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PubMed2005

A multicenter evaluation of the PanLeucogating method and the use of generic monoclonal antibody reagents for CD4 enumeration in HIV-infected patients in Thailand.

BACKGROUND: The current method of CD4 enumeration in Thailand, based on the three-tube, three-color method recommended by the Centers for Disease Control and Prevention, is expensive and thus unavailable to most patients who have the human immunodeficiency virus (HIV). Less expensive, simpler protocols (i.e., PanLeucogating and primary CD4 gating) have been described but require more published validation data to gain widespread acceptance. We describe a multicenter evaluation of the PanLeucogating method. METHODS: The PanLeucogating method using generic reagents was evaluated in comparison with the standard three-tube, three-color method using commercial reagents. Percentage of CD4+ T cells among lymphocytes and absolute CD4+ T-cell counts were determined in 611 HIV-infected individuals recruited from four sites. Linear regression and Bland-Altman tests were used for statistical analysis. RESULTS: The correlation of percentage of CD4+ T cells and absolute CD4+ T-cell counts obtained with the PanLeucogating strategy and the standard predicate method was high (r2 = 0.96 and 0.95, respectively, for the entire study population and r2 > 0.95 and 0.93, respectively, for each study group). Absolute CD4+ T-cell counts of the overall study pool and of the two subdivisions of absolute CD4+ T-cell counts (i.e., 0-250 cells/microl and > 250 cells/microl) derived from the two methods demonstrated excellent agreement, with mean biases of +18 cells/microl, +11 cells/microl, and +24 cells/microl, respectively. CONCLUSIONS: These observations demonstrate that CD4 enumeration by PanLeucogating is reliable and can be performed to an identical standard in a quality-assured network of collaborating laboratories as a new cost-effective approach to HIV monitoring.

Acquired Immunodeficiency Syndrome↗
PubMed1993

Spectrum of immunodeficiency in HIV-1-infected patients with pulmonary tuberculosis in Zaire.

Tuberculosis (TB) is the most common opportunistic infection in African patients who die from AIDS, yet the stage of immunodeficiency at which TB develops is uncertain. We studied the immune status of HIV-infected outpatients with pulmonary TB in relation to their clinical presentation in a cross-sectional study of 216 HIV-seropositive and 146 HIV-seronegative ambulatory incident cases of smear-positive and culture-positive pulmonary TB in Kinshasa, Zaire. HIV-seropositive and seronegative patients had median CD4 lymphocyte counts of 316.5/microL and 830.5/microL, respectively. Of the HIV-seropositive patients, 32.9% had less than 200 CD4 lymphocytes/microL, 37% between 200 and 499, and 30.1% 500 or more. Clinical AIDS, as defined by the WHO clinical case-definition or a modified version, was of similar limited use as a predictor of immunodeficiency. Among HIV-seropositive patients, oral candidosis, lymphopenia, a negative tuberculin purified protein derivative test, and cutaneous anergy were strongly associated with CD4 counts of less than 200/microL, and seemed to be better markers of immune dysfunction. We conclude that pulmonary TB develops across a broad spectrum of HIV-induced immunodeficiency and that a diagnosis of pulmonary TB is of limited use as a marker of stage of HIV disease in African HIV-infected outpatients.

AIDS-Related Opportunistic Infections↗
PubMed1989

Predictors of outcome in AIDS patients receiving zidovudine.

Fifty-eight AIDS patients who previously had Pneumocystis carinii pneumonia (PCP) were enrolled in an open trial of zidovudine therapy. We analyzed baseline clinical and laboratory parameters to identify predictors of outcome. Fifty-eight patients were followed for a mean of 26.5 weeks. There were 17 deaths; the probability of survival at 24 weeks was 0.81. Forty-one participants had unsuccessful outcomes, which included new opportunistic infections (24), progressive neurologic deterioration (2), and drug toxicity, excluding anemia, necessitating discontinuation of zidovudine (15). Only 24 subjects (41%) were receiving zidovudine at the end of the study period including 17 who had neither opportunistic infection nor toxicity. Low baseline hemoglobin level (p less than 0.001) and poor performance status as measured by the Karnofsky scale (p less than 0.01) independently predicted unsuccessful outcome and early death. Low hemoglobin (p = 0.001), low platelet count (p = 0.016), and increased time since PCP (p = 0.008) predicted development of drug toxicity. Neither CD4 lymphocyte count nor p24 antigenemia correlated with outcome.

