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PubMed2002

HIV-1 infection in rural Africa: is there a difference in median time to AIDS and survival compared with that in industrialized countries?

OBJECTIVES: To describe the progression times of HIV-1 infection from seroconversion to AIDS and to death, and time from first developing AIDS to death in rural Uganda. Also, to describe the proportion of individuals within the cohort dying with AIDS and the CD4 lymphocyte count before death. DESIGN: A prospective, longitudinal, population-based cohort. METHODS: Since 1990, 107 HIV-prevalent cases, 168 incident cases and 235 HIV-seronegative controls have been recruited into a cohort in rural Uganda. Participants are recruited from the general population and they are reviewed routinely every 3 months and at other times when ill. RESULTS: The median time from seroconversion to death was 9.8 years. Age over 40 years at seroconversion was associated with more rapid progression (P < 0.001, log rank test). For the first 4 years of the study, HIV contributed little to the death rates in the HIV incident cases, but after 5 years, the contribution of HIV became greater and was particularly marked in the oldest age group. Survival rates in the cohort were similar to those in the general population. The median time from seroconversion to AIDS was 9.4 years and from AIDS to death was 9.2 months. Of those infected with HIV-1, 80% died with AIDS and 20% had a CD4 count < 10 x 106 cells/l. CONCLUSIONS: Survival with HIV-1 infection is similar in Africa to industrialized countries before the use of antiretroviral therapy; when they do die, many of those in Africa are severely immunosuppressed and most have clinical features of AIDS.

Acquired Immunodeficiency Syndrome↗
PubMed2000

Fluctuations in HIV-1 viral load are correlated to CD4+ T-lymphocyte count during the natural course of infection.

Viral load fluctuates during the natural course of asymptomatic HIV-1 infection. It is often assumed that these fluctuations are random around a set point or underlying growth trend. Using longitudinal data, we tested whether fluctuations in viral load can be better explained by changes in CD4+ T-cell count than by a set point or trend of exponential growth. The correspondence between viral load and CD4+ T-cell count could be described by a simple mathematical relation. Using a bootstrapping approach, the hypothesis that viral load fluctuations are random around a set point was rejected with p < .00005. The hypothesis that viral load fluctuations are random around a trend of exponential growth was rejected with p < .005. Viral load data was explained better by changes in CD4+ T-cell counts than by a set point or by a trend of exponential growth. The implications of this finding for improved prognostication are discussed.

CD4 Lymphocyte Count↗
PubMed2000

Pharmacokinetic, pharmacodynamic and clinical effects of a humanized IgG1 anti-CD4 monoclonal antibody in the peripheral blood and synovial fluid of rheumatoid arthritis patients.

BACKGROUND: CD4(+) T cells are important mediators in the pathogenesis of rheumatoid arthritis (RA). In this open-label, dose-escalating study, we examined the pharmacokinetic (PK), clinical, biological and immunological effects of a humanized IgG1 anti-CD4 monoclonal antibody (mAb), 4162W94, in the peripheral blood (PB) and synovial fluid (SF) of RA patients. METHOD: Twenty-four patients in four cohorts (six patients in each cohort) were allocated to be treated with five consecutive daily doses of 4162W94 (10, 30, 100 or 300 mg i.v.). Disease activity was measured by the American College of Rheumatology (ACR) criteria and disease activity score (DAS). We also measured 4162W94 concentration, the percentage of 4162W94-coated CD4(+) lymphocytes, percentage down-modulation of CD4, interleukin-6 (IL-6) and tumour necrosis factor alpha (TNFalpha) levels in the PB and SF. RESULTS: A direct relationship between 4162W94 dose, biological response and clinical outcome was seen. Treatment with 10 and 30 mg of 4162W94 for 5 consecutive days resulted in transient coating and down-modulation of CD4(+) lymphocytes, with little effect observed beyond the final dose. However, treatment with 100 and 300 mg resulted in sustained coating and/or down-modulation for 3 weeks and 4 weeks, respectively, in PB and >4 weeks in SF in one patient from the 300 mg cohort. There was a dose-related moderate but transient depression in the CD4(+) lymphocyte count in most patients, with all but three returning to >0.40 x 10(9)/l or >75% baseline by the end of the study period. Significant clinical improvement (ACR 20%) was seen in only 1/6 patients in each of the 10- and 30-mg cohorts; however, 3/6 and 5/5 patients in the 100 and 300-mg cohorts, respectively, were ACR 20% responders. In addition, there were significant reductions in PB acute phase reactants as well as SF IL-6 and TNFalpha concentrations in parallel to clinical improvement. CONCLUSION: Data from this pilot study suggest that 4162W94 is a clinically active novel immunotherapeutic agent that may suppress inflammation in RA.

