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Results for “CD4 Lymphocyte Count”

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PubMed2003

[Anti-Toxoplasma gondii IgG antibodies in HIV-infected patients].

Toxoplasma gondii infection is mostly asymptomatic, since multiplication of the parasites is limited by immunological mechanisms. Immunocompromised patients are an exception. Immunity decrease in HIV-infected persons results in opportunistic infections, including toxoplasmosis reactivation. The basis of the diagnosis are serological investigations, revealing IgM, IgA and IgG antibodies in serum. In HIV-infected patients their titres are often low, what makes disease phase definition and therapeutic decisions difficult. Another marker of toxoplasmosis activity is the determination of IgG antibodies avidity. The aim of the study was determination of anti-T. gondii IgG antibodies presence and their avidity in HIV-infected patients with respect to CD4 lymphocyte count. The results suggest no effect of IgG antibodies presence on CD4 lymphocyte count. Low titres of IgG antibodies were noted in the patients but the high avidity index of the determined antibodies indicated chronic T. gondii infection.

Antibodies, Bacterial↗

PubMed1993

Clinical factors associated with weight loss related to infection with human immunodeficiency virus type 1 in the Multicenter AIDS Cohort Study.

The relation between a number of potential risk factors and change in body mass index per semester was examined in a community-based cohort of 1,809 homosexual and bisexual men seropositive for human immunodeficiency virus type 1 (HIV-1). The men were followed semiannually for up to 6.5 years between 1984 and 1990. A total of 9,735 person-semesters of observations were available for analysis. A Markov-type autoregressive model, adjusting for previous body mass index, was used to predict the change in body mass index over each person-semester. Overall, the cohort was gaining weight. An asymptomatic participant 1.8 m in height whose CD4+ cell count was > 750/microliters gained a mean of 0.5 kg each person-semester. In bivariate autoregressive models, diarrhea, fever, oral thrush, acquired immunodeficiency syndrome (AIDS), and CD4+ lymphocyte counts of < 100 and 100-199 cells/microliters were all associated with a significant decrease in body mass index. A significant inverse association was also found between change in body mass index and lymphadenopathy and herpes zoster, but when the intercept coefficient was added, no overall decrease in body mass index was seen in these models. In a final multivariate model, diarrhea was less strongly associated with a change in body mass index (p = 0.057), although AIDS (p = 0.009), fever (p = 0.006), thrush (p = 0.002), and a CD4+ lymphocyte count of < 100 cells/microliters (p < 0.001) all remained independently associated with a decrease in body mass index. Lymphadenopathy and a CD4+ lymphocyte count of 100-199 cells/microliters were also significant covariates in the final model, but neither of the beta coefficients exceeded that of the intercept, indicating that they were not independently associated with a decrease in body mass index. These findings suggest that the importance of diarrhea as a cause of HIV-related weight loss may have been over-estimated in previous clinic-based studies. AIDS and nonspecific markers of progression (fever, thrush, and a CD4+ count of < 100 cells/microliters) were the best predictors of weight loss during a semester.

Acquired Immunodeficiency Syndrome↗

PubMed2004

[Cause of hospitalization in patients with human immunodeficiency virus infection in a rural area. Role of chronic liver disease].

