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PubMed1998

Effects of protease inhibitors on the course of CMV retinitis in relation to CD4+ lymphocyte responses in HIV+ patients.

AIM: To gain insight into the course of CMV retinitis (CMVR) in AIDS patients receiving protease inhibitors (PI), and to evaluate whether certain patterns of CD4 response are indicative of the clinical outcome and the risk of recurrence. METHODS: 15 consecutive AIDS patients receiving maintenance therapy for CMVR were included in a prospective observational cohort study at the university hospital between July and October 1996. Patients were evaluated for signs of CMVR activity and intraocular inflammation. CMVR recurrence was defined as the primary clinical endpoint. Follow up was performed until July 1997. No patient was lost to follow up. Clinical outcome was related to CD4+ lymphocyte counts, which were monitored every 6 weeks. Highly active antiretroviral treatment regimen including PI was started at study entry. RESULTS: All recurrences (n = 7) were in patients who failed to have a sustained increase in CD4 counts, whereas CMVR remained inactive during a follow up of 42-52 weeks in those who were able permanently to restore their CD4 values to 100 x 10(6)/l or more (n = 5). The remaining three patients died after 12, 16, and 50 weeks, respectively, without recurrences. All relapses of CMVR were seen after 6-16 weeks, and at CD4 counts well below 100 x 10(6)/l. CONCLUSIONS: The beneficial effects of PI treatment correlate with the pattern of CD4 response. Sustained increases in CD4 counts achieved in the first 16 weeks of treatment are associated with a prolonged period of CMVR quiescence. Poor initial response is associated with a high risk of CMVR recurrence.

AIDS-Related Opportunistic Infections↗

PubMed1997

[Meningitis after acute Borrelia burgdorferi infection in HIV infection].

HISTORY AND CLINICAL FINDINGS: A 39-year-old HIV positive patient developed myalgia, headache and cough 4 weeks after a tick bite. His temperature was 37.4 degrees C and a circular pale erythema was noted over the left lower leg. INVESTIGATIONS: C-reactive protein was raised to 120 mg/l, white blood cell count was 5860/microliter, CD4-lymphocyte count 250/microliter. The chest radiogram showed pneumonitic infiltration in the left lower lobe. There were IgM antibodies against Borrelia burgdorferi. TREATMENT AND COURSE: Left lower lobe pneumonia and chronic erythema migrans were diagnosed and he was given oral azithromycin (500 mg on the first day and 250 mg for 4 days). The pneumonia cleared up, but 2 weeks later he developed symptoms of meningitis (496 cells per microliter, 87% lymphocytes, positive Borrelia burgdorferi antibody titer), which quickly and lastingly responded to ceftriaxon (2 g daily by brief infusion for 14 days). CONCLUSION: This immune-compromised HIV-infected patient developed disseminated borreliosis with CNS involvement 2 weeks after the occurrence of chronic erythema migrans. The initial treatment of the latter with azithromycin was unable to prevent the meningitis. It is unlikely that there was a causal connection between the borreliosis and the pneumonia.

Adult↗

PubMed1997

Trends in survival of HIV infected patients attending the Department of Genito-Urinary Medicine, Royal Infirmary of Edinburgh.

In the early 1980s, median survival for patients with the acquired immunodeficiency syndrome (AIDS) was only 11 months. Survival improved in the mid-1980s, reaching a median of 20 months. We have looked at the trends in survival of patients attending the Genito-urinary Medicine Department of Edinburgh Royal Infirmary between 1984 and 1996. Patients with an AIDS diagnosis between 1988 and 1991 had a median survival of 28 months, whereas patients given an AIDS diagnosis between 1992 and 1996 had a median survival of only 15 months (p = 0.01). However, survival from the point at which the CD4 lymphocyte count fell below 200 (CD4 200) remained unchanged. Patients diagnosed as AIDS after 1992 were more likely to have received prophylaxis against Pneumocystis carinii pneumonia or anti-retroviral therapy prior to an AIDS diagnosis. This may have resulted in the postponement of an AIDS defining diagnosis until the patients were more severely immuno-compromised, but has conferred no overall survival benefit.

