Last data update: May 13, 2024. (Total: 46773 publications since 2009)
Records 1-6 (of 6 Records) |
Query Trace: Mubiru A[original query] |
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Change in plasma CrAg titer is not associated with survival among HIV-infected persons receiving preemptive therapy for asymptomatic cryptococcal antigenemia
Pullen MF , Kakooza F , Nalintya E , Kiragga AN , Morawski BM , Rajasingham R , Mubiru A , Manabe YC , Kaplan JE , Meya DB , Boulware DR . Clin Infect Dis 2019 70 (2) 353-355 Current World Health Organization (WHO) guidelines recommend cryptococcal antigen (CrAg) screening in blood among those human immunodeficiency virus (HIV)-infected persons not receiving effective antiretroviral therapy (ART), with CD4 values <100 cells/µL, and to consider testing those not on ART with CD4 values between 100–200 cells/µL [1]. This recommendation is based on prior studies demonstrating that a “screen-and-treat” program identifying CrAg-positive persons and giving preemptive fluconazole therapy, in combination with an ART adherence intervention, prevents invasive cryptococcal disease and death [2]. |
Reflexive laboratory-based cryptococcal antigen screening and preemptive fluconazole therapy for cryptococcal antigenemia in HIV-infected individuals with CD4 <100 cells/microL: a stepped-wedge, cluster-randomized trial
Meya DB , Kiragga AN , Nalintya E , Morawski BM , Rajasingham R , Park BJ , Mubiru A , Kaplan JE , Manabe YC , Boulware DR . J Acquir Immune Defic Syndr 2018 80 (2) 182-189 BACKGROUND: HIV-infected persons with cryptococcal antigenemia (CrAg) are at high risk for meningitis or death. We evaluated the effect of CrAg screening and pre-emptive fluconazole therapy, as an adjunct to antiretroviral therapy (ART), on six-month survival among persons with advanced HIV disease. METHODS: We enrolled HIV-infected, ART-naive eligible participants with <100 CD4 cells/microL, in a stepped-wedge, cluster-randomized trial from July 2012 - December 2014 at 17 Ugandan clinics. Clinics participated in a prospective observational phase, followed by an interventional phase with lab-based, reflexive CrAg screening of residual CD4 count plasma. Asymptomatic CrAg-positive participants received preemptive fluconazole therapy for ten weeks. We assessed six-month survival using Cox-regression, adjusting for nadir CD4, calendar time, and stepped-wedge steps. RESULTS: We included 1,280 observational and 2,108 interventional participants, of whom 9.3% (195/2,108) were CrAg-positive. CD4-, time-, and stepped-wedge-adjusted analyses demonstrated no difference in survival in the observational vs the interventional arms (HR = 1.34; 95% CI, 0.86-2.10; P = 0.20), including when the analysis was limited to persons who started ART (HR=1.11; 95% CI, 0.62 - 1.79, P=0.86) However, six-month mortality of participants with CrAg titers <1:160 and CrAg-negative patients did not differ. Patients with CrAg titers >/=1:160 had 2.6-fold higher six-month mortality than patients with titers <1:160. CONCLUSION: We observed no overall survival benefit of the lab-based reflexive CrAg screen-and-treat intervention. However, preemptive antifungal therapy for asymptomatic cryptococcosis appeared to be effective in patients with CrAg titer <1:160. A more aggressive approach may be required for persons with CrAg titer >/=1:160.This is an open access article distributed under the terms of the Creative Commons Attribution License 4.0 (CC BY), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
A cross-sectional study of the magnitude, barriers, and outcomes of HIV status disclosure among women participating in a perinatal HIV transmission study, "the Nevirapine Repeat Pregnancy study"