OBJECTIVES: To investigate whether the use of highly active retroviral therapy (HAART) has resulted in changes in the causes of hospitalization in human immunodeficiency virus (HIV)-infected patients and to assess the influence of hepatitis C virus (HCV) infection in this population. METHODS: The causes of hospitalization in HIV-infected patients in our center were retrospectively studied according to two time periods: 1 January 1994 to 31 December 1997 (group 1, no patients treated with HAART) and 1 January 1998 to 30 June 2001 (group 2, 63% of patients treated with HAART). Epidemiological, virological and immunological parameters, and HCV infection data were studied. RESULTS: As compared to patients in group 1, patients admitted to the hospital in group 2 were older (34.7 +/- 6.3 versus 30.6 +/- 4.6 years, P = 0.0037), had a higher CD4+ lymphocyte count (256 +/- 243 versus 146 (178, P = 0.044) and their hospital stays were significantly lower (7.7 +/- 6.3 versus 17.5 +/- 16.7, P = 0.003). Moreover, the percentage of hospitalizations for AIDS-defining diseases was lower (29% versus 50%, P = 0.046) and the percentage of hospitalizations for decompensated liver disease was higher (22% versus 0%, P = 0.007) in group 2. Among patients who died during hospitalization, there was a higher frequency of low CD4+ lymphocyte counts (77.8% versus 43.3%, P = 0.05), active HCV infection (100% versus 57.9%, P = 0.02) and AIDS-defining disease or decompensated liver disease as the cause of hospitalization (81.8% versus 45%, P = 0.02) than among survivors. Low CD4+ lymphocyte count was independently associated with mortality (OR 1063.1; 95% CI 1.3-838855.5). CONCLUSIONS: Since the introduction of HAART in our setting, the frequency of opportunistic infections has decreased and the frequency of decompensated liver disease has increased among the causes of hospitalization in HIV-infected patients.

AIDS-Related Opportunistic Infections↗

PubMed1994

Direct comparison of the relationship between clinical outcome and change in CD4+ lymphocytes in human immunodeficiency virus-positive homosexual men and injecting drug users.

BACKGROUND AND METHODS: To compare rates of decline of CD4+ lymphocytes among human immunodeficiency virus-positive homosexual men and injecting drug users, we followed up prevalent human immunodeficiency virus-positive homosexual men and current or former injecting drug users from February 1988 through August 1991. Subjects were free of acquired immunodeficiency syndrome at study entry and had semiannual clinical and laboratory evaluation, including measurement of T-cell subsets, under common protocols. Initial levels and rates of change of CD4+ lymphocyte counts were compared according to cohort membership and clinical progression, defined by the development of thrush or an acquired immunodeficiency syndrome--defining illness. Median follow-up was 30 months for both cohorts. RESULTS: At study entry, homosexual men had lower absolute numbers of circulating CD4+ lymphocytes than did injecting drug users (459/microL [0.46 x 10(9)/L] vs 509/microL, respectively). During follow-up, homosexual men exhibited a faster decline in CD4+ lymphocyte counts as well as more frequent development of HIV-related symptoms (thrush or acquired immunodeficiency syndrome). In both cohorts, initial levels of CD4+ lymphocytes and rates of decline in these cells were strongly associated with progression of disease, defined as remaining asymptomatic, onset of thrush, or onset of acquired immunodeficiency syndrome. Once homosexual men and injecting drug users were stratified by disease progression, their initial levels and rates of decline of CD4+ lymphocyte counts were similar. Thus, crude differences between the two study groups largely resulted from differences in development of clinical symptoms. CONCLUSIONS: In these cohorts of homosexual men and injecting drug users, clinical outcome was much more important than risk group membership in determining changes in CD4+ lymphocyte numbers. The close similarity between the groups also suggests that drug use, ethnicity, and socioeconomic status play a minor role in the progression of human immunodeficiency virus infection.

Adult↗

PubMed1995

Incidence of symptomatic urinary tract infections in HIV seropositive patients and the use of cotrimoxazole as prophylaxis against Pneumocystis carinii pneumonia.