Acquired Immunodeficiency Syndrome↗
PubMed2001

Prevalence and cumulative incidence of and risk factors for anemia in a multicenter cohort study of human immunodeficiency virus-infected and -uninfected women.

We conducted a longitudinal study of 797 human immunodeficiency virus (HIV)-positive women (7732 visits) and 389 HIV-negative women (3651 visits) to characterize anemia. At enrollment, the prevalence of anemia was 28.1% among HIV-positive women and 15.1% among HIV-negative women (P<.0001), and during follow-up the cumulative incidence of anemia was 74% and 48%, respectively (P<.0001). Risk factors for anemia were African American race (odds ratio [OR], 2.15; 95% confidence interval [CI], 1.73-2.69), age (per 5-year increase; OR, 1.12; 95% CI, 1.03-1.21), body mass index (OR, 0.96; 95% CI, 0.94-0.97), history of pneumonia (OR, 1.41; 95% CI, 1.20-1.65), oral candidiasis (OR, 1.42; 95% CI, 1.22-1.66), CD4+ lymphocyte count <200 cells/microL (OR, 1.68; 95% CI, 1.46-1.94), history of fever (OR, 1.42; 95% CI, 1.13-1.80), and zidovudine use (OR, 1.14; 95% CI, 1.01-1.30). Anemia was common and associated with an increased risk of death (hazards ratio, 1.64; 95% CI, 1.21-2.23) among HIV-positive women.

Adult↗
PubMed1993

Idiopathic CD4+ lymphocyte deficiency. Report of an unusual case associated with atopic dermatitis and allergic contact dermatitis and review of the literature.

BACKGROUND: Idiopathic CD4+ lymphocyte deficiency is a newly described entity of apparently non-human immunodeficiency virus-associated helper T-cell depletion. The clinical spectrum continues to evolve, but, to date, it has included patients ranging from those with minimal symptoms to those who have died with acute opportunistic infections. Several individual cases have been previously reported, many with distinctive, primarily infectious, cutaneous manifestations. OBSERVATIONS: We describe a patient with idiopathic CD4+ lymphocyte deficiency distinguished by a unique clinical presentation of atopic dermatitis exacerbated by contact urticaria and allergic contact dermatitis. She has a persistent markedly diminished CD4+ lymphocyte count (absolute count less than 50), no serologic evidence of, or risk factors for, human immunodeficiency virus infection, and no history of opportunistic infections. CONCLUSIONS: We present a possible new cutaneous manifestation of idiopathic CD4+ lymphocyte disease and summarize the previously reported cases, with an emphasis on the cutaneous features.

Adult↗
PubMed2003

Phenotypic changes in lymphocyte subpopulations in pediatric renal-transplant patients after T-cell depletion.

BACKGROUND: T-cell depletion causes a novel homeostasis in lymphocyte subsets in adult transplant recipients. Little is known about long-term changes in pediatric patients. METHODS: Twenty-one pediatric renal-transplant patients (mean age 11.8 years) were selected according to their initial postoperative immunosuppressive therapy: (1) baseline immunosuppression (BI) with cyclosporine, azathioprine, and steroids, n=11; and (2) BI plus polyclonal antibodies, n=10. Lymphocyte surface markers were measured in the mean 2.3 years after transplantation and analyzed between the patient groups and in regard to 46 age-matched healthy controls. RESULTS: The patient groups did not differ with respect to age, sex, renal function, and previous infections. Total lymphocyte counts, CD4+ T-cell numbers, and distribution of naive to memory CD4+ T cells were not different between transplant groups and controls. However, patients with postoperative T-cell depletion showed significantly lower ratios of CD4+ to CD8+ T cells, elevated CD8+ T-cell numbers, increased counts of CD8+ T cells coexpressing CD57, and higher numbers of CD8+ cells with a naive phenotype. In addition, the numbers of double-positive T cells and lymphocytes bearing both natural killer (NK) and T-cell markers were elevated in the patients with postoperative depletion. NK and B-cell counts were lower in the transplant patient groups compared with the healthy controls. CONCLUSIONS: Pediatric transplant patients show characteristic long-term changes in lymphocyte subsets after T-cell depletion. In contrast with adult patients, these perturbations are less pronounced and predominant in the CD8+ T-cell compartment.

