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At least 19 recordsLinked to original sources
PubMed2003

Survival benefit of initiating antiretroviral therapy in HIV-infected persons in different CD4+ cell strata.

BACKGROUND: Optimal timing of antiretroviral therapy (ART) initiation for HIV-infected persons remains unclear. OBJECTIVE: To assess survival benefit of initiating ART at different CD4+ cell counts. DESIGN: Prospective observational study. SETTING: U.S. clinics in the HIV Outpatient Study (HOPS). PATIENTS: HIV-infected patients with CD4+ cell counts, plasma HIV RNA viral load, and ART use recorded from January 1994 through March 2002. MEASUREMENTS: Before initiation of ART, patients were grouped by their CD4+ cell counts into three subgroups: 0.201 to 0.350 x 10(9) cells/L (n = 399), 0.351 to 0.500 x 10(9) cells/L (n = 327), and 0.501 to 0.750 x 10(9) cells/L (n = 122). We compared mortality rates for each CD4+ subgroup among patients who initiated ART and patients who delayed ART until reaching a lower CD4+ subgroup. RESULTS: Mortality rates for 340 patients who initiated ART and 59 who delayed ART in the CD4+ subgroup of 0.201 to 0.350 x 10(9) cells/L were 15.4 and 56.4 deaths per 1000 person-years, respectively (rate ratio, 0.27 [95% CI, 0.14 to 0.55]; P < 0.001). For the CD4+ subgroup of 0.351 to 0.500 x 10(9) cells/L, mortality rates for 240 patients who initiated ART and 887 who delayed ART were 10.0 and 16.6 deaths per 1000 person-years, respectively (rate ratio, 0.61 [CI, 0.22 to 1.67]; P = 0.17). For the CD4+ subgroup of 0.501 to 0.750 x 10(9) cells/L, mortality rates in 55 patients who initiated ART and 67 who delayed ART were 7.5 and 3.1 deaths per 1000 person-years, respectively (rate ratio, 1.20 [CI, 0.17 to 8.53]; P > 0.2). Patients in the 0.201 to 0.350 x 10(9) cells/L and 0.351 to 0.500 x 10(9) cells/L CD4+ subgroups who initiated ART were more likely than those who delayed ART to achieve an undetectable HIV viral load (P = 0.03 and 0.04, respectively). CONCLUSIONS: Among HIV-infected persons with CD4+ cell counts of 0.201 to 0.350 x 10(9) cells/L, initiating ART is associated with reduced mortality compared with delaying such therapy. Survival benefits of earlier ART initiation (at CD4+ cell counts of 0.351 to 0.500 x 10(9) cells/L) are possible.

Adult↗
PubMed1990

Cell therapy in children with Down syndrome: a retrospective study.

Cell therapy, the administration of freeze-dried or lyophilized cells derived from fetal tissue of animals, has been suggested and accepted by some parents as a treatment for Down syndrome. Such therapy regimens have been purported to ameliorate dysmorphic features and to result in improvement in IQ, motor skills, social behavior, height, language, and memory. Interest in this therapy continues despite a lack of empirical support for its use and its illegality in the United States. In this study, 190 subjects of whom 21 had received cell therapy (from sources external to this study) were studied for 18 variables in the areas of growth, motor development, cognitive development, and adaptive/social status. Comparing the cell-treated group with a control group matched for sex, age, socioeconomic status, and cardiac history showed no statistically significant differences for any of the developmental or growth variables measured. These findings fail to support continued claims of improved functioning following cell therapy in persons with Down syndrome.

Adolescent↗
PubMed2026

Tumor microenvironment-simulated organoids for personalized therapy prediction in head and neck squamous cell carcinoma.

