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The effects of highly active antiretroviral therapy(HAART) of stavudine lamivudine and nevirapine on the CD4 lymphocyte count of HIV- infected Africans. The Nigerians experience
O Erhabor, OA Ejele, CA Nwauche
Nigerian Journal of Clinical Practice , 2006,
Abstract: Objectives: The objective of this study was to investigate the short-term effect of highly active antiretroviral therapy on the CD4 lymphocyte count of HIV-infected Nigerians. Design: A case control study of 70 HIV-infected subjects placed on highly active antiretroviral therapy. Thirty HIV-infected yet to start therapy due to unaffordability were observed as controls. Setting: This study was carried out at the Hematology Department of the University of Port Harcourt Teaching Hospital – a 500 bed tertiary hospital and one of the designated antiretroviral therapy pilot centers. Methods: CD4 lymphocyte count was determined at baseline for subjects and controls. Subjects were placed on HAART for 12 weeks while controls that were yet to start therapy were monitored as controls. CD4 lymphocyte count was repeated after 12 weeks and the differences compared statistically. Results: We observed that subjects and control patients did not differ significantly in their CD4 lymphocyte count at baseline (p>0.05), but after 12 weeks HAART in subjects and untreated control there was a mean increase in CD4 count of (39 cells/μL) in subjects, while untreated controls showed a mean decline of (12 cells/μL) p< 0.05. There was a statistically significant variation in the therapy dependent increases in CD4 count of HAART treated subjects based on pre-therapeutic baseline CD4 count (χ2 = 180.39, p<0.05). The HAART dependent increase in CD4 counts was higher in younger subjects 19-28 years (3l cells/μL) compared to older subjects 49-58 years (21 cells/μL) (p = 0.01). Similarly CD4 response was found higher in females compared to males ( p = 0.0l). Conclusion: This study indicates the importance of accessing the CD4 lymphocyte count of HIV infected patients before the initiation of HAART, its use as a prognostic maker in predicting the initial response to HAART and in determining the optimal time to initiate therapy. .
Factors Predicting Discordant Virological and Immunological Responses to Antiretroviral Therapy in HIV-1 Clade C Infected Zulu/Xhosa in South Africa  [PDF]
Boris Julg, Danielle Poole, Musie Ghebremichael, Carmen Castilla, Marcus Altfeld, Henry Sunpath, Richard A. Murphy, Bruce D. Walker
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0031161
Abstract: Factors predicting suboptimal CD4 cell recovery have been studied in HIV clade-B infected US and European populations. It is, however, uncertain to what extent these results are applicable to HIV clade-C infected African populations. Multivariate analysis using logistic regression and longitudinal analyses using mixed models were employed to assess the impact of age, gender, baseline CD4 cell count, hemoglobin, body mass index (BMI), tuberculosis and other opportunistic co-infections, and frequencies of regimen change on CD4 cell recovery at 12 and 30 months and on overtime change in CD4 cells among 442 virologically suppressed South Africans. Despite adequate virological response 37% (95% CI:32%–42%) and 83% (95% CI:79%–86%) of patients on antiretroviral therapy failed to restore CD4 cell counts ≥200 cells/mm3 after 12 and ≥500 cells/mm3 after 30 months, respectively, in this South African cohort. Critical risk factors for inadequate recovery were older age (p = 0.001) and nadir CD4 cell count at ART initiation (p<0.0001), while concurrent TB co-infection, BMI, baseline hemoglobin, gender and antiretroviral regimen were not significant risk factors. These data suggest that greater efforts are needed to identify and treat HAART-eligible patients prior to severe CD4 cell decline or achievement of advanced age.
