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Correlates of zidovudine phosphorylation with markers of HIV disease progression and drug toxicity.

OBJECTIVE: To determine the relationships between in vivo zidovudine (ZDV) phosphorylation in cells from HIV-infected patients and markers associated with disease progression and drug toxicity. DESIGN: A pharmacokinetic study of ZDV metabolism sponsored by the AIDS Clinical Trials Group (protocol 161). Plasma and intracellular pharmacokinetics following a 100 mg oral dose of ZDV were determined at weeks 4 and 24 of initial therapy in adult patients. Plasma concentrations and phosphorylated ZDV were determined by radioimmunoassay, and area under the concentration-time curves (AUC) were compared with clinical data collected during the pharmacokinetic study. SETTING: An outpatient setting at the University of Cincinnati AIDS Treatment Center, Cincinnati, Ohio, USA. PATIENTS: HIV-infected adults with CD4+ lymphocyte counts 200-500 x 10(6) cells/l with no prior history of anti-HIV therapy and no active infections requiring systemic therapy. Of 30 patients enrolled, 21 were evaluable. INTERVENTIONS: None. MAIN OUTCOME MEASURES: AUC of plasma ZDV and intracellular total phosphorylated ZDV were compared with change from baseline of the following surrogate markers: CD4+ lymphocyte count, %CD4+ lymphocytes, CD4+/CD8+ cell ratio, serum beta 2-microglobulin, serum neopterin, neutrophils, red cell count, and hemoglobin. RESULTS: No correlations between plasma AUC and markers of therapeutic response were observed. However, significant positive correlations were observed between the AUC of total phosphorylated ZDV and changes in the %CD4+ lymphocytes and CD4+/CD8+ lymphocyte ratio; a negative correlation was observed with change in hemoglobin. Patients who responded to ZDV therapy, as measured by these variables, demonstrated significantly higher intracellular AUC (> 3 pmol x h/10(6) cells) than those who did not (approximately 2 pmol x h/10(6) cells). CONCLUSIONS: The ability of HIV-infected patients to phosphorylate ZDV correlates with changes in markers associated with drug effect and toxicity. Potential individualization of therapy through monitoring of total phosphorylated ZDV in patients therefore warrants further exploration.

Adolescent↗

CD4+ T-lymphocyte counts in HIV infection: are European standards applicable to African patients?

CD4+ lymphocyte count (CD4+ LC) is a widely used marker of Human Immunodeficiency Virus (HIV) immune impairment. Physiological lymphocytosis is frequently encountered in Africans. Therefore, we tried to determine if given CD4+ LC levels are of similar significance in European versus African HIV-infected individuals. Lymphocyte phenotyping of 750 HIV-infected adults was retrospectively analyzed. Three hundred and seventy patients were consecutively selected in Paris, France; 185 in Abidjan, Côte d'Ivoire; and 195 in Bobo-Dioulasso, Burkina Faso. In the three settings, lymphocyte phenotyping was performed by flow cytometry using similar protocols. Data from Abidjan and Bobo-Dioulasso were combined on the basis of geographic proximity and contrasted with those from Paris. Geometric mean levels of Total Lymphocyte Count (TLC), CD4+ LC, CD8+ lymphocyte count (CD8+ LC), and CD4:CD8 ratio, adjusted for percentage of CD4+ T-cells (%CD4+), were compared between Africans and Europeans. For a given %CD4+, TLC and CD4+ LC but not CD8+ LC tended to be about one third higher in West African than in French adults (p < 0.0001). Approximate equivalencies of absolute CD4+ counts in French and West African HIV-infected adults suggest that where thresholds of 200 and 500 CD4+ cells/microliter are applied in Europe, it might be appropriate to apply a threshold of approximately 250 and 700 CD4+ cells/microliter in West Africa, respectively. Establishing indicators of progression of HIV infection with locally appropriate thresholds may represent important steps toward improvement of HIV disease management in Africa.