Patient-derived organoids (PDOs) have emerged as promising models for predicting personalized drug responses in cancer therapy. However, the absence of essential immune and stromal components limits their ability to recapitulate the tumor microenvironment. Here, we established a total of 30 patient-derived organoids (PDOs) from 79 patients with locally advanced (LA) and recurrent/metastatic (R/M) head and neck squamous cell carcinoma (HNSCC). These PDOs maintained sustained expansion capacity and preserved the histopathological characteristics and genomic heterogeneity of their parental tumors. By integrating autologous immune cells and cancer-associated fibroblasts (CAFs) into PDOs, respectively, microenvironment-simulated PDOs (MS-PDOs) were established using a feasible co-culture condition. Compared with conventional PDOs, MS-PDOs-PBMC exhibited specific cytotoxicity and responses to PD-1/PD-L1 inhibitors, while MS-PDOs-CAFs showed enhanced tolerance to chemotherapy drugs, indicating that microenvironment components modulate therapeutic responses in HNSCC. The drug response profiles of MS-PDOs exhibited diverse sensitivity to PD-1/PD-L1 inhibitors, chemotherapy drugs, and combination regimens. Notably, the therapeutic predictions of MS-PDOs were consistent with clinical treatment outcomes, supporting their translational relevance. Collectively, MS-PDOs serve as a robust platform for modeling the tumor microenvironment and predicting therapeutic responses, supporting precision medicine-guided clinical decision-making and offering personalized treatment strategies for HNSCC patients.

Humans↗
PubMedDate not supplied

Clinical proteomics: from biomarker discovery and cell signaling profiles to individualized personal therapy.

The discovery of new highly sensitive and specific biomarkers for early disease detection and risk stratification coupled with the development of personalized "designer" therapies holds the key to future treatment of complex diseases such as cancer. Mounting evidence confirms that the low molecular weight (LMW) range of the circulatory proteome contains a rich source of information that may be able to detect early stage disease and stratify risk. Current mass spectrometry (MS) platforms can generate a rapid and high resolution portrait of the LMW proteome. Emerging novel nanotechnology strategies to amplify and harvest these LMW biomarkers in vivo or ex vivo will greatly enhance our ability to discover and characterize molecules for early disease detection, subclassification and prognostic capability of current proteomics modalities. Ultimately genetic mutations giving rise to disease are played out and manifested on a protein level, involving derangements in protein function and information flow within diseased cells and the interconnected tissue microenvironment. Newly developed highly sensitive, specific and linearly dynamic reverse phase protein microarray systems are now able to generate circuit maps of information flow through phosphoprotein networks of pure populations of microdissected tumor cells obtained from patient biopsies. We postulate that this type of enabling technology will provide the foundation for the development of individualized combinatorial therapies of molecular inhibitors to target tumor-specific deranged pathways regulating key biologic processes including proliferation, differentiation, apoptosis, immunity and metastasis. Hence future therapies will be tailored to the specific deranged molecular circuitry of an individual patient's disease. The successful transition of these groundbreaking proteomic technologies from research tools to integrated clinical diagnostic platforms will require ongoing continued development, and optimization with rigorous standardization development and quality control procedures.

Biomarkers↗
PubMed1997

Patterns of T-cell repopulation, virus load reduction, and restoration of T-cell function in HIV-infected persons during therapy with different antiretroviral agents.

The effect of antiretroviral therapy on both T-cell numbers and T-cell function in peripheral blood was studied. CD4+ and CD8+ T-cell numbers, T-cell reactivity to CD3 monoclonal antibodies (mAb), and viral RNA load date were obtained from patients treated for at least 28 weeks with either the HIV-1 protease inhibitor ritonavir, the nonnucleoside HIV-1 reverse transcriptase (RT) inhibitor nevirapine, or the nucleoside-analogue RT inhibitor zidovudine. Compared with both RT inhibitors, treatment with the protease inhibitor ritonavir resulted in the most significant and persistent elevation of CD4+ and CD8+ T-cell counts. However, in vitro T-cell functional improvement was of limited duration in the ritonavir-treated group and was inversely correlated with viral RNA load changes during the entire follow-up period. Thus, despite what can be assumed of responses during RT inhibitor therapy, quantitative responses on therapy did not necessarily correlate with qualitative immunologic responses, as can be seen during treatment with ritonavir. For optimal immune reconstitution, both numeric and functional immunologic improvements are essential. During antiretroviral therapy, measurement of in vitro improvement in immune function will be useful as a correlate for transient drug-induced alteration of immunodeficiency.

