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PubMed1991

Effect of zidovudine and Pneumocystis carinii pneumonia prophylaxis on progression of HIV-1 infection to AIDS. The Multicenter AIDS Cohort Study.

Although used widely, the effectiveness of zidovudine therapy and primary prophylaxis for Pneumocystis carinii pneumonia (PCP) in HIV-1-infected individuals, has not been assessed in a large cohort. We have done an observational study between October, 1986, and October, 1990, of a cohort of 2145 HIV-1-seropositive men and 371 who seroconverted during the study. A Markov chain transitional analysis was used to examine the effect of zidovudine and PCP prophylaxis on the probability of progression of HIV-1 infection to AIDS (after 6, 12, 18, and 24 months) after follow-up visits categorised into one of six disease states. The six starting states were based on CD4+ lymphocyte counts and the presence of HIV-related symptoms. Use of pre-AIDS zidovudine and PCP prophylaxis was associated with significant reductions in rates of progression to AIDS at 6, 12, 18, and 24 months for participants starting with less than 350 CD4+ lymphocytes/microliter. For those starting with 350 or more CD4+ lymphocytes/microliter, non-significant protective trends were seen during 12, 18, and 24 month intervals. In multivariate log-linear models virtually all the treatment effect was due to zidovudine. However, after adjusting for the effects of zidovudine, PCP prophylaxis reduced significantly the probability of progression to a first episode of PCP during 6, 12, 18, and 24 month intervals. This study suggests that early primary PCP prophylaxis is effective in preventing first episodes of PCP, and that the efficacy of zidovudine demonstrated in clinical trials can be translated to the population level.

Acquired Immunodeficiency Syndrome↗
PubMedDate not supplied

Eight year prospective study of HIV infection in a cohort of homosexual men--clinical progression, immunological and virological markers.

Three hundred and fourteen homosexual/bisexual men at risk for human immunodeficiency virus (HIV) infection (170 seroprevalent HIV-positive, 144 seronegative) were prospectively studied over 8 years to assess rates of HIV infection and disease progression, in conjunction with cellular and HIV serological markers. In HIV-positive subjects, CD4+ lymphocyte counts rose strikingly during the period surrounding seroconversion, then fell progressively over the intervening period to a mean level of 300 cells/mm3 when AIDS developed. Changes in CD8+ lymphocyte counts were less consistent. The trend for HIV serological markers over the study period was of progressive decline in the proportion of subjects with anti-p24 antibody, associated with an increase in the proportion of subjects with detectable HIV antigenaemia. However, only 45% of subjects tested had lost anti-p24 antibody by the time of AIDS diagnosis, and HIV antigen was detectable up to 4 years before this. Different HIV serological patterns were also observed in subjects presenting either with Kaposi's sarcoma or opportunist infections. Our data support the continued use of cellular and virological markers in the evaluation of HIV disease; however, the variability observed in this study highlights their limited ability in predicting specific clinical events. Care should therefore be taken to encompass both clinical and laboratory information in the medical assessment of the HIV-infected individual.

Acquired Immunodeficiency Syndrome↗
PubMed1999

The immunosuppression and potential for EBV reactivation of fludarabine combined with cyclophosphamide and dexamethasone in patients with lymphoproliferative disorders.