OBJECTIVES: To determine the incidence of symptomatic urinary tract infections in HIV seropositive patients and to assess whether this varies with stage of disease, risk group or the use of co-trimoxazole as prophylaxis against Pneumocystis carinii pneumonia. METHODS: A retrospective case note review of 175 HIV-infected patients attending The Royal London Hospital between July 1988 and December 1992 was performed. A urinary tract infection was defined as a pure culture of > or = 10(5) colony forming units in a mid-stream specimen of urine from a patient with symptoms consistent with a urinary tract infection. RESULTS: Urinary tract infections occurred in 10 (5.7%) of 175 patients, with an incidence of 1.49 per hundred patient years. Urinary tract infections were significantly more common in patients with AIDS or a CD4 lymphocyte count below 0.2 x 10(9)/l (or both) when compared to those without AIDS and a CD4 lymphocyte count above 0.2 x 10(9)/l (5.4 vs. 0.5 urinary tract infections per hundred patient years, p = 0.00005). Women with AIDS or a CD4 count below 0.2 x 10(9)/l (or both) had an incidence of urinary tract infection of 18.5 per hundred patient years. No significant difference was found between the incidence of urinary tract infections in those taking co-trimoxazole as Pneumocystis carinii pneumonia prophylaxis and those taking alternative or no prophylaxis (2.6 vs 6.4 per hundred patient years, p = 0.39). CONCLUSIONS: Urinary tract infection represents a considerable health problem amongst HIV infected patients. Our data show that urinary tract infections are more common in patients with advanced compared with early HIV infection. Cotrimoxazole, when taken by patients as prophylaxis against Pneumocystis carinii pneumonia did not appear to reduce the incidence of urinary tract infection.

CD4 Lymphocyte Count↗

PubMed1998

Risk factors for primary Pneumocystis carinii pneumonia in human immunodeficiency virus-infected adolescents and adults in the United States: reassessment of indications for chemoprophylaxis.

Risk factors for the development of a first episode of Pneumocystis carinii pneumonia (PCP) were investigated in the Adult and Adolescent Spectrum of Disease Project, a medical record review study involving longitudinal follow-up of human immunodeficiency virus-infected adults in 9 US cities. Risk factors included decreasing CD4 lymphocyte count and history of AIDS-defining illness, non-P. carinii pneumonia, oral thrush, or unexplained fever for > or = 2 days; PCP prophylaxis was protective. PCP incidence/100 person-years of observation among persons not prescribed PCP prophylaxis was higher in those with CD4 lymphocyte counts < 250 cells/microL or CD4 cell percent < 14% (8.3; 95% confidence interval [CI], 7.7-9.0) than in persons with CD4 cell counts < 200 or history of thrush or fever, which constitute current criteria for prophylaxis against PCP (5.9; 95% CI, 5.5-6.4). Because of increased efficiency in capturing persons at highest risk, CD4 cell count < 250 or CD4 cell percent < 14% should be considered as criteria for prophylaxis against first episodes of PCP.

Adolescent↗

PubMed2006

C-reactive protein is a marker for human immunodeficiency virus disease progression.

BACKGROUND: Limited data on acute-phase C-reactive protein (CRP) levels in human immunodeficiency virus (HIV) infection exist. METHODS: We obtained a single measurement of CRP from 513 HIV-infected men in the Multicenter AIDS Cohort Study to examine the association between CRP and immune suppression and progression to AIDS. We estimated changes in CRP during the course of HIV infection in 81 of these individuals using specimens collected from October 1, 1984, to December 31, 1996. RESULTS: The cross-sectional associations between log(10) CRP were correlated inversely with CD4 lymphocyte counts (r=-0.17; P<.001) and directly with log10 HIV RNA levels (r=0.20; P<.001). Levels of CRP of more than 2.3 mg/L were associated with a decreased time to the development of AIDS (relative time to AIDS, 0.36; P<.001) compared with individuals with CRP levels of 1.2 mg/L or less, which remained significant after adjustment for CD4 lymphocyte counts and HIV RNA and hemoglobin concentrations. Levels of CRP significantly increased over time with mean slopes of 8.5% (95% confidence interval, 4.9%-12.2%) and 4.5% (95% confidence interval CI, 2.1%-6.9%) per year for individuals with and without progression to AIDS, respectively. Individuals had a geometric mean CRP level of 2.5 mg/L in the 6-month interval before progression to AIDS, which was an increase from a nadir of 1.0 mg/L at 6.5 years before progression to AIDS. CONCLUSIONS: Levels of CRP were associated with HIV disease progression independent of CD4 lymphocyte counts and HIV RNA levels. In addition, regardless of progression to AIDS, HIV-infected individuals had a significant increase in CRP over time. This may have implications for cardiovascular disease among HIV-infected individuals.

