The effect of acute severe illness on CD4+ lymphocyte counts in nonimmunocompromised patients.
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CD4+ T-lymphocytopenia in the absence of HIV infection is a heterogeneous disorder of unknown cause. Here we report a patient with idiopathic CD4+ T-lymphocytopenia, presenting with an opportunistic Rhodococcus equi infection. When aplastic anemia developed subsequently, allogeneic bone marrow transplantation was performed. Complete restoration of immune function was observed. We conclude that allogeneic bone marrow transplantation presents a potentially curative therapy for CD4+ T-lymphocytopenia.
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We encountered a case of cytomegalovirus (CMV) retinitis with spontaneous regression in association with an increased number of CD8+ but not CD4+ T lymphocytes in a patient with acquired immunodeficiency syndrome (AIDS). Thus, we examined the number of CD4 and CD8 counts at the diagnosis of CMV retinitis and compared with those of Pneumocystis carinii pneumonia (PCP). All 21 patients with a confirmed diagnosis of PCP (22 episodes) and 14 CMV retinitis patients were included in this study. Although PCP occurred after depletion of CD4 count to below 200/microl, CD8 count at that time varied widely and remained normal in some patients (median: 276.5/microl, range: 133-900/microl). In contrast, as CMV retinitis occurred after further depletion of CD4 count to below 50/microl, CD8 count decreased to below 500/microl (median: 238/microl, range: 43-448/microl) (p<0.05; PCP vs CMV retinitis). The values of the sensitivity and specificity for CMV retinitis obtained at the cutoff point of either 400/microl in CD8 count and 50/microl in CD4 count were similar. When these two cutoff points were combined, the positive predictive value was 46%. Monitoring of CD8 count may prove valuable as an additional predictor of CMV retinitis in patients with AIDS after CD4 depletion.
OBJECTIVE: To study the influence of the level of virologic rebound during combination antiretroviral therapy on the time course of the CD4 count. METHODS: Between January 1997 and December 1999, we enrolled 3736 patients from the French Hospital HIV Database who had an undetectable viral load on a first course of highly active antiretroviral therapy (HAART). Four levels of virologic rebound were defined on the basis of viral load values during the year following initial undetectability on HAART: group 1, all viral loads <500 copies/mL; group 2, all viral loads <5000 copies/mL; group 3, all viral loads <10,000 copies/mL; and group 4, at least 1 viral load >10,000 copies/mL. We developed a continuous time-homogeneous Markov process with 5 reversible stages defined by CD4 count intervals. RESULTS: CD4 counts increased continuously over time in each group. The smaller the virologic rebound, the stronger was the increase in the CD4 count (P < 0.0001). The mean CD4 cell count increments between months 2 and 6 were 26, 20, 11, and 2 cells/mm3 in groups 1, 2, 3, and 4, respectively. The rate of gain fell after month 6 and was almost nil in group 4. CONCLUSION: After achieving an undetectable viral load on HAART, immunologic reconstitution is possible whatever the subsequent level of viral replication, except among patients with high-level rebound, meaning that in patients with a long history of antiretroviral therapy and a reduced choice of antiretroviral drugs due to acquisition of resistances, delay in antiretroviral therapy switch can be possible in patients with low or intermediate rebound.
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.
This study was undertaken to establish local CD4+LC standards, which could be used as indicators of immune deficiency or monitor progress of HIV therapy, instead of relying on Caucasian standards, which may not exactly reflect Nigerian CD4+LC sub-populations. CD4+LC from 1232 Nigerian adults were studied. They included 852 apparently healthy individuals, 172 HIV-positive persons with no major AIDS defining illnesses (AIDSDIL) and 208 HIV infected individuals with AIDSDIL. The mean CD4+LC of healthy Nigerians (821 +/- 12) was more than two times higher than the mean CD4+LC of HIV-positive individuals without AIDSDIL (369 +/- 14) and almost five times higher than the mean of HIV-positive individuals with AIDSDIL (163 +/- 13) (p < 0.05). In addition, a CD4+LC of < 200 cells/uL can be considered as an AIDS defining laboratory criterion in Nigerians as the 208 individuals with AIDSDIL had a mean CD4+LC of 163 cells/uL. This study therefore establishes a local standard range for CD4+LC in healthy and HIV infected Nigerians which can serve as reliable indices for HIV induced immune impairment and for monitoring effectiveness of HIV therapy.
BACKGROUND & OBJECTIVES: The enumeration of CD4 and CD8 positive cells, surrogate markers for HIV disease progression, is helpful in management and follow up of immunocompromised HIV-positive patients. In assessing the degree of immune deficiency in HIV-positive patients of a particular region, knowledge of reference range of T-cell subset counts of healthy individuals of that particular region is essential. The present cross-sectional study was undertaken to determine the reference range of T-cell subsets in healthy north Indians and to compare the values with those in HIV-positives. METHODS: Blood samples from 125 HIV seronegative healthy volunteers comprising group I (88 males, 37 females) and 452 HIV- positive patients, divided into group II of asymptomatic (n=137; 93 males, 44 females) and group III of AIDS patients (n=315; 253 males, 62 females) in the age group of 17-60 yr, were analysed for enumeration of CD4+, CD8+ cells/microl by flow cytometry. RESULTS: In group I, the CD4 and CD8 levels were 687 +/- 219 and 611 +/- 288 cells/microl in males and 740 +/- 255 and 546 +/- 246 cells/microl in females. Overall, a significant depressed level of CD4 (525 +/- 207 cells/microl) and elevated level of CD8 (1174 +/- 484 cells/microl) in group II and (170 +/- 115 and 1051 +/- 586 cells/microl) respectively in group III were observed. Group II patients had highest level of CD8 cells. No asymptomatic women had CD4 count of <200 cells/microl. INTERPRETATION & CONCLUSION: Our findings on T-cell subset reference ranges of normal healthy north Indians validate the utility of determination of CD4 cell count as a useful predictor of AIDS in Indian conditions and confirm that a significant per cent of AIDS patients had CD4 cell count below 200/microl.