Fludarabine is effective in chronic lymphocytic leukaemia (CLL) and low-grade non-Hodgkin's lymphoma (NHL). A major side-effect of this purine analogue is immunosuppression which may favour opportunistic infections. Additionally, impairment of immunosurveillance might promote Epstein-Barr virus (EBV) reactivation and possibly favour transformation to high-grade malignancy. The aim of this study was to evaluate the immunosuppression-related effects of the fludarabine-based combination Flucyd in advanced low-grade NHL or CLL by serially monitoring T-lymphocyte subsets, opportunistic infections, EBV-reactivation, and histologic transformation. 24 patients with advanced NHL (n = 21) or CLL (n = 3) received fludarabine 25 mg/m2/d + cyclophosphamide 350 mg/m2/d + dexamethasone 20 mg/d in 3 d courses for a maximum of six courses. The overall response rate was 79% (eight CR, 11 PR, five failures); 11 patients relapsed or progressed between 3 and 19 months from response, and eight are in CR or PR at 3-27 months. The CD4+ lymphocyte counts decreased significantly during therapy from a median of 484/microliter pre-treatment (range 142-1865) to a median of 198/microliter (71-367). In 19 responders monitored off therapy every 3 months until relapse/progression, CD4+ counts were persistently low with minimal recovery over time. During treatment, 16 infections occurred in 11/24 patients. No delayed opportunistic infections occurred in responders while off therapy. The circulating EBV DNA load serially measured in 19 patients by a quantitative PCR assay showed an increase in four patients during treatment. A lymph node biopsy performed in two of these was PCR positive for EBV DNA, whereas LMP1 and EBERs were negative. Six NHL patients evolved into high-grade B-cell NHL. In conclusion, fludarabine combined with cyclophosphamide and dexamethasone is an effective therapy for recurrent indolent lymphoma. This combination produces prolonged T-lymphocytopenia and has the potential to reactivate a latent EBV infection. T-cell dysfunction, however, is not associated with higher incidence of clinical opportunistic infections and does not adversely influence clinical outcome.

Adult↗
PubMed1992

Detection of circulating p24 antigen-positive CD4+ cells during HIV infection by flow cytometry.

OBJECTIVES: To determine the amount of circulating CD4+ cells positive for intracellular p24 antigen during HIV infection, and to correlate the results with clinical, virological and therapeutic parameters. METHODS: Data were obtained from 24 anti-HIV-negative subjects (controls) and 47 anti-HIV-positive patients classified according to clinical diagnosis, serum p24-antigen assay results, and antiretroviral treatment with zidovudine, using a modified flow cytometric assay for the detection of intracellular HIV p24 antigen (p24-FCA) in circulating CD4+ lymphocytes. RESULTS: The proportion of CD4+ lymphocytes positive for p24-FCA correlated well with HIV infection (1.685 +/- 1.902 versus 0.160 +/- 0.152 in controls; P < 0.001) and clinical progression [Centers for Disease Control (CDC) stage II: 1.310 +/- 1.187; CDC stage III 1.145 +/- 1.442; CDC stage IVA/C2: 2.335 +/- 2.112; CDC stage IVC1: 2.066 +/- 2.420]. The percentage of CD4+ cells positive for HIV p24-FCA was inversely correlated with an absolute peripheral blood CD4+ lymphocyte count (Spearman's rank correlation = -0.324; P < 0.05). However, there was no statistically significant difference between patients in presence (n = 27; 1.938 +/- 2.095) or absence (n = 20; 1.343 +/- 1.594) of serum p24 Ag. The variable linked most strongly to the detection of intracellular p24 in anti-HIV-positive patients was zidovudine treatment: the proportion of p24-FCA-positive CD4+ lymphocytes was significantly lower (0.825 +/- 0.910) in the treated patients (n = 25) than in the untreated patients (n = 22; 2.662 +/- 2.248; P < 0.001). CONCLUSIONS: Our results suggest that CD4+ p24 Ag-FCA is a rapid and easy test for the identification of the proportion of CD4+ lymphocytes with intracellular p24 Ag, and that it could be more appropriate than serum p24 Ag assay in evaluating disease progression and efficacy of antiretroviral treatment.

Blood Circulation↗
PubMed2004

High levels of human immunodeficiency virus infection of CD8 lymphocytes expressing CD4 in vivo.