Effect of Nadir CD4+ T Cell Count on Clinical Measures of Periodontal Disease in HIV+ Adults before and during Immune Reconstitution on HAART  [PDF]
Lance T. Vernon, Catherine A. Demko, Denise C. Babineau, Xuelei Wang, Zahra Toossi, Aaron Weinberg, Benigno Rodriguez
PLOS ONE , 2013, DOI: 10.1371/journal.pone.0076986
Abstract: Background The contribution of HIV-infection to periodontal disease (PD) is poorly understood. ?We proposed that immunological markers would be associated with improved clinical measures of PD. Methods We performed a longitudinal cohort study of HIV-infected adults who had started highly active antiretroviral therapy (HAART) <2 years. PD was characterized clinically as the percent of teeth with ≥1 site with periodontal probing depth (PPD) ≥5.0mm, recession (REC) >0mm, clinical attachment level (CAL) ≥4.0mm, and bleeding on probing (BOP) at ≥4 sites/tooth and microbiologically as specific periodontopathogen concentration. Linear mixed-effects models were used to assess the associations between immune function and PD. Results Forty (40) subjects with median 2.7 months on HAART and median nadir CD4+ T-cell count of 212 cells/μl completed a median 3 visits. Over 24 months, CD4+ T-cell count increased by a mean 173 cells/μl (p<0.001) and HIV RNA decreased by 0.5 log10 copies/ml (p<0.001); concurrently, PPD, CAL and BOP decreased by a mean 11.7%, 12.1%, and 14.7% respectively (all p<0.001). Lower nadir CD4+ T-cell count was associated with worse baseline REC (-6.72%; p=0.04) and CAL (9.06%; p<0.001). Further, lower nadir CD4+ T-cell count was associated with a greater relative longitudinal improvement in PPD in subjects with higher baseline levels of Porphyromonas gingivalis (p=0.027), and BOP in subjects with higher baseline levels of Porphyromonas gingivalis or Treponema denticola (p=0.001 and p=0.006 respectively). Longitudinal changes from baseline in CD4+ T-cell count and level of HIV RNA were not independently associated with longitudinal changes in any clinical markers of PD. Conclusion Degree of immunosuppression was associated with baseline gingival recession. After HAART initiation, measures of active PD improved most in those with lower nadir CD4+ T-cell counts and higher baseline levels of specific periodontopathogens. Nadir CD4+ T-cell count differentially influences periodontal disease both before and after HAART in HIV-infected adults.
Predictive value of CD4 cell count nadir on long-term mortality in HIV-positive patients in Uganda
Bray S, Gedeon J, Hadi A, Kotb A, Rahman T, Sarwar E, Savelyeva A, Sévigny M, Bakanda C, Birungi J, Chan K, Yaya S, Deonandan R, Mills EJ
HIV/AIDS - Research and Palliative Care , 2012, DOI: http://dx.doi.org/10.2147/HIV.S35374
Abstract: edictive value of CD4 cell count nadir on long-term mortality in HIV-positive patients in Uganda Original Research (3258) Total Article Views Authors: Bray S, Gedeon J, Hadi A, Kotb A, Rahman T, Sarwar E, Savelyeva A, Sévigny M, Bakanda C, Birungi J, Chan K, Yaya S, Deonandan R, Mills EJ Published Date August 2012 Volume 2012:4 Pages 135 - 140 DOI: http://dx.doi.org/10.2147/HIV.S35374 Received: 26 June 2012 Accepted: 12 July 2012 Published: 17 August 2012 Sarah Bray,1 Jillian Gedeon,1 Ahsan Hadi,1 Ahmed Kotb, Tarun Rahman,1 Elaha Sarwar,1 Anna Savelyeva,1 Marika Sévigny,1 Celestin Bakanda,2 Josephine Birungi,2 Keith Chan,3 Sanni Yaya,1 Raywat Deonandan,1 Edward J Mills1,2 1Interdisciplinary School of Health Sciences, Faculty of Health Sciences, University of Ottawa, Ottawa, Canada; 2The AIDS Support Organization (TASO), Headquarters, Kampala, Uganda; 3British Columbia Centre for Excellence in HIV/AIDS, Vancouver, British Columbia, Canada Objective: Although international guidelines recommend initiating antiretroviral therapy (ART) when a patient’s CD4 cell count is ≤350 cells/μL, most patients in resource-limited settings present with much lower CD4 cell counts. The lowest level that their CD4 cell count reaches, the nadir, may have long-term consequences in terms of mortality. We examined this health state in a large cohort of HIV+ patients in Uganda. Design: This was an observational study of HIV patients in Uganda aged 14 years or older, who were enrolled in 10 major clinics across Uganda. Methods: We assessed the CD4 nadir of patients, using their CD4 cell count at initiation of ART, stratified into categories (<50, 50–99, 100–149, 150–249, 250+ cells/μL). We constructed Kaplan–Meier curves to assess the differences in survivorship for patients left-censored at 1 year and 2 years after treatment initiation. We used Cox proportional hazards regression to model the associations between CD4 nadir and mortality. We adjusted mortality for loss-to-follow-up. Results: Of 22,315 patients, 20,129 patients had greater than 1 year of treatment follow-up. Among these patients, 327 (1.6%) died and 444 (2.2%) were lost to follow-up. After left-censoring at one year, relative to lowest CD4 strata, patients with higher CD4 counts had significantly lower rates of mortality (CD4 150–249, hazard ratio [HR] 0.60, 95% confidence interval [CI]: 0.45–0.82, P = 0.001; 250+, HR 0.66, 95% CI, 0.44–1.00, P = 0.05). Male sex, older age, and duration of time on ART were independently associated with mortality. When left-censoring at 2 years, CD4 nadir was no longer statistically significantly associated with mortality. Conclusion: After surviving for 1 year on ART, a CD4 nadir was strongly predictive of longer-term mortality among patients in Uganda. This should argue for efforts to increase engagement with patients to ensure a higher CD4 nadir at initiation of treatment.
