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Attitudes of People in the UK with HIV Who Are Antiretroviral (ART) Na?ve to Starting ART at High CD4 Counts for Potential Health Benefit or to Prevent HIV Transmission  [PDF]
Alison J. Rodger, Andrew Phillips, Andrew Speakman, Richard Gilson, Martin Fisher, Ed Wilkins, Jane Anderson, Margaret Johnson, Rebecca O'Connell, Simon Collins, Jonathan Elford, Lorraine Sherr, Fiona C. Lampe, for the ASTRA (Antiretrovirals, Sexual Transmission Risk and Attitudes) Study Group
PLOS ONE , 2014, DOI: 10.1371/journal.pone.0097340
Abstract: Objective To assess if a strategy of early ART to prevent HIV transmission is acceptable to ART na?ve people with HIV with high CD4 counts. Design ASTRA is a UK multicentre, cross sectional study of 3258 HIV outpatients in 2011/12. A self-completed questionnaire collected sociodemographic, behavioral and health data, and attitudes to ART; CD4 count was recorded from clinical records. Methods ART na?ve participants with CD4 ≥350 cells/μL (n = 281) were asked to agree/disagree/undecided with the statements (i) I would want to start treatment now if this would slightly reduce my risk of getting a serious illness, and (ii) I would want to start treatment now if this would make me less infectious to a sexual partner, even if there was no benefit to my own health. Results Participants were 85% MSM, 76% white, 11% women. Of 281 participants, 49.5% and 45.2% agreed they would start ART for reasons (i) and (ii) respectively; 62.6% agreed with either (i) or (ii); 12.5% agreed with neither; 24.9% were uncertain. Factors independently associated (p<0.1) with agreement to (i) were: lower CD4, more recent HIV diagnosis, physical symptoms, not being depressed, greater financial hardship, and with agreement to (ii) were: being heterosexual, more recent HIV diagnosis, being sexually active. Conclusions A strategy of starting ART at high CD4 counts is likely to be acceptable to the majority of HIV-diagnosed individuals. Almost half with CD4 >350 would start ART to reduce infectiousness, even if treatment did not benefit their own health. However a significant minority would not like to start ART either for modest health benefit or to reduce infectivity. Any change in approach to ART initiation must take account of individual preferences. Transmission models of potential benefit of early ART should consider that ART uptake may be lower than that seen with low CD4 counts.
Population-Based CD4 Counts in a Rural Area in South Africa with High HIV Prevalence and High Antiretroviral Treatment Coverage  [PDF]
Abraham Malaza, Jo?l Mossong, Till B?rnighausen, Johannes Viljoen, Marie-Louise Newell
PLOS ONE , 2013, DOI: 10.1371/journal.pone.0070126
Abstract: Background Little is known about the variability of CD4 counts in the general population of sub-Saharan Africa countries affected by the HIV epidemic. We investigated factors associated with CD4 counts in a rural area in South Africa with high HIV prevalence and high antiretroviral treatment (ART) coverage. Methods CD4 counts, health status, body mass index (BMI), demographic characteristics and HIV status were assessed in 4990 adult resident participants of a demographic surveillance in rural KwaZulu-Natal in South Africa; antiretroviral treatment duration was obtained from a linked clinical database. Multivariable regression analysis, overall and stratified by HIV status, was performed with CD4 count levels as outcome. Results Median CD4 counts were significantly higher in women than in men overall (714 vs. 630 cells/μl, p<0.0001), both in HIV-uninfected (833 vs. 683 cells/μl, p<0.0001) and HIV-infected adults (384.5 vs. 333 cells/μl, p<0.0001). In multivariable regression analysis, women had 19.4% (95% confidence interval (CI) 16.1–22.9) higher CD4 counts than men, controlling for age, HIV status, urban/rural residence, household wealth, education, BMI, self-reported tuberculosis, high blood pressure, other chronic illnesses and sample processing delay. At ART initiation, HIV-infected adults had 21.7% (95% CI 14.6–28.2) lower CD4 counts than treatment-naive individuals; CD4 counts were estimated to increase by 9.2% (95% CI 6.2–12.4) per year of treatment. Conclusions CD4 counts are primarily determined by sex in HIV-uninfected adults, and by sex, age and duration of antiretroviral treatment in HIV-infected adults. Lower CD4 counts at ART initiation in men could be a consequence of lower CD4 cell counts before HIV acquisition.
