Current Issue : January - March Volume : 2014 Issue Number : 1 Articles : 7 Articles
Background: Chemokines can block viral entry by interfering with HIV co-receptors and are recognised mediators\r\nof atherosclerosis development. A number of experimental drugs that inhibit HIV entry arrest the development of\r\natherosclerosis in animal models. We hypothesised that the expression of chemokine receptors in circulating\r\nleukocytes is associated with the rate of atherosclerosis progression in HIV-infected patients.\r\nMethods: The increase in intima-media thickness during a 2-year follow-up was used to classify HIV-infected\r\npatients (n = 178) as progressors (n = 142) or non-progressors (n = 36) with respect to atherosclerosis. Logistic\r\nregression was used to assess variables associated with atherosclerosis progression. Mutations in the CCR5?32,\r\nCCR2 64I, and CX3CR1 (T280M and V249I) co-receptors as well as the levels of CCR5, CXCR4, CX3CR1, and CCR2\r\nmRNA expression in circulating leukocytes were analysed as independent variables.\r\nResults: Among the baseline variables, only genetic variants explained the dichotomous outcome. The expression\r\nof CCR2 and CXCR4 did not discriminate between progressors and non-progressors. Conversely, CCR5 and CX3CR1\r\nexpression was higher in not only progressors but also patients with detectable viral load. The logistic regression,\r\nhowever, demonstrated a significant role for CCR5 expression as a predictor of atherosclerosis progression\r\n(B = 2.1, OR = 8.1, p = 0.04) and a negligible effect for CXC3R1 and CCR2 expression.\r\nConclusions: Available CCR5 antagonists should be investigated for their potential to delay the course of\r\natherosclerosis in HIV-infected patients....
Background: Antiretroviral therapy (ART) roll-out is fraught with challenges, many with serious repercussions. We\r\nexplored and described patient behaviour-related challenges from the perspective of health care providers from\r\nnon-governmental organisations involved in ART programmes in KwaZulu-Natal, South Africa.\r\nMethods: A descriptive case study design using qualitative approach was applied during this study. Data was\r\ncollected from nine key informants from the three biggest NGOs involved in ART roll-out using in-depth semistructured\r\ninterviews. Transcribing and coding for emergent themes was done by two independent reviewers.\r\nEthical approval for the study was granted by the UNISA research ethics committee of The Faculty of Health\r\nSciences. Written consent was obtained from directors of the three NGOs involved and individual audio taped\r\ninformed consent was obtained from all study participants prior to data collection.\r\nResults: Findings revealed six broad areas of patient behaviour challenges. These were patient behaviour related to\r\nsocio-economic situation of patient (skipping of medication due to lack of food, or due to lack of transport fees),\r\nbelief systems (traditional and religious), stigma (non- disclosure), sexual practices (non-acceptability of condoms,\r\nteenage pregnancies), escapism (drug and alcohol abuse) and opportunism (skipping medication in order to access\r\ndisability grant, teenage pregnancies in order to access child grant).\r\nConclusion: New programmes need to address patient behaviour as a complex phenomenon requiring a multipronged\r\napproach that also addresses social norms and institutions. In the face of continued ART scale up, this is\r\nfurther evidence for the need for multi-sectoral collaboration to ensure successful and sustainable ART roll-out....
Background: Tuberculosis (TB) disease affects survival among HIV co-infected patients on antiretroviral therapy\r\n(ART). Yet, the magnitude of TB disease on mortality is poorly understood.\r\nMethods: Using a prospective cohort of 22,477 adult patients who initiated ART between August 2000 and June\r\n2009 in Uganda, we assessed the effect of active pulmonary TB disease at the initiation of ART on all-cause\r\nmortality using a Cox proportional hazards model. Propensity score (PS) matching was used to control for potential\r\nconfounding. Stratification and covariate adjustment for PS and not PS-based multivariable Cox models were also\r\nperformed.\r\nResults: A total of 1,609 (7.52%) patients had active pulmonary TB at the start of ART. TB patients had higher\r\nproportions of being male, suffering from AIDS-defining illnesses, having World Health Organization (WHO) disease\r\nstage III or IV, and having lower CD4 cell counts at baseline (p < 0.001). The percentages of death during follow-up\r\nwere 10.47% and 6.38% for patients with and without TB, respectively. The hazard ratio (HR) for mortality\r\ncomparing TB to non-TB patients using 1,686 PS-matched pairs was 1.37 (95% confidence interval [CI]: 1.08 ââ?¬â?? 1.75),\r\nless marked than the crude estimate (HR = 1.74, 95% CI: 1.49 ââ?¬â?? 2.04). The other PS-based methods and not PS-based\r\nmultivariable Cox model produced similar results.\r\nConclusions: After controlling for important confounding variables, HIV patients who had TB at the initiation of\r\nART in Uganda had an approximate 37% increased hazard of overall mortality relative to non-TB patients....