Immunological predictors of CD4+ T cell decline in antiretroviral treatment interruptions
Elena Seoane, Salvador Resino, Santiago Moreno, Juan de Quiros, Ana Moreno, Rafael Rubio, Juan Gonzalez-García, José Arribas, Federico Pulido, Ma ángeles Mu?oz-Fernández
BMC Infectious Diseases , 2008, DOI: 10.1186/1471-2334-8-20
Abstract: 27 HIV-infected patients participated in a prospective multicenter study in with a 24 month follow-up. Patients on stable highly active antiretroviral therapy (HAART), with CD4+ count > 600/μL, and HIV-RNA < 50 copies/ml for at least 6 months were offered the option to discontinue antiretroviral therapy. The main outcome was a decline in CD4+ cell count to < 350/μL.After 24 months of follow-up, 16 of 27 (59%) patients (who discontinued therapy) experienced declines in CD4+ cell count to < 350/μL. Patients with a CD4+ nadir of < 200 cells/μL had a greater risk of restarting therapy during the follow-up (RR (CI95%): 3.37 (1.07; 10.36)). Interestingly, lymphoproliferative responses to Mycobacterium tuberculosis purified protein derivative (PPD) below 10000 c.p.m. at baseline (4.77 (1.07; 21.12)), IL-4 production above 100 pg/mL at baseline (5.95 (1.76; 20.07)) in PBMC cultured with PPD, and increased IL-4 production of PBMC with p24 antigen at baseline (1.25 (1.01; 1.55)) were associated to declines in CD4+ cell count to < 350/μL.Both the number (CD4+ nadir) and the functional activity of CD4+ (lymphoproliferative response to PPD) predict the CD4+ decrease associated with discontinuation of ART in patients with controlled viremia.After more than ten years of use, combination antiretroviral therapy (ART) continues to have a significant impact on the morbidity and mortality of HIV infection [1,2]. Despite significant improvement in the toxicity profile and the convenience of administration of currently recommended therapies, the need for lifelong ART makes it desirable to find ways of decreasing the exposure to drugs [3]. Treatment interruption has been proposed as one such a possibility and it has been explored in several clinical studies in different contexts [4-6].Recently, large clinical trials have concluded that treatment interruptions can no longer be recommended due to the risk of clinical progression in some circumstances [4]. However, other studies, both retros
Reduced CD4 T cell activation and in vitro susceptibility to HIV-1 infection in exposed uninfected Central Africans
Evélyne Bégaud, Lo?c Chartier, Valéry Marechal, Julienne Ipero, Josianne Léal, Pierre Versmisse, Guillaume Breton, Arnaud Fontanet, Corinne Capoulade-Metay, Hervé Fleury, Fran?oise Barré-Sinoussi, Daniel Scott-Algara, Gianfranco Pancino
Retrovirology , 2006, DOI: 10.1186/1742-4690-3-35
Abstract: Analysis of T lymphocyte subsets and activation markers in whole blood showed that the absolute values and the percentage of HLA-DR+CD4 T cells and of CCR5+CD4 T cells were lower in the EUs than in the UCs (p = 0.0001). Mutations in the CCR5 coding region were not found in either group. Susceptibility to in vitro infection of unstimulated peripheral blood mononuclear cells, prior of PHA activation, was decreased in EUs compared to UCs, either using a CXCR4-tropic or a CCR5-tropic HIV-1 strain (p = 0.02 and p = 0.05, respectively). Levels of MIP-1β, but not of MIP-1α or RANTES, in the supernatants of PHA-activated PBMC, were higher in the EUs than in the UCs (p = 0.007).We found low levels of CD4 T cell activation and reduced PBMC susceptibility to HIV-1 infection in Central African EUs, indicating that both may contribute to the resistance to HIV-1 infection.Central African Republic (CAR) has a high prevalence rate of HIV-1 infection estimated at 18% among pregnant women [1]. The primary route of transmission is heterosexual. High rates of infection in HIV-1-infected individuals in Africa have been suggested to be related to immune hyperactivation driven by environmental factors, including high exposure to infectious agents and poor hygienic conditions [2]. Indeed, higher levels of CD4 and CD8 T cell activation have been reported in HIV-1 infected Africans in comparison with European populations [3]. In particular, HLA-DR expression on CD4 T cells was correlated with CD4 T cell count, viral load and coinfections [4]. Successful antiretroviral therapy was reported to decrease the levels of T cell activation markers, with a stronger effect on CD8 than on CD4 T cell activation [4,5]. A pattern of immune activation, including an increase of activated T cell subsets and of the HIV-1 CCR5 co-receptor expression, has been reported not only in HIV-infected but also in HIV-uninfected African populations [6-9]. Interestingly, peripheral blood mononuclear cells (PBMC) from ind