Acquired Immunodeficiency Syndrome↗
PubMed1997

Zidovudine monotherapy versus zidovudine plus zalcitabine combination therapy in HIV-positive persons with CD4 cell counts 300-500 cells/mm3: a double-blind controlled trial. The M50003 Study Group Coordinating and Writing Committee.

OBJECTIVE: To assess the safety and clinical and immunological activity of zalcitabine/zidovudine combination therapy compared with zidovudine monotherapy in persons with no or limited antiretroviral experience and CD4 counts of 300-500 cells/mm3. DESIGN AND SETTING: A double-blind controlled multi-centre study conducted in specialist human immunodeficiency virus (HIV) care centres in Spain, Portugal and Australia. Participants were randomized at study entry to zidovudine (200 mg three times daily) plus zalcitabine (0.75 mg three times daily) or matched placebo. The primary end point was the proportion of patients with CD4 above baseline value at 24 months. The secondary end points were time to AIDS/death, quality of life (by MOS-30) and safety. RESULTS: The study was terminated prematurely following the results of the Delta and ACTG 175 studies. Two-hundred and fifty-six patients entered the protocol of whom all but 15 were treatment naive. One hundred and twenty-seven patients commenced zidovudine and 129 commenced a combination of zidovudine/zalcitabine. The median duration of follow-up was 634 days with a median time on blinded therapy of 500 days. Using the last available CD4 count data, 32.4% randomized to zidovudine and 65.1% randomized to zidovudine/zalcitabine remained above baseline at study close (P < 0.001). No significant differences were observed in the time taken for CD4 count to return to baseline. Over 104 weeks, median CD4 counts rose in the combination group from 399 to 509 cells/mm3 whereas those randomized to zidovudine fell from 410 to 374 cells/mm3. Only 12 AIDS events and two deaths (both accidental) occurred during the study with no differences between groups. No differences in quality of life were observed. Adverse events were the cause of treatment discontinuation in 8.6% of patients with no differences between treatment arms. A further 8.2% of patients were lost to follow-up. At least one adverse event (all severities, all relationships) was experienced by 80.3% of patients randomized to zidovudine and 79.8% of patients on combination. Peripheral neuropathy (all grades) was reported in 10.1% of patients randomized to the combination and 3. 1% in the zidovudine arm (P = 0.026). Oral ulcers were reported in 7.8% and 4.7% of combination and zidovudine monotherapy arms, respectively. Neutropenia was more common in the zidovudine group (22%) than the combination group (14%). CONCLUSIONS: Combination of zidovudine/zalcitabine as initial therapy maintains CD4 count above commencement levels in a significantly greater proportion of patients than zidovudine monotherapy. In persons with CD4 counts > or = 300 cells/mm3 inclusion of zalcitabine with zidovudine does not increase the incidence of adverse events or adversely affect quality of life.

Adult↗
PubMed1988

[Clinical aspects and therapy of Merkel cell tumor--report of 4 personal cases and review of the literature].

Four cases of Merkel cell tumor located in the face or on the trunk are presented. In a literature review 339 cases were found and analysed. The Merkel cell tumor is a neuroendocrine tumor of the skin derived from the Merkel cells. It is located most often in the face and neck area. Typically, it is an exophytic node, has a red-blue color and measures 25 mm in diameter on the average. Since it is metastasizing it is a malignant tumor. Regional node metastases were found in 27%, local recurrences occur in 51%, and distant metastases were seen in 32% of the cases. The best therapy is excision with wide margins as is the rule for a malignant skin tumor. While the tumor reacts to radiotherapy, chemotherapy seems to be of no help.