Acquired Immunodeficiency Syndrome↗

PubMed1991

Virological markers in the cerebrospinal fluid from HIV-1-infected individuals.

We analysed 127 specimens of cerebrospinal fluid (CSF) from 118 HIV-1-infected individuals at different stages of infection. Intrathecal antibody synthesis was evident in 23 samples tested and was more frequently directed against HIV than against rubella virus, herpes simplex virus, varicella zoster virus or cytomegalovirus. HIV was isolated from only 14% of the 127 CSF specimens, but from 82% of CSF-paired blood samples. HIV antigen was detected in 12% of CSF specimens and 44% of paired plasma samples. Twenty specimens analysed using the polymerase chain reaction (PCR) detected proviral DNA in 75% of CSF specimens. The low rate of virus recovery from CSF was caused by neither the freezing of specimens prior to culture nor therapy. In contrast, virus isolation from CSF was significantly associated with CSF cell count. Virus isolation and antigen detection in CSF were not correlated with either the Centers for Disease Control disease stage or the peripheral CD4+ lymphocyte count, whereas viraemia was significantly associated with a low CD4+ lymphocyte count. Moreover, virus isolation and antigen detection in CSF were not associated with symptoms of subacute HIV encephalitis, suggesting that these markers are not of potential value in the diagnosis of HIV-specific neurologic complications. The value of PCR in this field merits further investigation.

AIDS Dementia Complex↗

PubMed2000

A randomised, open-label comparison of three highly active antiretroviral therapy regimens including two nucleoside analogues and indinavir for previously untreated HIV-1 infection: the OzCombo1 study.

BACKGROUND: Highly active antiretroviral therapy (HAART) including two nucleoside analogues and a potent protease inhibitor is standard of care initial therapy for HIV-infected adults. The best-tolerated and most potent initial HAART regimen is unknown and was investigated in this study. METHODS: One hundred and nine HIV-infected adults with no prior antiretroviral therapy, and CD4 lymphocyte counts < 500 x 10(6) cells/l or plasma HIV RNA > 30,000 copies/ml were randomized to zidovudine-lamivudine-indinavir (ZDV-3TC-IDV), stavudine-lamivudine-indinavir (d4T-3TC-IDV) or stavudine-didanosine-indinavir (d4T-ddI-IDV) for 52 weeks. The primary endpoints were plasma HIV RNA and drug-related adverse events. Other assessments were overall safety, adherence and adverse events, CD4 lymphocyte counts, cutaneous delayed type hypersensitivity (DTH) responses and quality of life (Euroqol). RESULTS: Only 58% patients had HIV RNA < 50 copies/ml plasma at 12 months, with no significant difference between the three regimes (P = 0.34). Drug-related adverse events sufficiently severe to warrant drug discontinuation were less common (P = 0.06) in patients receiving d4T-3TC-IDV (18%) than in those receiving ZDV-3TC-IDV (34%) or d4T-ddI-IDV (41%). The percentages of patients who remained on their assigned therapy with plasma HIV RNA < 50 copies/ml at 52 weeks were 60% with d4T-3TC-IDV, 53% with ZDV-3TC-IDV and 35% with d4T-ddI-IDV. Virological failure at 52 weeks was more likely in those whose adherence was estimated to be < 100% in the first 4 weeks of therapy (P = 0.02), but not in those who developed grade 3 or 4 drug-related adverse events. At 52 weeks, the mean CD4 lymphocyte count increase was 200 x 10(6) cells/l with only 7% of patients having counts lower than at baseline; DTH responses improved but remained clinically impaired in most patients. Quality of life improved significantly in all groups. CONCLUSIONS: Initial HAART regimens including IDV failed to suppress plasma HIV RNA to < 50 copies/ml in > 40% patients after only 12 months of therapy although there was significant overall improvement immunologically and in quality of life. The type of dual nucleoside combination used was less important in predicting virological failure than was imperfect adherence early in therapy. Consideration should be given to modifying a HAART regimen relatively early in non-adherent patients.

Adult↗

PubMed1997

The prevalence of Enterocytozoon bieneusi in acquired immunodeficiency syndrome (AIDS) patients from the north west of England: 1992-1995.