Background: Increasing rates of non-AIDS defining illnesses, and in particular liver diseases, have been found after\r\nthe initiation of highly active antiretroviral therapy. However, there is little evidence concerning the risk factors for\r\nand clinical characteristics of liver disease in antiretroviral (ARV)-treated HIV infection, in the absence of hepatitis B\r\nor C viral co-infection.\r\nMethods: A nested caseââ?¬â??control study of HIV infected volunteers, matched by starting date of anti-retroviral\r\ntreatment, was conducted in a Thai cohort studied from Nov 2002 - July 2012. Cases were defined as those\r\nsubjects with an elevated alanine aminotransferase (ALT = 40 IU/L) at two consecutive visits six months apart, while\r\ncontrols were defined as individuals who never demonstrated two consecutive elevated ALT results and had a\r\nnormal ALT result (< 40 IU/L) at their last visit. Both groups had normal ALT levels prior to ARV initiation. Clinical\r\ndemographics and risk factors for chronic hepatitis including HIV-related illness, ARV treatment and metabolic\r\ndiseases were collected and analyzed. Conditional logistic regression was used to determine risk factors for chronic\r\nhepatitis in HIV infection.\r\nResults: A total of 124 matched pairs with HIV infection were followed over 3,195 person-years. The mean age\r\n(Ã?±SD) was 33.0 Ã?± 7.3 years, with 41.1% of subjects being male. The incidence of chronic hepatitis was 5.4 per 100\r\nperson-years. The median time from initiation of ARV to chronic hepatitis was 1.3 years (IQR, 0.5-3.5). From\r\nunivariate analysis; male sex, plasma HIV-1 RNA level > 5 log 10 copies/ml, metabolic syndrome at baseline visit, high\r\nBMI > 23 kg/m2, abnormal HDL cholesterol at time of ALT elevation and treatment experience with NNRTI plus\r\nboosted PI were selected (p value < 0.2) to the final model of multivariate analysis. Male sex had 3.1 times greater\r\nrisk of chronic hepatitis than the females by multivariate analysis (adjusted OR, 95% CI: 3.1, 1.5-6.3, p =0.002). High\r\nBMI = 23 kg/m2 was also associated with 2.4 times greater risk of chronic hepatitis (adjusted OR, 95% CI: 2.4, 1.2-4.8,\r\np = 0.01).\r\nConclusions: Chronic hepatitis in ARV-treated HIV-infected patients is common and may lead to a major health\r\ncare problem. Male sex and high BMI = 23 kg/m2 carry higher risks for developing chronic hepatitis in this study.\r\nTherefore, these patients should be closely monitored for long-term hepatotoxicity....