Acquired Immunodeficiency Syndrome↗

PubMed1991

CD4 T-lymphocyte counts and Pneumocystis carinii pneumonia in pediatric HIV infection.

The relationship between CD4 T-lymphocyte counts and infection with the human immunodeficiency virus (HIV) is retrospectively investigated for 266 HIV-infected and uninfected children who were born to infected women, including 39 with Pneumocystis carinii pneumonia (PCP), in a population-based surveillance study. Of 21 perinatally HIV-infected children with PCP only 10 (48%) had CD4 T-lymphocyte counts that were less than 500 x 10(6) cells/L (500 cells/mm3), compared with all 18 who were infected via blood transfusions or clotting factors. Among 68 children who were 1 year or younger, 18 (90%) of 20 PCP cases had CD4 T-lymphocyte counts that were less than 1500 x 10(6) cells/L (1500 cells/mm3) compared with only five (10%) of 48 children who did not have the acquired immunodeficiency syndrome (odds ratio, 77.4; 95% confidence interval, 19.7 to 313.4). The mean CD4 T-lymphocyte count was lower for the 39 PCP cases when compared with the 188 children who were at different stages of HIV infection and did not have the acquired immunodeficiency syndrome (AIDS) independent of age. The majority of perinatally HIV-infected children with PCP were 6 months or younger and 50% were previously unknown to be infected. Thus, HIV-positive children should be identified early and followed closely. CD4 T-lymphocyte counts may be useful in monitoring HIV-positive children and determining when to begin PCP prophylaxis.

Acquired Immunodeficiency Syndrome↗

PubMed1999

Changes in hepatitis B serologic titers in HIV+ and HIV- children with haemophilia.

This longitudinal study examines differences in hepatitis B immune titres in children and adolescents with haemophilia to determine if they are dependent on how immunity was acquired (vaccination or natural infection), and whether they are related to the child's HIV status and/or are influenced by HIV disease progression. Serologic titres (HBcAb, HBsAb) and HBsAg were measured prospectively at baseline, and at years 1, 2 and 3 of follow-up in 126 HIV- and 207 HIV+ children and adolescents with haemophilia. Analyses were performed to assess the impact of HIV status on the measured titres, and for HIV+ subjects to examine the association with CD4+ lymphocyte counts and p24 antigen status. The results show that HIV+ children were more likely than HIV- children to lose vaccine-induced immunity as indicated by the loss of HBsAb. There was an increased risk of losing HBsAb with higher CD4+ counts and younger age. Re-immunization was not successful in seven of eight HIV+ children. Two subjects (one HIV+, one HIV-) entered the study HBsAg- but became HBsAg+ over the course of follow-up. Seven HIV+ subjects lost natural immunity as indicated by the loss of HBcAb. The loss of either HBsAb or HBcAb in HIV--subjects was negligible to absent. In conclusion, because of the loss of immunity in HIV+ children the viral safety of factor replacement concentrates for these children is an important consideration. HIV- children rarely lose immunity, therefore frequent measures of HBsAb are not necessary.

CD4 Lymphocyte Count↗

PubMed1999

Virologic and immunologic response to nucleoside reverse-transcriptase inhibitor therapy among human immunodeficiency virus-infected infants and children.

Plasma human immunodeficiency virus RNA and CD4 lymphocyte response to nucleoside reverse-transcriptase therapy were evaluated in a large, comparative pediatric trial. Both baseline values and changes in the two laboratory markers over time correlated well with clinical outcome and possessed independent predictive value. In comparison of RNA reduction from baseline between the dideoxyinosine (ddI) and zidovudine+ddI therapeutic arms, marginal superiority of the combination arm was not correlated with an observed clinical benefit. Despite the size of this trial and the significantly higher rate of clinical end points in the zidovudine monotherapy group, attempts to establish surrogacy for plasma RNA were difficult. Nevertheless, plasma RNA and CD4 lymphocyte count together possess strong clinical predictive power and are valuable tools for both the clinician and the evaluation of new therapies.