Human immunodeficiency virus (HIV)-infected CD8 lymphocytes have been reported in vivo, but the mechanism of infection remains unclear. Experiments using the thy/hu mouse model support export of intrathymically infected CD8 precursors, while recent in vitro data suggest that mature CD8 lymphocytes upregulate CD4 upon activation (generating a CD8bright CD4dim phenotype) and are susceptible to HIV infection. To determine whether these mechanisms operate in vivo and to assess their relative importance in the generation of circulating HIV-infected CD8 lymphocytes, we quantified HIV long terminal repeat (LTR) DNA in CD8+ CD4- and CD8bright CD4dim lymphocytes isolated from HIV-infected individuals by fluorescence-activated cell sorting. HIV infection of CD8 lymphocytes was demonstrated in 17 of 19 subjects, with a significant inverse relationship between level of infection and CD4 lymphocyte count (R = -0.73; P < 0.001). The level of HIV infection of CD8bright CD4dim lymphocytes was significantly higher (median, 1,730 HIV LTR copies/10(6) cells; n = 9) than that of CD8+ CD4- lymphocytes (undetectable in seven of nine individuals; P < 0.01) and approached that of CD4 lymphocytes from the same individuals (median, 3,660 HIV LTR copies/10(6) cells). CD8bright CD4dim lymphocytes represented 0.8 to 3.3% of total CD8 lymphocytes and were most prevalent in the memory subset. Thus, HIV-infected CD8 lymphocytes commonly circulate in HIV-infected individuals and are generated through infection of activated CD8 lymphocytes rather than through export of intrathymically infected precursors. The high level of infection of CD8bright CD4dim lymphocytes could have a direct role in the decline in CD8 lymphocyte function that accompanies HIV disease progression.

Adult↗
PubMed2005

FIV-infected cats respond to short-term rHuG-CSF treatment which results in anti-G-CSF neutralizing antibody production that inactivates drug activity.

The hematological and virological effects of recombinant human granulocyte colony-stimulating factor (rHuG-CSF) were evaluated in feline immunodeficiency virus (FIV)-infected cats. Six age-matched, FIV-infected cats used in this cross-over study were injected subcutaneously with 5 microg/kg of rHuG-CSF daily for 3 weeks, while six control cats received a placebo. Five of six rHuG-CSF-treated cats had significant increases in neutrophil counts that peaked on days 11-21 of treatment. All rHuG-CSF-treated cats exhibited an increase in myeloid:erythroid ratios of the bone marrow cells without significant changes in lymphocyte, CD4 counts, CD4/CD8 ratios, RBC counts, FIV antibody titers, and FIV loads in peripheral blood, and without clinical and hematological toxicities. Five of six rHuG-CSF-treated cats developed antibodies to rHuG-CSF by 14-21 days of treatment, which correlated with decreasing neutrophil counts and increasing neutralizing antibodies to rHuG-CSF. Three cats re-treated with rHuG-CSF rapidly developed neutralizing antibodies to rHuG-CSF, while one cat also developed neutralizing antibodies to recombinant feline G-CSF (rFeG-CSF). Overall, rHuG-CSF treatment increased neutrophil counts in FIV-infected cats without affecting the infection status of cats. However, long-term use of rHuG-CSF is not recommended in cats because of the neutralizing antibody production to rHuG-CSF that affects the drug activity. In addition, a preliminary finding suggests that repeated treatment cycle can also induce cross-neutralizing antibodies to rFeG-CSF, which may potentially affect the homeostasis of endogenous FeG-CSF.

Animals↗
PubMed1999

The changing face of AIDS-related opportunism: cryptococcosis in the highly active antiretroviral therapy (HAART) era. Case reports and literature review.

Only nine cases of AIDS-related cryptococcosis have been reported until now in patients receiving highly active antiretroviral therapy (HAART), all of them with abnormal clinical features. Two HIV-infected patients who experienced an atypical relapse of cryptococcosis shortly after the start of HAART and despite maintenance antifungal treatment, are described. Six different relapses of cryptococcal meningitis were observed in a 28-month period in a patient who obtained a poor immune recovery after HAART (as shown by a CD4+ lymphocyte count ranging from 78 to 149 cells/microL, opposed to a baseline level of 98 cells/microL). On the other hand, a patient with favorable immunological response to HAART (as expressed by a CD4+ count growing from 7 to 186 cells/microL), experienced isolated multiple indolent cryptococcal abscesses involving head, neck, the anterior thoracic wall, and regional lymph nodes, with repeatedly negative cultures, and diagnosis obtained by both histopathologic study and positive serum antigen assay. Both our case reports are representative of novel correlations between opportunistic pathogens and immune reactivity, descending from the introduction of HAART. The first episode describes an exceedingly elevated number of disease relapses despite HAART and antifungal maintenance treatment, which may descend from an incomplete immune response to antiretroviral therapy, possibly responsible for failure in obtaining eradication of yeasts, but also for lack of disease dissemination (usually leading to a lethal multivisceral involvement in the pre-HAART era). The abnormal disease course and localization of second reported patient well depicts an "immune reconstitution syndrome" probably representing a flare-up of a latent fungal infection, caused by a rapidly effective HAART. In patients treated with HAART, AIDS-related cryptococcosis cannot therefore be ruled out by the absence of neurological involvement, and by persistingly negative cultures.