Kiweewa FM , Bakaki PM , McConnell MS , Musisi M , Namirembe C , Nakayiwa F , Kusasira F , Nakintu D , Mubiru MC , Musoke P , Fowler MG . BMC Public Health 2015 15 (1) 988 BACKGROUND: HIV status disclosure is a difficult emotional task for HIV-infected persons and may create the opportunity for both social support and rejection. In this study, we evaluated the proportions, patterns, barriers and outcomes of HIV- 1 status disclosure among a group of women in Uganda. METHODS: An exit interview was conducted one year post-partum for 85 HIV-infected women who participated in a study of HIV-1 transmission rates among NVP-experienced compared with NVP-naive women in "The Nevirapine Repeat Pregnancy (NVP-RP) Study" at the Makerere University-Johns Hopkins University Research Collaboration, Kampala-Uganda, between June 2004 and June 2006. RESULTS: Of the 85 women interviewed, 99 % had disclosed their HIV status to at least one other person. Disclosure proportions ranged between 1 % to employer(s) and 69 % to a relative other than a parent. Only 38 % of the women had disclosed to their sex partners. Women with an HIV-infected baby were more likely than those with an uninfected baby to disclose to their sex partner, OR 4.9 (95 % CI, 2.0 -11.2), and women were less likely to disclose to a partner if they had previously disclosed to another relative than if they had not, OR 0.19 (95 % CI, 0.14-0.52). The most common reasons for non-disclosure included fear of separation from the partner and subsequent loss of financial support 34 %, and not living with the partner (not having opportunities to disclose) 26 %. While most women (67 %) reported getting social support following disclosure, 22 % reported negative outcomes (neglect, separation from their partners, and loss of financial support). Following disclosure of HIV status, 9 % of women reported that their partner (s) decided to have an HIV test. CONCLUSION: Results from this study show high overall HIV disclosure proportions and how this disclosure of HIV status can foster social support. However, proportions of disclosure specifically to male sex partners were low, which suggests the need for interventions aimed at increasing male involvement in perinatal care, along with supportive counseling. |
Shifts in geographic distribution and antimicrobial resistance during a prolonged typhoid fever outbreak - Bundibugyo and Kasese Districts, Uganda, 2009-2011
Walters MS , Routh J , Mikoleit M , Kadivane S , Ouma C , Mubiru D , Mbusa B , Murangi A , Ejoku E , Rwantangle A , Kule U , Lule J , Garrett N , Halpin J , Maxwell N , Kagirita A , Mulabya F , Makumbi I , Freeman M , Joyce K , Hill V , Downing R , Mintz E . PLoS Negl Trop Dis 2014 8 (3) e2726 BACKGROUND: Salmonella enterica serovar Typhi is transmitted by fecally contaminated food and water and causes approximately 22 million typhoid fever infections worldwide each year. Most cases occur in developing countries, where approximately 4% of patients develop intestinal perforation (IP). In Kasese District, Uganda, a typhoid fever outbreak notable for a high IP rate began in 2008. We report that this outbreak continued through 2011, when it spread to the neighboring district of Bundibugyo. METHODOLOGY/PRINCIPAL FINDINGS: A suspected typhoid fever case was defined as IP or symptoms of fever, abdominal pain, and ≥1 of the following: gastrointestinal disruptions, body weakness, joint pain, headache, clinically suspected IP, or non-responsiveness to antimalarial medications. Cases were identified retrospectively via medical record reviews and prospectively through laboratory-enhanced case finding. Among Kasese residents, 709 cases were identified from August 1, 2009-December 31, 2011; of these, 149 were identified during the prospective period beginning November 1, 2011. Among Bundibugyo residents, 333 cases were identified from January 1-December 31, 2011, including 128 cases identified during the prospective period beginning October 28, 2011. IP was reported for 507 (82%) and 59 (20%) of Kasese and Bundibugyo cases, respectively. Blood and stool cultures performed for 154 patients during the prospective period yielded isolates from 24 (16%) patients. Three pulsed-field gel electrophoresis pattern combinations, including one observed in a Kasese isolate in 2009, were shared among Kasese and Bundibugyo isolates. Antimicrobial susceptibility was assessed for 18 isolates; among these 15 (83%) were multidrug-resistant (MDR), compared to 5% of 2009 isolates. CONCLUSIONS/SIGNIFICANCE: Molecular and epidemiological evidence suggest that during a prolonged outbreak, typhoid spread from Kasese to Bundibugyo. MDR strains became prevalent. Lasting interventions, such as typhoid vaccination and improvements in drinking water infrastructure, should be considered to minimize the risk of prolonged outbreaks in the future. |