Adolescent↗
PubMed1992

[Esophageal candidiasis in HIV positive patients. Lack of statistical correlation with CD4 lymphocytes].

One hundred and twenty-nine upper gastrointestinal endoscopies were performed between November, 1986, and November, 1990, at the Fort-de-France Hospital (Martinique), on 92 patients who were seropositive for the human immunodeficiency virus (HIV). Blood samples were drawn at the same time as 75 endoscopic examinations and the number of CD4 lymphocytes/mm3 was determined. The incidence of esophageal candidiasis was 23.1% and lesions were observed in 17.2% of the endoscopies performed systematically at the time that the patient's seropositivity was first established. No significant relationship was found between the presence of esophageal candidiasis and peripheral blood CD4 lymphocyte counts.

AIDS-Related Opportunistic Infections↗
PubMed1993

Idiopathic CD4+ T-lymphocytopenia--immunodeficiency without evidence of HIV infection.

BACKGROUND: The human immunodeficiency virus (HIV), the etiologic agent of the acquired immunodeficiency syndrome (AIDS), infects and depletes CD4+ T lymphocytes. Recently, patients have been described with profound CD4+ T-lymphocytopenia but without evident HIV infection, a condition now termed idiopathic CD4+ T-lymphocytopenia, and a national surveillance network has been set up to investigate such cases. METHODS: We studied 12 patients with CD4+ T-lymphocytopenia who were referred to us from three U.S. cities. Blood samples were tested for HIV with specific antibody assays, viral cultures, and polymerase-chain-reaction (PCR) techniques. RESULTS: The patients (10 men and 2 women) ranged in age from 30 to 69 years. Eight had risk factors for HIV infection. The clinical manifestations were heterogeneous: five patients had opportunistic infections, five had syndromes of unknown cause, and two had no symptoms. Two patients died from acute complications of their immunodeficiency. The patients' lowest CD4+ lymphocyte counts ranged from 3 to 308 per cubic millimeter (mean, 149). Three patients had complete or partial spontaneous reversal of the CD4+ T-lymphocytopenia. Concomitant CD8+ T-lymphocytopenia was noted in three patients, and abnormal immunoglobulin levels were found in five. Multiple virologic studies by serologic testing, culture, and PCR were completely negative for HIV in all patients. CONCLUSIONS: Our 12 patients with idiopathic CD4+ T-lymphocytopenia appear to be epidemiologically, clinically, and immunologically heterogeneous. It is unclear whether this syndrome is new, transmissible, or acquired. Many of the clinical and immunologic features are distinct from those found in AIDS, and our extensive virologic studies found no evidence of HIV infection. The cause of this condition remains unknown.

Adult↗
PubMed1993

Cellular and plasma viral load in patients infected with HIV-2.