AIDS-Related Opportunistic Infections↗
PubMed2002

Response and relapse rates of candidal esophagitis in HIV-infected patients treated with caspofungin.

Caspofungin is a new antifungal drug of the echinocandin class. We analyzed the clinical efficacy of caspofungin (50 mg/day) in the treatment of HIV-infected adults with endoscopically documented Candida esophagitis and enrolled in four clinical trials of caspofungin. Symptoms were evaluated daily; a favorable outcome required complete resolution of all esophageal symptoms assessed at the time of discontinuation of therapy. Relapse was defined as recurrent symptoms during the subsequent 2 weeks. A multivariate logistic regression model was developed to identify potential factors (including severity of symptoms at presentation, CD4(+) cell count on entry, extent of disease [assessed endoscopically at baseline], causative Candida species, duration of therapy [overall and after resolution of symptoms], time on treatment before symptom resolution, and antifungal prophylaxis) that might predict symptomatic relapse in the 2 weeks following completion of therapy. The median CD4(+) lymphocyte count for the entire population was 31/mm(3). Candida albicans was isolated from 109 of 110 patient samples cultured for the pathogen and constituted the sole isolate in 77%. Extensive esophageal involvement was present in 55% of patients at the time of pretreatment endoscopy. The duration of therapy ranged from 7 to 20 days (median, 12 days). Symptoms resolved in 117 of 123 patients (95%; 95% confidence interval, 90-98%) with a median time of ~4 days. Response rates were 43 of 46 (93%) and 70 of 73 (96%) for patients with greater or fewer than 50 CD4(+) cells/mm(3), and 80 of 85 (94%) and 23 of 24 (96%) in infections caused by C. albicans alone or in association with non-albicans isolates, respectively. Symptoms recurred within 2 weeks of stopping caspofungin in 19 of 115 evaluable patients (17%), including 3 of 16 (19%) receiving antifungal prophylaxis. Relapse rates were similar for patients with greater or fewer than 50 CD4(+) cells/mm(3). In this relatively small number of patients, only symptom severity and extent of disease judged endoscopically at baseline were significantly (p < 0.10) associated with early relapse in the multivariate model.

AIDS-Related Opportunistic Infections↗
PubMed1991

Lymphocyte subsets as surrogate markers in antiretroviral therapy.

Efficacy of antiretroviral treatment is evaluated usually according to reduction of serious events (e.g. opportunistic infections while on therapy) and improvement of survival time. In stages of asymptomatic disease treatment trials have to cover very long time periods to fulfil these requirements. In asymptomatic stages, when viremia is commonly absent, monitoring the host's immune response is an indirect means of measuring antiviral efficacy. CD4+ lymphocyte counts are generally accepted as surrogate in all major trials. The subsets of the CD8+ compartment reflect early and late activation and cytotoxic immune response. CD38+, CD57, CD8+ HLA/DR+ subsets reflect the host's vigorous cellular immune response even in early stages. These subsets are candidate surrogate markers in early and late stages of HIV infection. On the other hand, CD3+ CD4- CD8-, CD19/20 (B lymphocytes) and CD16+ (natural killer cells) do not exhibit any properties of candidate surrogate markers. Established and experimental cellular surrogate markers are discussed including own data and a review of the literature.