Adult↗
PubMed2002

[Nocardiosis in patients with HIV infection].

OBJECTIVE: To know the characteristics of nocardiosis in HIV infected patients. PATIENTS AND METHODS: Retrospective analysis of HIV infected patients with a concomitant Nocardia spp. infection in nine Andalusian hospitals. RESULTS: Eighteen cases of nocardiosis were studied. Seventeen patients were males and the mean age was 33.1 years. The risk behaviour for acquiring HIV infection was parenteral drug use in 15 patients (83.3%) and seven of them were active users when acquiring nocardiosis. The mean CD4 lymphocyte count was 66.3 106/l. The nocardiosis was manifested as disseminated disease in eight patients, only pulmonary disease in four cases, lymphocutaneous or soft-tissue nocardiosis in five, and pericarditis in the remaining patient. In the ten cases with pulmonary involvement, the chest X-ray revealed an alveolar, interstitial, and mixed pattern in five, three, and two patients, respectively. Most patients were treated with cotrimoxazole, with good clinical and microbiological responses in 88.8% of them. Some surgical procedures were required in six patients. Eight patients died, three on account of nocardiosis and five on account of other causes. There were three relapses. CONCLUSIONS: Nocardia spp. infection is rare among patients with AIDS and occurs in immunosuppressed patients and drug users. The pulmonary, cutaneous, and soft-tissue were the most commonly observed forms in our series. Despite the high frequency of disseminated infection, the response to th

Adult↗
PubMed1999

Effects of human immunodeficiency virus type 1 on CD4 lymphocyte subset activation.

The pathogenesis of the decline of CD4 lymphocyte counts accompanying the typical course of HIV-1 infection is not completely defined and might be related to a differential susceptibility of naive and memory cells to HIV-1 exposure. Here, we examined the effects induced by heat-inactivated HIV-1 virions on these lymphocyte populations. Exposure of CD45RA naive T cells to inactivated viral particles induced a marked decrease of both mitogenic responses and activation-induced apoptosis. Conversely, the growth of CD45RO cells was less severely restrained. Analysis of intracellular levels of cell cycle regulatory proteins revealed an arrest at the G1/S restriction point of the naive but not memory subset. This effect was associated with alterations in phosphotyrosine profile and with a marked decrease of ERK and NJK kinase activation. Finally, up-regulation of the cAMP-dependent protein kinase A (PKA) activity induced by mitogens was not affected by virus. Altogether, these findings show that interaction of HIV-1 with the T cell surface is sufficient to inhibit the proliferative response of the CD4CD45RA subset by disturbing proximal TCR signaling. This mechanism would affect renewal of naive lymphocytes, contributing in such a way to the impairment of T cell turnover during the course of HIV-1 infection.

Apoptosis↗
PubMed1997

Lymphocytic subpopulation changes after open and laparoscopic cholecystectomy: a prospective and comparative study on 38 patients.

