square meter per day of TX and 80 milligrams per square meter per day of LV. Further control studies are recommended to compare the safety and effectiveness of these drugs with other medications used to treat Pc pneumonia. (Consumer Summary produced by Reliance Medical Information, Inc.)

Health aspects, Patient outcomes, Mortality, Complications and side effects, Drug therapy, Pneumocystis carinii pneumonia, Dosage and administration, Leucovorin, Folinic acid, Trimetrexate

---

Similar abstracts:

• Abstracts: Interferon-alpha with asymptomatic human immunodeficiency virus (HIV) infection: a randomized, placebo-controlled trial
• Abstracts: Visceral leishmaniasis in patients infected with human immunodeficiency virus (HIV). Tuberculous meningitis in patients infected with the human immunodeficiency virus
• Abstracts: Routine human immunodeficiency virus infection screening of women requesting induced first-trimester abortion in an inner-city population
• Abstracts: Kaposi's sarcoma in three HIV-1-infected cohorts. Effect of knowledge of human immunodeficiency virus infection status on sexual activity among homosexual men
• Abstracts: A Phase I study of chronic daily dosing of oral etoposide in combination with cisplatin for patients with advanced cancer

This website is not affiliated with document authors or copyright owners. This page is provided for informational purposes only. Unintentional errors are possible.