Evaluation Studies as Topic↗
PubMed1992

Methods for detecting early signs of AIDS dementia complex in asymptomatic HIV-1-infected subjects.

OBJECTIVES: To determine the optimal diagnostic procedures for identifying early signs of AIDS dementia complex (ADC) in asymptomatic HIV-1-infected individuals, in order to prevent further cognitive function impairment by early treatment. DESIGN: Study patients had been referred electively and consecutively to hospital; all had been referred for the first time and gave informed consent. Inclusion criteria were (1) lack of history and/or symptoms of psychosis and neurological disorders; (2) lack of active viral, protozoan or fungal pathology; (3) abstinence from heroin and/or cocaine for at least 6 months before baseline evaluation. SETTINGS: Subjects were seen at the L. Spallanzani Hospital for Infectious Diseases, Rome, Italy between March 1989 and March 1991. PARTICIPANTS: Eighty-two asymptomatic HIV-1-infected subjects: 41 drug users, 27 homosexuals and 14 heterosexuals. MAIN OUTCOME MEASURES: All subjects were evaluated using Wechsler-Bellevue I, Benton C form and Bender tests. Thirty-nine subjects underwent single-photon emission computed tomography (SPECT) and 12 magnetic resonance imaging (MRI). The immunological status of each subject was determined. RESULTS: On psychometric testing, 23 out of the 82 (28%) asymptomatic subjects had a mental decay percentage (MD%) > or = 20%. Cerebral perfusion abnormalities were detected in 31 out of 39 (79.48%) subjects who underwent SPECT; MRI abnormalities were observed in seven out of 12 (58%) subjects. Twelve out of 23 subjects with MD% > or = 20, 15 out of 29 subjects with SPECT abnormalities and four out of seven patients with MRI abnormalities had total CD4+ lymphocyte counts > or = 500 x 10(6)/l. CONCLUSIONS: The high incidence of abnormal SPECT and of MD% > or = 20 in asymptomatic HIV-1-infected patients, and the lack of correlation between immunological status and degree of mental decay, SPECT and MRI abnormalities raise many questions about subclinical HIV-1 neurological disease.

AIDS Dementia Complex↗
PubMed1994

Reduced rate of disease development after HIV-2 infection as compared to HIV-1.

Human immunodeficiency virus type-2 (HIV-2) is a close relative of the prototype acquired immunodeficiency syndrome (AIDS) virus, HIV-1. HIV-2 is biologically similar to HIV-1, but information is lacking concerning clinical outcomes of HIV-2-infected individuals. From 1985 to 1993, a prospective clinical study was conducted in women with HIV-2 and HIV-1 infection to determine and compare rates of disease development. HIV-1-infected women had a 67% probability of AIDS-free survival 5 years after seroconversion in contrast with 100% for HIV-2-infected women. In addition to having significantly less HIV-related disease outcome in HIV-2 enrollees compared to HIV-1 enrollees, the rate of developing abnormal CD4+ lymphocyte counts with HIV-2 infection was also significantly reduced. This natural history study demonstrates that HIV-2 has a reduced virulence compared to HIV-1.

Acquired Immunodeficiency Syndrome↗
PubMed1998

Combination therapy of resistant warts in a patient with AIDS.

BACKGROUND: An AIDS patient on anti-HIV therapy consisting of two reverse transcriptase inhibitors had a low CD4+ lymphocyte count, a high HIV viral RNA load, and facial warts that were resistant to ablative therapy. OBJECTIVE: To find a regimen to treat resistant warts in an AIDS patient with a depressed CD4 count and high HIV viral load. METHODS: A protease inhibitor was added to his regimen and he was treated with ablative therapy using a 585 nm flashlamp-pumped pulsed dye laser (FPPDL). RESULTS: Observed resolution of the warts one month later, with no recurrence at seven-month follow-up. CONCLUSIONS: Treatment of resistant warts in patients with AIDS may be enhanced by triple-drug therapy which includes a protease inhibitor, used in combination with ablative therapy, such as the FPPDL.

