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Effect of baseline CD4 cell counts on the clinical significance of short-term immunologic response to antiretroviral therapy in individuals with virologic suppression.

ABSTRACT: BACKGROUND:Achieving virologic suppression is a clear therapeutic goal for patients receiving combination antiretroviral therapy (cART). However, the effects of immunologic responses, whether measured as CD4 count changes from baseline or CD4 counts at follow-up, in patients with virologic suppression, have not been clearly established. METHODS:Treatment-naive individuals aged > or =16 years, who initiated cART between 1998 and 2005 in participating cohorts of the ART Cohort Collaboration and achieved viral load < or =400 copies per milliliter 6 months after cART initiation, were included. We used Cox models to examine associations of CD4 change from baseline to 6 months, and absolute CD4 counts at 6 months, with subsequent rates of mortality and AIDS. Analyses were stratified by baseline CD4 count. RESULTS:Among 23,679 eligible participants, the median increase in CD4 count at 6 months, and the implications of these increases for subsequent mortality and AIDS, varied with baseline CD4 count. Mortality hazard ratios for increases of 0-50 cells per microliter, compared with >100 cells per microliter, were 1.87 (95% confidence interval: 1.28 to 2.73), 1.60 (1.13 to 2.28), 0.98 (0.58 to 1.65) and 1.24 (0.70 to 2.18) in participants with baseline CD4 cell count <50, 50-199, 200-349 and > or =350 cells per microliter, respectively. In contrast, hazard ratios for mortality or AIDS associated with absolute CD4 cell counts at 6 months were similar across all but the highest baseline CD4 cell count strata. CONCLUSION:It is not possible to derive thresholds for change in CD4 count that define an adequate immunologic response in individuals receiving cART. Absolute CD4 counts at 6 months are a more useful measure of immunologic response and subsequent prognosis.

SUBMITTER: Moore DM

PROVIDER: S-EPMC3032437 | biostudies-literature | 2009 Nov

REPOSITORIES: biostudies-literature

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Effect of baseline CD4 cell counts on the clinical significance of short-term immunologic response to antiretroviral therapy in individuals with virologic suppression.

Moore David M DM Harris Ross R Lima Viviane V Hogg Bob B May Margaret M Yip Benita B Justice Amy A Mocroft Amanda A Reiss Peter P Lampe Fiona F Chêne Geneviève G Costagliola Dominique D Elzi Luigia L Mugavero Michael J MJ Monforte Antonella D'Arminio AD Sabin Caroline C Podzamczer Daniel D Fätkenheuer Gerd G Staszewski Schlomo S Gill John J Sterne Jonathan A C JA

Journal of acquired immune deficiency syndromes (1999) 20091101 3

<h4>Background</h4>Achieving virologic suppression is a clear therapeutic goal for patients receiving combination antiretroviral therapy (cART). However, the effects of immunologic responses, whether measured as CD4 count changes from baseline or CD4 counts at follow-up, in patients with virologic suppression, have not been clearly established.<h4>Methods</h4>Treatment-naive individuals aged > or =16 years, who initiated cART between 1998 and 2005 in participating cohorts of the ART Cohort Colla ...[more]

PMID: 19668084

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Project description:BACKGROUND:An undetectable serum HIV-1 load is key to effectiveness of antiretroviral (ARV) therapy, which depends on adherence to treatment. We evaluated factors possibly associated with ARV adherence and virologic response in HIV-infected heterosexual individuals. METHODS:A cross-sectional study was conducted in 200 HIV-1 serodiscordant couples and 100 unpartnered individuals receiving ARV treatment at a tertiary hospital in southern Brazil. All subjects provided written informed consent, answered demographic/behavioral questionnaires through audio computer-assisted self-interviews (ACASI), and collected blood and vaginal samples for biological markers and assessment of sexually transmitted infections (STIs). HIV-negative partners were counseled and tested for HIV-1. RESULTS:The study population mean age was 39.9 years, 53.6% were female, 62.5% were Caucasian, 52.6% had incomplete or complete elementary education, 63.1% resided in Porto Alegre. Demographic, behavioral and biological marker characteristics were similar between couples and single individuals. There was an association between adherence reported on ACASI and an undetectable serum viral load (P<0.0001). Logistic regression analysis demonstrated that single-tablet ARV-regimens were independently associated with adherence (OR = 2.3; 95CI%: 1.2-4.4; P = 0.011) after controlling for age, gender, education, marital status, personal income, ARV regimen, and median time of ARV use. A positive correlation between genital secretion PCR results and serum viral load was significant in the presence of STIs (r = 0.359; P = 0.017). Although HIV PCR detection in vaginal secretions was more frequent in women with detectable viremia (9/51, 17.6%), it was also present in 7 of 157 women with undetectable serum viral loads (4.5%), p = 0.005. CONCLUSIONS:ARV single tablet regimens are associated with adherence. Detectable HIV-1 may be present in the genital secretions of women with undetectable viremia which means there is potential for HIV transmission in adherent individuals with serologic suppression.