OBJECTIVE: To determine circulating viral load in HIV-2-infected individuals. METHODS: Viral load was determined in 40 HIV-2-infected adults using standardized quantitative cell and qualitative plasma viraemia assays. We also tested for proviral HIV-2 DNA using single and nested polymerase chain reaction (PCR) in fresh lymphocytes from 27 subjects. The results were compared, on the basis of the CD4+ lymphocyte count, with our published data for HIV-1 infection. RESULTS: HIV-2 was isolated from peripheral blood mononuclear cells (PBMC) from 19 individuals and plasma from four patients. The rate of cell and plasma viraemia positivity correlated with the CD4+ cell count and HIV-2 virus load increased as the CD4+ cell count fell. The cellular HIV-2 load in the patients with a CD4+ count < 200 x 10(6)/l was similar to reported values for HIV-1, but the HIV-2 isolation rate from the plasma of these individuals was significantly lower than for HIV-1. When the CD4+ count was between 200 and 500 x 10(6)/l, the rate of HIV-2 isolation from plasma and the cellular virus load were both significantly lower than for HIV-1. When the CD4+ count was > 500 x 10(6)/l, HIV-1 and HIV-2 were undetectable in plasma and HIV-1 was isolated from PBMC in significantly more cases than HIV-2. By single PCR, amplification were positive in 14 out of 27 subjects and there was a correlation between positivity and CD4+ cell count. By nested PCR, only four of the 27 subjects, all with a high CD4+ count, remained negative. CONCLUSIONS: Differences in viral load between individuals infected with HIV-2 and those infected with HIV-1 could partly account for reported differences in the pathogenicity of the two viruses.

Adult↗
PubMed1994

Transfusion of blood components to persons infected with human immunodeficiency virus type 1: relationship to opportunistic infection.

BACKGROUND: Although a recent study reported shorter survivals in human immunodeficiency virus type 1 (HIV-1)-infected patients who received transfusions, no study has analyzed the relationship in such patients between the frequency of opportunistic infection and transfusion. STUDY DESIGN AND METHODS: Records of 196 HIV-1-infected subjects with CD4 lymphocyte counts below 250 cells per mm3 were reviewed to determine if there were more opportunistic infections in patients who previously received transfusions than in those who received no transfusions. The decline in CD4 cells was also compared, and the frequency of transfusion reactions and red cell alloantibodies was assessed. RESULTS: The frequency of cytomegalovirus (CMV), wasting, and bacterial infections (p < 0.01), but not the frequency of Pneumocystis carinii pneumonia (PCP) (p > 0.2), was significantly increased in the patients who had previously received transfusions, and this effect was independent of CD4 count, race, or risk factor. The frequency of CMV infection, but not of PCP, was also related to the number of units of blood received (p < 0.01). Significant bacterial infections occurred primarily in persons with CMV infection, of whom there were more in the transfusion cohort. When analyzed separately in the group of patients without CMV infection, the frequency of bacterial infection was unrelated to transfusion. The death rate in those who received transfusions was also greater than that in patients who had never received a transfusion. None of the 130 patients who received red cell transfusions developed red cell alloantibodies. CONCLUSION: The higher incidence of certain infectious complications in HIV-1-infected patients who received transfusions indicates that the relationship of transfusion to virus activation in patients with acquired immunodeficiency syndrome and the potential benefits of modifying the preparation of blood components should be investigated further.

AIDS-Related Opportunistic Infections↗
PubMed1997

Cryptococcosis associated with AIDS in the Muñiz Hospital of Buenos Aires.

Some epidemiologic, diagnostic and immunologic aspects of 93 (75 males and 18 women) cases of cryptococcosis (CRY) associated with AIDS, hospitalized in the Muñiz Hospital (MH) in Buenos Aires during 1994, were retrospectively studied. The median age (MA) of the patients under study was 28 years (17-49 y); 30 (17-49) y for males and 23 (22-34) y for women. Intravenous drug addiction (34% of patients) and homo/bisexuality in men (17%) were the most frequent risk factors for HIV infection. The MA of these groups were 27.5 (17-41) y and 34 (25-41) y, respectively. Microscopic CSF examination with India ink and the blood cultures (lysis-centrifugation) achieved the diagnosis of CRY in 67 (72%) and 16 (17%) patients, respectively. At diagnosis, the median titers for Cryptococcus neoformans capsular antigen were 1/1,000, 1/100 and 1/1 in serum, CSF and urine, respectively. Sixty five strains of C. neoformans were insolated from clinical samples; all were identified at variety neoformans employing the culture medium proposed by Salkin & Hurd and the D-proline assimilation test. At diagnosis, CD4+ lymphocytes counts were < 50/microliter in 46 patients (83.63%), and were between 51 and 200/microliter in 9 (16.4%). The CD4+/CD8+ ratio was < 1 in all patients. Most patients were born (83%) and lived at diagnosis (96%) in Buenos Aires (Bs As) city, Bs As outskirts towns and cities located in Bs As province.

