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Results for “CD4 Lymphocyte Count”

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PubMed1999

Quantitative pp65-antigenemia assay for the prediction of human cytomegalovirus disease in HIV-infected patients.

OBJECTIVE: To evaluate the ability of a quantified pp65-antigenemia assay to predict the development of human cytomegalovirus (HCMV) disease in patients with an advanced HIV infection. DESIGN: A prospective longitudinal study between March 1993 and December 1996. Blood samples for the pp65-antigenemia assay were drawn at 2-3 month intervals. SETTING: AIDS department of an institutional tertiary care centre. PATIENTS: A total of 101 HIV-infected patients with CD4 lymphocyte counts of 100/mm3 or less were enrolled. Ninety-seven patients were eligible for analysis. All patients gave informed consent. MAIN OUTCOME MEASURES: The development of HCMV disease. RESULTS: Of the 97 patients, 24 developed HCMV disease after a median follow-up of 10.6 months. Three months before the development of HCMV disease, an increase in the median number of pp65-antigen-positive leukocytes was observed. The highest combination of sensitivity (45%) and specificity (94%) for the development of HCMV disease within the next 3 months was found when an assay cut-off level of 48/10(5) pp65-antigen-positive leukocytes was applied, with a positive predictive value (PPV) for the development of HCMV disease of 75%. The Kaplan-Meier estimate of HCMV disease-free survival after patients reached 48/10(5) or more antigen-positive leukocytes on longitudinal follow-up was a median 3.7 months [95% confidence interval (CI), 2.5-8.5]. The hazard ratio (HR) of this threshold level for the development of HCMV disease was 9.6 (95% CI, 4.2-21.8). CONCLUSION: Longitudinal follow-up using the pp65-antigenemia assay of HIV-infected patients with a low CD4 lymphocyte count improves the identification of patients who will develop HCMV disease in the foreseeable future, and should be considered for the selection of patients who may benefit from pre-emptive HCMV treatment.

Adult↗

PubMed1997

A comparative trial of zidovudine administered every four versus every twelve hours for the treatment of advanced HIV disease.

Zidovudine is approved for administration in doses given every 4 hours. Less frequent dosing has been used in many clinical trials, but the toxicity and efficacy of such regimens have not been formally compared with the approved regimen. In this multicenter, randomized, double-blind, controlled trial, the safety, tolerance and efficacy of 600 mg of zidovudine given daily in two or six divided doses were compared. Three hundred and twenty patients with a CD4 lymphocyte count < 250 cells/mm3 (mean, 104 cells/mm3) or a prior AIDS-defining illness were treated with zidovudine 100 mg every 4 hours (regimen A) or 300 mg every 12 hours (regimen B). Eighty-eight patients (56%) and 94 patients (58%), assigned to regimens A and B, respectively, completed the planned 48 weeks of treatment. Serious anemia (hemoglobin < or = 7.5 g/dl) occurred in 13% and 7% of patients treated with regimens A and B, respectively (difference, 6%, 95% confidence interval [CI], 2, 12%; p = .13). The mean duration of treatment and the frequency of neutropenia and symptomatic complaints including nausea and headache were similar in the two treatment groups. The number of patients experiencing a new opportunistic infection (18% versus 20% for regimens A and B, respectively), and the number of deaths (five in each group) did not differ significantly between groups. The effect of treatment on CD4 lymphocyte counts and HIV p24 antigenemia also was similar for both regimens. Zidovudine given at the more convenient dose of 300 mg twice daily has similar safety, and tolerance and appears to have similar efficacy to the currently approved regimen. Use of this regimen should help simplify the treatment of HIV disease.

Adult↗

PubMed2001

A phase I/II study of the safety and activity of a microsphere formulation of KNI-272 in patients with HIV-1 infection.

Eighteen patients with symptomatic HIV disease were enrolled into a phase I/II study of a microsphere formulation of the HIV protease inhibitor KNI-272, with doses escalated up to a maximum dose of 60 mg/kg/day. One patient developed reversible elevation in hepatic transaminase. The plasma half-life of the drug was very short, varying between 0.25 and 1.1 h. No consistent effect on plasma HIV RNA levels or CD4(+) lymphocyte counts was seen.

Adult↗

PubMed1993

CD4+ lymphocyte depletion in HIV-infected patients is associated with gp120-immunoglobulin-complement attachment to CD4+ cells.