The effect of cigarette smoking on CD4+ T lymphocytes was investigated in the San Francisco Men's Health Study cohort. The cohort was established by probability sampling in 1984 to study infection with HIV. Smoking showed an association with increased CD4+ cell counts in all men but the effect was attenuated in HIV-seropositive men (85 cells/microliter difference in median counts, non-smokers compared with smokers) compared with HIV-seronegative men (230 cells/microliter difference in median counts). The positive dose response between packs smoked per day and CD4+ counts observed in uninfected men was substantially reduced in infected men (slope 87 versus 27 cells/microliter). Analysis of data from HIV seroconverters suggest that smokers' counts fall faster than non-smokers' following infection, and that response to smoking becomes less pronounced soon after infection. This report demonstrates that those who monitor CD4+ cell counts in HIV-infected individuals for clinical and/or research purposes should also consider smoking status.
We detected by PCR (Polymerase Chain Reaction) HIV-1 proviral sequences in saliva cells of 89 HIV+ subjects at different stages of disease. Twenty negative individuals not at risk of HIV infection were considered as controls. The amplification of DNA was performed using the primers of genomic env region SK68 and SK69. The presence of HIV-1 in DNA was found in 16/89 (18.0%) saliva samples from HIV-1 subjects but in none of the 20 saliva samples from healthy subjects. No statistically significant difference in the presence of HIV-1 proviral sequences in saliva was observed when comparing patients receiving AZT or no treatment and patients at different stages of infection. Conversely, a statistically significant difference among subjects with CD4+ cell counts > 400/cmm and those with CD4+ cell counts from 200 to 400/cmm, was found stratifying the subjects according to their CD4+ cell counts.
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OBJECTIVE: To establish the probability to discriminate the evolution to "AIDS case" in relation to the common laboratory parametres in the follow-up of the HIV infection. MATERIAL AND METHODS: We have studied a cohort of 118 patients (1986-95) with HIV infection, 14 of them (12%) had clinical criteria for AIDS (CDC/93) during the follow-up. Clinical evaluations and CD4+ and CD8+ lymphocytes, beta 2M, IgG, IgA, IgM and E.S.R determinations were done. Multivariate analysis (RSIGMA) was done. with the initial laboratory values, according to the clinical diagnostic (AIDS and NO AIDS) done during the follow-up. RESULTS: By multiple logistic regression those laboratory variables with more predictor value for "AIDS CASE" were selected. With the initial value of these variables (E.S.R., beta 2M, IgA, IgM and CD4+ lymphocytes) and the clinical diagnostic of AIDS done during the follow-up, we did the linear discriminatory analysis between two groups (AIDS, NO AIDS) obtaining generalized distance between both groups of 3,4609 and a probability of classification error of 4%. A very significant difference (p < 0.001) was obtaining when we compare the variables' mean of each of the clinical groups. CONCLUSION: In the HIV infection the values of ESR, beta 2M, IgA and IgM in combination with the absolute value of the CD4+ lymphocytes allows to discriminate those patients who will develop AIDS with a probability of classifications error of 4%. This has clinical interest in absence of viral load and helps to take therapeutical decisions.
OBJECTIVE: To elucidate the relationship between HIV, CD4+ count and pleural TB. METHOD: In a prospective study, 94 patients presenting at two large Harare hospitals with clinically suspected pleural TB were enrolled over a 10-month period. All underwent standardized evaluation, closed pleural aspiration and biopsy. Patients receiving directly observed anti-TB therapy were followed-up. RESULTS: Pleural TB was diagnosed in 90 individuals (median age 33 years; range 18-65; 64 males); the seroprevalence of HIV was 85%. HIV-positive patients were older than HIV-negative individuals (median age 33 vs 23 years, P = 0.013) and had a significantly lower median CD4+ count (191 vs 1106 x 10(6)/l respectively, P = 0.004). A CD4+ count of <200 x 10(6)/l was associated with a length of illness >30 days (65% vs 37%; P = 0.05), a positive pleural fluid smear (37% vs 0%; P = 0.0006) and a positive pleural biopsy Ziehl-Neelsen stain (35% vs 7%; P = 0.021). However, a relationship between CD4+ count and either pleural granuloma formation or radiological evidence of disseminated disease was not observed. CONCLUSION: In sub-Saharan Africa, TB pleural effusions have become associated with older age, a chronic onset, and an increased mycobacterial load. These data emphasize the complex relationship between pleural TB, HIV infection and a low CD4+ count.