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Results for “CD4 Lymphocyte Count”

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PubMed1994

Coinfection with human T-cell lymphotropic virus type I and HIV in Brazil. Impact on markers of HIV disease progression.

OBJECTIVES: To study the effect of human T-cell lymph-tropic virus type I (HTLV-I) on markers of human immunodeficiency virus (HIV) disease progression. DESIGN: A retrospective, nested case-control study. SETTING: A university hospital outpatient HIV clinic in Rio de Janeiro, Brazil. PARTICIPANTS: Human immunodeficiency virus-seropositive adults participating in a prospective HIV cohort study. MAIN OUTCOME MEASURES: The HIV clinical stage, CD4+ lymphocyte counts, and other laboratory parameters in 27 individuals infected with HIV and HTLV-I (coinfection) and 99 age-matched, HIV-seropositive, HTLV-seronegative controls (single infection). RESULTS: Variables independently associated with coinfection included higher CD4+ lymphocyte count (odds ratio [OR], 2.3; 95% confidence limits [CL], 1.3, 4.1), higher CD4+ percentage (OR, 2.0; 95% CL, 1.3, 3.2), beta 2-microglobulin level of 254 nmol/L or more (OR, 6.8; 95% CL, 1.3, 35.4), World Health Organization stages 3 and 4 (OR, 4.4; 95% CL, 1.1, 18.0), and reporting a parenteral risk factor (OR, 7.4; 95% CL, 1.4, 38.9). When stratified by p24 antigenemia, coinfection was associated with an estimated 82% higher CD4+ lymphocyte count (P < .05). CONCLUSION: Coinfection was associated with higher CD4+ lymphocyte counts, more advanced clinical disease, and higher beta 2-microglobulin levels than HIV infection alone. The higher mean CD4+ lymphocyte count does not appear to offer immunologic benefit. Caution should be exercised when using CD4+ lymphocytes as a surrogate marker in studies of HIV infection in populations where HTLV-I is prevalent. Further studies are needed to address whether current CD4+ lymphocyte values for the initiation of antiretroviral therapy and chemoprophylaxis against opportunistic infections in HIV infection are appropriate in coinfection.

Adult↗

PubMed2000

Impact of pulmonary tuberculosis on survival of HIV-infected adults: a prospective epidemiologic study in Uganda.

BACKGROUND: Retrospective cohort studies of tuberculosis suggest that active tuberculosis accelerates the progression of HIV infection. The validity of these findings has been questioned because of their retrospective design, diverse study populations, variable compliance with anti-tuberculous therapy and use of anti-retroviral medication. To assess the impact of tuberculosis on survival in HIV infection we performed a prospective study among HIV-infected Ugandan adults with and without tuberculosis. METHODS: In a prospective cohort study, 230 patients with HIV-associated tuberculosis and 442 HIV-infected subjects without tuberculosis were followed for a mean duration of 19 months for survival. To assess changes in viral load over 1 year, 20 pairs of tuberculosis cases and controls were selected and matched according to baseline CD4 lymphocyte count, age, sex and tuberculin skin test status. RESULTS: During the follow-up period, 63 out of of 230 tuberculosis cases (28%) died compared with 85 out of 442 controls (19%), with a crude risk ratio of 1.4 [95% confidence interval (CI), 1.07-1.87]. Most deaths occurred in patients with CD4 lymphocyte counts < 200 x 10(6) cells/l at baseline (n = 99) and occurred with similar frequency in the tuberculosis cases (46%) and the controls (44%). When the CD4 lymphocyte count was > 200 x 10(6)/l, however, the relative risk of death in HIV-associated tuberculosis was 2.1 (95% CI, 1.27-3.62) compared with subjects without tuberculosis. For subjects with a CD4 lymphocyte count > 200 x 10(6)/l, the 1-year survival proportion was slightly lower in the cases than in the controls (0.91 versus 0.96), but by 2 years the survival proportion was significantly lower in the cases than in the controls (0.84 versus 0.91; P < 0.02; log-rank test). For subjects with a CD4 lymphocyte count of 200 x 10(6) cells/l or fewer, the survival proportion at 1 year for the controls was lower than cases (0.59 versus 0.64), but this difference was not statistically significant (P = 0.53; logrank test). After adjusting for age, sex, tuberculin skin test status, CD4 lymphocyte count, and history of HIV-related infections, the overall relative hazard for death associated with tuberculosis was 1.81 (95% CI, 1.24-2.65). In a nested Cox regression model, the relative hazard for death was 3.0 (95% CI, 1.62-5.63) for subjects with CD4 lymphocyte counts > 200 x 10(6)/l and 1.5 (95% CI, 0.99-2.40) for subjects with a CD4 lymphocyte count of 200 x 10(6)/l or fewer. CONCLUSION: The findings from this prospective study indicate that active tuberculosis exerts its greatest effect on survival in the early stages of HIV infection, when there is a reserve capacity of the host immune response. These observations provide a theoretical basis for the treatment of latent tuberculous infection in HIV-infected persons.