Adolescent↗

PubMed2003

Interleukin-2 Increases CD4+ lymphocyte numbers but does not enhance responses to immunization: results of A5046s.

To ascertain whether CD4(+) lymphocyte increases induced by interleukin (IL)-2 enhanced in vivo immune responses, 38 human immunodeficiency virus (HIV)-infected patients who had received highly active antiretroviral therapy (HAART) or HAART and IL-2 for at least 60 weeks were immunized with tetanus toxoid, inactivated glycoprotein 120-depleted HIV-1, and hepatitis A and B vaccines. Despite dramatic increases in CD4(+) lymphocyte counts, IL-2 did not enhance immunization responses.

AIDS Vaccines↗

PubMed1994

MT-2 cell tropism of human immunodeficiency virus type 1 isolates as a marker for response to treatment and development of drug resistance.

The correlation of the tropism of human immunodeficiency virus type 1 (HIV-1) isolates for MT-2 cells with response to zidovudine and didanosine treatment and with development of drug resistance was studied. Patients with MT-2-negative but not MT-2-positive HIV-1 had a significant increase in CD4+ lymphocyte counts during the first 6 months of treatment. In both groups and for both drugs, the rate of CD4+ lymphocyte decline decreased after the start of treatment. MT-2-positive isolates were more likely than MT-2-negative isolates to show reduced sensitivity to zidovudine and didanosine. Because the differences in zidovudine sensitivity were first evident after 12 months of treatment, drug resistance was probably not the cause of poor response early in zidovudine treatment in patients with MT-2-positive HIV-1. Thus, patients with MT-2-positive virus have limited benefit from treatment with single nucleoside analogues. Knowledge of MT-2 cell tropism may be important in clinical trials and for choosing treatments for patients.

Adult↗

PubMed1996

Pneumocystis carinii infection: current treatment and prevention.

Pneumocystis carinii is a common cause of pneumonia in individuals who are immunosuppressed by HIV infection. Use of molecular biological techniques show that P. carinii is a fungus and that infection in man is not a zoonosis. Invasive tests such as sputum induction or bronchoscopy are used to make the diagnosis of P. carinii pneumonia. Life long primary prophylaxis is given to HIV positive individuals with CD4+ lymphocyte counts < 0.20 x 10(9)/L or a CD4: total lymphocyte ratio of < 1.5, constitutional symptoms, or with other AIDS defining diseases. Secondary prophylaxis is given after a first episode to prevent a recurrence. First choice for primary and secondary prophylaxis is oral co-trimoxazole 960 mg od or three times a week. In patients who are intolerant to co-trimoxazole, nebulised pentamidine or dapsone (with or without pyrimethamine) are second and third choices. In a patient with acute PCP disease, severity should be assessed using clinical, radiographic and blood gas criteria as those with moderate or severe disease will benefit from adjuvant glucocorticoids. Co-trimoxazole (120 mg/kg/day in divided doses for 21 days) is first choice therapy for PCP of all degrees of severity. In patients who fail to respond to co-trimoxazole or who are intolerant to it, second line treatment is iv pentamidine in those with severe disease and oral dapsone with trimethoprim, oral clindamycin with primaquine or iv pentamidine in those with mild or moderately severe disease.

Animals↗

PubMed1995

Differences in androgens of HIV positive patients with and without Kaposi sarcoma.

