Current Issue : July - September Volume : 2012 Issue Number : 3 Articles : 7 Articles
Background: We investigated the impact of antimicrobials in cervicovaginal lavage (CVL) from HIV(+) and HIV(2) women on\r\ntarget cell infection with HIV. Since female reproductive tract (FRT) secretions contain a spectrum of antimicrobials, we\r\nhypothesized that CVL from healthy HIV(+) and (2) women inhibit HIV infection.\r\nMethodology/Principal Findings: CVL from 32 HIV(+) healthy women with high CD4 counts and 15 healthy HIV(2) women\r\nwere collected by gently washing the cervicovaginal area with 10 ml of sterile normal saline. Following centrifugation, anti-\r\nHIV activity in CVL was determined by incubating CVL with HIV prior to addition to TZM-bl cells. Antimicrobials and antigp160\r\nHIV IgG antibodies were measured by ELISA. When CXCR4 and CCR5 tropic HIV-1 were incubated with CVL from\r\nHIV(+) women prior to addition to TZM-bl cells, anti-HIV activity in CVL ranged from none to 100% inhibition depending on\r\nthe viral strains used. CVL from HIV(2) controls showed comparable anti-HIV activity. Analysis of CH077.c (clone of an R5-\r\ntropic, mucosally-transmitted founder virus) viral inhibition by CVL was comparable to laboratory strains. Measurement of\r\nCVL for antimicrobials HBD2, trappin-2/elafin, SLPI and MIP3a indicated that each was present in CVL from HIV(+) and\r\nHIV(2) women. HBD2 and MIP3a correlated with anti-HIV activity as did anti-gp160 HIV IgG antibodies in CVL from HIV(+)\r\nwomen.\r\nConclusions/Significance: These findings indicate that CVL from healthy HIV(+) and HIV(2) women contain innate and\r\nadaptive defense mechanisms that inhibit HIV infection. Our data suggest that innate endogenous antimicrobials and HIVspecific\r\nIgG in the FRT can act in concert to contribute toward the anti-HIV activity of the CVL and may play a role in\r\ninhibition of HIV transmission to women....
Background: There are limited data of immunologic and virologic failure in Asian HIV-infected children using nonnucleoside\r\nreverse transcriptase inhibitor (NNRTI)-based highly active antiretroviral therapy (HAART). We examined\r\nthe incidence rate of immunologic failure (IF) and virologic failure (VF) and the accuracy of using IF to predict VF in\r\nThai HIV-infected children using first-line NNRTI-based HAART.\r\nMethods: Antiretroviral (ART)-na�¯ve HIV-infected children from 2 prospective cohorts treated with NNRTI-based\r\nHAART during 2001-2008 were included. CD4 counts were performed every 12 weeks and plasma HIV-RNA\r\nmeasured every 24 weeks. Immune recovery was defined as CD4%=25%. IF was defined as persistent decline of\r\n=5% in CD4% in children with CD4%<15% at baseline or decrease in CD4 count =30% from baseline. VF was\r\ndefined as HIV-RNA>1,000 copies/ml after at least 24 weeks of HAART. Clinical and laboratory parameter changes\r\nwere assessed using a paired t-test, and a time to event approach was used to assess predictors of VF. Sensitivity\r\nand specificity of IF were calculated against VF.\r\nResults: 107 ART-naive HIV-infected children were included, 52% female, % CDC clinical classification N:A:B:C\r\n4:44:30:22%. Baseline data were median (IQR) age 6.2 (4.2-8.9) years, CD4% 7 (3-15), HIV-RNA 5.0 (4.9-5.5)\r\nlog10copies/ml. Nevirapine (NVP) and efavirenz (EFV)-based HAART were started in 70% and 30%, respectively.\r\nAt 96 weeks, none had progressed to a CDC clinical classification of AIDS and one had died from pneumonia.\r\nOverall, significant improvement of weight for age z-score (p = 0.014), height for age z-score, hemoglobin, and\r\nCD4 were seen (all p < 0.001). The median (IQR) CD4% at 96 weeks was 25 (18-30)%. Eighty-nine percent of\r\nchildren had immune recovery (CD4%=25%) and 75% of children had HIV-RNA <1.7log10copies/ml.\r\nThirty five (32.7%) children experienced VF within 96 weeks. Of these, 24 (68.6%) and 31 (88.6%) children had VF in\r\nthe first 24 and 48 weeks respectively.\r\nOnly 1 (0.9%) child experienced IF within 96 weeks and the sensitivity (95%CI) of IF to VF was 4 (0.1-20.4)% and\r\nspecificity was 100 (93.9-100)%.\r\nConclusion: Immunologic failure, as defined here, had low sensitivity compared to VF and should not be\r\nrecommended to detect treatment failure. Plasma HIV-RNA should be performed twice, at weeks 24 and 48, to\r\ndetect early treatment failure....
