The timing and location of the establishment of the viral reservoir during acute HIV infection remain unclear. Using longitudinal blood and tissue samples obtained from HIV-infected individuals at the earliest stage of infection, we demonstrate that frequencies of infected cells reach maximal values in gut-associated lymphoid tissue and lymph nodes as early as Fiebig stage II, before seroconversion. Both tissues displayed higher frequencies of infected cells than blood until Fiebig stage III, after which infected cells were equally distributed in all compartments examined. Initiation of antiretroviral therapy (ART) at Fiebig stages I to III led to a profound decrease in the frequency of infected cells to nearly undetectable level in all compartments. The rare infected cells that persisted were preferentially found in the lymphoid tissues. Initiation of ART at later stages (Fiebig stages IV/V and chronic infection) induced only a modest reduction in the frequency of infected cells. Quantification of HIV DNA in memory CD4+ T cell subsets confirmed the unstable nature of most of the infected cells at Fiebig stages I to III and the emergence of persistently infected cells during the transition to Fiebig stage IV. Our results indicate that although a large pool of cells is infected during acute HIV infection, most of these early targets are rapidly cleared upon ART initiation. Therefore, infected cells present after peak viremia have a greater ability to persist.
The aim of this study was to evaluate the effect of silk sericin, a protein from silkworm cocoon, on scratch wound healing in vitro. For applicable result in clinical use, we also study the efficacy of sericin added to a standard antimicrobial cream, silver zinc sulfadiazine, for open wound care in the treatment of second-degree burn wounds. In vitro scratch assays show that sericin at concentration 100 μg/mL can promote the migration of fibroblast L929 cells similar to epidermal growth factor (positive control) at 100 μg/mL. After 1 day of treatment, the length of scratch in wounds treated with sericin was significantly shorter than the length of negative control wounds (culture medium without sericin). For clinical study, a total of 29 patients with 65 burn wounds which covered no less than 15 % of total body surface area were randomly assigned to either control (wounds treated with silver zinc sulfadiazine cream) or treatment (wounds treated with silver zinc sulfadiazine with added sericin cream) group in this randomized, double-blind, standard-controlled study. The results showed that the average time to reach 70 % re-epithelialization of the burned surface and complete healing in the treatment group was significantly shorter, approximately 5-7 days, than in the control group. Regarding time for complete healing, control wounds took approximately 29.28 ± 9.27 days, while wounds treated with silver zinc sulfadiazine with added sericin cream took approximately 22.42 ± 6.33 days, (p = 0.001). No infection or severe reaction was found in any wounds. This is the first clinical study to show that silk sericin is safe and beneficial for burn wound treatment when it is added to silver sulfadiazine cream.
The aim of this study was to investigate safety and impact of temporary external lumbar drainage for continuous release of cerebrospinal fluid among patients with HIV-associated cryptococcal meningitis and elevated intracranial pressure (ICP). We conducted a retrospective cohort study among patients with cryptococcal meningitis in whom temporary external lumbar drains were placed to reduce intractable elevated ICP between January 2002 and December 2005. Patients were followed for three months after the procedure. Among 601 HIV-infected patients with cryptococcal meningitis, 54 (8.9%) underwent lumbar drain placement. Of these patients, mean age was 33 years and 80% were males. The median duration of an indwelling lumbar drain was seven days. There were 61 placement procedures among 54 patients, totalling to 473 device-days of observation. Overall incidence of secondary bacterial infections was 6.3 per 1000 device-days, and three (4.9%) of 61 catheters became secondarily infected with nosocomially acquired bacteria. All three drains were removed and appropriate antibiotics were given. There was no difference in median duration of placement between infected and uninfected drains (six days vs. seven days, P=0.572). The overall mortality rate was 5.6% in this cohort of 54 patients. In conclusion, the incidence of nosocomial infection of external lumbar drains is low. In resource-limited settings, the use of temporary external lumbar drainage is a safe and effective management strategy for intractable elevated ICP in HIV-infected patients with cryptococcal meningitis.
The objective of the study was to determine cumulative incidence and risk factors of nevirapine (NVP)-associated rashes that lead to NVP discontinuation among HIV-infected patients with CD4 <250 cells/microL. A retrospective cohort study was conducted among antiretroviral-naïve HIV-infected patients who had baseline CD4 <250 cells/microL and were initiated NVP-based antiretroviral therapy (ART) between January 2003 and October 2005. There were 910 patients with a mean age of 35.4 years and 43% were women. Median CD4 cell count was 27 cells/microL and median HIV RNA was 5.5 log copies/mL. Cumulative incidences of rashes at 0.5, 1, 2, 3 and 6 months after ART were 3.7%, 6.2%, 8.1%, 8.5% and 8.5%, respectively. By Kaplan-Meier analysis, the higher baseline CD4 cell counts had a higher probability of NVP-associated rashes (log-rank test, P=0.041). By Cox regression analysis, higher baseline CD4 cell count was associated with a higher incidence of rashes (hazard ratio=1.244, 95% confidence interval=1.045-1.482, for every 50 cells/microL increment of baseline CD4 stratum). In conclusion, NVP-associated skin rashes that lead to NVP discontinuation are common among HIV-infected patients with baseline CD4 <250 cells/microL. Despite the low baseline in this population, the higher number of baseline CD4 cells is continuously associated with a higher risk for skin rashes.
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