The mechanism of CD4+ lymphocyte depletion, which is the main immunological feature in HIV-infected patients, is unclear. We investigated whether gp120-immunoglobulin-complement complexes on the surface of CD4+ cells might be involved in the elimination of CD4+ lymphocytes. The results obtained in 63 HIV-infected patients show that gp120 is attached to a variable degree to CD4+ cells. Importantly, the percentage of CD4+gp120+ lymphocytes is inversely associated with CD4+ lymphocyte counts in the peripheral blood (p = 0.0004). CD4+gp120+ blood lymphocytes bind IgM (p = 0.0027) and IgG antibodies (p = 0.0001) and complement (p = 0.0005). These results suggest that immune complex-mediated cell elimination is an important mechanism of CD4+ cell depletion in patients with AIDS.

Antigen-Antibody Complex↗

PubMed2001

Visceral leishmaniasis in human immunodeficiency virus (HIV)-infected and non-HIV-infected patients. A comparative study.

Visceral leishmaniasis is an endemic infection in Mediterranean countries, where it has become a frequent complication of acquired immunodeficiency syndrome (AIDS). The incidence of visceral leishmaniasis is increasing in Spain due to human immunodeficiency virus (HIV)-related cases, but some aspects of its epidemiology, clinical features, and management remain unknown. In addition, no comparative clinical studies about the disease in HIV-infected and non-HIV-infected patients have been reported. During a 24-year period, 120 cases of visceral leishmaniasis were diagnosed at our institution and 80 (66%) were associated with HIV infection. The mean age at diagnosis was higher in HIV-infected that in non-HIV-infected patients (33.2 versus 23.2 yr; p = 0.002), but the male/female ratio was similar in both groups. The main risk factor for HIV infection was intravenous drug abuse (78.7%). The clinical presentation of leishmaniasis was similar in both groups, but HIV-infected patients had a lower frequency of splenomegaly than HIV-negative individuals (80.8% versus 97.4%; p = 0.02). HIV-infected patients had a greater frequency and degree of leukopenia, lymphocytopenia, and thrombocytopenia. Most of them were profoundly immunosuppressed (mean CD4+ lymphocyte count, 90 cells/mm3) at the time of diagnosis of leishmaniasis, and 53.7% had AIDS. The sensitivity of serologic studies for Leishmania was significantly lower in HIV-infected than in non-HIV-infected patients (50% versus 80%; p < 0.001), but the diagnostic yield of bone marrow aspirate (67.1% versus 79.4%) and bone marrow culture (62.9% versus 66.6%) was similar in both groups. After initial treatment, the response rate was significantly lower in HIV-infected than in non-HIV-infected individuals (54.8% versus 89.7%; p = 0.001). The relapse rate was 46.2% and 7.5%, respectively (p < 0.001). Secondary prophylaxis with antimonial compounds or amphotericin B seems to be useful in preventing relapses in HIV-infected patients. The mortality rate was higher (53.7% versus 7.5%; p < 0.001) and the median survival time shorter (25 versus > 160 mo; p < 0.001) in AIDS patients than in HIV-negative individuals. Although leishmaniasis could contribute to death in a significant number of HIV-infected patients, it was the main cause of death in only a few of them. The CD4+ lymphocyte count and the use of highly active antiretroviral therapy and secondary prophylaxis for leishmaniasis were the most significant prognostic factors for survival in AIDS patients. Visceral leishmaniasis behaves as an opportunistic infection in HIV-infected individuals and should be considered as an AIDS-defining disease.

AIDS-Related Opportunistic Infections↗

PubMed1994

Neuropsychological characterization of the AIDS dementia complex and rationalization of a test battery.