Up to now it has been unclear whether laparoscopic surgery has fewer immunosuppressive effects than traditional laparotomic procedures. In a series of 38 patients affected by symptomatic gallstone disease and operated on either by laparoscopy (group 1) or by traditional open surgery (group 2), we determined the postoperative changes in lymphocyte subpopulations up to postoperative day (POD) 30. We collected 15 ml of venous blood from all patients in both groups on the day before surgery and on POD 1, 7, 15, and 30. A control group (group 3) comprised 56 healthy volunteers; the control group was used only to ensure that baseline values were totally comparable with a normal population; only one blood sample was obtained from the subjects in group 3. Patients undergoing open cholecystectomy had a significant decrease in total lymphocyte count on POD 1. Basal levels of lymphocyte subpopulations did not differ significantly in the study and control groups. No differences were found in the preoperative lymphocyte cell counts in the two groups who underwent cholecystectomy. Pan-T cells (CD3) showed a statistically significant marked reduction throughout the observation period. The counts of helper (CD4), suppressor (CD8), and natural killer NK (CD16) T cells were reduced on POD 1; the NK cell (CD16) count remained low until POD 30, B lymphocytes showed no postoperative reduction. In patients who underwent laparoscopic cholecystectomy, a significant postoperative decrease in total lymphocyte count, and in CD3, CD4, and CD8 subpopulations was observed on day 1 only. There was no reduction in CD16 and CD19 subpopulations. A comparative statistical analysis of lymphocyte subpopulations in the two groups was carried out: In the open cholecystectomy group, compared with the laparoscopy group, CD3, CD4, CD8, and CD16 lymphocyte subpopulations showed marked reductions at different time points. In particular, statistically significant differences were found in CD3 levels from POD 1 through POD 30, in CD4 from day 1 through day 7, and in CD8 and CD16 only on day 1.

B-Lymphocytes↗
PubMed2000

Topical treatment of cutaneous lesions of acquired immunodeficiency syndrome-related Kaposi sarcoma using alitretinoin gel: results of phase 1 and 2 trials.

OBJECTIVE: To evaluate the efficacy and safety of topical alitretinoin gel (9-cis-retinoic acid [LGD1057], Panretin gel; Ligand Pharmaceuticals, Inc, San Diego, Calif) in cutaneous Kaposi sarcoma (KS). DESIGN: Open-label, within-patient, controlled, dose-escalating phase 1 and 2 clinical trials. In all patients, 1 or more cutaneous KS lesions were treated with alitretinoin gel, and at least 2 other lesions served as untreated controls for up to 16 weeks. Alitretinoin (0.05% or 0.1% gel) was applied twice daily for the first 2 weeks and up to 4 times daily thereafter, if tolerated. SETTING: Nine academic clinical centers. PATIENTS: One hundred fifteen patients with biopsy-proven acquired immunodeficiency syndrome (AIDS)-related KS. MAIN OUTCOME MEASURES: AIDS Clinical Trials Group response criteria. RESULTS: Statistically significant clinical responses were observed in 31 (27%) of 115 patients for the group of treated index lesions compared with 13 (11%) for the group of untreated control lesions (P<.001). Responses occurred with low CD4(+) lymphocyte counts (<200 cells/microL) and in some patients with refractory response to previous systemic anti-KS therapy. The incidence of disease progression was significantly lower for treated index lesions compared with untreated control lesions (39/115 [34%] vs 53/115 [46%]; P =.02). Alitretinoin gel generally was well tolerated, with 90% of treatment-related adverse events confined to the application site and only mild or moderate in severity. CONCLUSIONS: Alitretinoin gel has significant antitumor activity as a topical treatment for AIDS-related KS lesions, substantially reduces the incidence of disease progression in treated lesions, and is generally well tolerated.

AIDS-Related Opportunistic Infections↗
PubMed1995

Serum neopterin level predicts HIV-related mortality but not progression to AIDS or development of neurological disease in gay men and parenteral drug users.

OBJECTIVE: To investigate the ability of elevated serum neopterin levels to predict independently mortality, progression to acquired immunodeficiency syndrome, and development of neurological disease. DESIGN: Cross-sectional and longitudinal study of gay and/or bisexual men and parenteral drug users. SETTING AND PATIENTS: Patients included human immunodeficiency virus (HIV)-negative and -positive gay and/or bisexual men and parenteral drug-using men and women who volunteered for an outpatient study of the natural history of HIV infection. RESULTS: Serum neopterin levels were significantly elevated in HIV-positive patients (mean, 18.0 nmol/L; SD, 19.2 nmol/L), compared with those in HIV-negative patients (mean, 7.5 nmol/L; SD, 5.5 nmol/L) (P < .001). No differences in the serum neopterin levels could be detected between gay men and parenteral drug users. In HIV-positive patients, women had a higher serum neopterin level than did men (P = .03). The elevated serum neopterin levels were associated with an advanced clinical stage of HIV infection. After adjusting for the CD4 lymphocyte count and other potential confounders, the serum neopterin level was a significant independent predictor of mortality. The elevated serum neopterin levels did not predict progression to acquired immunodeficiency syndrome or development of clinically significant neurological disease. CONCLUSION: An elevated serum neopterin level predicts mortality, but it does not predict progression to acquired immunodeficiency syndrome or development of neurological disease among HIV-infected individuals.