Antiretroviral Treatment Cohort Analysis Using Time-Updated CD4 Counts: Assessment of Bias with Different Analytic Methods  [PDF]
Katharina Kranzer, James J. Lewis, Richard G. White, Judith R. Glynn, Stephen D. Lawn, Keren Middelkoop, Linda-Gail Bekker, Robin Wood
PLOS ONE , 2011, DOI: 10.1371/journal.pone.0027763
Abstract: Background Survival analysis using time-updated CD4+ counts during antiretroviral therapy is frequently employed to determine risk of clinical events. The time-point when the CD4+ count is assumed to change potentially biases effect estimates but methods used to estimate this are infrequently reported. Methods This study examined the effect of three different estimation methods: assuming i) a constant CD4+ count from date of measurement until the date of next measurement, ii) a constant CD4+ count from the midpoint of the preceding interval until the midpoint of the subsequent interval and iii) a linear interpolation between consecutive CD4+ measurements to provide additional midpoint measurements. Person-time, tuberculosis rates and hazard ratios by CD4+ stratum were compared using all available CD4+ counts (measurement frequency 1–3 months) and 6 monthly measurements from a clinical cohort. Simulated data were used to compare the extent of bias introduced by these methods. Results The midpoint method gave the closest fit to person-time spent with low CD4+ counts and for hazard ratios for outcomes both in the clinical dataset and the simulated data. Conclusion The midpoint method presents a simple option to reduce bias in time-updated CD4+ analysis, particularly at low CD4 cell counts and rapidly increasing counts after ART initiation.
Utility of CD4 cell counts for early prediction of virological failure during antiretroviral therapy in a resource-limited setting
Motasim Badri, Stephen D Lawn, Robin Wood
BMC Infectious Diseases , 2008, DOI: 10.1186/1471-2334-8-89
Abstract: In this study, we used a novel modelling approach that accounted for all CD4 cell count and VL values measured during follow-up from the first date that VL suppression was achieved. We determined the associations between CD4 counts (absolute values and changes during ART), VL measurements and risk of virological failure (VL > 1,000 copies/ml) following initial VL suppression in 330 patients in South Africa. CD4 count changes were modelled both as the difference from baseline (ΔCD4 count) and the difference between consecutive values (CD4 count slope) using all 3-monthly CD4 count measurements during follow-up.During 7093.2 patient-months of observation 3756 paired CD4 count and VL measurements were made. In patients who developed virological failure (n = 179), VL correlated significantly with absolute CD4 counts (r = - 0.08, P = 0.003), ΔCD4 counts (r = - 0.11, P < 0.01), and most strongly with CD4 count slopes (r = - 0.30, P < 0.001). However, the distributions of the absolute CD4 counts, ΔCD4 counts and CD4 count slopes at the time of virological failure did not differ significantly from the corresponding distributions in those without virological failure (P = 0.99, P = 0.92 and P = 0.75, respectively). Moreover, in a receiver operating characteristic (ROC) curve, the association between a negative CD4 count slope and virological failure was poor (area under the curve = 0.59; sensitivity = 53.0%; specificity = 63.6%; positive predictive value = 10.9%).CD4 count changes correlated significantly with VL at group level but had very limited utility in identifying virological failure in individual patients. CD4 count is an inadequate alternative to VL measurement for early detection of virological failure.Access to antiretroviral therapy (ART) is expanding in low- and middle-income countries with over 2 million people receiving treatment by December 2006, representing 28% of the 7.1 million estimated to be in need [1]. Recent studies from sub-Saharan Africa have shown