OBJECTIVE: To define the neuropsychological deficits present in mild human immunodeficiency virus type 1 (HIV-1) associated with the acquired immunodeficiency syndrome (AIDS) dementia complex (ADC) and to develop a rational neuropsychological test battery for its diagnosis. DESIGN: Survey. SETTING: Subjects were recruited from large metropolitan hospital outpatient clinics and were all living independently in the general community. PATIENTS: Three volunteer samples of homosexual-bisexual men: (1) 15 patients who met clinical and research criteria for mild ADC; (2) 27 HIV-seronegative (HIV-) controls; and (3) 17 patients with AIDS who were neurologically intact (NI-AIDS) who were matched with the ADC subjects by CD4 lymphocyte counts for severity of systemic HIV disease. MAIN OUTCOME MEASURES: Neuropsychological test performance; z score comparisons were made with the HIV-control group using 2.25-SD cutoffs for abnormality. RESULTS: Compared with NI-AIDS subjects, performance of patients with mild ADC was markedly worse in the cognitive areas of executive function, memory, and complex attention but not in affect or the cognitive areas of simple motor function, orientation, language, or visuospatial construction. Within the areas of executive function, memory, and complex attention, all of the HIV-controls and 95% of the NI-AIDS subjects had impaired test performance in a maximum of one area only. In marked contrast, 14 (93%) of the 15 patients with mild ADC had abnormal test performances in all three of these cognitive areas. Using a criterion of abnormal performance in at least two of the cognitive areas of executive function, memory, and complex attention, all patients with mild ADC could be differentiated from HIV-controls with 100% sensitivity and specificity and from NI-AIDS subjects matched for disease severity by CD4 lymphocyte count with 100% sensitivity and 94% specificity, which increased to 100% with the requirement of impairment in all three cognitive areas. CONCLUSIONS: If time constraints or patient compliance limit neuropsychometric testing, examination to detect mild ADC first should be directed to the areas of executive function, memory, and complex attention. This pattern of neuropsychological deficits in patients with mild ADC is suggestive of subcortical dementia.

AIDS Dementia Complex↗

PubMed1997

Survival after diagnosis of AIDS: a prospective observational study of 2625 patients. Royal Free/Chelsea and Westminster Hospitals Collaborative Group.

OBJECTIVE: To estimate median survival and changes in survival in patients diagnosed as having AIDS. DESIGN: Prospective observational study. SETTING: Clinics in two large London hospitals. SUBJECTS: 2625 patients with AIDS seen between 1982 and July 1995. MAIN OUTCOME MEASURES: Survival, estimated using lifetable analyses, and factors associated with survival, identified from Cox proportional hazards models. RESULTS: Median survival (20 months) was longer than previous estimates. The CD4 lymphocyte count at or before initial AIDS defining illness decreased significantly over time from 90 x 10(6)/1 during 1987 or earlier to 40 x 10(6)/1 during 1994 and 1995 (P < 0.0001). In the first three months after diagnosis, patients in whom AIDS was diagnosed after 1987 had a much lower risk of death (relative risk 0.44, 95% confidence interval 0.22 to 0.86; P = 0.017) than patients diagnosed before 1987. When the diagnosis was based on oesophageal candidiasis or Kaposi's sarcoma, patients had a lower risk of death than when the diagnosis was based on Pneumocystis carinii pneumonia (0.21 (0.07 to 0.59). P = 0.0030 and 0.37 (0.16 to 0.83), P = 0.016). Three months after AIDS diagnosis, the risk of death was similar in patients whose diagnosis was made after and before 1987 (1.02 (0.79 to 1.31), P = 0.91). There were no differences in survival between patients diagnosed during 1988-90, 1991-3, or 1994-5. CONCLUSIONS: In later years, patients were much more likely to survive their initial illness, but long term survival has remained poor. The decrease in CD4 lymphocyte count at AIDS diagnosis indicates that patients are being diagnosed as having AIDS at ever more advanced stages of immunodeficiency.

Acquired Immunodeficiency Syndrome↗

PubMed1995

Neurosyphilis in HIV-infected patients.