Acquired Immunodeficiency Syndrome↗
PubMed1997

Neurocognitive impairment is an independent risk factor for death in HIV infection. San Diego HIV Neurobehavioral Research Center Group.

OBJECTIVE: To determine if mortality is increased in individuals with human immunodeficiency virus type 1 (HIV-1)-associated neurocognitive disorders less severe than frank dementia. DESIGN: A prospective cohort study; median duration of follow-up was 2.4 years. Kaplan-Meier analysis and Cox proportional hazards models were used to compare survival times according to neurocognitive classification. SETTING: University-based research unit. PARTICIPANTS: A volunteer sample of 414 individuals seropositive for HIV-1. Subjects were classified at their baseline evaluation as neuropsychologically (NP) normal or abnormal (impaired in > or = 2 NP test domains). A subgroup of NP abnormal subjects met operational criteria for HIV-associated minor cognitive motor disorder; the remaining subjects were designated NP impaired. Subjects with frank dementia were excluded. MAIN OUTCOME MEASURE: Mortality. RESULTS: At the baseline evaluation, 256 (62%) of 414 subjects were designated normal; 109 (26%). NP impaired; and 49 (12%), minor cognitive motor disorder. One hundred six participants (26%) died during follow-up. Compared with the NP normal group, the unadjusted relative risk (RR) of death for all NP abnormal subjects (minor cognitive motor disorder and NP impaired) was significantly increased (RR, 1.7; 95% confidence interval [CI], 1.2-2.6; P < .005). After adjusting for concurrently measured predictors of survival (CD4 lymphocyte counts, Centers for Disease Control and Prevention HIV disease classification, hemoglobin concentration, and serum beta 2-microglobulin) in proportional hazards models, mortality for all NP abnormal subjects remained elevated (RR, 1.8; 95% CI, 1.2-2.8; P < .01). The elevation in mortality risk for subjects with minor cognitive motor disorder was statistically significant (RR, 2.2; 95% CI, 1.2-3.8; P < .01); for NP impaired subjects it was marginally significant (RR, 1.6; 95% CI, 1.0-2.8; P = .06). CONCLUSIONS: The HIV-infected individuals with NP impairment had a higher risk of dying than those without impairment. This was particularly true for those meeting syndromic diagnostic criteria.

Adult↗
PubMed1996

Combination chemotherapy with doxorubicin, bleomycin, and vindesine for AIDS-related Kaposi's sarcoma.

BACKGROUND: Kaposi's sarcoma is the most common neoplasm in patients with human immunodeficiency virus (HIV) infection. Although the best therapeutic approach is still unclear, patients with advanced KS are usually treated with systemic chemotherapy. METHODS: A prospective multiinstitutional Italian study evaluated the efficacy and toxicity of combination chemotherapy with doxorubicin, bleomycin, and vindesine (ABVi) in patients with progressive and extensive HIV-related KS. Patients were given doxorubicin, 20 mg/m2 on Day 1; bleomycin, 15 mg on Day 1, and vindesine, 4 mg on Day 1 biweekly +/- granulocyte-colony stimulating factor. RESULTS: Overall, 21 of 38 evaluable patients (55%) achieved an objective response (OR): there was 1 complete response and 20 partial responses. The most important bone marrow toxicity was granulocytopenia in 61% of the evaluable patients; 34% had Grades 3-4 toxicity, according to the World Health Organization Classification. The majority of patients (64%) developed some type of opportunistic infection (OI) during chemotherapy or the follow-up, with cytomegalovirus infection being the most frequent OI observed. The median duration of survival from KS diagnosis and from the start of ABVi therapy was 19 months (range, 3.4-88.5 months) and 9.9 months (range, 0.1-42.4 months), respectively. CONCLUSIONS: The high rate of OI during ABVi chemotherapy and the follow-up is of concern, although these infections possibly could be due to our patients' low CD4+ lymphocyte counts. However, no toxic death was observed in our patients, suggesting that ABVi could be used in patients with aggressive disease, especially those who were previously untreated.