Effect of antiretroviral drugs on maternal CD4 lymphocyte counts, HIV-1 RNA levels, and anthropometric parameters of their neonates
El Beitune, Patrícia;Duarte, Geraldo;Machado, Alcyone Artioli;Quintana, Silvana Maria;Figueiró-Filho, Ernesto A.;Abduch, Renata;
Clinics , 2005, DOI: 10.1590/S1807-59322005000300005
Abstract: purpose: to study the effect of antiretroviral drugs administered during pregnancy on cd4 lymphocyte counts and hiv-1 rna levels of pregnant women and on the anthropometric parameters of their neonates. methods: a prospective study was conducted on 57 pregnant women and their neonates divided into 3 groups: zdv group, hiv-infected mothers taking zidovudine (n = 20); triple therapy (tt) group, mothers taking zidovudine + lamivudine + nelfinavir (n = 25), and control group, normal women (n = 12). cd4 lymphocyte counts and hiv-1 rna levels of pregnant women were analyzed during two periods of pregnancy. the perinatal prognosis took into account preterm rates, birth weight, intrauterine growth restriction, perinatal death, and vertical transmission of hiv-1. data were analyzed statistically using the nonparametric chi-square, mann-whitney, friedman, kruskal-wallis, and wilcoxon matched pairs tests, with the level of significance set at p <.05. results: the major maternal demographic and anthropometric data were homogeneous for the various groups. hiv-1 viral burden, which was initially elevated, median of 14,370 copies/ml, was significantly reduced in the tt group, reaching 40 copies/ml. with respect to t-cd4+ lymphocyte counts, there was a significant recovery in group tt at the end of pregnancy, this value being significantly different from that for the zdv group (p =.0052). there was no difference between groups regarding gestation length, apgar scores, or neonatal anthropometric classification. there was no case of vertical hiv-1 transmission. conclusions: the results obtained for the present series demonstrate the efficiency and suggest safety of the use of antiretroviral drugs during pregnancy as revealed by anthropometric parameters of the neonate.
Safety of nevirapine in HIV-infected pregnant women initiating antiretroviral therapy at higher CD4 counts: A systematic review and meta-analysis
E Bera, R Mia
South African Medical Journal , 2012,
Abstract: Background. The package insert for nevirapine (NVP) cautions against use in HIV-infected women (including pregnant women) with CD4 counts .250 cells/ êl. However, recent studies showed that the CD4 count of pregnant women receiving antiretroviral therapy (ART) was not predictive of NVP toxicity. Objectives. To determine whether ART-naive pregnant women initiating NVP-based ART at higher CD4 counts experience greater toxicity compared with pregnant women at lower CD4 counts. Methods. We reviewed studies comparing serious adverse NVPrelated events among ART-naive pregnant women who commenced therapy at higher v. lower CD4 counts. Relevant studies were extracted from PubMed, SCOPUS and EMBASE, major journals and conference proceedings prior to December 2011. Authors were contacted for additional data. Data were independently extracted and entered into Review Manager. Results. Fourteen studies (2 663 participants) were included for analysis. The odds ratio (OR) for overall NVP toxicity among pregnant women with CD4 <250 cells/ êl was 0.61 (95% confidence interval (CI) 0.43 - 0.85). When analysis was restricted to prospective studies only (7 studies, 1 318 participants), the results were consistent for overall NVP toxicity (OR 0.43; 95% CI 0.25 - 0.73) and severe hepatotoxicity (OR 0.45; 95% CI 0.22 - 0.90), but not for severe cutaneous reaction (OR 0.53; 95% CI 0.26 - 1.10). Conclusion. Initiating NVP-based ART during pregnancy at CD4 .250 cells/ êl increases toxicity risk and should be avoided, necessitating urgent revision of current guidelines supporting this practice.