AIDS-Related Opportunistic Infections↗

PubMed2002

Evaluation and management of HIV-infected women.

The rate of newly diagnosed AIDS in the United States is increasing fastest in women, who are infected with HIV primarily through heterosexual transmission. Approximately 60% of these women are African American, and 18% are Latina. A gynecologic infection is the most common symptom that leads to initial medical evaluation. Specific studies at baseline should include CD4 lymphocyte count, HIV-1 RNA level, and gynecologic examination with Papanicolaou smear. Decisions about initiation of antiretroviral therapy depend on the patient's clinical diagnoses, her willingness to adhere to treatment, and CD4 lymphocyte and HIV-1 RNA levels. Levels of HIV-1 RNA may be somewhat lower in women than in men at the same CD4 count, whereas women have higher CD4 lymphocyte counts at the time of AIDS diagnosis. However, prospective trials have not yet indicated the need to change the threshold CD4 lymphocyte counts or HIV-RNA levels for initiation of therapy in women. The efficacy of antiretroviral therapy appears to be similar in men and women, although women are more likely to experience toxicities. Abnormal Papanicolaou smears occur in approximately 40% of women at baseline, and 58% are infected with human papillomavirus. The prevalence of both conditions increases with lower CD4 lymphocyte counts and higher HIV-1 RNA levels. Precursor lesions to cervical cancer may be effectively treated, but almost 50% recur within 1 year, mandating careful follow-up. Referral should be sought for specialized gynecologic care and for issues related to HIV itself, since survival is prolonged in patients treated by physicians who are experienced in treating HIV. When they are provided the same access to care, HIV-infected women have similar prognoses as HIV-infected men.

Adult↗

PubMed1996

The use of auxiliary events to improve the analysis of survival for HIV-infected patients: application to the French Prospective Multicenter Cohort (SEROCO).

SUMMARY: A multicenter prospective cohort study, including 512 patients for whom date of HIV infection was known, showed that the use of an appropriate auxiliary event can improve the analysis of survival data and lead to an earlier detection of risk factors for HIV patients. Age at seroconversion and primary symptomatic infection were used as risk factors. Two age groups were defined as age at seroconversion >30 years (n = 203) and < or = 30 years (n = 309). Patients with primary symptomatic infection PSI (n = 215) were compared with patients without any clinical manifestation during primary infection (n = 297). Death was considered as the endpoint of primary interest and occurred in 76 patients in the study. Classical non-parametric methods (Kaplan-Meier estimate and long-rank test) and parametric regression model (Weibull model) were used for a standard analysis of survival data. A parametric approach using auxiliary information was used to estimate the survival function and to test the effect of age at seroconversion and PSI. We also applied a recently proposed distribution-free method to produce a non-parametric estimate of the survival function and to test age at seroconversion and PSI with respect to survival estimates. Both methods are compared for two distinct auxiliary events (Karnofsky score below 75 and a first drop of CD4 lymphocyte counts below 200 cells/MM3). The use of CD4 lymphocyte counts below 200 cells/MM3 as an auxiliary event improved the analysis of survival data available in December 1994. For both methods incorporating CD4 counts below 200 cells/mm3 in addition to survival data, the effect of age at seroconversion on survival was significant in April 1992 whereas it was not significant with standard methods. For PSI exposure group, results shown in this work do not indicate any improvement in using auxiliary information. Conditions for using an appropriate auxiliary event as well as advantages and shortcomings of both methods are discussed. Methods used in this work, with appropriate auxiliary information, are promising either through a reduction in the time to follow-up to detect risk factors for cohort studies or the time needed for drug development in clinical trials.