Adult↗
PubMed2002

"Discordant" increases in CD4 cell count relative to plasma viral load in a closely followed cohort of patients initiating antiretroviral therapy.

BACKGROUND: In HIV-positive persons receiving antiretroviral therapy, CD4 cell responses are associated with optimal suppression of viral replication. However, increases in CD4 cell counts in the absence of viral suppression have been reported. We characterized plasma viral load (pVL) and CD4 cell count increases in closely followed patients to evaluate determinants and the prevalence of CD4 cell responses at a populational level. METHODS: All HIV-positive patients in the province of British Columbia, Canada, who were antiretroviral naive and initiated therapy between August 1996 and May 1998 were eligible for the study. The selection criteria were that patients had to have CD4 cell counts and pVLs measured at baseline and at least once during eight 16-week periods after the initiation of therapy. We characterized CD4 cell responses and sought patients who had a "discordant" increase at 1 year, which was defined as an increase in CD4 cell count of >or=50/mm3 with a <1 log10 decrease in pVL. We also evaluated adherence and antiretroviral use. RESULTS: Overall, when baseline and 1-year pVLs and CD4 cell counts were compared, 6.2% of patients had CD4 cell count increases without pVL decreases of >or=1 log10. However, when all pVLs before 1 year were considered, 92% of the discordant increases could be attributed to prior transient or partial viral suppression. Furthermore, although substantial increases in CD4 cell counts were observed in transient virologic responders, the cumulative number of antiretroviral agents used by this group was significantly higher than that used by full virologic responders (p <.001). CONCLUSIONS: Our results demonstrate that virtually all CD4 cell count increases can be attributed to transient or partial pVL suppression. Unmeasured pVL suppression likely explains discordant responses that have been previously reported. Similarities between transient and full virologic responders also appear to be time limited and are often associated with greater cumulative use of antiretroviral therapy by transient virologic responders.

Adult↗
PubMed1993

[Keratinocytes from cell culture for therapy of skin defects. Review and personal results].

The development of a method to cultivate and expand human keratinocytes in vitro by Rheinwald and Green in the mid-1970s can be considered a milestone in the search for the ideal biological skin substitute. For more than 10 years, cultured keratinocytes have now been used for the treatment of various wounds. In this paper the present status knowledge and the authors own experience after treating 29 patients are discussed.

Adult↗
PubMed2025

Assessing data size requirements for training generalizable sequence-based TCR specificity models via pan-allelic MHC-I point-mutation ligandome evaluation.

Rapid identification of T cell receptors (TCRs) that specifically bind patient-unique neoepitopes is a critical challenge for personalized TCR-based therapies in oncology. Due to enormous diversity of both TCR and neoepitope repertoires, a machine learning predictor of TCR-pMHC specificity for personalized therapy must generalize to TCRs and epitopes not seen in the training data. We estimate the necessary size of such training data. We first confirm that published models fail to generalize beyond a single-residue dissimilarity to the epitope training set distribution. We then impute the point-mutation ligandome across the 34 most prevalent human MHC alleles and represent it as a graph based on our established dissimilarity cutoff. By finding the dominating set of this graph, we estimate that between one and 100 million epitopes are required to train a generalizable sequence-based TCR specificity prediction model-1000 times the size of current public data.

Humans↗
PubMedDate not supplied

[The effect of propylthiouracil on function of phagocytic peripheral blood cells in persons with thyroid hyperfunction].