Acquired Immunodeficiency Syndrome↗
PubMed1996

Severe complications of perianal sepsis in patients with human immunodeficiency virus.

Fifty human immunodeficiency virus (HIV)-infected patients with perianal sepsis were studied. Seven (14 per cent) had serious septic complications, four patients with severe necrotizing gangrene, and three with abscesses in the mediastinum, liver and brain respectively. CD4+ lymphocyte counts were significantly lower in patients with severe septic complications as compared with those with uncomplicated perianal sepsis (P < 0.05). In patients with HIV presenting with rare (metastatic) abscesses, perianal sepsis must always be kept in mind as a possible focus. Although HIV-infected patients have a limited life expectancy perianal fistulas and abscesses should be aggressively treated, because of the high risk of severe complications.

AIDS-Related Opportunistic Infections↗
PubMed2002

Characteristics of indolent non-Hodgkin lymphoma in patients with type 1 human immunodeficiency virus infection.

BACKGROUND: There is recent evidence that the incidence of indolent non-Hodgkin lymphoma (NHL) appears to be increased in persons with the acquired immunodeficiency syndrome (AIDS). The current study was conducted to describe the clinical, immunologic, and pathologic characteristics of indolent B-cell lymphoma in patients infected with the human immunodeficiency virus (HIV). METHODS: The current report was a retrospective study of 10 cases of indolent NHL identified from the AIDS-Lymphoma Registry at the University of Southern California School of Medicine. These patients were compared with 336 consecutive patients with systemic intermediate/high-grade AIDS-related NHL who were diagnosed and treated at a single institution. RESULTS: The pathology of the indolent cases included follicular lymphoma (five patients), small lymphocytic lymphoma (two patients), and one case each of mucosa-associated lymphoid tissue (MALT), monocytoid B-cell, and marginal zone lymphoma. When comparing the indolent lymphomas with the intermediate/high-grade AIDS-NHL cases, no differences were observed with regard to demographic characteristics or history of prior opportunistic infection. HIV patients with indolent lymphomas were found to have a significantly higher median CD4+ lymphocyte count compared with patients with intermediate/high-grade NHL (531 /mm3 vs. 90 /mm3) (P < 0.0001). Bone marrow involvement was significantly more common in indolent NHL cases (50%) versus intermediate/high-grade NHL cases (17%) (P = 0.02). The median survival for patients with indolent NHL was significantly longer compared with patients with intermediate/high-grade NHL (66.8 months vs. 7.1 months) (P = 0.007). CONCLUSIONS: Indolent lymphomas occurring in patients infected with HIV appear to differ from intermediate/high-grade lymphomas with regard to immune status and propensity for bone marrow involvement and prolonged survival. The median survival in the group of HIV-seropositive patients with indolent NHL examined in the current study was found to be comparable to that reported in HIV-negative individuals.

Adult↗
PubMed2002

Multicenter trial of low-dose paclitaxel in patients with advanced AIDS-related Kaposi sarcoma.