Microsporidia are increasingly being recognised as important enteric pathogens in patients with advanced human immunodeficiency virus (HIV) disease, i.e. acquired immunodeficiency syndrome (AIDS). The aims of this study were to investigate the frequency of detection of microsporidia associated with diarrhoea in patients with advanced HIV disease in the north west of England, and to determine the species involved and their prevalence. During the period from April 1992 to the end of December 1995, chronic diarrhoea in 88 patients in the late stage of HIV disease was investigated. Duodenal biopsies, duodenal aspirates or jejunal biopsies were received from 38 patients, and stool samples from 63 patients, as part of the routine investigation of possible causes of diarrhoea in these patients. Biopsies and aspirates were examined by thin-section electron microscopy (EM), and stool samples were examined by epi-fluorescence microscopy after staining with Calcofluor. Putative stool positives were confirmed by transmission electron microscopy. CD4-lymphocyte counts were available from all patients who provided samples. Nine out of 63 patients (14.3%) were found to be excreting microsporidial spores on stool examination. The species was confirmed as Enterocytozoon bieneusi. The mean CD4-lymphocyte count for this group was 37 x 10(6)/L (normal range 517-1677 x 10(6)/L). Three out of 38 biopsy specimens (7.9%) were also found to be infected with this microsporidian. The mean CD4-lymphocyte count for this group was 72 x 10(6)/L. Encephalitozoon intestinalis was not found in any samples examined. The prevalence of microsporidial infection in AIDS patients in the north west of England appears to be similar to that of patients in London, but less than that reported in studies from other developed countries.

AIDS-Related Opportunistic Infections↗

PubMed2000

Clinical spectrum, morbidity, and mortality of acquired immunodeficiency syndrome in Taiwan: a 5-year prospective study.

The clinical spectrum of AIDS and changes of morbidity and mortality associated with HIV infection following initiation of highly active antiretroviral therapy (HAART) are rarely described in the less developed countries in the Asia-Pacific region. We prospectively observed on a follow-up basis 309 HIV-infected patients (82.8% with AIDS) at National Taiwan University Hospital in Taiwan, where highly active antiretroviral therapy (HAART) has been provided to all patients at no charge at any stage of HIV infection since April 1, 1997, to describe the spectrum of HIV-associated opportunistic diseases and evaluate changes of morbidity and mortality from June 24, 1994 through June 23, 1999. Of the patients, 59.3% at study entry had a CD4+ lymphocyte count of <50 cells/microliter. The five leading HIV-associated opportunistic infections included oroesophageal candidiasis (195 patients), Pneumocystis carinii pneumonia (93), tuberculosis (77), mucocutaneous herpes simplex infection (74), and cytomegalovirus diseases (73). The incidence rates of seven major AIDS-defining opportunistic diseases were declining though the changes of the relative proportions varied. The median duration of hospitalization decreased from 36 days in 1995 to 12 days in 1999 (p =.0001). Overestimated mortality rate declined from 148.4 per 100 patient-years in 1995 to 7.4 per 100 patient-years in 1999 (p =.0001) whereas the underestimated mortality rate declined from 110.5 to 5.39 per 100 patient-years (p =.0001). Risk ratio (RR) for mortality in patients who received HAART compared with those who did not was 0.410 (95% confidence interval [CI], 0.249-0.674; p =.0004) and the RR was 0.250 (95% CI, 0.127-0.492; p =.0001) when the analysis was limited to patients with an initial CD4+ lymphocyte count <100 cells/microliter and follow-up duration >30 days after adjusting for their age, gender, type of risk behavior, and CD4+ lymphocyte count. Morbidity and mortality were declining with each study year even in a population consisting mainly of patients at the advanced stage of HIV infection in Taiwan. Earlier diagnosis, accumulation of clinical experience, and use of HAART were associated with lower mortality rates.

AIDS-Related Opportunistic Infections↗

PubMedDate not supplied

[Nutrition problems experienced by adults infected with the human immunodeficiency virus in Abidjan (Ivory Coast)].