INTRODUCTION: It is known that hyperthyroidism as well as thyrosuppressive therapy can influence the cells of immunological system. OBJECTIVE: To examine the function of phagocyte cells in persons with hyperthyroidism and to examine if propylthiouracil (PTU) influences this function. METHOD: The study included 15 patients with hyperthyroidism and 10 healthy persons. The parameters of phagocytic activity of mononuclear and polymorphonuclear leucocytes were tested by method of ingestion of particles of inactivated yeast labeled with neutral-red. RESULTS: It was demonstrated that patients with hyperthyroidism, before the onset of therapy as well as 14 days after introduction of PTU, had decreased number of leucocytes (before PTU: 6.7 +/- 3.2 x 10(9)/l, after PTU: 6.1 +/- 2.0 x 10(9)/l and control: 8.0 +/- 1.6 x 10(9)/l; p=0.039), PMN leucocytes (before PTU: 3.9 +/- 2,4 x 10(9)/l, after PTU: 3.5 +/- 1.6 x 10(9)/l and control: 4.8 +/- 0.9 x 10(9)/l; p=0.037) and number of phagocyte PMN cells (before PTU: 0.9 +/- 0.9 x 10(9)/l, after PTU: 0.9 +/- 0.7 x 10(9)/l and control: 1.3 +/- 0.6 x 10(9)/l; p<0,05), but they had increased index of phagocytosis (before PTU: 2.0 +/- 0.2, after PTU: 1.9 +/- 0.2 and control: 1.7 +/- 0.2; p=0.029), while capacity of phagocytosis remained unchanged (before PTU: 1.9 +/- 1.7 x 10(9)/l, after PTU: 1.6 +/- 1.9 x 10(9)/l and control: 2.4 +/- 1.4 x 10(9)/l; p>0.05). The number of mononuclear leucocytes and parameters of phagocytic activity of mononuclear phagocytes in persons with hyperthyroidism did not change significantly in comparison with the control group. CONCLUSION: Patients with hyperthyroidism had decreased number of leucocytes, PMN leucocytes and number of phagocyte PMN cells, and increased index of phagocytosis, while capacity of phagocytosis remained unchanged. The number and parameters of phagocytic activity of mononuclear leucocytes did not change. PTU therapy had no effect on the examined parameters.

Adult↗
PubMed1999

[Development of insulinoma cells as therapy in insulin-dependent diabetes mellitus].

In healthy persons insulin secreting beta-cells of the pancreas regulate blood glucose levels within a narrow physiological range. Since the detection of insulin in 1922 by Banting and Best, subcutaneous insulin replacement has remained the sole treatment modality for insulin-dependent diabetes mellitus (IDDM). However, even trained patients undergoing intensive insulin therapy fail to achieve normal function of the pancreatic beta-cells. One approach to solve this problem is pancreas and islet cell transplantation. Because of technical problems, limited number of transplantable organs and toxicity of immunosuppressive therapy, both are still in an experimental state. An alternative approach is the development of genetically modified insulin secreting cell lines for replacement of islet cells. So far, experiments support the expectation to develop genetically manipulated cell lines who imitate the function of islet beta-cells and are protected from the immune response. The ultimate goal is the development of an engineered human beta-cell line and, after animal experiments, to use it for treatment of patients with IDDM.

Animals↗
PubMed2002

An anti-CD45RO immunotoxin kills latently infected human immunodeficiency virus (HIV) CD4 T cells in the blood of HIV-positive persons.

Highly active antiretroviral therapy has decreased the morbidity and mortality of human immunodeficiency virus (HIV) infection, but latently infected cells remain for prolonged periods. CD4(+) CD45RO(+) T cells are a major latent virus reservoir in HIV-infected persons. Replication-competent, latently HIV-infected T cells can be generated in vitro by infecting peripheral blood mononuclear cells with HIV and then eliminating the HIV-producing cells with an anti-CD25 immunotoxin (IT). The CD25(-) latently infected cells then can be eliminated with an anti-CD45RO IT. This study determined whether this IT also could kill latently infected CD4 T cells from HIV-infected persons with or without detectable plasma viremia. The results show that ex vivo treatment of cells from HIV-positive persons by anti-CD45RO IT reduces the frequency of both productively and latently infected cells. In contrast, CD4(+) CD45RA(+) naive T cells and a proportion of CD4(+) CD45RO(lo) memory T cells are spared.