AIDS-Related Opportunistic Infections↗
PubMedDate not supplied

[Campylobacter gastroenteritis in patients with human immunodeficiency virus infection].

BACKGROUND: Campylobacter bacteria are frequent, and usually slight causes of diarrhea in a normal host while in an immunosuppressed host the diarrhea may lead to severe pictures. The aim of this study was to analyze the clinical features of gastroenteritis by Campylobacter spp. in hospitalized seronegative patients and in those with HIV infection. METHODS: A retrospective study of the cases of gastroenteritis by Campylobacter spp. in adult patients admitted in the authors' hospital from January 1988 to July 1993 was carried out. RESULTS: Of the 20 patients studied with gastroenteritis by Campylobacter spp., 13 (65%) had HIV infection. The mean age of the patients was 38 years (range: 18-68 years) with 70% of the cases being males. Seventy seven percent of the HIV positive patients showed diagnostic criteria for AIDS while 71% of the seronegative patients showed a base disease and/or received steroid therapy. The length of the diarrhea was greater in the patients with HIV infection on comparison with the seronegative patients (25 vs. 6 days). The diarrhea persisted for more than 2 weeks in more than half of the cases of seropositive patients. Fever continued a mean of 24 days in the HIV positive patients as compared with only 5 days in the HIV negative cases. Most of the former patients were treated with erythromycin with good response. Gastroenteritis recurred in one patient and another patient with HIV infection presented a pseudoappendicular picture. No case of bacteremia was detected in either the seropositive or seronegative patients. Campylobacter jejuni was isolated in most of the cases with a high percentage of resistence to quinolone drugs. The mean CD4 lymphocyte count in HIV positive patients was 131/mm3 (range: 1-774). Mean survival following diagnosis of gastroenteritis by Campylobacter spp. was 8.9 months (range: 1-17) in the patients with AIDS. CONCLUSIONS: Gastroenteritis by Campylobacter spp. in hospitalized patients was related with immunosuppressive states. A clinical profile of prolonged febrile diarrhea was common in HIV positive patients and was associated with a low number of CD4 lymphocytes, advanced HIV infection and short survival.

Acquired Immunodeficiency Syndrome↗
PubMed2005

High plasma HIV load in the CRF01-AE outbreak among injecting drug users in Finland.

An explosive outbreak of HIV-1 caused by the recombinant subtype AE (CRF01-AE) was detected in 1998 among Finnish injecting drug users (IDUs). These IDUs were compared with IDUs from the Amsterdam Cohort Study (ACS) infected with subtype B, to detect possible differences between 2 western IDU cohorts infected with different subtypes. Markers for progression (viral load and CD4+lymphocyte count) were compared between 93 IDUs with CRF01-AE and 63 IDUs with subtype B. Only persons with a seroconversion interval =2 y were included. During 48 months of follow-up, both cohorts were similar in CD4+ cell decline, but the Finnish IDUs had 0.34-0.94 log10 copies/ml higher viral loads. The Amsterdam IDUs had a low viral load (<1000 copies/ml) significantly more often than the Finnish IDUs. The difference could not be explained by the use of antiretrovirals. The higher viral load may have contributed to the rapid spread of the recombinant virus in the Finnish outbreak.

Adolescent↗
PubMed1992

Survival and disease progression in human immunodeficiency virus-infected women after an index delivery.

OBJECTIVE: Our objective was to provide information on survival and disease progression in human immunodeficiency virus antibody-positive pregnant women undergoing prospective evaluation. STUDY DESIGN: After an index delivery, 103 human immunodeficiency virus antibody-positive pregnant women were identified and underwent follow-up for 3 years. The patients were assessed medically and/or gynecologically when hospitalized for a human immunodeficiency virus-related illness or at each follow-up visit. The life-table method was used to estimate the cumulative probabilities of survival and remaining free of acquired immunodeficiency syndrome. Cox's proportional-hazards analyses were used to identify prognostic factors for survival and progression to acquired immunodeficiency syndrome. RESULTS: The majority of human immunodeficiency virus-infected pregnant women were alive 3 years later. Lymphadenopathy syndrome or herpes genitalis was significantly associated with a subsequent diagnosis of acquired immunodeficiency syndrome. Of the 103 original patients, six had acquired immunodeficiency syndrome at the index delivery and acquired immunodeficiency syndrome developed in 24. Approximately 94% of evaluable patients with development of acquired immunodeficiency syndrome had CD4-lymphocyte counts < 200/mm3. The most common opportunistic infection was Pneumocystis carinii pneumonia. Acquired immunodeficiency syndrome and postpartum zidovudine therapy were independent prognostic factors affecting survival. CONCLUSION: Survival was affected by Centers for Disease Control group status of human immunodeficiency virus infection at the index delivery.