Rapid CD4 decline after interruption of non-nucleoside reverse transcriptase inhibitor-based antiretroviral therapy in a resource-limited setting
Somnuek Sungkanuparph, Sasisopin Kiertiburanakul, Anucha Apisarnthanarak, Kumthorn Malathum, Siriorn Watcharananan, Boonmee Sathapatayavongs
AIDS Research and Therapy , 2007, DOI: 10.1186/1742-6405-4-26
Abstract: A prospective study was conducted in January 2005 to December 2006 and enrolled HIV-infected patients with HIV-1 RNA <50 copies/mL, CD4 > 350 cells/mm3, and willing to interrupt ART. CD4 cell count, HIV-1 RNA, lipid profile, and lipodystrophy were assessed at baseline and every 3 months. ART was resumed when CD4 declined to <250 cells/mm3 or developed HIV-related symptoms. Patients were grouped based on ART regimens [NNRTI or protease inhibitor (PI)] prior to TI.There were 99 patients, 85 in NNRTI group and 14 in PI group. Mean age was 40.6 years; 46% were males. Median duration of ART was 47 months. Median nadir CD4 and baseline CD4 were 151 and 535 cells/mm3, respectively. Median CD4 change at 3 months after TI were -259 (NNRTI) and -105 (PI) cells/mm3 (p = 0.038). At 13-month median follow-up, there was no AIDS-defining illness; 38% (NNRTI) and 29% (PI) of patients developed HIV-related symptoms. ART was resumed in 51% (NNRTI) and 36% (PI) of patients (p = 0.022). By Kaplan-Meier analysis, median time to resume ART was 5.5 (NNRTI) and 14.2 (PI) months (log rank test, p = 0.026). By Cox's regression analysis, NNRTI-based ART (HR 4.9; 95%CI, 1.5–16.3), nadir CD4 <100 cells/mm3 (HR 2.7; 95%CI 1.4–5.3) and baseline CD4 <500 cells/mm3 (HR 1.6; 95%CI, 1.2–3.1) were predictors for early ART resumption.TI of NNRTI-based ART leads to rapid CD4 decline and high probability of early ART resumption and should be avoided. It is necessary to scale-up the options for HIV-infected patients with lipodystrophy in resource-limited settings.Highly active antiretroviral therapy (HAART) has dramatically changed the course of human immunodeficiency virus type 1 (HIV-1) disease, with a substantial reduction in morbidity and mortality [1-3]. New antiretroviral drugs and combinations with better safety and tolerability profiles have become available in developed countries [4,5], but these options are still not available or are not affordable in resource-limited settings. Non-nucleoside re
CD4 testing at clinics to assess eligibility for Antiretroviral therapy
R Lumala, T van den Akker, CA Metcalf, E Diggle, B Zamadenga, K Mbewa, A Akkeson
Malawi Medical Journal , 2012,
Abstract: Background In 2011, the Ministry of Health raised the CD4 threshold for antiretroviral therapy (ART) eligibility from <250 cells/μl and <350 cells/μl, but at the same time only 8.8% of facilities in Malawi with HIV services provided CD4 testing. We conducted a record review at 10 rural clinics in Thyolo District to assess the impact of introducing CD4 testing on identifying patients eligible for ART. Methods: We abstracted CD4 counts of all ART-na ve, HIV-infected patients with WHO clinical stages 1 and 2 and an initial CD4 test between May 2008 and June 2009. At four clinics, we also abstracted CD4 counts of patients not initially eligible for ART who were retested before April 2010. Results Of 1,113 patients tested, the initial CD4 was “≤250 cells/μl” and “≤350 cells/μl” in 534 (48.0%). Of 203 patients with follow-up results, the most recent CD4 was ≤250 cells/μl in 34 (24.5%), and ≤350 cells/μl in 64 (46.0%). Conclusions CD4 testing in rural clinics is feasible and identifies many patients eligible for ART who would not be identified without CD4 testing. CD4 testing needs to be scaled-up to identify patients eligible for ART. ART services need to be scaled-up concurrently to meet the resulting increased demand.