Antiretroviral Therapy, Highly Active↗
PubMed2006

CD4+ cell count 6 years after commencement of highly active antiretroviral therapy in persons with sustained virologic suppression.

BACKGROUND: Sustained suppression of the human immunodeficiency virus (HIV) type 1 RNA load with the use of highly active antiretroviral therapy (HAART) results in immunologic improvement, but it is not clear whether the CD4(+) cell count increases to normal levels or whether it reaches a less-than-normal plateau. We characterized the increase in the CD4(+) cell count in patients in clinical practice who maintained sustained viral suppression for up to 6 years. METHODS: All patients were from the Johns Hopkins HIV Clinical Cohort, a longitudinal observational study of patients receiving primary HIV care in Baltimore, Maryland, who were observed for >1 year while receiving HAART and who had sustained suppression of the HIV RNA load at <400 copies/mL. We analyzed annual change in the CD4(+) cell count for up to 6 years after the start of HAART, stratified by baseline CD4(+) cell counts of < or =200, 201-350, >350 cells/microL, and we assessed the development of clinical events (death and new acquired immunodeficiency syndrome-defining illness) by Kaplan-Meier analysis. RESULTS: A total of 655 patients were observed for a median of 46 months (range, 13-72 months). The median change from baseline to most recent CD4(+) cell count was +274 cells/microL, with 92% of patients having an increase in CD4(+) cell count. By 6 years, the median CD4(+) cell count was 493 cells/microL among patients with baseline CD4(+) cell counts < or =200 cells/microL, 508 cells/microL among those with baseline CD4(+) cell counts of 201-350 cells/microL, and 829 cells/microL among those with baseline CD4(+) cell counts >350 cells/microL. In addition to baseline CD4(+) cell count, injection drug use and older age were associated with a lesser CD4(+) cell count response, and duration of therapy was associated with a greater CD4(+) cell count response. CONCLUSION: Only patients with baseline CD4(+) cell counts >350 cells/microL returned to nearly normal CD4(+) cell counts after 6 years of follow-up. Significant increases were observed in all CD4(+) cell count strata during the first year, but there was a lower plateau CD4(+) cell count at lower baseline CD4(+) cell strata. These data suggest that waiting to start HAART at lower CD4(+) cell counts will result in the CD4(+) cell count not returning to normal levels.

Adult↗
PubMed1989

Inhibitory effect of azidothymidine, 2'-3'-dideoxyadenosine, and 2'-3'-dideoxycytidine on in vitro growth of hematopoietic progenitor cells from normal persons and from patients with AIDS.

Therapy of patients with the acquired immunodeficiency syndrome (AIDS) or AIDS-related complex (ARC) with azidothymidine (AZT) and 2'-3'-dideoxycytidine (ddC) is complicated by severe anemia, neutropenia, and thrombocytopenia, the cause of which is unknown. We therefore tested the effect of AZT, ddC, and an additional 2'-3'-dideoxynucleoside analogue, 2'-3'-dideoxyadenosine (ddA), on the hematopoietic progenitor cells derived from the bone marrow of normal persons and patients with AIDS/ARC. All three substances dose-dependently inhibited the in vitro colony formation of the pluripotent (CFU-GEMM), as well as the erythroid (BFU-E) and granulocyte-macrophage progenitor cells (CFU-GM). The 50% inhibition of normal progenitors by AZT occurred at 0.13 microM for CFU-GEMM, 0.32 microM for BFU-E, and 1.9 microM for CFU-GM, by ddA at 15 microM for CFU-GEMM, 40 microM for BFU-E, and 140 microM for CFU-GM. ddC was the most toxic agent and already inhibited 71% +/- 16% (mean +/- standard error of the mean [SEM]) of CFU-GEMM and 52% +/- 22% of BFU-E at 0.1 microM, whereas the 50% inhibition of CFU-GM was reached at 0.3 microM. Hematotoxicity occurred at concentrations lower than necessary to inhibit the human immunodeficiency virus (HIV), except for ddA, which is 100 times less toxic than AZT whereas its antiviral effect is only 10 times less. The inhibition of progenitor cells from AIDS patients by the 2'-3'-dideoxynucleosides was comparable to normal progenitors, except for a higher sensitivity of AIDS-derived CFU-GEMM and BFU-E to AZT.