To determine the prevalence and the clinical and serological findings of neurosyphilis in HIV-infected patients, Treponema pallidum hemagglutination (TPHA) tests, CD4+ lymphocyte counts and determination of rapid plasma reagin (RPR) titers were performed in 972 HIV-infected patients over a period of 3.5 years. Patients were scored according to the Centers for Disease Control's classification for HIV infection. Reactive serum syphilis tests and positive cerebrospinal fluid (CSF)-Venereal Disease Research Laboratory (VDRL) tests, with or without clinical symptoms, were used as the criteria for diagnosis of neurosyphilis. The TPHA test was positive in 31 patients, representing 3.1% of all HIV-infected patients included in the study. Of these, 13 were intravenous drug addicts, 14 were homosexuals and 4 were heterosexuals. Diagnosis of syphilis was concurrent with HIV infection in 19 patients, prior to HIV infection in 6 patients and after HIV infection in 6 patients. CSF examinations were performed in 28 of the 31 (90.3%) patients with serologically evident syphilis. Four patients had positive CSF-VDRL tests with pleocytosis (23.5% of untreated syphilis patients in whom CSF was examined), three of whom reported mild headache, which was considered a doubtful manifestation of neurosyphilis. Patients with syphilis diagnosed and treated prior to diagnosis of HIV infection did not have evidence of neurosyphilis. Seven patients had pleocytosis with a negative CSF-VDRL test, without any clinical manifestations of neurosyphilis. There was no significant difference in the mean CD4+ lymphocyte count between patients with and without neurosyphilis (p = 0.5). RPR titers in neurosyphilis patients were greater than those in patients previously treated for syphilis and in those with pleocytosis only (p = 0.046 and 0.036, respectively). All neurosyphilis patients had an RPR titer > 1:8. After therapy, neurosyphilis patients had negative CSF-VDRL tests with a lower level of pleocytosis. The prevalence of neurosyphilis was 0.4% in HIV-infected patients and 23.5% in HIV-infected patients with untreated syphilis. This high prevalence of neurosyphilis warrants CSF examination in HIV-infected patients with syphilis, regardless of the stage of syphilis.

Adult↗

PubMed2000

Rapid restoration of CD4 T cell subsets in subjects receiving antiretroviral therapy during primary HIV-1 infection.

OBJECTIVE: To compare the effect of highly active antiretroviral therapy on immune reconstitution in subjects with acute and chronic HIV-1 infection. DESIGN: Prospective study including 58 treatment-naive subjects who commenced indinavir or nelfinavir and two nucleosides during primary (PHI; n = 28) or chronic HIV-1 infection (CHI; n = 30). METHODS: Naive (CD45RA+ 62L+), memory (CD45RA-) and activated (CD38+ HLA-DR+) T cell subsets were quantified at 1-2 monthly time intervals using 4-colour flow cytometry. RESULTS: At 1 year, HIV-1 RNA declined in both cohorts to undetectable levels (< 50 copies/ml), while median CD4 lymphocyte count increased from 470 to 758 x 10(6) cells/l in PHI and from 204 to 310 x 10(6) cells/l in CHI, reaching > 500 x 10(6) cells/l in 93% of PHI, but only in 37% of CHI subjects (P < 0.001). Naive CD4 lymphocytes increased from 106 to 176 x 10(6) cells/l in PHI and from 41 to 44 x 10(6) cells/l in CHI (PHI versus CHI at 12 months: P = 0.003), while memory cells rose from 368 to 573 x 10(6) cells/l in PHI and from 148 to 223 x 10(6) cells/l in CHI (P < 0.001). Early increases (< 3 months) of CD4 lymphocytes were larger in subjects with PHI, consisting of naive CD45RA+ CD62L+ as well as memory CD45RA- CD62L+ cells (P = 0.001). CD4 activation declined from 5 to 2% in PHI and from 13 to 6% in CHI (P = 0.001), while CD8 cell activation was reduced from 33 to 15% in PHI and from 42 to 19% in CHI (P = 0.02). CONCLUSION: Immune reconstitution was more complete, occurred earlier and comprised both naive and memory CD4 T lymphocytes in subjects who commenced antiretroviral therapy during primary HIV-1 infection.

Acute Disease↗

PubMed2001

Incidence of primary opportunistic infections in two human immunodeficiency virus-infected French clinical cohorts.

BACKGROUND: Clinical guidelines for the prevention of opportunistic infections in human immunodeficiency virus (HIV)-infected individuals have been developed on the basis of natural history data collected in the USA. The objective of this study was to estimate the incidence of primary opportunistic infections in HIV-infected individuals in geographically distinct cohorts in France. METHODS: We conducted our study on 2664 HIV-infected patients from the Tourcoing AIDS Reference Centre and the hospital-based information system of the Groupe d'Epidémiologie Clinique du SIDA en Aquitaine enrolled from January 1987 to September 1995 and followed through December 1995. We estimated: (1) CD4-adjusted incidence rates of seven primary opportunistic infections in the absence of prophylaxis for that specific infection or any antiretroviral drugs other than zidovudine; and (2) CD4 lymphocyte count decline. RESULTS: The highest incidence rates for all opportunistic infections studied occurred in patients with CD4 counts < 200/microl. With CD4 counts < 50/microl, the most common opportunistic infections were toxoplasmic encephalitis (12.6 per 100 person-years) and Pneumocystis carinii pneumonia (11.4 per 100 person-years). Mycobacterium tuberculosis was the least common opportunistic infection (< 5.0/100 person-years). Even with CD4 counts > 300/microl, cases of Pneumocystis carinii pneumonia and toxoplasmic encephalitis were reported. The mean CD4 lymphocyte decline per month was 4.6 cells/microl. There was a significant association between HIV risk behaviour and the incidence of cytomegalovirus infection, between calendar year and the incidence of Pneumocystis carinii pneumonia, toxoplasmic encephalitis and Candida esophagitis, and between geographical area and the incidence of Pneumocystis carinii pneumonia and cytomegalovirus infection. CONCLUSIONS: Geographical differences exist in the incidence of HIV-related opportunistic infections. These results can be used to define local priorities for prophylaxis of opportunistic infections.