Background: The use of combination antiretroviral therapy (cART) has become a standard of care for the\r\ntreatment of HIV infection. However, cost and resistance to cART are major obstacles for access to treatment\r\nespecially in resource-limited settings. In this study, we aimed to determine the incidence and risk factors of\r\ntreatment failure in a cohort of treatment-na�¯ve Thai HIV-infected patients.\r\nMethods: A retrospective cohort study was conducted among HIV-infected patients initiating their first cART at\r\nChiang Mai University Hospital, Thailand.\r\nResults: From January 2002 to December 2008, 788 patients were enrolled; 365 were male (46.3%), and the mean\r\nage was 37.9 �± 8.6 years. The median baseline CD4 count was 57.7 cells/mm3 (IQR 22, 127). GPO-VIR�® (a fixed-dose\r\ncombination of lamivudine, stavudine, and nevirapine) was the most common prescribed cART (657 patients,\r\n83.4%). Seventy-six patients developed virological failure given the cumulative incidence of 9.6%. The incidence of\r\nvirological failure was 2.79 (95% CI 2.47, 3.14) cases per 100 person years. Poor adherence was the strongest\r\npredictor for virological failure. Of 535 immunologically evaluable patients, 179 (33.5%) patients developed\r\nimmunological failure. A low CD4 cell count at baseline (< 100 cells/mm3) and the increment of CD4 cell count of\r\n< 50 cell/mm3 after 6 months of cART were the predictors for immunological failure (p < 0.001).\r\nConclusions: This study demonstrated that even in resource-limited settings, the high rate of success could be\r\nexpected in the cohort with good and sustainable drug adherence. Poor adherence, older age, and low baseline\r\nCD4 cell count are the predictors for unfavorable outcome of cART....
Human immunodeficiency virus/acquired immune deficiency syndrome (HIV/AIDS) is the most\r\ndevastating disease that mankind has ever faced. For being neighboring country of India, Bangladesh\r\nhas been highly vulnerable to HIV infection. Though Bangladesh continues to maintain low HIV\r\nprevalence status, however the infection rate is on the rise at Rajshahi Division. Some studies have\r\nbeen carried out on the knowledge about HIV/AIDS among some risk groups, but studies on blood\r\ndonor�s awareness about HIV/AIDS are rarely found. This study aims at investigating the knowledge\r\nand awareness about HIV/AIDS among the blood donors at Rajshahi Metropolitan of Bangladesh. In this\r\nstudy, primary data was used. Data reveals that, though about 89% blood donors knew it is transmitted\r\nthrough blood transfusion, only 1% of them had undertaken blood test before donation, which is\r\nalarming. The odds of having preliminary and preventive knowledge fell with the increase in age of the\r\nrespondents. Besides these, blood donors who were educated and who were in service were found\r\nmore aware about the HIV/AIDS than the others. Strict rules and regulations should be maintained\r\nregarding blood screening. Overall people should be encouraged to use condoms and abide by the\r\nreligious rules to avoid HIV/AIDS infection. Both, Government and Non-Government organizations\r\nshould augment their educational and focused group discussion (FGD) programs on HIV/AIDS\r\nknowledge....
Plasmacytoid dendritic cells (pDC) provide an important link between innate and acquired immunity, mediating their action\nmainly through IFN-a production. pDC suppress HIV-1 replication, but there is increasing evidence suggesting they may also\ncontribute to the increased levels of cell apoptosis and pan-immune activation associated with disease progression. Although\nhaving the same clinical spectrum, HIV-2 infection is characterized by a strikingly lower viremia and a much slower rate of CD4\ndecline and AIDS progression than HIV-1, irrespective of disease stage. We report here a similar marked reduction in circulating\npDC levels in untreated HIV-1 and HIV-2 infections in association with CD4 depletion and T cell activation, in spite of the\nundetectable viremia found in the majority of HIV-2 patients. Moreover, the same overexpression of CD86 and PD-L1 on\ncirculating pDC was found in both infections irrespective of disease stage or viremia status. Our observation that pDC\ndepletion occurs in HIV-2 infected patients with undetectable viremia indicates that mechanisms other than direct viral\ninfection determine the pDC depletion during persistent infections. However, viremia was associated with an impairment of\nIFN-a production on a per pDC basis upon TLR9 stimulation. These data support the possibility that diminished function in\nvitro may relate to prior activation by HIV virions in vivo, in agreement with our finding of higher expression levels of the IFN-a\ninducible gene, MxA, in HIV-1 than in HIV-2 individuals. Importantly, serum IFN-a levels were not elevated in HIV-2 infected\nindividuals. In conclusion, our data in this unique natural model of ââ?¬Ë?ââ?¬Ë?attenuatedââ?¬â?¢Ã¢â?¬â?¢ HIV immunodeficiency contribute to the\nunderstanding of pDC biology in HIV/AIDS pathogenesis, showing that in the absence of detectable viremia a major depletion\nof circulating pDC in association with a relatively preserved IFN-a production does occur....