Adult↗

PubMed1998

The incidence of AIDS-defining illnesses in 4883 patients with human immunodeficiency virus infection. Royal Free/Chelsea and Westminster Hospitals Collaborative Group.

BACKGROUND: Acquired immunodeficiency syndrome (AIDS)-defining illnesses are known to occur at different levels of immunosuppression, and the incidence of diagnoses may also vary according to the CD4 lymphocyte count strata. Information about the incidence of disease at different levels of immunosuppression would help clinicians monitoring patients and would allow prophylaxis to be targeted at the most appropriate population. METHODS: Between 1982 and July 1995, 4883 patients testing positive for the human immunodeficiency virus were seen at either the Royal Free or Chelsea and Westminster Hospitals in London, England. The incidence of each diagnosis, both overall and stratified by CD4 lymphocyte count, was calculated using a person-years analysis. Patients who had no CD4 lymphocyte counts measured during follow-up were excluded from the analysis. RESULTS: During a median follow-up period of 27.6 months, 3875 AIDS-defining illnesses were reported in 1713 patients. The incidence of AIDS-defining illnesses ranged from 6.22 per 100 person-years of follow-up for Pneumocystis carinii pneumonia (95% confidence interval, 5.74-6.70) to 0.37 for extrapulmonary tuberculosis (95% confidence interval, 0.26-0.48). The incidence of each AIDS-defining illness increased as the CD4 lymphocyte count declined; diagnoses such as cytomegalovirus and Mycobacterium avium-intracellulare complex infection had a low incidence at CD4 lymphocyte counts above 0.05x10(9)/L (50/mm3), while Kaposi sarcoma, P carinii pneumonia, and esophageal candidiasis had a high incidence throughout all CD4 lymphocyte count strata. CONCLUSIONS: This study provides important information about the risk of AIDS-defining illnesses at lower CD4 lymphocyte counts, enabling disease-specific prophylaxis to be targeted at the most appropriate population. In the future, as more prophylactic therapies are developed, this study will provide historical data of the incidence of diseases before specific prophylaxis was introduced.

AIDS-Related Opportunistic Infections↗

PubMed1993

Evaluation of two staging systems for HIV infection for use in developing countries.

OBJECTIVE: To evaluate the clinical axis of the World Health Organization (WHO) clinical staging system and the modified WHO staging system proposed by Montaner et al. using the lymphocyte strata > 1500, 1500-1000 and < 1000 cells x 10(6)/l. DESIGN: Cross-sectional study. PATIENTS: Four hundred and fifteen consecutive patients with HIV infection attending three HIV reference centres in Belgium. METHODS: Absolute CD4 lymphocyte counts were compared between stages within the two staging systems. RESULTS: Median CD4 lymphocyte counts decreased with increasing stage of disease in both staging systems. Differences in median CD4 lymphocyte counts between stages of each staging system were statistically significant (Kruskal-Wallis one-way analysis of variance, P < 0.001). The WHO clinical stage 1 and the modified WHO stage I had positive predictive values of 56 and 58%, respectively, for identifying patients with CD4 lymphocyte levels > 500 cells x 10(6)/l. The WHO clinical stage 4 and the modified WHO stage IV had positive predictive values of 79 and 80%, respectively, for identifying patients with CD4 lymphocyte levels < 200 cells x 10(6)/l. CONCLUSIONS: The WHO clinical staging system or a modified version of this system using lymphocytes stratification may be a good alternative in developing countries to the CD4 lymphocyte count-based HIV staging system used in the developed world. Cohort studies in developing countries are needed to assess their prognostic value.