Adult↗

Predicting CD4 count using total lymphocyte count: a sustainable tool for clinical decisions during HAART use.

Understanding the total lymphocyte count (TLC)-CD4 count relationship could aide design predictive instruments for making clinical decisions during antiretroviral therapy, especially in underserved resource-poor settings. We performed multiple regression analyses to assess the prediction of CD4 count using TLC on 771 participants with 4,836 visits. In linear and logistic regression TLC, hemoglobin, gender, history of AIDS, and weight predicted CD4 count and CD4 < 200, respectively, before and after highly active antiretroviral therapy (HAART) use. On HAART, the adjusted odds ratios (OR) for TLC < 1500 (optimal TLC cutoff) were 5.1 (95%CI 4.0, 6.5; P < 0.001), and off HAART, 4.6 (95%CI 3.4, 6.2: P < 0.001) with high predictive power. TLC predicts CD4 count and CD4 < 200 cells/microL well during HAART. Including the additional factors improves performance. TLC is simple and inexpensive and can be used in many ways to develop clinical decision-making tools in underserved resource-poor settings during HAART therapy.

Acquired Immunodeficiency Syndrome↗

Correlation among total lymphocyte count, absolute CD4+ count, and CD4+ percentage in a group of HIV-1-infected South African patients.

Depletion of CD4+ T cells is one of the hallmarks of progression of HIV-1 infection. However, measurement of the CD4+ T-cell count is expensive and often unavailable in less developed areas. Previous studies have suggested that the total lymphocyte count (TLC) can be used to predict a low absolute CD4+ T-cell count. To determine the relationship between TLC and CD4+ T-cell count in HIV-1-infected South African patients, 2777 HIV-1-seropositive patients visiting the Immunology clinic at the Pelonomi Hospital in Bloemfontein, South Africa from April 1991 to April 1997 were included in the study. In total, 3237 observations were used to determine sensitivity, specificity, and likelihood ratios, with 95% confidence intervals, of various cutpoints of the TLC to predict an absolute CD4+ T-cell count of <200 cells/mm3, CD4+ percentage <20%, and CD4+ percentage <15%. Spearman rank correlations were calculated between TLC and CD4+ T cells, CD4+ percentage and CD8+ T cells, as well as between CD4+ and CD8+ T cells. Results demonstrated that a TLC of 2 x 10(9)/L or less had a sensitivity of 90.3% to detect patients with a CD4+ T-cell count of <200 cells/mm3, but a specificity of only 53.7%. When the TLC cutoff value was lowered, specificity increased but sensitivity decreased. For the observations as a group, a correlation (r = 0.704) between CD4+ T-cell count and TLC was demonstrated, but if the patients were divided into three groups according to their CD4+ T-cell count, this correlation weakened considerably. Therefore, although TLC shows a correlation with CD4+ T-cell count, it is not a good predictor of the CD4+ T-cell count in this population and should preferably not be used in the clinical care of HIV/AIDS patients.

Adolescent↗

Pneumocystis carinii pneumonia in patients with connective tissue disease.