Background: Although the Centres for disease Control and Prevention (CDC) recommends empiric treatment for\r\nschistosomiasis and strongyloidiasis (prevalent but treatable parasitic infections) in some refugee groups it is unclear\r\nif these guidelines should be extended to non-refugee immigrants from endemic areas. We aimed to assess\r\nseroprevalence of, and risk factors for, positive schistosomiasis and strongyloides serology in HIV-infected patients\r\nfrom endemic areas attending a European Infectious Diseases clinic.\r\nMethods: In a prospective cohort study, HIV-infected patients from helminth endemic areas underwent clinical\r\nassessment and blood draw for schistosomiasis and strongyloides serology, routine haematology and inflammatory\r\nmarkers (ESR and CRP). Between-group differences were analyzed by Wilcoxin Signed Rank and Fisher�s t tests as\r\nappropriate.\r\nResults: Ninety HIV-infected patients (mean [standard deviation (SD)] age 34 [6] years, 29% male) were recruited\r\nfrom May 2008 to June 2009. Nine (10%) subjects tested positive for helminth infections. Seven tested positive for\r\nschistosomiasis (8%) while two tested positive for strongyloides (2%). Seropositive subjects were more likely to have\r\nhigher eosinophil counts (mean [SD]) (0.3 [0.3] vs. 0.15 [0.2] x103cells/cm, P = 0.021) with a trend towards lower\r\nCD4+ T-cell counts (mean [SD]) (280 [218] vs. 395 [217] cells/mm3, P = 0.08).\r\nConclusion: The high prevalence of helminth infections (10%) in asymptomatic HIV infected adults identified in this\r\nstudy supports routine screening of immigrants from helminth endemic areas or with exposure history...
Susac�s Syndrome (SS) is an autoimmune endotheliopathy of cerebral, retinal and cochlear arterioles. We report of\r\nan HIV-infected woman who developed a first SS episode following a spontaneous reduction of plasma viral load\r\nand several relapses six years later, following initiation of combined antiretroviral therapy (cART). Corticosteroids and\r\nintravenous immunoglobulins alone did not control the disease, which improved after combined treatment with\r\nacyclovir and ganciclovir. SS onset in HIV infection and relapses during cART-induced immune reconstitution are\r\nconsistent with the dysimmune nature of the disease. The response to anti-herpes drugs suggests a viral contribute\r\nin this case of SS....
Background: HIV/TB coinfection remains a major challenge even after the initiation of HAART. Little is known\r\nabout Mycobacterium tuberculosis (Mtb) specific immune restoration in relation to immunologic and virologic\r\noutcomes after long-term HAART during co-infections with latent and active TB.\r\nMethods: A total of 232 adults, including 59 HIV patients with clinical TB (HIV TB), 125 HIV patients without\r\nclinical TB (HIV TB-), 13 HIV negative active TB patients (HIV-TB), and 10 HIV negative Tuberculin Skin TST positive\r\n(HIV-TST), and 25 HIV-TST- individuals were recruited. HAART was initiated in 113 HIV patients (28 TB and\r\n85 TB-), and anti-TB treatment for all TB cases. CD4 T-cell count, HIV RNA load, and IFN-? responses to ESAT-6/\r\nCFP-10 were measured at baseline, 6 months (M6), 18 months (M18) and 24 months (M24) after HAART initiation.\r\nResults: The majority of HIV TB- (70%, 81%, 84%) as well as HIV TB patients (60%, 77%, 80%) had virologic\r\nsuccess (HIV RNA < 50 copies/ml) by M6, M18 and M24, respectively. HAART also significantly increased CD4 T-cell\r\ncounts at 2 years in HIV TB (from 110.3 to 289.9 cells/�µl), HIV TB- patients (197.8 to 332.3 cells/�µl), HIV TST-\r\n(199 to 347 cells/�µl) and HIV TST individuals (195 to 319 cells/�µl). Overall, there was no significant difference in\r\nthe percentage of patients that achieved virologic success and in total CD4 counts increased between HIV\r\npatients with and without TB or LTBI. The Mtb specific IFN-? response at baseline was significantly lower in HIV TB\r\n (3.6 pg/ml) compared to HIV-TB patients (34.4 pg/ml) and HIV TST (46.3 pg/ml) individuals; and in HIV-TB \r\npatients compared to HIV-TST individuals (491.2 pg/ml). By M18 on HAART, the IFN-? response remained impaired\r\nin HIV TB patients (18.1 pg/ml) while it normalized in HIV TST individuals (from 46.3 to 414.2 pg/ml).\r\nConclusions: Our data show that clinical and latent TB infections do not influence virologic and immunologic\r\noutcomes of ART in HIV patients. Despite this, HAART was unable to restore optimal TB responsiveness as measured\r\nby Mtb specific IFN-? response in HIV/TB patients. Improvement of Mtb-specific immune restoration should be the\r\nfocus of future therapeutic strategies...
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