CD4-Positive T-Lymphocytes↗

PubMed1997

[Serum levels of soluble tumor necrosis factor receptors as markers for disease progression of human immunodeficiency virus infection].

We studied whether the serum levels of soluble tumor necrosis factor receptor(sTNFR) type I or II correlate with clinical progression of human immunodeficiency virus type 1(HIV-1) infection. Serum levels of sTNFR type I and II were measured by an enzyme-linked immunosorbent assay in sixty five patients with HIV-1 infected hemophiliacs and 10 healthy controls. In a longitudinal study, we assessed whether the decline of CD4+ lymphocyte counts were associated with increased serum concentrations of sTNFRs. Elevated serum concentrations of sTNFRs were found among the HIV-1 infected patients and higher in patients with advanced clinical stage. We noticed there were two distinct patient groups in change of CD4+ lymphocyte count when twenty-eight patients were followed retrospectively for a median period of 65 months. 14 patients represented stable CD4+ lymphocyte counts, but another 14 patients had more than 40% decrease of CD4+ lymphocyte counts over the course of this study. Serum sTNFR type II levels were 3.49 +/- 0.71 to 3.11 +/- 0.31 ng/ml in the former group, and 4.88 +/- 0.91 to 4.26 +/- 0.71 ng/ml in the latter group during the study. Significantly higher levels of sTNFR type II were already revealed at early time in the latter group. There was, however, no significant difference in the level of sTNFR type I between the two. These results suggest that serum levels of sTNFR type II provided useful information as a predictor of disease progression related to the decline of CD4+ lymphocyte counts.

Adult↗

PubMed1995

CD4 T lymphocyte count and the radiographic presentation of pulmonary tuberculosis. A study of the relationship between these factors in patients with human immunodeficiency virus infection.

BACKGROUND: Pulmonary infection and tumor in the AIDS population has a variable clinical and radiographic presentation. The association between the radiographic presentation of pulmonary tuberculosis and CD4 T lymphocyte count in the HIV-infected patient is investigated in order to provide an empirical approach for early diagnosis, treatment, and isolation of infected subjects. METHODS: A retrospective analysis of chest radiographs, CD4 T lymphocyte counts, and clinical history of 35 subjects from 3 urban hospitals was performed. All subjects were HIV-seropositive and had culture-proven pulmonary tuberculosis. Radiographs were evaluated for the presence of either a pattern characteristic of post-primary tuberculosis (typical pattern) or a pattern uncharacteristic of post-primary infection (atypical pattern). RESULTS: Twenty-one of 26 subjects with a CD4 T lymphocyte count less than 0.20 x 10(9) cells/L, whereas only 1 of 9 subjects with a CD4 T lymphocyte count of 0.20 x 10(9) cells/L or more presented with an atypical pattern of pulmonary tuberculosis (p < 0.001). The mean CD4 T lymphocyte counts of those subjects presenting with atypical versus typical radiographic pattern of post-primary pulmonary tuberculosis were 0.069 x 10(9) cells/L (n = 22) and 0.323 x 10(9) cells/L (n = 13), respectively (p < 0.01). Twenty-one of the 22 subjects with an atypical radiographic pattern of pulmonary tuberculosis were significantly immunosuppressed (CD4 < 0.20 x 10(9) cells/L). Atypical radiographic pattern included diffuse and lower lobar opacities, pleural effusion, mediastinal adenopathy, interstitial nodules, and a normal chest radiograph. CONCLUSION: AIDS patients presenting with CD4 count less than 0.20 x 10(9) cells/L and an atypical radiographic pattern for pulmonary tuberculosis are at risk for tuberculous infection requiring appropriate treatment and isolation until the diagnosis of pulmonary tuberculosis has been excluded.

AIDS-Related Opportunistic Infections↗

PubMed1999

Response in Patients with Chronic HCV Hepatitis to Treatment with Interferon-alpha.