BACKGROUND: Although the association of Pneumocystis carinii pneumonia (PCP) with connective tissue disease (CTD) has been noted for a long time, there are few series reported. OBJECTIVE: The objective of this study was to describe clinical features and prognosis of PCP infections in patients with CTD in China. METHODS: We retrospectively reviewed the characteristics, clinical features, and prognosis of PCP in patients with CTD in a single hospital. RESULTS: A total of 7 cases were reviewed (systemic lupus erythematosus n = 2, microscopic polyangiitis n = 2, dermatomyositis n = 2, polymyositis n = 1). Eighty-six percent of patients developed PCP within 3 months of the diagnosis of CTD. All patients were receiving daily glucocorticoid therapy and cytotoxic drugs before the diagnosis of PCP. Most patients had fever, progressive dyspnea, and dry cough at onset of PCP. The mean duration of symptoms before PCP diagnosis was 7 days. Absolute lymphocyte counts ranged from 126 to 528/microL. The CD4 lymphocyte counts of all patients were 87 +/- 78/microL. One patient was diagnosed by induced sputum; 6 patients were diagnosed by bronchoalveolar lavage fluid. Complicating fungal infection was found in 4 of 7 patients at the time of diagnosis of PCP. All patients were treated by trimethoprim-sulfamethoxazole and corticosteroids. Six (86%) patients died. The mean duration of the time from diagnosis to death was 14 +/- 4 days. CONCLUSIONS: Our results suggest that PCP is an uncommon and fatal opportunistic infection in patients with CTD. When patients with CTD who are receiving immunosuppressive therapy have low lymphocyte counts and/or CD4 lymphocyte counts less than 250/microL develop fever, dry cough, dyspnea, and chest radiography shows diffuse interstitial infiltrate, the diagnosis of PCP should be highly suspected. Induced sputum or BAL must be quickly performed to confirm diagnosis. Further study is needed as to whether earlier treatment will improve prognoses or whether patients with CTD with low CD4 counts should receive PCP prophylaxis.

Adult↗

Failure of multiple-site intradermal postexposure rabies vaccination in patients with human immunodeficiency virus with low CD4+ T lymphocyte counts.

Human immunodeficiency virus (HIV)-infected patients with low CD4(+) T lymphocyte counts had a poor neutralizing antibody response to pre- and postexposure rabies vaccination. This study of HIV-infected patients with CD4(+) T lymphocyte counts < 200/microL indicated that patients had a poor response after 4-site intradermal vaccinations (4-4-4-0-2-2, doubling the intradermal doses of cell-culture rabies vaccine).

Adolescent↗

A microchip CD4 counting method for HIV monitoring in resource-poor settings.

BACKGROUND: More than 35 million people in developing countries are living with HIV infection. An enormous global effort is now underway to bring antiretroviral treatment to at least 3 million of those infected. While drug prices have dropped considerably, the cost and technical complexity of laboratory tests essential for the management of HIV disease, such as CD4 cell counts, remain prohibitive. New, simple, and affordable methods for measuring CD4 cells that can be implemented in resource-scarce settings are urgently needed. METHODS AND FINDINGS: Here we describe the development of a prototype for a simple, rapid, and affordable method for counting CD4 lymphocytes. Microliter volumes of blood without further sample preparation are stained with fluorescent antibodies, captured on a membrane within a miniaturized flow cell and imaged through microscope optics with the type of charge-coupled device developed for digital camera technology. An associated computer algorithm converts the raw digital image into absolute CD4 counts and CD4 percentages in real time. The accuracy of this prototype system was validated through testing in the United States and Botswana, and showed close agreement with standard flow cytometry (r = 0.95) over a range of absolute CD4 counts, and the ability to discriminate clinically relevant CD4 count thresholds with high sensitivity and specificity. CONCLUSION: Advances in the adaptation of new technologies to biomedical detection systems, such as the one described here, promise to make complex diagnostics for HIV and other infectious diseases a practical global reality.

Algorithms↗

The influence of drug use patterns on the rate of CD4+ lymphocyte decline among HIV-1-infected injecting drug users.

OBJECTIVES: To assess the relationship between various injecting drug use patterns and the rate of CD4+ lymphocyte decline in HIV-1-infected injecting drug users in Baltimore, Maryland, USA. METHODS: A cohort of 605 HIV-1-infected injecting drug users was recruited between 1988 and early 1989 in East Baltimore using extensive community outreach techniques. The participants were interviewed semi-annually to collect information on drug use practices. The outcome measure of interest was the rate of CD4+ lymphocyte decline between pairs of CD4+ lymphocyte counts. A mixed model was used to evaluate the relationship between the change in CD4+ lymphocyte count per month and previous CD4+ lymphocyte count and various drug use variables. RESULTS: The 605 HIV-infected injecting drug users had a median initial CD4+ lymphocyte count of 513 cells x 10(6)/l. Using 3209 paired observations, the mean change in CD4+ lymphocyte count was -3.2 cells x 10(6)/l per month. The rate of decline was higher in those with a higher level of CD4+ lymphocytes (P < 0.01) and length of drug use (P < 0.01), but did not vary by injection frequency or injection intensity of specific drug types. Although animal studies have suggested that the pattern of drug administration (continuous versus intermittent) and episodes of withdrawal or overdose might impact the rate of CD4+ lymphocyte decline, this was not observed in the present study. CONCLUSION: Patterns of injecting drug use, based on self-report, were not associated with the rate of decline in CD4+ lymphocytes.