AIDS-Related Complex↗
PubMedDate not supplied

Surrogate markers in AIDS and cancer trials.

There is significant need for rapid yet reliable evaluation of promising new interventions for the treatment of patients with cancer or HIV infection. Considerable attention has been given to identifying replacement or 'surrogate' endpoints for the true clinical efficacy endpoints, in order to reduce the cost, size and duration of clinical trials. We discuss issues which affect the validity of surrogate markers. The reliability of the CD4 lymphocyte count marker is carefully considered in clinical trials of anti-retroviral agents in HIV infected individuals. The nature of surrogate markers and their reliability is discussed in cancer prevention, screening and treatment trials. Some suggested uses of marker information are also considered.

Acquired Immunodeficiency Syndrome↗
PubMed1990

Reduced oxidative burst responses in monocytes and monocyte-derived macrophages from HIV-infected subjects.

Oxidative burst responses of monocytes and monocyte-derived macrophages (MDM) were studied in 40 subjects with HIV infection of different clinical stages. Oxidative burst was assessed as reduction of nitroblue tetrazolium (NBT) with or without stimulants. Results were determined as oxidative burst responses per cell and as a stimulatory ratio between stimulated and unstimulated NBT reduction. Cells from 12 HIV-seronegative homosexual men and 38 blood donors served as control groups. In patients with asymptomatic HIV infection, monocyte oxidative burst responses were reduced compared with the blood donors. In MDM from the same patients, stimulatory ratios were reduced. In AIDS patients, stimulatory ratios of both monocytes and MDM were reduced compared with controls. In contrast to the progressive deterioration of CD4+ lymphocyte counts as well as other immune functions in HIV infection, monocyte oxidative burst responses are impaired already in the asymptomatic phase of the infection, almost to the same extent as in patients with AIDS.

Adult↗
PubMed1994

Survival of patients receiving zidovudine before or after AIDS diagnosis: results of a German multicenter study. German AIDS Study Group.

While efficacy of zidovudine (ZDV) in the acquired immunodeficiency syndrome (AIDS) is well established, the issue of survival after early ZDV treatment is still controversial. To assess survival benefits of ZDV treatment prior to AIDS, as compared to treatment after the onset of AIDS, we used an observational analysis of infected individuals infected with human immunodeficiency virus treated with ZDV and/or prophylaxis against Pneumocystis carinii pneumonia prior to or after AIDS in comparison to patients never treated with ZDV. Nine German AIDS treatment centers entered case reports dating from January 1988 to January 1992. A total of 1425 HIV-infected patients were included, mainly homo-/bisexuals: 1338 males and 87 females, with a mean age of 38.9 years. Of these, 262 had received ZDV prior to AIDS, 376 after AIDS, and 787 had never received ZDV. Survival from a first CD4 lymphocyte count below 0.200 x 10(9)/l (or below 0.500 x 10(9)/l) to death was assessed by means of Kaplan-Meier analysis. Survival did not differ significantly when the first CD4 count below 0.200 x 10(9)/l was taken as baseline. The median survival of patients receiving ZDV prior to AIDS was 662 days as compared to 572 days in patients treated after AIDS. Patients with earlier therapy showed longer survival in a subset of patients who were observed from their first CD4 count below 0.500 x 10(9)/l.(ABSTRACT TRUNCATED AT 250 WORDS)

AIDS-Related Opportunistic Infections↗