Biomedical subjects
Roger Bedimo
Publications and source records attributed to Roger Bedimo.
A placebo-controlled pilot study of intensification of antiretroviral therapy with mycophenolate mofetil.
PURPOSE: We studied the safety, tolerability, virologic, and immunologic effects of mycophenolate mofetil (MMF) added to a stable antiretroviral therapy (ART) in the setting of low-level viremia. METHODS: MMF 500 mg BID or placebo was given to patients thought to be adherent on stable ART with plasma viremia between 200 and 4000 copies/mL. At week 4 unblinding was performed and patients on placebo were offered open-label MMF. RESULTS: Six patients were enrolled. At entry mean plasma HIV-1 RNA (VL) was 2.98 log10 copies/mL; mean CD4 count was 523. All subjects randomized to placebo elected to cross over to open label MMF. No significant adverse events were observed during MMF therapy. Three patients on MMF achieved VL < 50 copies/mL by week 4; a fourth had VL decline of > 0.5 log. Two patients on placebo had declines of VL. One of these had further decline on open label MMF. Cell surface markers of apoptosis, activation, and proliferation on CD4+ and CD8+ cells declined modestly or remained low. CD4 counts were stable at week 24. All but one subject had rebound of viremia by week 24, universally associated with missed doses of medication by pill count. CONCLUSION: MMF appears to be safe, and its administration lead to decreased T cell activation. During periods of adherence to therapy, the use of MMF was correlated with declines in viremia, but this small pilot study could not prove this association. Further study of MMF in patients with viremia should be considered for whom additional or alternative antiretrovirals are impractical.
Sustained HIV viral suppression following treatment interruption: an observational study.
Treatment of HIV-infected patients with HAART can result in long-term suppression of viral loads to undetectable levels. Rapid virologic rebound typically follows treatment interruption (TI), with a potential for significant loss of CD4+ cells. Patients who maintain virologic suppression despite interrupting treatment have not been well described. All patients with a pretreatment viral load (VL) > or = 5000 copies/ml, who had been on therapy for > or = 2 weeks, and who underwent a TI lasting > or = 180 days were analyzed. Patients whose maximum VL did not exceed 5000 copies/ml > or = 6 months after starting TI ("nonrebounders") were compared with those whose VL exceeded 5000 copies/ml (rebounders). Seventy-one patients were included in the analysis. Nineteen (27%) were nonrebounders. Ninety-four percent of patients in each group interrupted treatment for reasons unrelated to virologic response. Median change in CD4 count during TI was not significantly different between the nonrebounder and rebounder groups (-20.5/microl vs. -64.0/microl; p < 0.086). In a multivariate logistic regression analysis, the following factors predicted nonrebounder status: peak VL before TI (log10 copies/ml) (OR = 0.14, 95% CI = 0.04-0.48, p = 0.0016); having received HAART (vs. mono/dual therapy) as initial regimen (OR: 11.0, 95% CI: 2.04-59.8, p = 0.0054); and female gender (OR = 4.8, 95% CI = 1.09-21.5, p = 0.0384). The large majority of chronically infected HIV patients with a TI > or = 180 days interrupted treatment for reasons unrelated to virologic response. Almost 30% did not have a significant virologic rebound. Those patients were more likely to be female, had a lower peak VL prior to treatment, and their initial regimen was more likely to be HAART. Examining the immune responses of nonrebounders may contribute to the understanding of protective immunity to HIV.
Trends in AIDS-defining and non-AIDS-defining malignancies among HIV-infected patients: 1989-2002.
In a comparison of rates of acquired immunodeficiency syndrome (AIDS)-defining malignancies (ADMs) for 1989-1996 versus 1997-2002, we found a decrease in ADMs (rate ratio, 0.31; P<.0001) and a significant increase in non-AIDS-defining malignancies (non-ADMs; rate ratio, 10.87; P<.0002). The mean CD4 cell count was lower among patients with ADMs than among those with non-ADMs. A longer duration of survival during highly active antiretroviral therapy might explain the increasing incidence of non-ADMs.
Leukemoid reactions complicating colitis due to Clostridium difficile.