Acquired Immunodeficiency Syndrome↗

Modeling the relationship between survival and CD4 lymphocytes in patients with AIDS and AIDS-related complex.

CD4 lymphocyte and survival data from two completed trials, a double-blind placebo-controlled trial of zidovudine in patients with advanced human immunodeficiency virus type 1 (HIV) disease (BW-02 study) and a randomized trial of two different doses of zidovudine in patients with advanced HIV disease (ACTG-002 study) were used to determine the degree to which CD4 lymphocyte counts reflect zidovudine-associated survival benefit. Proportional hazards models were used, and CD4 lymphocyte counts were smoothed by using empirical Bayes estimates. The geometric mean of the CD4 lymphocyte counts increased by 71 and 46 cells/mm3 for patients in the BW-02 and ACTG-002 studies, respectively, followed by a progressive decline. Higher pretreatment CD4 lymphocyte counts (p = 0.001), greater increases in CD4 lymphocytes at 8 weeks (p = 0.1), and smaller declines in the slope (p = 0.001) were associated with a lower risk of death. The most current CD4 lymphocyte count was most prognostic of death (p = 0.001). The risk of death was greater for patients with lower CD4 lymphocytes and this risk increased sharply when the CD4 lymphocyte counts fell below 50 cells/mm3. The hazard of death was higher for placebo recipients at all levels of CD4 lymphocytes compared with zidovudine recipients. Although higher CD4 lymphocyte counts are associated with improved survival, these increases account for only a small proportion of the survival benefit of zidovudine in these two studies.

AIDS-Related Complex↗

Effect of HIV infection on atypical squamous cells of undetermined significance.

BACKGROUND: Detection of atypical squamous cells of undetermined significance (ASCUS) is a cervical cytologic finding that is suggestive but not definitive of squamous intraepithelial lesions (SILs). METHODS: We examined the risk, characteristics, and progression of ASCUS in women with and without human immunodeficiency virus (HIV) infection. Cervical Papanicolou (Pap) test and colposcopy data were obtained at the first 10 semiannual visits for the HIV Epidemiology Research study of 774 HIV-infected and 480 demographically similar, HIV-uninfected women in the United States. Multiple logistic regression models and Cox proportional hazards models were utilized. RESULTS: ASCUS was more common among HIV-infected women (odds ratio [OR], 1.6 [95% confidence interval {CI}, 1.3-2.0] to 2.6 [95% CI, 1.9-3.6]) after adjustment for human papillomavirus (HPV) infection and other risk factors (e.g., race, condyloma, and prior Pap test result). Among women with normal Pap test results at enrollment, the cumulative incidence of ASCUS was 78% among HIV-infected women and 38% among HIV-uninfected women. HIV-infected and HIV-uninfected women with ASCUS did not differ by prevalence of indices of inflammation (inflammation on Pap test and leukocytes on cervical gram stain). HPV infection, including high risk types, was more common among HIV-infected women with ASCUS. Among women with ASCUS, 60% of HIV-infected and 25% of HIV-uninfected women developed SILs (P < .01). Compared with HIV-infected women with higher CD4+ lymphocyte counts, HIV-infected women with CD4+ lymphocyte counts < 200 cells/microL were more likely to present subsequently with a SIL detected by Pap test (OR, 1.7; 95% CI, 0.8-3.6). CONCLUSIONS: Higher risk of SIL following the appearance of ASCUS among HIV-infected women, especially women with low CD4+ lymphocyte counts, supports the need for follow up with colposcopy and histologic examination, as indicated, to allow early detection and treatment of SIL.