AIDS-Related Opportunistic Infections↗

PubMed1999

Disease progression in HIV-positive women with moderate to severe immunosuppression: the role of depression. Dana Consortium on Therapy for HIV Dementia and Related Cognitive Disorders.

Thirty-seven HIV-positive women were recruited in a 2-year prospective investigation into the role of depression in HIV disease progression. All participants had CD4+ cell counts of 200 or less at baseline and at least 3 CD4+ cell counts during follow-up. Participants were evaluated semiannually for CD4+ lymphocyte counts, B2Microglobulin (B2M), hemoglobin data, and new AIDS-defining illnesses. The Center for Epidemiologic Studies Depression Scale was used to assess for depressed mood. Over time, average rates of change in CD4+ counts did not differ significantly between depressed and nondepressed women, even after adjustment for age, antiretroviral use, and baseline CD4 count, and depressed women did not differ from nondepressed women in numbers of new AIDS-defining illnesses. The authors concluded that depression may not be a significant determinant of disease progression in women with advanced disease and called for further investigations with larger samples and women at earlier stages of the infection.

Adult↗

PubMed2002

Clinical profile and immunological status of cytomegalovirus retinitis in organ transplant recipients.

PURPOSE: Cytomegalovirus retinitis (CMV) is the most common ocular opportunistic infection in transplant recipients. This retrospective study attempts to report the differences in occurrence of cytomegalovirus retinetis in transplant recipients from those reported in patients with acquired immunodeficiency syndrome (AIDS). METHODS: 25 eyes of 15 transplant recipients (14 renal and one cardiac) with cytomegalovirus retinitis were retrospectively reviewed. Immunological profile included CD4+ and CD8+ T lymphocyte counts, CD4+/CD8+ cell ratio (5 cases) and serology for the viral antibodies (8 cases). RESULTS: A predominantly bilateral presentation (60%) was noted. Active cytomegalovirus retinitis (72%) in zone 2 (92%) of the inferotemporal quadrant (68%) was noted. The average cell counts were within normal limits (mean CD4 cell count-711/microliter), unlike in late stages of AIDS with cytomegalovirus retinitis (CD4 count < 50/microliter). Serology revealed an IgM positivity of 53%. Retinal detachment (52%) was the most common complication occurring after an average of 5.4 months. CONCLUSION: CMV retinitis in organ transplant recipients appears to differ from that in AIDS patients. CMV retinitis presents early and has different immunological profile, probably owing to differences in pathogenesis.

Adult↗

PubMed2001

Protease inhibitor-resistant HIV-1 from patients with preserved CD4 cell counts is cytopathic in activated CD4 T lymphocytes.

OBJECTIVE: To evaluate CD4 T-cell cytopathicity of protease inhibitor (PI)-resistant isolates from patients with preserved CD4 cell counts after long-term virologic failure. METHODS: PI-resistant primary isolates from 14 patients with stable or increasing CD4 T-cell counts despite long-term virologic failure during continuous combination therapy were examined. Replication and cytopathicity were assessed in activated peripheral blood mononuclear cell cultures in the presence and absence of PI using titered stocks of primary HIV-1 isolates and during initial viral isolation. Also studied were PI-sensitive isolates from four of these patients after therapy discontinuation and reversion to PI-sensitive virus and from seven antiretroviral drug-naive patients. Coreceptor use, syncytia-inducing (SI) phenotype and protease sequences were determined by standard methods. RESULTS: All isolates obtained during continued therapy showed genetic markers of PI resistance and decreased phenotypic susceptibility. PI-resistant SI isolates were highly to moderately cytopathic whereas non-syncytia-inducing isolates were moderately to weakly cytopathic. PI-susceptible and PI-resistant isolates obtained after discontinuation of therapy were equally cytopathic at similar replication levels. The cytopathicity of PI-resistant isolates was not altered by PI and was similar to that of isolates from untreated subjects. CONCLUSIONS: Primary isolates from patients showing virologic rebound without net CD4 T-cell loss during continued therapy are as cytopathic as PI-sensitive isolates with equivalent input infectious titer. As with PI-sensitive isolates, cytopathicity of PI-resistant viruses was determined primarily by coreceptor preference. These results suggest that the sustained immunologic response observed after failure of PI-containing regimens is not due to the emergence of PI-resistant strains that are intrinsically less cytopathic for activated peripheral CD4 lymphocytes.