Human Herpesvirus Replication and Abnormal CD8+ T Cell Activation and Low CD4+ T Cell Counts in Antiretroviral-Suppressed HIV-Infected Patients  [PDF]
Mark A. Jacobson, Dirk P. Ditmer, Elizabeth Sinclair, Jeffrey N. Martin, Steven G. Deeks, Peter Hunt, Edward S. Mocarski, Caroline Shiboski
PLOS ONE , 2009, DOI: 10.1371/journal.pone.0005277
Abstract: Background Most HIV-infected patients receiving virologically suppressive antiretroviral therapy continue to have abnormal, generalized T cell activation. We explored whether the degree of ongoing cytomegalovirus (CMV), Epstein-Barr virus (EBV) and Kaposi's sarcoma herpesvirus (KSHV) replication was associated with higher virus-specific T cell activation and the failure to achieve normal absolute CD4+ T cell counts in the face of long-term suppressive antiretroviral therapy. Methodology Longitudinally collected PBMC and saliva specimens obtained from HIV-infected patients on effective antiretroviral therapy for at least one year (plasma HIV RNA <75 copies/mL) were examined using a multiplex CMV, EBV and KSHV DNA PCR assay. Eleven cases were chosen who had CD8+ T cell CD38+HLA-DR+ expression >10% and plateau absolute CD4+ T cell counts <500 cells/μL. Five controls from the same study had CD8+ T cell CD38 expression <10% and plateau absolute CD4+ T cell counts >500 cells/μL. Results and Conclusions Among all subjects combined, 18% of PMBC samples were positive for CMV DNA, and 27%, 73% and 24% of saliva samples were positive for CMV, EBV and KSHV DNA, respectively. No significant differences or trends were observed between cases and controls in proportions of all CMV, EBV or KSHV DNA positive specimens, proportions of subjects in each group that intermittently or continuously shed CMV, EBV or KSHV DNA in saliva, or the median number of genome copies of CMV, EBV and KSHV DNA in saliva. Overall, number of genome copies in saliva were lower for KSHV than for CMV and lower for CMV than for EBV. Although replication of CMV, EBV and KSHV persists in many antiretroviral-suppressed, HIV-infected patients, we observed no evidence in this pilot case-control study that the magnitude of such human herpesvirus replication is associated with abnormally increased CD8+ T cell activation and sub-normal plateau absolute CD4+ T cell counts following virologically suppressive antiretroviral therapy.
The Effect of Highly Active Antiretroviral Therapy on CD4 Counts and Body Weight in HIV/AIDS Patients in South West Nigeria
Olatunji Mabayoje,Musa Muhibi,Adekunle Mustapha,Olufemi Fadiora,Taiwo Adewole
Research Journal of Medical Sciences , 2012, DOI: 10.3923/rjmsci.2012.228.231
Abstract: Prior to the advent of HAART the diagnosis of HIV/AIDS was a death sentence. Research has shown that this is no more the case. This retrospective study was aimed at determining the effect of HAART on CD4 counts and body weight of HIV-positive subjects. The CD4 counts and body weight of HIV-positive patients were accessed from the records of HIV clinic of LAUTECH Teaching Hospital, Oshogbo. The data comprised of records of the CD4 counts and body weight of fifty HIV-positive patients not on HAART treatment and that of fifty HIV-positive patients on HAART treatment for a period of 1 year. Results showed a significant difference between mean CD4 counts of control subjects and test subjects (p<0.05). This significant difference represents an increase in CD4 count of HIV patients on HAART. This study also shows no significant difference between mean body weight of control subjects and test subjects (p>0.05). This study highlights the need for importance of regular monitoring of the CD4 count and body weight in HIV patients in order to determine when to start treatment with HAART therapy to prevent the invasion of life threatening opportunistic infections.