CD4 Lymphocyte Count↗

Diarrhea and Clostridium difficile infection in Latin American patients with AIDS. Working Group on AIDS in Peru.

Diarrhea and wasting are among the most debilitating and deadly manifestations of AIDS, yet only limited information is available regarding the etiology, clinical consequences, and immunologic effects of infection with diarrheal agents. Peruvian AIDS patients presenting with and without diarrhea were followed prospectively to examine the relations among diarrheal pathogens, clinical presentations, CD4 lymphocyte count, weight loss, and survival. Patients with chronic diarrhea had lower CD4 lymphocyte counts (P = .001) and lost more weight (P < .001). Weight loss and a decreased CD4 lymphocyte count were associated with increased mortality (P = .011 and P = .003, respectively). Mean CD4 lymphocyte count varied significantly by diarrheal agent. Clostridium difficile was the most prevalent pathogen and was associated with significantly increased mortality before and after adjustment for coinfection, length of follow-up, CD4 lymphocyte count, and weight loss (P = .006). C. difficile may be a more important and more prevalent etiologic agent in AIDS than previously recognized and may represent a preventable cause of death in patients with immunosuppression.

AIDS-Related Opportunistic Infections↗

Effects of combination chemotherapy and highly active antiretroviral therapy on immune parameters in HIV-1 associated lymphoma.

OBJECTIVE: To measure the effects of combined chemotherapy and highly active antiretroviral therapy (HAART) on immune cell counts and plasma HIV-1 RNA loads in patients with AIDS-related lymphoma (ARL) to determine the implications for opportunistic infection prophylaxis and medium-term immune function. DESIGN AND METHODS: Peripheral blood total lymphocyte count, CD4 T-cell count, CD8 T-cell count, CD19 B-cell count, CD16/CD56 natural killer cell count and plasma HIV-1 RNA load were prospectively measured at ARL diagnosis, at 1 and 3 months during and 1, 3 and 6 months after chemotherapy in twenty patients receiving HAART. RESULTS: Significant declines in T-helper cell (CD4) count, natural killer cell (CD16/CD56) and B lymphocyte count (CD19 cells) occurred during the first 3 months of chemotherapy. There was no significant alteration in the T-cytotoxic cell (CD8) count, CD4 percentage or HIV-1 RNA load during the study period. The T-helper cell and natural killer cell counts recovered to pre-treatment levels within 1 month of finishing chemotherapy. The recovery of B-cells was slower with pre-treatment levels only being achieved after 3 months. The recovery of CD4 T-cell count following completion of chemotherapy was more rapid than described for ARL patients who were not receiving concomitant HAART. CONCLUSIONS: By combining chemotherapy with HAART, immune function is better maintained in the medium term. The CD4 T-cell count falls by 50% during chemotherapy and this will help to identify patients who require opportunistic infection prophylaxis during chemotherapy.

Adult↗

Serum malondialdehyde in HIV seropositive children.

Human immunodeficiency virus (HIV) infection is associated with oxidative stress as it has been demonstrated in adult seropositive individuals. We show in this study that serum malondialdehyde (MDA) concentration of HIV infected children was significantly higher than in control children. Moreover, a statistically significant decreased serum antioxidant status was detected in HIV infected children when compared with controls. No correlation was found in HIV infected children between their clinical or immunological categories, CD4+ lymphocyte count or CD4+/CD8+ ratio, and MDA concentration or serum antioxidant status. Newborn from HIV seropositive mothers had also a higher MDA concentration in cord blood serum than their corresponding controls from HIV seronegative mothers, whereas no difference could be established in the serum antioxidant status between both groups. No apparent correlation could be established between birth weight, gestational age or APGAR test values, and MDA in any of these groups. The results presented, (i.e., the increase of MDA concentration in HIV seropositive infants and children, and the decrease in serum total antioxidants in HIV seropositive children) confirm the involvement of oxidative stress in the pathophysiology of this infection also in childhood. Because of the importance of oxidative stress and antioxidants for HIV viral replication, the adequacy of an adjuvant therapy with antioxidants should be considered; an adequate candidate for it could be N-acetyl-cysteine.