Acquired Immunodeficiency Syndrome↗
PubMed2006

Association of CD4+ T-lymphocyte counts and new thymic emigrants in HIV-infected children during successful highly active antiretroviral therapy.

BACKGROUND: In a cohort of children receiving highly active antiretroviral therapy (HAART) with sustained plasma HIV-1 RNA < 50 copies/mL, children who reached undetectable RNA after week 8 (slow responders, median: week 20) had higher HIV-1 intracellular DNA (HIV-1 DNA) and equal or greater CD4+ T-lymphocyte counts compared with children who reached undetectable plasma HIV-1 RNA by week 8 (rapid responders) throughout HAART. OBJECTIVE: To determine whether levels of T-cell receptor excision circles (TRECs) could explain the apparent inconsistency between the quantity of HIV-1 DNA and CD4+ T-lymphocyte counts in HIV-1-infected children receiving HAART with sustained virologic suppression. METHODS: T-cell receptor excision circles and HIV-1 DNA and plasma HIV-1 RNA were quantified longitudinally by PCR in 31 children (median age, 5.6 years) with sustained undetectable plasma HIV-1 RNA for >104 weeks of HAART. RESULTS: There was a positive correlation between TREC and HIV-1 DNA during HAART, notably at weeks 48 and 80 (P < .004). During the early stage of HAART, TREC levels positively correlated with CD4+ T-lymphocyte percentages (P < .02) and naive CD4+ T-lymphocyte counts (P < .001) and percentages (P = .05). Median TREC levels were consistently equal or higher in slow responders compared with rapid responders (P < .001) despite slow responders having consistently greater quantities of HIV-1 DNA. CONCLUSION: To maintain adequate levels of CD4+ T-lymphocytes, children with high HIV-1 DNA maintain high levels of TREC while receiving HAART. Thus, a thymic control mechanism is required to maintain new CD4+ T lymphocytes in the presence of persistent virus. CLINICAL IMPLICATIONS: The TREC level is a useful marker of thymic function in HIV-infected children.

Adolescent↗
PubMed1992

Zidovudine-interferon-alpha combination therapy in patients with advanced human immunodeficiency virus type 1 infection: biphasic response of p24 antigen and quantitative polymerase chain reaction.

In an open-label dose-ranging pilot trial, 13 homosexual men with human immunodeficiency virus type 1 (HIV-1) p24 antigenemia after at least 6 weeks of zidovudine monotherapy were continued on zidovudine and given interferon-alpha, 1.25-7.5 x 10(6) units/m2 subcutaneously three times/week. Plasma p24 antigen levels demonstrated a biphasic response, falling initially in 11 patients by a mean of 50% (95% confidence interval, 36%-64%; P = .001) at a median of 11 weeks, but rising steadily thereafter (P = .001). CD4+ cell counts fell by a mean of 7.1 cells/mm3/week (P = .01). Higher initial CD4+ counts predicted greater p24 antigen reductions. At higher interferon doses no greater reductions in p24 antigen occurred, but side effects were more severe and CD4+ lymphocyte counts fell faster. Polymerase chain reaction quantification of HIV-1 DNA in 3 patients showed a biphasic pattern paralleling the p24 antigen response. In sum, although evidence of short-term effects was found, the combination showed no evidence of lasting antiviral activity beyond that achieved with zidovudine alone in patients with advanced HIV-1 infection.

AIDS-Related Complex↗
PubMed1994

The use of intravenous immunoglobulins in symptomatic HIV infection. Results of a randomized study.