AIDS-Related Complex↗
PubMed2000

Decreased CD95 expression on naive T cells from HIV-infected persons undergoing highly active anti-retroviral therapy (HAART) and the influence of IL-2 low dose administration. Irhan Study Group.

The functional recovery of the immune system in HIV-infected persons receiving HAART and the role of adjuvant immune therapy are still matters of intensive investigation. We analysed the effects of HAART combined with cytokines in 22 naive asymptomatic individuals, randomized to receive HAART (n = 6), HAART plus a low dose (1000 000 U/daily) of rIL-2 (n = 8), and HAART plus rIL-2 after previous administration of granulocyte colony-stimulating factor (n = 8). After 3 months of therapy, increased CD4+ T cell counts and diminished viral loads were observed in all patients, independently of cytokine addition. A decreased expression of CD95 (Apo 1/Fas) was evident in all groups when compared with values before therapy. The percentages of peripheral blood mononuclear cells (PBMC) expressing CD95 after therapy decreased by 15%, 22% and 18% in the three treatment groups, respectively (P < 0.05). Analysis of PBMC subsets demonstrated that CD95 expression was significantly reduced on CD45RA+CD62L+ naive T cells (25.3%, 22.4%, and 18.6%, respectively; P < 0.05) in each group, after therapy. Accordingly, all patients showed a reduced rate of in vitro spontaneous apoptosis (P < 0.05). Another effect induced by HAART was a significant increase in IL-2Ralpha expression on total PBMC (P < 0.05), independently of cytokine addition. Altogether, our results suggest that very low dose administration of rIL-2 (1000 000 U/daily) may be not enough to induce a significant improvement in the immune system as regards HAART alone. The employment of higher doses of recombinant cytokines and/or different administration protocols in clinical trials might however contribute to ameliorate the immune reconstitution in patients undergoing HAART.

Adult↗
PubMed2004

Factors influencing increases in CD4 cell counts of HIV-positive persons receiving long-term highly active antiretroviral therapy.

BACKGROUND: Highly active antiretroviral therapy (HAART) results in an improvement in immunologic function. We sought to investigate the factors associated with increases in CD4 cell count among human immunodeficiency virus (HIV)-positive antiretroviral-naive patients starting HAART. METHODS: Five hundred ninety-six subjects were followed for a median of 2.5 years (interquartile range, 1.0-4.0 years). Factors associated with changes in CD4 cell counts in the first 3 months of HAART and from 3 months onwards were analyzed. RESULTS: After 6, 12, and 24 months of HAART, the median increases in CD4 cell counts were 114, 181, and 248 cells/mm3, respectively; 84%, 84%, and 80% of subjects had a virus load of <400 copies/mL during the same periods. White ethnicity, higher pre-HAART virus load, and lower pre-HAART CD4 and CD8 cell counts were associated with greater increases in CD4 cell counts during the first 3 months of HAART. From 3 months onward, a greater cumulative proportion of time spent with virus load <400 copies/mL was associated with a more favorable change in CD4 cell count (an average increase of 5.2 cells/mm3/year [95% confidence interval [CI], 3.8-6.7 cells/mm3/year] for each extra 10% cumulative time spent with a virus load <400 copies/mL) (P<.0001). For every 100 cells/mm3 higher in baseline CD4 cell count, the increase was 6 cells/mm3/year less (95% CI, 2-11 cells/mm3/year) (P=.02). Sex, risk group, age, and HAART regimen were not associated with increases in CD4 cell counts. CONCLUSIONS: These findings emphasize the importance of maintaining virological suppression and suggest other factors that influence long-term CD4 cell response.

Age Factors↗