AIM: Since most forms of Kaposi sarcoma are much more common in men than in women, the aim of this study was to examine serum concentrations of sex steroids in HIV positive men with and without Kaposi sarcoma. METHODS: Blood samples from 34 HIV positive men without Kaposi sarcoma (KS-) and 28 with Kaposi sarcoma (KS+) and from 35 HIV negative men (controls) were analysed for adrenal and gonadal steroids. Further analysis was done in subgroups classified by CD4 lymphocyte counts. RESULTS: KS+ patients had significantly higher serum dehydroepiandrosterone (DHEA) and testosterone concentrations than the KS- patients, and their DHEA, DHEA sulphate, testosterone, and androstenedione values were higher than in the controls. The KS+ patients with more than 500 CD4 lymphocytes per mm3 had significantly higher serum DHEA, DHEA sulphate, and testosterone than the KS- patients with the same CD4 counts; those with 500-200 CD4 cells/mm3 had higher serum DHEA and testosterone than the equivalent KS- men; and those with < 200 CD4 cells/mm3 had raised DHEA only compared with KS- men. Both KS+ and KS- men had higher serum progesterone and oestradiol than the controls. Glucocorticoids were not significantly altered. CONCLUSIONS: The high androgen levels in KS+ patients, particularly in the early stages of the disease (> 500 CD4 cells/mm3), may affect the immune system by inducing an abnormal cytokine profile, or by increasing T8 proliferation and activation, or both. This raises the question of the relationship between androgens and Kaposi sarcoma.

Adult↗

PubMed1998

Optic nerve head neovascularization in a patient with inactive cytomegalovirus retinitis and immune recovery.

PURPOSE: To report a case of optic nerve head neovascularization in a patient with acquired immunodeficiency syndrome (AIDS) associated with inactive cytomegalovirus retinitis and immune recovery. METHOD: Case report. RESULTS: We examined a 29-year-old man with AIDS and inactive cytomegalovirus retinitis and found vitritis and prominent optic nerve head neovascularization. The patient had been treated with reverse transcriptase and protease inhibitors, resulting in a notable rise in CD4+ lymphocyte count and an undetectable human immunodeficiency virus (HIV)-RNA viral load. No cause of neovascularization other than intraocular inflammation was detected. CONCLUSION: Immune recovery in a setting of inactive cytomegalovirus retinitis can result in optic nerve head neovascularization, as seen in our patient.

AIDS-Related Opportunistic Infections↗

PubMedDate not supplied

[Immunological effectiveness of the nucleoside/nucleotide analog combinations, tenofovir + lamivudine, didanosine + lamivudine and tenofovir + didanosine, in patients with HIV infection and sustained viral suppression].

BACKGROUND: Several recent studies have shown that the combination of ddI plus TDF can produce an unexpected drop in CD4 cell counts, even after correcting the ddI dose. OBJECTIVE: Comparative study of the immunological effectiveness of various once-daily NRTI backbones (ddI plus TDF, ddI plus 3TC or TDF plus 3TC) in antiretroviral-experienced HIV-infected patients achieving viral suppression (PCR, HIV-RNA < 50 copies/microl). METHODS: Prospective cohort study of 48 weeks' duration following viral load suppression with any of the NRTI combinations studied. The main outcome variable was the increase in CD4+ lymphocyte count from the time that viral load was undetectable or treatment was changed for simplification or toxicity (baseline) up to 48 weeks of follow-up. Differences between the assigned therapies were compared. The variables included in analysis were age, sex, risk group, HCV infection, clinical categories of HIV (CDC criteria), lowest CD4 cell count, reason for change of NRTI backbone, type of antiretroviral treatment (PI, NNRTI, or 3 NRTI) and duration of suppressed viral load. RESULTS. Regimens including ddI plus TDF showed significant decreases in CD4 cell counts with adjustments by type of HAART, reason for change, and duration of suppressed viral load. In patients treated with TDF + 3TC, CD4 count increased by 160 cel/microl (95% CI, 53-266) more than in patients treated with TDF + ddI; and in patients receiving ddI + 3TC, CD4+ count increased by 138 cel/microl (95% CI, 25-266) more than in patients receiving TDF + ddI. CONCLUSIONS: The ddI plus TDF backbone seems unadvisable because of the lower associated CD4 cell counts, and because it is poorer than the other options from the immunological standpoint.