Kinetics of nevirapine and its impact on HIV-1 RNA levels in maternal plasma and breast milk over time after perinatal single dose nevirapine
Aizire J , McConnell MS , Mudiope P , Mubiru M , Matovu F , Parsons TL , Elbireer A , Nolan M , Janoff EN , Fowler MG . J Acquir Immune Defic Syndr 2012 60 (5) 483-8 OBJECTIVE: To determine kinetics after single dose nevirapine (sdNVP) and the impact on HIV RNA (viral load: VL) in maternal plasma and breast milk (BM). METHODS: Cohort of 120 HIV-1 infected pregnant Ugandan women received perinatal sdNVP alone and followed with their infants through 24 weeks post-delivery.We assessed the relationship of nevirapine concentration (tandem mass-spectroscopy) and HIV-1 VL (Roche AMPLICOR HIV-1 Kit, v1.5) in maternal plasma and BM over time. RESULTS: At week 1 postpartum, NVP (≥10ng/ml) was detected in all 53 plasma and 47/51(92.2%) BM samples with median (interquartile ranges: IQR) of, respectively, 171(78-214) ng/ml and 112(64-158) ng/ml, p=0.075, which decreased subsequently with traces persisting through week 4 in plasma. Plasma and BM VL dropped by week 1 and were highly correlated at delivery: R=0.71, p<0.001 and week1: R=0.69, p<0.001 but not thereafter. At week 1, VL correlated inversely with NVP concentration in plasma: R=0.39, p=0.004 and BM: R=0.48, p=0.013. There was a VL rebound in both compartments which peaked at week 4 to levels greater than at week 1, (significantly in plasma (p<0.001) but not in BM) and remained stable thereafter. Median VL was consistently greater (11-50 fold) in plasma than BM at all time points (all p<0.001). CONCLUSION: After sdNVP, NVP concentration was comparably high through week 1, accompanied by suppression of plasma and BM VL. A longer "tail" (>1 week) of potent postnatal antiretroviral drugs is warranted to minimize the observed VL rebound and potential for NVP resistance as a result of persistent NVP traces. |
Emergence and persistence of nevirapine resistance in breast milk after single-dose nevirapine administration
Hudelson SE , McConnell MS , Bagenda D , Piwowar-Manning E , Parsons TL , Nolan ML , Bakaki PM , Thigpen MC , Mubiru M , Fowler MG , Eshleman SH . AIDS 2010 24 (4) 557-61 OBJECTIVE: Single-dose nevirapine (NVP) (sdNVP) can reduce the risk of HIV vertical transmission. We assessed risk factors for NVP resistance in plasma and breast milk from sdNVP-exposed Ugandan women. METHODS: Samples were analyzed using the Roche AMPLICOR HIV-1 Monitor Test Kit, version 1.5, and the ViroSeq HIV-1 Genotyping System. NVP concentrations were determined by liquid chromatography with tandem mass spectroscopy. RESULTS: HIV genotypes (plasma and breast milk) were obtained for 30 women 4 weeks after sdNVP (HIV subtypes: 15A, 1C, 12D, two recombinant). NVP resistance was detected in 12 (40%) of 30 breast milk samples. There was a nonsignificant trend between detection of NVP resistance in breast milk and plasma (P = 0.06). There was no association of HIV resistance in breast milk with median maternal pre-NVP viral load or CD4 cell count, median breast milk viral load at 4 weeks, breast milk sodium more than 10 mmol/l, HIV subtype, or concentration of NVP in breast milk or plasma. CONCLUSION: NVP resistance was frequently detected in breast milk 4 weeks after sdNVP exposure. In this study, we were unable to identify specific factors associated with breast milk NVP resistance. |
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