Twelve patients with chronic hepatitis C received interferon-alpha at doses of 3 million units (11 patients) or 6 millions units (1 patient) 3 times per week for 52 weeks. The patients were evaluated for clinical response, and total blood cell count, B and T lymphocyte count, subtyping of CD4+ and CDS+ lymphocytes, blastic transformation of lymphocytes after stimulation with phytohemagglutinin and concanavalin-A, and liver function tests. Liver biopsies with immunohistochemical methods were done before and after treatment in 7 patients. Blood tests were done every 4 weeks in all 12 patients. Serum beta-2-microglobulin was measured before treatment and after 32 and 52 weeks. Patients with liver disease due to other causes (autoimmune disease and HIV infection) were excluded. The following results were obtained: 1) Four patients improved with treatment (4/12 = 33%) during the 52 week treatment period; 3 of them responding completely and one partially. Two others who were not considered responders maintained ALT levels below 1.5x the normal range after the end of therapy. One of these had received the higher dose of interferon-alpha. Histopathologically, 10 patients improved (10/12 = 83%), one presented progression of the disease and one did not show significant changes with treatment; 2) Immunological evaluation before and after treatment did not show significant differences except for total blood lymphocyte count, which was decreased after treatment; 3) T and CD4+ lymphocyte counts in liver tissue were significantly decreased after treatment, but there was no change in the pattern of their distribution within the hepatic parenchyma. These findings confirm that interferon-alpha is effective in patients with hepatitis C, and suggest that the drug has a predominantly antiviral effect in chronic hepatitis caused by C virus, and that the hepatocellular damage observed in these cases is mainly due to the cytopathic effect of the virus rather than immunopathologic processes.

Journal Article↗

PubMed1992

Differences in laboratory values in HIV infection by sex, race, and risk group.

OBJECTIVES: To determine differences in CD4+ and CD8+ lymphocyte values, beta 2-microglobulin (beta 2M), and HIV p24 antigenemia by sex and race among HIV-seropositive and HIV-seronegative injecting drug users (IDU), and to compare these values with those in homosexual men of equivalent status. DESIGN: Baseline values from a cohort of 206 HIV-seropositive and 173 HIV-seronegative IDU were compared with values from a cohort of 288 HIV-seropositive homosexual men and 176 HIV-seronegative controls, who were prospectively followed at 6-month intervals, to examine differences in laboratory values in HIV-infected individuals by sex, race, and risk group. METHODS: Among HIV-seropositives, we compared white and black IDU only (n = 167), and white male IDU (n = 38) with white homosexual men (n = 256). Laboratory values from the cohort of homosexual men at 24, 36 and 48 months of follow-up were compared with IDU values. RESULTS: HIV-infected female IDU had significantly higher CD4+ lymphocyte counts (P < 0.03) and percentages of CD4+ lymphocytes (P < 0.004) than male IDU, resulting in higher CD4:CD8 ratios (P < 0.002). White IDU had significantly higher serum beta 2M levels than black IDU (P < 0.02). Black female IDU were much less likely to be HIV p24-antigenemic (1%) than all other groups (P < 0.005). Compared with homosexual men, male IDU had significantly elevated beta 2M levels (0.58 mg/l higher). When controlled for CD4+ lymphocyte values as a surrogate for length of time HIV-infected, beta 2M and HIV p24 antigenemia differences persisted. CONCLUSIONS: These differences should be considered when HIV p24 antigen, CD4+ lymphocyte counts and beta 2M levels are used as surrogate markers in clinical trials and management of HIV disease.

Adult↗

PubMed2000

Risk for preventable opportunistic infections in persons with AIDS after antiretroviral therapy increases CD4+ T lymphocyte counts above prophylaxis thresholds.

To determine incidence and risk for preventable opportunistic infections (Pneumocystis carinii pneumonia [PCP] and disseminated Mycobacterium avium-complex [MAC] infection) in persons whose CD4(+) T lymphocyte counts had increased by >/=100 cells/microL to exceed the threshold of risk and in persons whose CD4(+) counts had never dropped below the threshold of risk, we analyzed data collected during the period 1990-1998 in the Adult/Adolescent Spectrum of HIV (Human Immunodeficiency Virus) Disease Project. Using a counting-process formulation of the Cox model, we analyzed observation time in these 2 groups for persons who were prescribed antiretroviral therapy but not prophylaxis. The incidences of the infections were low for patients whose CD4(+) count rose above the threshold of risk (PCP, 0.6 cases per 100 person-years [PY]; MAC, 1. 0 cases per 100 PY) and not higher than in persons whose CD4(+) counts had not decreased below these thresholds, which suggests that discontinuation of primary prophylaxis for opportunistic infections may be considered for some patients.