Acquired Immunodeficiency Syndrome↗

PubMed1995

Sicca syndrome in patients infected with the human immunodeficiency virus.

PURPOSE: To investigate an association of the severity of the human immunodeficiency virus (HIV) disease with decreased tear production in a controlled setting. PATIENTS AND METHODS: Seventy-two patients (144 eyes) and 30 age- and sex-matched control subjects (60 eyes) were studied prospectively. Tear production was measured using the Schirmer I test (measured in millimeters after 5 minutes). Patients were classified into three clinical groups: asymptomatic HIV infection, lymphadenopathy syndrome (LAS) or acquired immune deficiency syndrome (AIDS)-related complex (ARC), and AIDS. Additionally, patients were classified according to the CD4+ lymphocyte count. RESULTS: Tear production (mean +/- standard deviation) did not differ (P = 0.32) among eyes of patients with asymptomatic HIV infection (17.1 +/- 10.8; n = 14), LAS or ARC (18.3 +/- 10.3; n = 70), and AIDS (20.7 +/- 10.3; n = 60). In addition, mean tear production was not decreased significantly when comparing each clinical group with the control subjects (17.8 +/- 4.4). However, the relative frequency of eyes with significantly decreased tear production (< 9 mm) was 23.6% in all 144 eyes. In addition, the relative frequency of significantly decreased tear production did not differ (P = 0.52) between eyes of patients with asymptomatic HIV infection (35.7%), LAS or ARC (21.4%), and AIDS (24.1%). In addition, the relative frequency of significantly decreased tear production did not differ (P = 0.30) between eyes of patients with a CD4+ count of more than 400 cells/microliters (23.1%; n = 26), 400 to 200 cells/microliters (31.3%; n = 48), 200 to 50 cells/microliters (14.3%; n = 42), and less than 50 cells/microliters (21.4%; n = 28). CONCLUSION: The authors data show that decreased tear production occurs in approximately 20% to 25% of patients with HIV infection. This increased frequency of decreased tear production is not associated with the CD4+ count, or related to the severity of HIV disease, respectively. The possibility of an autoimmune-like pathogenesis of abnormalities of tear production in patients with HIV infection should be studied intensively.

Adult↗

PubMed1994

Keynote address: variations in the natural history of HIV infection.

In general, the natural history of HIV infection as revealed by prospective cohort studies such as the Multicenter AIDS Cohort Study (MACS) is consistent with our current understanding of the immunopathogenesis of HIV disease. Although the limitations of CD4+ T cell counts as a predictor of response to therapy are now recognized, enumeration of these cells remains an important predictor of outcome. Additional information regarding prognosis can be obtained using other immunological and virological information. Analysis of data from cohort studies has revealed varying patterns of CD4+ lymphocyte count decline associated with differing evidence of immune activation, specific antibody responses, CD8+ T cell responses, and level of viral burden. Of interest, some asymptomatic HIV-infected persons appear to show immune stability in the absence of therapeutic interventions. In addition, the combination of antiretroviral therapy and prophylaxis for Pneumocystis carinii pneumonia (but apparently not prophylaxis for fungal or Mycobacterium avium-intracellulare infections) has prolonged survival in patients with AIDS.

CD4 Lymphocyte Count↗

PubMed2005

Comparison of a new, affordable flow cytometric method and the manual magnetic bead technique for CD4 T-lymphocyte counting in a northern Nigerian setting.

We compared two techniques for CD4 T-lymphocyte counting: flow cytometry (Cyflow) and magnetic beads (Dynabead). Similar results with good correlation were obtained from the 40 adult blood samples counted (P=0.057, r=0.93). The Cyflow technique is more precise and cost-effective than the Dynabead method ($3 to $5 versus $12 to $22 per test, respectively), since as many as 200 samples can be measured per day.