sub-Saharan Africa, but it is unclear how mortality compares to the non-HIVââ?¬â??infected population. We compared mortality\r\nrates observed in HIV-1ââ?¬â??infected patients starting ART with non-HIVââ?¬â??related background mortality in four countries in sub-\r\nSaharan Africa.\r\nMethods and Findings: Patients enrolled in antiretroviral treatment programmes in CoÃ?â? te dââ?¬â?¢Ivoire, Malawi, South Africa, and\r\nZimbabwe were included. We calculated excess mortality rates and standardised mortality ratios (SMRs) with 95%\r\nconfidence intervals (CIs). Expected numbers of deaths were obtained using estimates of age-, sex-, and country-specific,\r\nHIV-unrelated, mortality rates from the Global Burden of Disease project. Among 13,249 eligible patients 1,177 deaths were\r\nrecorded during 14,695 person-years of follow-up. The median age was 34 y, 8,831 (67%) patients were female, and 10,811\r\nof 12,720 patients (85%) with information on clinical stage had advanced disease when starting ART. The excess mortality\r\nrate was 17.5 (95% CI 14.5ââ?¬â??21.1) per 100 person-years SMR in patients who started ART with a CD4 cell count of less than 25\r\ncells/ml and World Health Organization (WHO) stage III/IV, compared to 1.00 (0.55ââ?¬â??1.81) per 100 person-years in patients\r\nwho started with 200 cells/ml or above with WHO stage I/II. The corresponding SMRs were 47.1 (39.1ââ?¬â??56.6) and 3.44 (1.91ââ?¬â??\r\n6.17). Among patients who started ART with 200 cells/ml or above in WHO stage I/II and survived the first year of ART, the\r\nexcess mortality rate was 0.27 (0.08ââ?¬â??0.94) per 100 person-years and the SMR was 1.14 (0.47ââ?¬â??2.77).\r\nConclusions: Mortality of HIV-infected patients treated with combination ART in sub-Saharan Africa continues to be higher\r\nthan in the general population, but for some patients excess mortality is moderate and reaches that of the general\r\npopulation in the second year of ART. Much of the excess mortality might be prevented by timely initiation of ART....
Background\r\nThe objective of the study was to compare rates of adverse events (AEs) related to male\r\ncircumcision (MC) in HIV-positive and HIV-negative men in order to provide guidance for MC\r\nprograms that may provide services to HIV-infected and uninfected men.\r\nMethods and Findings\r\nA total of 2,326 HIV-negative and 420 HIV-positive men (World Health Organization [WHO]\r\nstage I or II and CD4 counts . 350 cells/mm3) were circumcised in two separate but\r\nprocedurally identical trials of MC for HIV and/or sexually transmitted infection prevention in\r\nrural Rakai, Uganda. Participants were followed at 1ââ?¬â??2 d and 5ââ?¬â??9 d, and at 4ââ?¬â??6 wk, to assess\r\nsurgery-related AEs, wound healing, and resumption of intercourse. AE risks and wound healing\r\nwere compared in HIV-positive and HIV-negative men. Adjusted odds ratios (AdjORs) were\r\nestimated by multiple logistic regression, adjusting for baseline characteristics and postoperative\r\nresumption of sex. At enrollment, HIV-positive men were older, more likely to be\r\nmarried, reported more sexual partners, less condom use, and higher rates of sexually\r\ntransmitted disease symptoms than HIV-negative men. Risks of moderate or severe AEs were\r\n3.1/100 and 3.5/100 in HIV-positive and HIV-negative participants, respectively (AdjOR 0.91,\r\n95% confidence interval [CI] 0.47ââ?¬â??1.74). Infections were the most common AEs (2.6/100 in HIVpositive\r\nversus 3.0/100 in HIV-negative men). Risks of other complications were similar in the\r\ntwo groups. The proportion with completed healing by 6 wk postsurgery was 92.7% in HIVpositive\r\nmen and 95.8% in HIV-negative men (pÃ?¼0.007). AEs were more common in men who\r\nresumed intercourse before wound healing compared to those who waited (AdjOR 1.56, 95% CI\r\n1.05ââ?¬â??2.33).\r\nConclusions\r\nOverall, the safety of MC was comparable in asymptomatic HIV-positive and HIV-negative\r\nmen, although healing was somewhat slower among the HIV infected. All men should be\r\nstrongly counseled to refrain from intercourse until full wound healing is achieved....
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