Acquired Immunodeficiency Syndrome↗

PubMed1996

Lymphocyte counts of patients who have had skin cancer.

BACKGROUND: Investigations of lymphocyte counts in patients with skin cancer have given conflicting results, possibly because homogeneous groups of patients were not studied. OBJECTIVE: Our purpose was to measure lymphocyte counts in patients with skin cancer to determine whether any abnormalities were associated with the number of cancers removed and to determine whether a lymphocyte count could identify patients at risk of the development of large numbers of cancers. METHODS: Apparently otherwise normal patients who had histologically confirmed skin cancers removed were studied. One group consisted of patients who had one skin cancer removed but had not had another within a minimum of 5 years. The other group consisted of patients who had had three or more skin cancers. Standard flow cytometry was used to determine the total lymphocyte count, CD4 (helper cell) count, and CD8 (cytotoxic cell) count. RESULTS: Ninety-six patients with multiple skin cancers, and 24 with one skin cancer were studied. Only basal cell carcinomas (BCCs) were removed from 84 patients and the results from this homogeneous group were as follows: women had a higher CD4 cell count than men (p < 0.05); patients with 20 or more BCCs had a lower lymphocyte count (p < 0.01); and patients with one BCC had a higher CD4/CD8 ratio than those who had multiple BCCs (p < 0.05). CONCLUSION: Differences were found between men and women, as well as between subgroups of patients with skin cancer. However, the range of lymphocyte counts was large and it was not possible to determine a threshold below which patients had a worse prognosis. A lymphocyte count is not a reliable way of predicting which patients will have a large number of skin cancers.

Adult↗

PubMed2002

[Clinical study on treatment of HIV infected persons based on viral load detection and CD4+ T lymphocyte counting].

OBJECTIVE: To study the usage of viral load and CD4+ cell count methods in evaluating the effects of clinical treatment in HIV infected people. METHODS: Totally 73 cases of HIV infected persons were studied with clinical observation and laboratory examinations, six cases were treated with cocktail therapy, 36 cases with chinese herbs and the other 31 cases were untreated. RESULTS: The results indicated that the viral load levels in cocktail therapy group were significantly lower than the other two groups within 3 months and then kept at very low level. The CD4+ T lymphocyte levels showed a significant increase after 3 months and kept rising up. The chinese herb group, however, had no significant difference in viral load level and CD4+ T lymphocyte level as compared with untreated group. But in clinical observation chinese herbs showed the effect of improving clinical status in some cases. CONCLUSIONS: The authors conclude that the viral load and CD4+ count are efficient methods in clinical evaluation of HIV treatment, especially in routine anti-HIV therapy. As for the chinese herbs treatment, these two monitors did not reflect changes in clinical status.

Anti-HIV Agents↗

PubMed1997

Aeroallergen-specific IgE changes in individuals with rapid human immunodeficiency virus disease progression.