Adult↗

PubMed2002

[Cytomegalovirus retinitis after highly active antiretroviral therapy: a case report].

CASE REPORT: An HIV infected patient with cytomegalovirus retinitis with a CD4 lymphocyte count of 498 cells/mm3 after a good response to highly active antiretroviral therapy is described. COMMENT: Some aspects of the immune system after highly active antiretroviral therapy remain unknown. CD4 T lymphocyte count might not be a good marker to identify some patients at risk of developing cytomegalovirus retinitis after this therapy.

AIDS-Related Opportunistic Infections↗

PubMed1999

Immunological changes in human immunodeficiency virus (HIV)-infected individuals during HIV-specific protease inhibitor treatment.

The present study examines the influence of effective anti-retroviral treatment on immune function, evaluated by a broad array of immunological tests. We followed 12 individuals infected with human immunodeficiency virus (HIV) for 6 months after initiation of combination anti-retroviral treatment including a protease inhibitor. Unstimulated and pokeweed mitogen (PWM)-, interleukin (IL)-2- and phytohaemagglutinin (PHA)-stimulated lymphocyte proliferative responses increased during follow-up reaching average levels from 1.3-fold (PHA) to 3.7-fold (PWM) above baseline values. The total CD4+ lymphocyte count increased mainly due to increases in numbers of CD4+ CD28+ and CD4+ CD45RO+ cells, whereas increases in numbers of CD4+ CD45RA+ cells contributed little to the increase in CD4+ cell count. The total cytotoxic T-cell (CTL) killing of autologous B cells infected with HIV-encoding recombinant Vaccinia virus was increased after 3-6 months, whereas the specific HIV-directed CTL activity and the concentration and lytic activity of natural killer (NK) cells were unchanged during follow-up. These results demonstrate that the initiation of a treatment including an HIV protease inhibitor is followed by an increase in lymphocyte proliferation and lymphocyte-mediated cytotoxicity. However, unchanged levels of specific HIV CTL and NK cell activity warn us that not all measures of immune function may respond simultaneously to anti-retroviral treatment.

Adult↗

PubMed1999

The pharmacokinetics of lamivudine phosphorylation in peripheral blood mononuclear cells from patients infected with HIV-1.

OBJECTIVE: To assess the pharmacokinetics of lamivudine phosphorylation in peripheral blood mononuclear cells (PBMC) from patients infected with HIV-1. DESIGN: Single-center, open-label, randomized, two-period, cross-over study in 10 asymptomatic, antiretroviral-experienced, HIV-1-infected patients who had a CD4+ lymphocyte count of 200-500 x 10(6)/l and had received combination treatment with lamivudine 150 mg twice a day plus zidovudine 600 mg a day (divided into two or three doses) for > or = 16 weeks prior to study entry. METHODS: Patients were randomly assigned to receive lamivudine 150 mg twice a day or lamivudine 300 mg twice a day for 14 days, with at least a 48-h washout period between treatments. Serial blood samples were collected over 36 h for determination of lamivudine serum concentrations using liquid chromatography/mass spectrometry and intracellular phosphate PBMC concentrations using high performance liquid chromatography/radioimmunoassay methods. Pharmacokinetic parameters were calculated based on lamivudine and lamivudine anabolite concentration-time data. RESULTS: Intracellular pharmacokinetic parameters were highly variable between patients (coefficient of variations approximately 50%). The two regimens produced lamivudine-total phosphate (totP) values of a similar magnitude. Although the 300-mg regimen tended to produce higher lamivudine-monophosphate (MP) and -triphosphate (TP) values, differences from values produced by the 150-mg regimen were not statistically significant. As lamivudine diphosphate (DP) was the predominant anabolite, accounting for 50-55% of lamivudine-totP (compared with 30-35% for lamivudine-MP and 15-20% for lamivudine-TP), the conversion of lamivudine-DP to lamivudine-TP can be regarded as the rate-limiting step. The median lamivudine-TP intracellular half-life (t1/2) for the 150-mg and 300-mg regimens did not differ significantly (15.3 and 16.1 h, respectively). Serum lamivudine pharmacokinetic parameters were consistent with those observed in previous studies in HIV-1-infected patients. No apparent linear relationships were observed between lamivudine intracellular anabolite and serum data. CONCLUSIONS: The intracellular pharmacokinetics of lamivudine phosphorylation in PBMC from asymptomatic HIV-1-infected patients are highly variable and do not differ statistically between the 150- and 300-mg twice a day regimens. The variations in intracellular lamivudine-TP concentrations following these two lamivudine dosage regimens are unlikely to result in differences in clinical effect. This was confirmed by the results of a large phase III study in HIV-1-infected patients which showed no differences in HIV-1 RNA or CD4+ lymphocyte counts between the 150- and 300-mg lamivudine regimens in combination with zidovudine.