Adolescent↗

Do HIV type 1 RNA levels provide additional prognostic value to CD4(+) T lymphocyte counts in patients with advanced HIV type 1 infection?

Our objective was to assess whether HIV-1 RNA levels provide additional prognostic information beyond CD4(+) T lymphocyte counts in the prediction of subsequent HIV-1 disease progression among patients with advanced HIV-1 disease. In a nested case-control study conducted in patients with baseline CD4(+) T lymphocyte counts < 300 cells/mm(3) and receiving nucleoside reverse transcriptase inhibitors, 102 patients who progressed to an AIDS-defining event or death were matched within 10 CD4(+) T lymphocyte cells/mm(3) to patients who did not progress. The relationship between plasma HIV-1 RNA levels and HIV-1 disease progression was studied using conditional logistic regression analysis, which adjusts for the matching by baseline CD4(+) T lymphocytes. We observed a 0.10 log(10) copies/ml difference in baseline HIV-1 RNA levels between cases and their matched controls (p = 0.027). The relative risk for HIV-1 disease progression increased with increasing baseline HIV-1 RNA levels (odds ratio [OR] for a 3-fold higher HIV-1 RNA level, 1.42; 95% confidence interval [CI], 1.08--1.86), and remained important when also controlling for clinical status at baseline and CD4(+) T lymphocytes at 2 months (p = 0.038). Higher baseline HIV-1 RNA levels were associated with HIV-1 disease progression among patients with a baseline CD4(+) T lymphocyte count of 100 cells/mm(3) or greater (OR, 1.80; 95% CI, 1.15--2.81), but not among patients with a baseline CD4(+) T lymphocyte count < 100 cells/mm(3) (OR, 1.09; 95% CI, 0.73--1.63). We concluded that HIV-1 RNA levels predict subsequent HIV-1 disease progression independent of CD4(+) T lymphocyte counts. The magnitude and importance of the prognostic information contained in the HIV-1 RNA levels appear to depend on the CD4(+) T lymphocyte counts.

Adult↗

Microbiological infections in HIV positive Bahraini patients with low CD4+ T-lymphocyte count.

The correlation of CD4+ T-lymphocyte count and the distribution of pathogenic or opportunistic microbial infection most commonly found in HIV positive individuals differ from one area to the other. The present study reports such findings in 67 HIV positive Bahraini patients in the period May 1997 to Nov. 1998. CD4+ T-lymphocyte count was measured using flow cytometry. Bacterial and fungal cultures were performed. Serological diagnosis was performed when indicated. Viral study was done serologically. The distribution of CD4+ T-lymphocyte count in the studied group was: 21 patients (31.3%) less than 100 cells/microl, 5 patients (7.5%) 100-200 cells/microl, 25 patients (37.3%) 201-500 cells/microl and 16 patients (23.9%) with count more than 500 cells/microl. Among patients with low CD4 count (less than 100 cells/microl) (n=21), microbial infections varied from fungal infections 66%, bacterial infections 57% and viral infections 4.8%. Bacterial infections included Salmonellosis (14.3%), Staphylococcus epidermidis (14.3%), Pseudomonas aeruginosa (9.5%), H. influenzae (9.5%), Legionellosis (4.8%) and E. coli (4.8%). Fungal infection included Candida albicans (52.4%), Pneumocystis carinii (9.5%), Cryptococcus neoformans (4.8%). Viral infection included H. simplex to (4.8%). Fungal infections were the highest common infection in thus study. The most common microbial infection was Candida albicans. P. carinii and Cryptococcus neoformans were less common than found in other studies world wide.

AIDS-Related Opportunistic Infections↗

Estimation of survival after AIDS diagnosis: CD4 T lymphocyte count versus clinical severity.