Project description:There are limited data of immunologic and virologic failure in Asian HIV-infected children using non-nucleoside reverse transcriptase inhibitor (NNRTI)-based highly active antiretroviral therapy (HAART). We examined the incidence rate of immunologic failure (IF) and virologic failure (VF) and the accuracy of using IF to predict VF in Thai HIV-infected children using first-line NNRTI-based HAART.Antiretroviral (ART)-naïve HIV-infected children from 2 prospective cohorts treated with NNRTI-based HAART during 2001-2008 were included. CD4 counts were performed every 12 weeks and plasma HIV-RNA measured every 24 weeks. Immune recovery was defined as CD4%?25%. IF was defined as persistent decline of ?5% in CD4% in children with CD4%<15% at baseline or decrease in CD4 count ?30% from baseline. VF was defined as HIV-RNA>1,000 copies/ml after at least 24 weeks of HAART. Clinical and laboratory parameter changes were assessed using a paired t-test, and a time to event approach was used to assess predictors of VF. Sensitivity and specificity of IF were calculated against VF.107 ART-naive HIV-infected children were included, 52% female, % CDC clinical classification N:A:B:C 4:44:30:22%. 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) log10copies/ml. Nevirapine (NVP) and efavirenz (EFV)-based HAART were started in 70% and 30%, respectively.At 96 weeks, none had progressed to a CDC clinical classification of AIDS and one had died from pneumonia. Overall, significant improvement of weight for age z-score (p = 0.014), height for age z-score, hemoglobin, and CD4 were seen (all p < 0.001). The median (IQR) CD4% at 96 weeks was 25 (18-30)%. Eighty-nine percent of children had immune recovery (CD4%?25%) and 75% of children had HIV-RNA <1.7log10copies/ml.Thirty five (32.7%) children experienced VF within 96 weeks. Of these, 24 (68.6%) and 31 (88.6%) children had VF in the first 24 and 48 weeks respectively.Only 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 specificity was 100 (93.9-100)%.Immunologic failure, as defined here, had low sensitivity compared to VF and should not be recommended to detect treatment failure. Plasma HIV-RNA should be performed twice, at weeks 24 and 48, to detect early treatment failure.Clinicaltrials.gov identification number NCT00476606.

Project description:BackgroundEvidence favoring earlier HIV ART initiation at high CD4+ T-cell counts (CD4>350/uL) has grown, and guidelines now recommend earlier HIV treatment. However, the cost of providing ART to individuals with CD4>350 in Sub-Saharan Africa has not been well estimated. This remains a major barrier to optimal global cost projections for accelerating the scale-up of ART. Our objective was to compute costs of ART delivery to high CD4+count individuals in a typical rural Ugandan health center-based HIV clinic, and use these data to construct scenarios of efficient ART scale-up.MethodsWithin a clinical study evaluating streamlined ART delivery to 197 individuals with CD4+ cell counts >350 cells/uL (EARLI Study: NCT01479634) in Mbarara, Uganda, we performed a micro-costing analysis of administrative records, ART prices, and time-and-motion analysis of staff work patterns. We computed observed per-person-per-year (ppy) costs, and constructed models estimating costs under several increasingly efficient ART scale-up scenarios using local salaries, lowest drug prices, optimized patient loads, and inclusion of viral load (VL) testing.FindingsAmong 197 individuals enrolled in the EARLI Study, median pre-ART CD4+ cell count was 569/uL (IQR 451-716). Observed ART delivery cost was $628 ppy at steady state. Models using local salaries and only core laboratory tests estimated costs of $529/$445 ppy (+/-VL testing, respectively). Models with lower salaries, lowest ART prices, and optimized healthcare worker schedules reduced costs by $100-200 ppy. Costs in a maximally efficient scale-up model were $320/$236 ppy (+/- VL testing). This included $39 for personnel, $106 for ART, $130/$46 for laboratory tests, and $46 for administrative/other costs. A key limitation of this study is its derivation and extrapolation of costs from one large rural treatment program of high CD4+ count individuals.ConclusionsIn a Ugandan HIV clinic, ART delivery costs--including VL testing--for individuals with CD4>350 were similar to estimates from high-efficiency programs. In higher efficiency scale-up models, costs were substantially lower. These favorable costs may be achieved because high CD4+ count patients are often asymptomatic, facilitating more efficient streamlined ART delivery. Our work provides a framework for calculating costs of efficient ART scale-up models using accessible data from specific programs and regions.

Dataset Information

Effect of baseline CD4 cell counts on the clinical significance of short-term immunologic response to antiretroviral therapy in individuals with virologic suppression.

Publications

Effect of baseline CD4 cell counts on the clinical significance of short-term immunologic response to antiretroviral therapy in individuals with virologic suppression.

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