Anti-HIV Agents↗

PubMed2000

Attention in HIV-infected children: results from the Hemophilia Growth and Development Study.

Attentional functioning was examined in three groups of 7- to 19-year-old male participants with hemophilia: (1) HIV seronegative controls (HIV-, N = 66), (2) HIV seropositive participants with CD4+ lymphocyte counts greater than or equal to 200 (HIV+ CD4+ > or = 200, N = 79), and (3) severely immune suppressed HIV seropositive participants (HIV+ CD4+ < 200, N = 28). Two measures sensitive to attention deficits were used: the Continuous Performance Test (CPT) and the Span of Apprehension (Span). On the CPT, there was a decrement in attention in both HIV+ groups, as indexed by an increase in false alarm rate from Block 1 to Block 3, that was not present in the HIV- group. The longer the HIV+ children were required to sustain attention to the CPT, the more they responded to the incorrect stimulus. This effect decreased as age increased. Span percent correct and latency to correct were associated with the presence of a premorbid history of intracerebral hemorrhage, but were not sensitive to HIV status or degree of immune suppression in the HIV+ children, suggesting morbidity related to hemophilia. The remaining CPT and Span variables--hit rate, sensitivity, latency, percent correct, and latency to correct--showed the expected associations with age, but none showed conclusive associations with HIV status or immune suppression in the HIV+ participants.

Adolescent↗

PubMed1997

Cytomegalovirus retinitis after initiation of highly active antiretroviral therapy.

BACKGROUND: In previous natural history studies and clinical trials, AIDS-related cytomegalovirus (CMV) retinitis has occurred primarily in patients with absolute CD4 counts of 50 cells/microL or less (0.05 x 10(9)/L) at the time of diagnosis. METHODS: We report five patients identified from our clinical practices who were diagnosed with CMV retinitis while their CD4 counts were above 195 cells/microL. We also analysed, based on CD4 counts, 76 AIDS patients with newly diagnosed CMV retinitis whose CD4 lymphocyte enumerations were done in laboratories that maintained certification in a common external quality control programme. FINDINGS: 5-24 weeks before retinitis was diagnosed, all five patients had had absolute CD4 lymphocyte counts of less than 85 cells/microL, and 4-7 weeks before diagnosis, all five patients had started taking highly active antiretroviral treatment (HAART) regimens. Only one (4%) of 27 patients enrolled in the trial between July, 1995, and February, 1996, had an absolute CD4 count of more than 50 cells/microL, and none of 27 had an absolute CD4 count of more than 100/microL on entry to the trial. However, from March, 1996 (when indinavir and ritonavir were approved by the FDA for marketing in the USA), to August, 1996, 14 (29%) of 49 patients had CD4 counts of more than 50/microL and seven (14%) of 49 had a CD4 count of more than 100 cells/microL on entry. INTERPRETATION: These findings suggest that the early immunological effects of HAART may not provide sufficient protection to prevent CMV retinitis in patients who have very low CD4 counts when therapy is started. Clinicians should note that CMV retinitis may now occur in patients who have CD4 counts of more than 100 cells/microL.

AIDS-Related Opportunistic Infections↗