BACKGROUND: Progression of human immunodeficiency virus type 1 (HIV-1) infection to the acquired immunodeficiency syndrome (AIDS) is associated with elevated total IgE; however, previous cross-sectional studies have differed in their assessment of concurrent changes in allergic disease prevalence. OBJECTIVE: Assessment of changes in aeroallergen-specific IgE during progression from early to late HIV disease. METHODS: Total IgE, aeroallergen-specific IgE (rye grass, ragweed, Alternaria, dust mite, and cat), IFN-gamma, IL-4, and soluble CD23 (sCD23) were measured in a longitudinal study of 20 subject who had progressed from early-HIV infection (mean CD4 lymphocyte count of 650/mm3) to AIDS (mean CD4 lymphocyte count of 40/mm3) over an average of 4 years. RESULTS: Prevalence of positive aeroallergen specific-IgE assays in early HIV disease (T1 subjects with 13 positives) decreased with progression to late disease (five subjects with nine positive, P = .057), while total IgE increased from a median of 69 to 116 IU/mL. IFN-gamma and IL-4 were unchanged, while sCD23 decreased from a median of 72 to 9 U/mL (P = .0005) with disease progression in the full cohort. In contrast to other subjects, the subgroup of individuals with total IgE > 150 IU/mL in both early and late HIV disease demonstrated an increased frequency of aeroallergen-specific IgE. CONCLUSIONS: The elevation of total IgE associated with rapid HIV-1 disease progression was unexplained by concurrent changes in aeroallergen-specific IgE, IL-4, IFN-gamma, or sCD23. Overall, aeroallergen-specific IgE expression was less prevalent with HIV-1 progression, except in those individuals with elevated total IgE both before and after progression to AIDS.

Acquired Immunodeficiency Syndrome↗

PubMed1998

Treatment history and baseline viral load, but not viral tropism or CCR-5 genotype, influence prolonged antiviral efficacy of highly active antiretroviral treatment.

BACKGROUND: The efficacy of highly active antiretroviral treatment (HAART) in HIV-1 disease may vary between nucleoside-naive and experienced patients as well as between patients with different viral phenotypes and in different stages of disease. OBJECTIVE: To investigate variables of importance for successful long-term viral suppression by analysing virological, clinical and immunological characteristics at initiation of protease inhibitor treatment on suppression of HIV RNA over 1 year. DESIGN: An open, non-randomized, observational clinical study. SETTING: Venhälsan, Department of Dermatovenereology, Söder Hospital, Stockholm, Sweden. PATIENTS: A total of 147 unselected advanced patients with known HIV-1 infection for a mean of 7 years, of whom 37% had AIDS and who started treatment with a protease inhibitor during 1996. INTERVENTIONS: All patients received HAART with at least two nucleoside analogues in combination with either indinavir (81%) or ritonavir (19%). The majority (77%) had been previously treated with nucleoside analogues for a mean of 39 months. MEASUREMENTS: CD4+ lymphocyte count, plasma HIV-1 RNA, viral phenotype and HIV-1 coreceptor CCR-5 genotype at baseline. Viral load and CD4+ lymphocyte count were determined every 3 months. RESULTS: Patients were analysed on an intention-to-treat basis. The mean CD4+ lymphocyte count at baseline was 170 x 10(6)/l and the median viral load was 68 600 copies/ml. Heterozygosity for the delta32 deletion of the CCR-5 gene (delta32/wt) was found in 27%. MT-2 positive virus (syncytium-inducing) was isolated in 46%. Logistic regression revealed that nucleoside analogue experience and baseline log10 HIV-1 RNA were the only factors independently related to plasma HIV-1 RNA levels below 500 copies/ml after 1 year of treatment, which was found in 69%. CONCLUSION: The virological outcome after 1 year of HAART was strongly correlated to prior treatment history and baseline viral load, whereas CD4+ lymphocyte count, CCR-5 genotype and viral biological phenotype had less influence. The long-term antiviral efficacy of HAART was lowest in individuals with previous nucleoside analogue treatment and a high baseline viral load. In these individuals an even more aggressive treatment should be considered.

Adult↗

PubMed1999

Surrogate markers of disease progression in HIV-infected children in Rio de Janeiro, Brazil.