Prevalence of Intestinal Parasites and Profile of CD4+ Counts in HIV+/AIDS People in North of Iran, 2007-2008  [PDF]
A. Daryani,M. Sharif,M. Meigouni,F. Baba Mahmoudi
Pakistan Journal of Biological Sciences , 2009,
Abstract: In this study 142 stool samples (64 HIV+/AIDS patients and 78 non-HIV infected individuals) collected from Mazandaran province and screened for intestinal parasites, using direct wet mont, formalin-ether sedimentation concentration, modified Ziehl Neelsen and modified trichrome techniques. Each person in this study was examined for CD4+ counts. Intestinal parasites were found in 11/64 (17.2%) of patients in HIV+/AIDS group and in 14/78 (17.9%) of controls. Prevalence of parasites detected in HIV+/AIDS individuals was as follow: Cryptosporidium sp. 9.4%, Giardia lamblia 3.1%, Entamoeba coli 1.6%, E. histolytica 1.6% and Chilomastix mesnili 1.6%. Prevalence of parasites in controls was as follow: Trichostrongylus sp. 6.4%, G. lamblia 3.8%, Cryptosporidium sp. 2.5% , E. coli 2.5% , E. histolytica 1.2% , Hookworms 1.2%. The mean of CD4+ counts in HIV-positive group (430 cells μL-1) was remarkedly less than controls (871 cells μL-1) (p = 0.00l). As patients usually belong to poor socio-economic backgrounds and they can hardly afford treatment, therefore, it is suggested screening and free treatment of intestinal parasites in these individuals should be taken by health centers to prevent the occurrence of these diseases in HIV+/AIDS patients, as often the disease may take a fulminant form.
Trends in CD4 counts in HIV-infected patients with HIV viral load monitoring while on combination antiretroviral treatment: results from The TREAT Asia HIV Observational Database
Jialun Zhou, Thira Sirisanthana, Sasisopin Kiertiburanakul, Yi-Ming A Chen, Ning Han, Poh_Lian Lim, Nagalingeswaran Kumarasamy, Jun Choi, Tuti Merati, Evy Yunihastuti, Shinichi Oka, Adeeba Kamarulzaman, Praphan Phanuphak, Christopher KC Lee, Patrick CK Li, Sanjay Pujari, Vanthanak Saphonn, Matthew G Law
BMC Infectious Diseases , 2010, DOI: 10.1186/1471-2334-10-361
Abstract: Treatment-naive HIV-infected patients who started cART with three or more and had three or more CD4 count and HIV VL tests were included. CD4 count slopes were expressed as changes of cells per microliter per year. Predictors of CD4 count slopes from 6 months after initiation were assessed by random-effects linear regression models.A total of 1676 patients (74% male) were included. The median time on cART was 4.2 years (IQR 2.5-5.8 years). In the final model, CD4 count slope was associated with age, concurrent HIV VL and CD4 count, disease stage, hepatitis B or C co-infection, and time since cART initiation. CD4 count continues to increase with HIV VL up to 20 000 copies/mL during 6-12 months after cART initiation. However, the HIV VL has to be controlled below 5 000, 4 000 and 500 copies/mL for the CD4 count slope to remain above 20 cells/microliter per year during 12-18, 18-24, and beyond 24 months after cART initiation.After cART initiation, CD4 counts continued to increase even when the concurrent HIV VL was detectable. However, HIV VL needed to be controlled at a lower level to maintain a positive CD4 count slope when cART continues. The effect on long-term outcomes through the possible development of HIV drug resistance remains uncertain.Studies show that latent infection of CD4 cells provides a mechanism for lifelong persistence of HIV-1, even in patients on effective anti-retroviral therapy [1]. To suppress viral replication so that the VL is below the level of detection with standard assays is thus one of the aims at the start of antiretroviral treatment. Maximal and durable suppression of HIV VL prevents or delays development of drug resistant mutations, preserves CD4 cells, and eventually results in better clinical outcomes. According to the US guidelines, if HIV VL suppression is not achieved, it is necessary to change to a new regimen, a second or third line regimen, with at least two active drugs [2].HIV-infected patients in most developing countries h
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