Denutrition is frequent among HIV-infected (HIV+) adults in sub-Saharan Africa. One of the risk factors for denutrition is a reduction in dietary intake. Eating disorders may be partly responsible for such decreases in food intake. We prospectively analyzed the frequency, associated factors and progression of anorexia, dysphagia and food aversion in a cohort of 330 HIV-infected adults included in a trial of early chemoprophylaxis with cotrimoxazole in Abidjan, Ivory Coast. Patients were followed-up by means of scheduled monthly visits. Eating disorders were assessed using a standardized questionnaire after 6, 12 and 18 months of follow-up. After six months of follow-up, 28% of the patients reported anorexia, 9% dysphagia and 28% food aversion. Multivariate analysis showed that anorexia was significantly more frequent in women than in men (odds ratio (OR) = 2.0 [95% confidence interval: 1.2-3.5]) and in patients with a CD4+ lymphocyte count < 200/mm3 (OR = 1.8 [1.0-3.5]). The risk of dysphagia was also higher for women than for men (OR = 1.8 [1.0-3.5]). The risk of dysphagia was also higher for women than for men (OR = 3.3 [1.3-8.4]). Patients with < 200 CD4+ lymphocytes/mm3 were more likely than those with CD4+ lymphocyte counts of over 200 to suffer food aversion (OR = 1.8 [1.1-3.0]). We analyzed the progression of dietary problems during follow-up and found that anorexia and dysphygia tended to disappear from one evaluation to the next whereas the number of patients reporting food aversion tended to increase. For patients reporting anorexia at the 6-month evaluation, significantly more women than men reported the persistence of anorexia at the 12-month evaluation (16% versus 5%; p = 0.03). Among patients with dysphagia at six months, those with a CD4+ lymphocyte count below 200/mm3 were much more likely than those with a CD4+ count above 200 to report persistent dysphagia at the 12-month evaluation (7% versus 0%; p = 0. 02, Fischer's exact test). For patients with no dietary problems after six months, those taking cotrimoxazole were significantly more likely than those of the placebo group to report food aversion at the 12-month evaluation (21% versus 8%; p = 0.01). We found that dietary problems were associated more with the stage of immunodeficiency that with socioeconomic factors, with the exception of sex, which was associated with several outcomes. These data stress the importance of detecting these frequent dietary problems as part of the overall clinical management of HIV+ adults in Africa, and of providing affected individuals with early nutritional counseling.

Adult↗

PubMed2001

Multicenter case-control study of risk factors for histoplasmosis in human immunodeficiency virus-infected persons.

We conducted a multicenter case-control study to identify risk factors for histoplasmosis among persons with acquired immunodeficiency syndrome (AIDS) and to evaluate predictors of a poor outcome (defined as death or admission to the intensive care unit). Patients with histoplasmosis were each matched by age, sex, and CD4 lymphocyte count to 3 controls. From 1996 through 1999, 92 case patients and 252 controls were enrolled. Of the case patients, 81 (89%) were men, 50 (55%) were black, 78 (85%) had a CD4 lymphocyte count of <100 cells/microL, 80 (87%) were hospitalized, and 11 (12%) died. Multivariable analysis found that receipt of antiretroviral therapy and of triazole drugs were independently associated with a decreased risk of histoplasmosis. Chronic medical conditions and a history of infections with herpes simplex virus were associated with poor outcome. Triazoles should be considered for chemoprophylaxis for persons with AIDS, especially those who take part in high-risk activities that involve frequent exposure to soil, who have CD4 lymphocyte counts of <100 cells/microL, and who live in areas where histoplasmosis is endemic.

AIDS-Related Opportunistic Infections↗

PubMed1998

Production of monoclonal antibody to CD4 antigen and development of reagent for CD4+ lymphocyte enumeration.