In order to test the predictive value of immune complex-dissociated p24 antigenaemia (ICD-p24Ag), beta 2 microglobulin (beta 2-M), and neopterin as markers of disease progression, 53 HIV-1 infected children (mean age 68 months) and nine HIV-negative controls (mean age 65 months) were studied prospectively for 9 months. Five were classified in category E (CDC-1994) and seroreverted during the study, 14 in category A, nine in category B, and 25 in category C (CDC-1994). Blood samples were taken at medium intervals of 61 days and tested for ICD-p24Ag, beta 2 microglobulin, and neopterin. The results were correlated with clinical outcome and CD4-lymphocyte counts. All three groups (A, B, C) of symptomatic children had similar positivity in an ICD-p24Ag test (48.1, 58.8, and 51.0 per cent, respectively), and all in group E had negative p24 antigenaemia. beta 2 microglobulin and neopterin tests showed no correlation with clinical stages of HIV-1 infection. There was no significant correlation between these three tests with age-matched CD4 lymphocyte counts (p > 0.05). In contrast, the CD4 lymphocyte count correlated well with disease stages. These data suggest that the markers evaluated in the present study do not correlate well with clinical findings or with CD4 lymphocyte counts. Of all the markers tested, CD4 count was the best to predict prognosis of HIV disease in this cohort.

Biomarkers↗

PubMed2004

Differential CD4 T-cell response in HIV-1-infected patients using protease inhibitor-based or nevirapine-based highly active antiretroviral therapy.

OBJECTIVES: To study the dynamics of CD4 T-lymphocyte counts (CD4 counts) after the initiation of either protease inhibitor (PI)-based or nevirapine (NVP)-based first-line highly active antiretroviral therapy (HAART). DESIGN AND METHODS: A retrospective cohort study of 1029 HIV-infected antiretroviral therapy-naive patients initiating either PI-based or NVP-based HAART was carried out. Patients were censored as soon as they experienced virological failure, or changed their original antiretroviral regimen for any reason. RESULTS: In total, 920 and 109 patients initiated PI- and NVP-based HAART, respectively. The patients in the PI group more often had AIDS (15 vs. 6% in the NVP group), had a lower median baseline CD4 count (234 vs. 250 cells/microL in the NVP group) and had higher median baseline plasma HIV-1 RNA levels (pVL) (5.0 vs. 4.7 log10 HIV-1 RNA copies/mL in the NVP group). After 96 weeks of follow-up, the mean increase from baseline in CD4 count, adjusted for baseline CD4 count, age, gender and baseline pVL, was 310 cells/microL in the PI group and 212 cells/microL in the NVP group (P=0.003). This difference was mainly attributable to the patients in the NVP group initiating HAART with a baseline CD4 count below 200 cells/microL. There were no differences between the PI and NVP groups with respect to the change in the number of CD4 cells as a proportion of the total number of lymphocytes. CONCLUSION: Patients successfully treated with NVP-based HAART have a smaller increase in absolute CD4 cells compared with those treated with PI-based HAART.

Adult↗

PubMed2003

Time-updated CD4+ T lymphocyte count and HIV RNA as major markers of disease progression in naive HIV-1-infected patients treated with a highly active antiretroviral therapy: the Aquitaine cohort, 1996-2001.

In naive HIV-1 infected patients who start a highly active antiretroviral therapy (HAART), the relationship between time-updated CD4+ cell count, HIV RNA, and clinical progression (new AIDS-defining event or death) is incompletely understood. A 2-step statistical approach was adopted: first, modeling the evolution of the 2 markers taking into account left-censoring of HIV RNA and, second, studying their respective effect on clinical progression. The study sample consisted in 551 previously untreated patients of the Aquitaine Cohort who started their first HAART regimen between 1996 and 2000. During a median follow-up of 33 months, 46 patients experienced a new AIDS-defining diagnosis and 23 died. In multivariate survival analysis, time-updated CD4+ cell count (hazard ratio [HR] = 1.92 for 100 cells/mm3 lower, P < 10(-4) and HIV RNA (HR = 1.30 for 1 log(10) copies/mL higher, P = 0.04) on continuous scale were associated with clinical progression. When analyzing the effect of updated biomarkers using usual thresholds, the association with clinical progression was weaker for CD4+ but still significant (P = 0.007) whereas it remained only significant for updated HIV RNA above 4 log(10) copies/mL (P = 0.01). The prognostic information of updated HIV RNA adjusted on updated CD4+ is significant but depends on how the markers are taken into account. Clinical decisions and interpretation of clinical trial results must weigh the signification of each of these 2 biomarkers.

Adult↗