We compared the relative contribution to estimating survival after AIDS diagnosis of a clinical severity measure, the Severity Index for Adults with AIDS (SIAA), and laboratory values at AIDS diagnosis that are often used prognostically. Three SIAA categories were defined from the first AIDS-defining condition and the most severe complication within 3 months. We studied 421 Italian patients surviving > or = 3 months after AIDS diagnosis. Survival curves for laboratory measures grouped by quartile showed poorest survival for CD4 count <100/microliter, hemoglobin <8 g/dl, total lymphocyte count <400/microliter, and albumin <3 g/dl. Adjusting for demographics and zidovudine therapy, the estimated hazard of death was 2.4 (95% CI, 1.6-3.5) for CD4 counts <100/microliter versus higher counts and 4.9 (95% CI, 3.0- 7.8) for the most versus the least severe SIAA category. SIAA offered greater prognostic discrimination than CD4 count at AIDS diagnosis.

AIDS Serodiagnosis↗

Disappearance of CD4 lymphocyte circadian cycles after autologous bone marrow transplantation.

Circadian variations are observed in CD4 lymphocyte count in healthy people. Samples taken of the basal value occurring around 08.00 hr and peak value at midnight made it possible to define the range of cyclic variations. Movement of lymphocytes seems important in accounting for the observed circadian variations. CD4 circadian cycle amplitudes were investigated in 12 patients with autologous bone marrow transplantation. Cycle abnormalities were observed in 7 patients. Two of them had a normal CD4 lymphocyte count. It was therefore possible for functional abnormalities in CD4 lymphocytes to be detected in patients with a normal CD4 count. Because of these results, we are of the opinion that the evaluation of CD4 lymphocyte cycle might be a more sensitive test than the absolute CD4 count itself.

Bone Marrow Transplantation↗

The unmasking of Pneumocystis jiroveci pneumonia during reversal of immunosuppression: case reports and literature review.

BACKGROUND: Pneumocystis jiroveci pneumonia (PCP) is an important opportunistic infection among immunosuppressed patients, especially in those infected with human immunodeficiency virus (HIV). The clinical presentation of PCP in immunosuppressed patients have been well-reported in the literature. However, the clinical importance of PCP manifesting in the setting of an immunorestitution disease (IRD), defined as an acute symptomatic or paradoxical deterioration of a (presumably) preexisting infection, which is temporally related to the recovery of the immune system and is due to immunopathological damage associated with the reversal of immunosuppressive processes, has received relatively little attention until recently. CASE PRESENTATION: We aim to better define this unique clinical syndrome by reporting two cases of PCP manifesting acutely with respiratory failure during reversal of immunosuppression in non-HIV infected patients, and reviewed the relevant literature. We searched our databases for PCP cases manifesting in the context of IRD according to our predefined case definition, and reviewed the case notes retrospectively. A comprehensive search was performed using the Medline database of the National Library of Medicine for similar cases reported previously in the English literature in October 2003. A total of 28 non-HIV (excluding our present case) and 13 HIV-positive patients with PCP manifesting as immunorestitution disease (IRD) have been reported previously in the literature. During immunorestitution, a consistent rise in the median CD4 lymphocyte count (28/microL to 125/microL), with a concomitant fall in the median HIV viral load (5.5 log10 copies/ml to 3.1 log10 copies/ml) was observed in HIV-positive patients who developed PCP. A similar upsurge in peripheral lymphocyte count was observed in our patients preceding the development of PCP, as well as in other non-HIV immunosuppressed patients reported in the literature. CONCLUSIONS: PCP manifesting as IRD may be more common than is generally appreciated. Serial monitoring of total lymphocyte or CD4 count could serve as a useful adjunct to facilitate the early diagnosis and pre-emptive treatment of this condition in a wide range of immunosuppressed hosts, especially in the presence of new pulmonary symptoms and/or radiographic abnormalities compatible with the diagnosis.

Adult↗