A hybridoma secreting monoclonal antibody (mAb) specific to CD4 protein was generated. This monoclonal antibody, named MT4, was proved to be specific to CD4 protein as it reacted with CD4-DNA transfected COS cells, CD4+ cell lines and CD4+ lymphocytes. Furthermore, MT4 mAb inhibited the binding of standard CD4 monoclonal antibodies to CD4 proteins on CD4+ cells. To develop a home made reagent for CD4+ lymphocyte determination by flow cytometry, fluorescein isothiocyanate (FITC) was conjugated to MT4 mAb. To evaluate the developed reagent, 30 HIV infected and 30 healthy individuals were determined for CD4+ lymphocytes by using both a commercial Simultest reagent kit and home made FITC labeled MT4 mAb simultaneously. The study has shown that both percentages and absolute CD4+ lymphocyte counts obtained from both reagents were equivalent. The correlation coefficient for regression analysis was 0.995 and 0.996 for percentages and absolute CD4+ lymphocyte counts, respectively. The results suggest that home made FITC labeled MT4 reagent is an acceptable alternative reagent for monitoring CD4+ lymphocytes in blood samples by flow cytometry.

Animals↗

PubMed1998

Anti-retroviral therapy reverses HIV-associated abnormalities in lymphocyte apoptosis.

The objective of this study was to assess the role of anti-retroviral therapy (ART) on the susceptibility of peripheral blood lymphocytes (PBL) from HIV-1-infected individuals to activation-induced apoptosis and in comparison with changes in CD4 lymphocyte counts. Eleven symptomatic HIV+ patients were studied. Ex vivo apoptosis was measured in phytohaemagglutinin (PHA)-stimulated PBL and CD4 subsets by flow cytometry, at baseline and after 1 month (4-6 weeks) and 2/3 months of ART. Six patients had extended studies of the effects of therapy to a maximum of 21 months. Lymphocyte apoptosis was significantly elevated in HIV+ patients at baseline (median 22% compared with 7.5% in HIV- risk-matched controls; P < 0.05). This decreased to control levels on ART (7.4% at 4-6 weeks, P < 0.01, and 6.2% at 8-12 weeks, P < 0.05, compared with baseline). Similar changes occurred in the CD4+ subpopulation. The decrease in apoptosis was maintained for several months, but the effect was rapidly lost if ART was discontinued. CD4 counts showed a reciprocal relationship to changes in apoptosis. The association of changes in apoptosis with those in CD4 counts suggests a link between programmed cell death and lymphocyte depletion. Apoptosis reduced in some individuals without any reduction in viral load, suggesting apoptosis may be influenced by factors in addition to the overall extent of HIV replication.

Acquired Immunodeficiency Syndrome↗

PubMed1993

Decreased efficacy of inhaled pentamidine in the prevention of Pneumocystis carinii pneumonia among HIV-infected patients with severe immunodeficiency.

STUDY OBJECTIVE: To determine the relationship between the degree of immune deficiency and the risk of Pneumocystis carinii pneumonia (PCP) among HIV-infected patients receiving inhaled pentamidine prophylaxis. DESIGN: Retrospective chart review. SETTING: AIDS clinic of inner-city hospital. PATIENTS: Patients attending inhaled pentamidine clinic between 1989 and 1991. INTERVENTION: Review of medical records of patients receiving inhaled pentamidine, 300 mg/month, via nebulizer (Respirgard II) as primary or secondary prophylaxis of PCP. Statistical analysis of lymphocyte subset results and selected clinical data. RESULTS: Ten of 57 patients developed PCP during the period of analysis. Patients with CD4 counts less than 60/mm3 were significantly more likely to develop PCP (p = 0.01; Fisher's exact test) with a relative risk of 7.55 compared to patients with CD4 lymphocyte counts greater than 60/mm3. CONCLUSION: Failure of inhaled pentamidine prophylaxis is seen almost exclusively among patients with CD4 lymphocyte counts below 60/mm3.

AIDS-Related Opportunistic Infections↗

PubMed1997

Correspondence between the effect of zidovudine plus lamivudine on plasma HIV level/CD4 lymphocyte count and the incidence of clinical disease in infected individuals. North American Lamivudine HIV Working Group.