BACKGROUND: We sought to describe the characteristics of patients who had Clostridium difficile colitis complicated by leukemoid reactions (total leukocyte count greater than 35 x 10(9)/L) and to determine whether this complication is associated with higher morbidity or mortality than C difficile colitis without leukemoid reactions. METHODS: We performed a retrospective case series analysis of patients with a positive fecal assay for C difficile toxin and a peak leukocyte count greater than 35 x 10(9)/L during 1998 and 1999. Twenty cases that met these criteria were compared with 65 randomly selected control patients (patients with a positive C difficile toxin and a peak leukocyte count less than 35 x 10(9)/L). RESULTS: The mean peak leukocyte count was 52 +/- 18.2 x 10(9)/L (+/- SD) in the case group and 14.9 +/- 6.5 x 10(9)/L in the control group. Patients with a leukemoid reaction had a lower temperature, a lower serum albumin level, and a higher hematocrit value. Multivariable logistic regression showed respiratory tract infection and lower temperature to be independent predictors of a leukemoid reaction. There were 10 deaths (50%) in the leukemoid reaction group and 5 deaths (7.7%) in the control group. All seven patients with a peak leukocyte count greater than 50 x 10(9)/L died, compared with eight deaths (10.3%) among the remaining 78 patients whose peak leukocyte count was less than 50 X 10(9)/L. CONCLUSION: Patients with C difficile colitis and a leukocyte count greater than 35 x 10(9)/L have a poor prognosis with a much higher mortality rate than patients who have C difficile colitis without a leukemoid reaction.
The management of musculoskeletal infection in HIV carriers.
Over a three-year period, the authors prospectively implemented a protocol for management of musculoskeletal sepsis (MSS) in HIV carriers in Yaounde, Cameroon. The diagnosis of MSS was based on conventional criteria. HIV carriage was screened by an ELISA test and confirmed with the Western Blot technique. The immune status was based on CD4 lymphocyte count by flow cytometry; patients were classified as non-immunodepressed (NID), mildly immunodepressed (MID), or severely immunodepressed (SID) based on their CD4 lymphocyte count, as the latter was respectively over 500, between 200 and 500 or less than 200 per ml. Infection was treated by surgical debridement followed by a long-course targeted antibiotic therapy. All SID patients and some MID patients with AIDS-related symptoms also had standard antiretroviral (ARV) therapy. Thirty-one of 294 patients seen with musculoskeletal sepsis during the study period and tested for HIV were found to be HIV carriers. Their mean age was 33 years; the male/female ratio was 1.58. The following clinical pictures were observed: chronic osteomyelitis (COM) in 32.3% of the cases, septic arthritis (SA) in 38.7%, soft tissue infection (STI) in 25.8%; the last case was a severe leg complication of Buruli Ulcer (BU). Among these 31 patients, 38.7% were classified as SID (5 COM, 4 SA, 2 STI and the BU patient), 25.8% as MID (2 COM, 4 SA, 2 STI) and 35.5% as NID (3 COM, 6 SA, 2 STI). The organisms involved were not specific. Fifteen patients were managed conventionally, while the other 16 had the usual treatment associated with ARV therapy. The immediate outcome of MSS was good in 29 patients, after a mean hospital stay of five weeks; in two cases of septic arthritis of the knee, a second debridement was needed, due to persistent drainage, and the sinuses all closed. Three months after discharge, one patient with COM of the humerus developed a low-flow fistula which was closed after a revision sequestrectomy. After one year, none of the patients complained of any symptom suggesting reactivation of their MSS. There is no evidence that HIV carriage is in itself a high risk factor for musculoskeletal sepsis; the incidence of HIV carriage was indeed virtually similar in the 294 patients with MSS and in the general population, i.e. around 10%. However, in order to improve the outcome following musculoskeletal infections in patients with HIV, their management should take into account their immune status, based on a CD4 lymphocyte count. NID patients should be treated as any other patients with MSS, while SID should have additional standard ARV treatment. For those who are MID, the indication for antiretroviral therapy should depend on the presence of one or more AIDS-related signs.
Recurrent extraintestinal clostridium difficile infection.
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