Adult↗

PubMed2003

Immunological response in HIV-positive patients vaccinated against tick-borne encephalitis.

BACKGROUND: Vaccination against infectious diseases is a recommended preventive measure in patients with impaired immunity. The aim of the study was to estimate the immunogenicity of the vaccine against tick-borne encephalitis (TBE) in HIV-infected patients and to determine its safety for this group. PATIENTS AND METHODS: The TBE vaccine FSME-IMMUN-inject was tested on 29 HIV-positive patients and the response compared to that of 40 healthy controls. The vaccination protocol for the HIV-positive group was modified by the addition of a fourth dose according to a 0/1/2/9-month schedule. RESULTS: No serious adverse reactions were observed in patients with deficient immunity. A better response was obtained in HIV-infected patients with CD4 counts >or= 500/microl (55% of the patients had levels of IgG antibody > 126 VIEU/microl) than in those with CD4 counts of 200-499/microl (40%). However, the difference did not reach significance. 85% of healthy controls achieved protective antibody titers after a full course of vaccination. CONCLUSION: The correlation between post-vaccine seroconversion and CD4 lymphocyte count showed that the FSME-IMMUN-inject vaccine can be considered to be a CD4 cell-independent vaccine. The examinations carried out 1 year after the completed vaccination protocol showed maintenance of the anti-TBE response acquired after the third vaccination in healthy subjects and in HIV-infected patients.

Adult↗

PubMed1997

H. pylori infection in HIV-positive patients. A serohistological study.

Sixty-seven consecutive patients infected with the human immunodeficiency virus (HIV-1), 72% of which with overt AIDS, were examinated by upper endoscopy due to various indications and evaluated for the prevalence of H. pylori infection. The infection was studied by performing both histological examination of gastric biopsies and serological testing for anti-H. pylori IgG antibodies. The H. pylori prevalence rate was 55% in histology; no significant differences were observed in HIV-infected subjects and those with overt AIDS (52% vs 63%, respectively; P = NS). Positive histological testing appeared to be directly related to the peripheral CD4+ lymphocyte count (minimum rates of 43% were detected in patients with CD4+ < 100 x 10(6)/liter and maximum rates of 78% in patients with CD4+ > 200 x 10(6)/liter, respectively; P < 0.05) and inversely related to the frequency of antibiotic treatments performed over the six months prior to endoscopy. Low CD4+ counts were also apparently associated with low-grade H. pylori infection. Serological testing was positive for anti-H. pylori IgG antibodies in 39% of patients; compared to histology, serology displayed a sensitivity of 57% and a specificity of 81%. The discrepancy between histological and serological positive results for H. pylori was noted to be higher in the more advanced phases of HIV infection. Based upon our results, the serological testing for anti-H. pylori IgG antibodies seems to require cautious interpretation in HIV-positive patients.

Acquired Immunodeficiency Syndrome↗

PubMed2003

Alternatives to HIV-1 RNA concentration and CD4 count to predict mortality in HIV-1-infected children in resource-poor settings.

Cheaper, simpler alternatives to CD4 lymphocyte count and HIV-1 RNA detection for assessing the prognosis of HIV-1 infection are needed for resource-poor settings. However, little is known about the predictive value of alternative assays, in particular in children. We assessed the prognostic value of total lymphocyte count, immune complex-dissociated p24 antigen, white blood cell count, packed-cell volume (haematocrit), and serum albumin for mortality in 376 HIV-1-infected, mainly African-American or Hispanic children enrolled during March, 1988 to January, 1991. In a Cox proportional hazards model, including all assay-alternatives to CD4 and RNA, total lymphocyte count (p<0.0001) and serum albumin (p=0.0107) independently predicted mortality. Further assessment of these markers is warranted in resource-poor settings.

Biomarkers↗