HIV-Infected Individuals with Low CD4/CD8 Ratio despite Effective Antiretroviral Therapy Exhibit Altered T Cell Subsets, Heightened CD8+ T Cell Activation, and Increased Risk of Non-AIDS Morbidity and Mortality  [PDF]
Sergio Serrano-Villar ,Talia Sainz,Sulggi A. Lee,Peter W. Hunt,Elizabeth Sinclair,Barbara L. Shacklett,April L. Ferre,Timothy L. Hayes,Ma Somsouk,Priscilla Y. Hsue,Mark L. Van Natta,Curtis L. Meinert,Michael M. Lederman,Hiroyu Hatano,Vivek Jain,Yong Huang,Frederick M. Hecht,Jeffrey N. Martin,Joseph M. McCune,Santiago Moreno,Steven G. Deeks
PLOS Pathogens , 2014, DOI: doi/10.1371/journal.ppat.1004078
Abstract: A low CD4/CD8 ratio in elderly HIV-uninfected adults is associated with increased morbidity and mortality. A subset of HIV-infected adults receiving effective antiretroviral therapy (ART) fails to normalize this ratio, even after they achieve normal CD4+ T cell counts. The immunologic and clinical characteristics of this clinical phenotype remain undefined. Using data from four distinct clinical cohorts and three clinical trials, we show that a low CD4/CD8 ratio in HIV-infected adults during otherwise effective ART (after CD4 count recovery above 500 cells/mm3) is associated with a number of immunological abnormalities, including a skewed T cell phenotype from na?ve toward terminally differentiated CD8+ T cells, higher levels of CD8+ T cell activation (HLADR+CD38+) and senescence (CD28? and CD57+CD28?), and higher kynurenine/tryptophan ratio. Changes in the peripheral CD4/CD8 ratio are also reflective of changes in gut mucosa, but not in lymph nodes. In a longitudinal study, individuals who initiated ART within six months of infection had greater CD4/CD8 ratio increase compared to later initiators (>2 years). After controlling for age, gender, ART duration, nadir and CD4 count, the CD4/CD8 ratio predicted increased risk of morbidity and mortality. Hence, a persistently low CD4/CD8 ratio during otherwise effective ART is associated with increased innate and adaptive immune activation, an immunosenescent phenotype, and higher risk of morbidity/mortality. This ratio may prove useful in monitoring response to ART and could identify a unique subset of individuals needed of novel therapeutic interventions.
Adua, Sulaiman Sheu
Academic Research International , 2012,
Abstract: The contact of Islam with Africa and Africans could not be considered a matter of recent development. The continent had been in existence ver before the time of the Prophet, while Islam had been known to the time long as early as the prophet was called to the prophet hood. Thispaper examines the roles played by the Africans towards the development of Islam as far back as the time of the Prophet, as well as the efforts made by them to spread the religion and its tenets.Also it looks at the honour accorded the continent in Islam and in the Prophet’s treatment of the Africans during his timer. This gives an impression that Islam is not a new religion in Africa and to Africans.
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