OBJECTIVES: To investigate whether apparently beneficial changes in plasma HIV RNA level and CD4 lymphocyte count that are induced by antiretroviral therapy are associated with a corresponding clinical benefit. METHODS: For 620 patients in two randomized, double-blind trials of lamivudine (3TC) and zidovudine (ZDV) plasma HIV RNA and CD4 lymphocyte count changes were compared in patients randomized to 3TC plus ZDV and patients randomized to other treatment arms. The effect of therapy on the HIV RNA level and CD4 count was compared with the effect of therapy on clinical endpoints over the same time period. RESULTS: Median baseline values for all subjects were 42 420 copies/ml for HIV RNA and 277 x 10(6)/l for CD4 count. During the trial a significantly lower HIV RNA level and higher CD4 count was sustained in the ZDV/3TC group compared with the other group, with a difference in the median area under the curve from baseline per month of follow-up of 0.38 log10 copies/ml HIV RNA and 0.18 log2 x 10(6)/l CD4 cells (P < 0.001 in each case). For patients who were initially asymptomatic or in CDC stage B, the adjusted relative hazard (RH) of AIDS for a twofold lower CD4 count was 3.14 [95% confidence interval (CI), 1.44-6.83] and for a 10-fold higher HIV RNA level was 3.22 (1.20-8.59). The RH progression to AIDS expected with ZDV/3TC compared with the control treatments, given the observed effects of treatment on CD4 cell counts and HIV RNA levels, is 0.52, whereas the observed value was 0.16 (0.03-0.74). After adjustment for HIV RNA and CD4 changes over time the observed RH of progression to AIDS for ZDV/3TC treatment compared with controls was increased to 0.36 and was no longer significant (95% CI, 0.07-1.85). CONCLUSION: In this analysis of two trials, the effects of ZDV/3TC in reducing plasma HIV RNA and raising peripheral blood CD4 counts were associated with concurrent clinical benefits and the effect of treatment on these markers could account for at least part of the clinical benefits of therapy that were observed.

Anti-HIV Agents↗

PubMed1998

A randomized comparative trial of stavudine (d4T) versus zidovudine (ZDV, AZT) in children with human immunodeficiency virus infection. AIDS Clinical Trials Group 240 Team.

OBJECTIVES: To compare the safety and tolerance of stavudine (d4T) versus zidovudine (ZDV, AZT) in symptomatic human immunodeficiency virus-infected children 3 months to 6 years of age. METHODS: In an initially double-blind trial, 212 evaluable human immunodeficiency virus-infected children who had received no more than 6 weeks of previous antiretroviral therapy were randomized to receive either d4T (1 mg/kg orally every 12 hours, maximum 40 mg orally every 12 hours) or zidovudine (180 mg/m2 orally every 6 hours, maximum 200 mg orally every 6 hours). The study was unblinded after a median follow-up period of 6.3 months; median follow-up at study closure was 17.3 months. Tolerance, safety, disease progression, and immunologic responses were evaluated. RESULTS: The patient population was young (median age, 1.2 years; range, 0.3 to 6.4 years), with a median baseline CD4+ lymphocyte count of 965 cells/microL (range, 18 to 4238 cells/microL). Neutropenia < 400/microL occurred significantly more commonly among zidovudine recipients (1-year event rates of 20% both up to the time of unblinding and throughout the entire study) than among children receiving d4T (1-year event rates of 5% up to the time of unblinding and 6% throughout the entire study). In exploratory activity analyses using all data collected until study closure, children treated with d4T showed consistently greater positive changes from baseline in weight-for-age-and-gender z scores. As expected in this population of young children, median absolute CD4+ lymphocyte counts decreased in both treatment groups. Smaller changes from baseline were noted among d4T recipients. CONCLUSIONS: In children between the ages of 3 months and 6 years, d4T and zidovudine are largely comparable in terms of safety and tolerance. Neutropenia occurs significantly less commonly among children treated with d4T. There was evidence that weight gain and absolute CD4+ lymphocyte counts were better maintained in children receiving d4T.

Anti-HIV Agents↗