To study the efficacy of intravenous immunoglobulin in symptomatic infection with human immunodeficiency virus (HIV) we enrolled 35 patients with CD4 lymphocyte counts below 300/microliter in a randomized three-arm study. In addition to standard HIV treatment (e.g., zidovudine, aerosolized pentamidine), 13 patients were treated with 7.5 g and 11 with 40 g of a 7 S intravenous IgG preparation every 4 weeks over a period of 1 year. A control group of 11 patients remained on standard treatment. Clinical and laboratory parameters, including lymphocyte proliferation and in vitro immunoglobulin synthesis were evaluated prior to intravenous IgG administration. HIV-specific immunological abnormalities such as increased B-cell activation and B-cell immaturity were observed in all three study groups at the beginning of the study. Mitogen-induced lymphocyte proliferation was diminished. These disturbances were not influenced by intravenous IgG treatment. Further laboratory data and the course of the HIV infection (fever, antibiotic treatment, hospitalization, Candida and herpes simplex or cytomegalovirus infection) remained unchanged. Thus, our data with an observation period of 12 months do not support the use of intravenous IgG treatment in adult symptomatic HIV-infected patients with CD4 counts lower than 300/microliter.

AIDS-Related Opportunistic Infections↗
PubMed2002

Kinetics of early FIV infection in cats exposed via the vaginal versus intravenous route.

To determine the influence of route of virus exposure on early pathogenesis of feline immunodeficiency virus (FIV) infection, cats were exposed to either of two FIV isolates (FIV-B-2542 or FIV-A-PPR) by vaginal or intravenous (IV) inoculation. Exposure to either virus clade by either route of inoculation resulted in vaginal and systemic infection. Peak plasma viremia and tissue proviral burden were 1-3 log(10) greater in cats infected with FIV-B-2542 vs. FIV-A-PPR, irrespective of inoculation route. Plasma RNA levels paralleled provirus titers in FIV-B-2542-infected cats and were highest in those exposed IV. In contrast, plasma RNA titers were higher in cats infected vaginally with FIV-A-PPR than in those infected IV. Despite early differences, PBMC provirus titers were similar in all groups by 9 weeks postinfection. In cats infected IV, but not vaginally, CD4(+) lymphocyte counts declined significantly independent of the magnitude of viremia. Mitogen-induced lymphoproliferation was decreased in all infected cats regardless of CD4(+) cell counts; this decline correlated with the magnitude of peak plasma viremia in FIV-B-2542, but not FIV-A-PPR, infected cats. These results establish that the kinetics of early FIV infection differ with route of exposure as well as virus isolate and that properties extrapolated from one virus isolate may not be universal.

Animals↗
PubMed2001

Virologic and immunologic parameters that predict clinical response of AIDS-associated Kaposi's sarcoma to highly active antiretroviral therapy.

The purpose of the work was to assess the predictive value of biologic factors on the efficacy of highly active antiretroviral therapy alone or combined with chemotherapy on AIDS-associated Kaposi's sarcoma. Twenty-six AIDS-Kaposi's sarcoma patients who started therapy with protease inhibitors were investigated. No baseline chemotherapy was associated with less severe initial clinical status. Median follow-up was 652 d. The main outcome measures were as follows: best Kaposi's sarcoma clinical response; Kaposi's-sarcoma-associated herpesviral load in peripheral blood mononuclear cells using real-time quantitative polymerase chain reaction (non-detectable if less than 100 copies per microg); human immunodeficiency viral charge in plasma (non-detectable if less than 200 copies per ml); and CD4 lymphocyte count. Time to undetectable Kaposi's-sarcoma-associated herpesviral load, time to undetectable human immunodeficiency viral charge, and time to CD4 >or= 150 per microl were also recorded over time, from 2 mo measurements. Patients were staged according to the AIDS Clinical Trials Group-based tumor, immune, systemic staging system criteria. At baseline, Kaposi's sarcoma was progressive for 25 (96%) of the 26 enrolled patients. Complete or partial response to highly active antiretroviral therapy alone or combined with chemotherapy was achieved in 22 patients (85%). Median time to clinical response was estimated at 251 d. Clinical response was faster in patients without chemotherapy at baseline (p = 0.003) as well as in patients not previously treated with reverse transcriptase inhibitors (p = 0.0012). Using univariable analyses, predictive factors of clinical response were undetectable Kaposi's-sarcoma-associated herpesviremia (p = 0.013), undetectable human immunodeficiency viremia (p = 0.03), and relative variation of CD4 lymphocytes (p = 0.004). Using multivariable analysis, undetectable Kaposi's-sarcoma-associated herpesviremia (p = 0.009) and relative variation of CD4 (p = 0.005) were independently selected as having a predictive value for clinical response. Occurrence of nondetection of either Kaposi's-sarcoma-associated herpesvirus or human immunodeficiency virus was not associated with baseline CD4 value. Kaposi's-sarcoma-associated herpesvirus quantitative viral charge is an independent predictive factor of the efficacy of highly active antiretroviral therapy on AIDS-Kaposi's sarcoma. Our results support immune reconstitution as a mechanism of response of Kaposi's sarcoma to highly active antiretroviral therapy.

Acquired Immunodeficiency Syndrome↗
PubMed2000

Primary thymic endocrine failure in HIV-1-infected children.

Thymulin, an essential hormone for the T lymphocyte differentiation process and function, was evaluated to asses thymic endocrine function in a cohort of 17 HIV-1-infected children aged between 2 months and 14 years, 18 seroreverted subjects and 47 normal controls. The rosette inhibition assay by Dardenne and Bach (1975) is the only method available to evaluate the biologically active form of this hormone (thymulin or Zn-facteur thymique sérique, Zn-FTS), as immunoassays cannot discriminate between thymulin and the inactive form of the hormone not containing Zn (FTS). HIV-1 patients presented undetectable or significantly lowered plasma levels of thymulin. Plasma zinc levels were significantly reduced in patients although inactive, zinc-unbound thymulin molecules were not demonstrated. The investigation of inhibitory anti-thymulin molecules performed in all patients was negative. Thymulin titers did not correlate with CD4+ lymphocyte count at the different disease stages. This study suggests that a primary thymic endocrine deficiency is present in HIV children. The critical importance of these results in assessing disease progression and a potential therapeutic approach are discussed.

Adolescent↗
PubMedDate not supplied

Preliminary experiences with ritonavir in children with advanced HIV infection.

The aim of this study was to obtain information on the feasibility (tolerance, safety) of antiretroviral combination therapy, including ritonavir, in children. In eight children (median age 8.9 years; range 3 to 13 years) with advanced HIV disease (median CD4+ lymphocyte count at baseline, 80 cells/microliter; range 0 to 280 cells/ microliter), drug combinations including ritonavir (approximately 300 mg/m2 b.i.d.) were administered. In seven children, previous therapy using a combination of at least two nucleoside reverse transcriptase inhibitors (NRTI) had failed. Four patients had ritonavir added to an already existing regimen of two NRTI; two patients had one NRTI replaced by a new one; and in two patients two new NRTI were initiated. The number of CD4 T cells, plasma HIV RNA concentration, CBC and blood chemistry profile were monitored. Medication had to be discontinued in two children because of severe nausea and vomiting. In the remaining six children, ritonavir was tolerated and treatment was maintained for at least 6 months. The number of CD4 cells increased in five of six patients. The median number of CD4 cells increased from 66 +/- 110 cells/microliter at baseline to 92 +/- 99 cells/microliter, 161 +/- 88 cells/microliter, and 252 +/- 25 cells/microliter after 1, 3 and 6 months of therapy, respectively. The plasma HIV RNA concentration decreased below the detection limit of 500 copies/ml in three children. In the remaining children a maximum reduction of 0.8, 1.0 and 1.8 log10 was observed. In one child the HIV RNA concentration reincreased after 6 months by 0.7 log10 above the nadir. Antiretroviral combinations including ritonavir were tolerated by six of eight children and produced substantial benefits with respect to increased numbers of CD4 cells and a decline in plasma viral RNA concentration. It can be concluded that the administration of ritonavir is possible in a significant proportion of HIV-infected children, and leads to improvement of the CD4 cell count and viral load.

Adolescent↗