BACKGROUND: Treatment options are limited for patients with advanced acquired immunodeficiency syndrome (AIDS)-related Kaposi sarcoma (AIDS-KS) whose disease has progressed after receiving therapy with liposomal anthracyclines or combination chemotherapy with doxorubicin (Adriamycin), bleomycin, and vincristine (ABV). This study was performed to assess the safety and efficacy of a novel dose and schedule of paclitaxel in patients with AIDS-KS who failed to respond to previous systemic chemotherapy. METHODS: This was an open-label, multicenter Phase II study. Eligible patients had advanced AIDS-KS consisting of at least 25 mucocutaneous lesions, visceral disease, or lymphedema, and had failed to respond to at least one previous systemic chemotherapy regimen. Patients were treated with paclitaxel at a dose of 100 mg/m(2) given intravenously over 3 hours, every 2 weeks. Primary efficacy end points were tumor response, time to progression, time to treatment failure, and survival. Quality of life and adverse events were evaluated using the Symptom Distress Scale (SDS) and the World Health Organization Toxicity Criteria, respectively. RESULTS: One hundred and seven male patients with advanced AIDS-KS were enrolled from nine participating sites. The median entry CD4+ lymphocyte count was 41/mm(3) (range 0-1139). Previous treatment regimens included ABV in 52, liposomal daunorubicin in 49, and liposomal doxorubicin in 40 patients. Forty-one patients (38%) received two or more previous chemotherapy regimens. Protease inhibitor use during the study was reported by 82 (77%) patients overall; 47 patients (44%) were receiving a protease inhibitor before study entry. Complete or partial response was documented in 60 patients (56%). The median duration of response was 8.9 months. Major response rate was similar when comparing patients not on a protease inhibitor at the time of response (59%) with patients on a protease inhibitor at time of response (54%). However, protease inhibitor use had a significant impact on survival (P = 0.04). Grade 4 neutropenia was reported in 35% of patients; other life-threatening side effects were uncommon. Significant improvements were seen in the total quality of life scores measured by the SDS, including significant improvement in KS-related symptoms such as facial disease, tumor-associated edema, and pulmonary involvement. CONCLUSION: Paclitaxel given every 2 weeks induces major tumor regression in the majority of patients with advanced KS who failed to respond to previous systemic chemotherapy. Paclitaxel is associated with significant improvement in quality of life with acceptable toxicity and should be considered as an effective treatment option for patients with advanced KS.

Acquired Immunodeficiency Syndrome↗
PubMed1993

Valaciclovir (BW256U87): the L-valyl ester of acyclovir.

Valaciclovir (BW256U87) is an L-valyl ester of acyclovir, which is extensively and almost completely converted to acyclovir. In healthy human volunteers, single valaciclovir doses of 100-1000 mg resulted in dose-proportional increases in acyclovir area under the curve (AUC). The 1,000 mg dose produced an acyclovir peak plasma concentration (Cmax) of 5-6 micrograms/ml, AUC6 of 19 hr. micrograms/ml, time to maximum plasma concentration (Tmax) of 1-2 hr, and half-life (T1/2) of 2.8 hr. Plasma valaciclovir peak levels were < 0.3 micrograms/ml, and the prodrug was undetectable after 3 hr. Multiple valaciclovir doses of 250-2,000 mg given four times daily for 10 days resulted in dose-proportional increases in acyclovir Cmax. There were less than proportional increases in the AUCs. No serious or unexpected adverse events or laboratory abnormalities were reported. In volunteers with advanced human immunodeficiency virus (HIV) disease (absolute CD4 lymphocyte count < 150 cells/microliters), acyclovir and valaciclovir pharmacokinetic results were nearly identical to those in healthy volunteers. At the 2 g dose administered four times daily, steady-state acyclovir Cmax = 8.4 micrograms/ml, Tmax = 2.0 hr, AUC6 = 30.5 hr. micrograms/ml, and T1/2 = 3.3 hr. Nausea, vomiting, diarrhoea, and abdominal pain were commonly reported; however, only one adverse event (diarrhoea) was causally linked to valaciclovir exposure. There were no renal or neurologic adverse events. Valaciclovir is well absorbed and is rapidly converted to acyclovir, resulting in three- to fourfold higher acyclovir levels than can be achieved with oral acyclovir, even in patients with advanced HIV disease. The safety profile is generally favourable, with no evidence of nephrotoxicity or neurotoxicity.

Acyclovir↗
PubMed1996

Abnormal levels of circulating adhesion molecules in HIV-1 infection with characteristic alterations in opportunistic infections.

Adhesion molecules enabling leukocytes to communicate and adhere are essential for immunological and inflammatory responses. Circulating forms of these adhesion molecules are detected, although their influence on immunological functions is unknown. We have measured soluble levels of E-selectin, vascular adhesion molecules-1 (VCAM-1), and intercellular adhesion molecule-1 (ICAM-1) in sera from 65 HIV-1-seropositive patients and controls. We found significantly higher levels of soluble VCAM-1 (sVCAM-1) and ICAM-1 (sICAM-1) in both symptomatic and asymptomatic HIV-1-infected patients than in controls (P <0.01). Both sICAM-1 and sVCAM-1 correlated to serum levels of neopterin (r = 0.40, P < 0.001; r = 0.46, P <0.001, respectively) and TNFalpha (r = 0.44, P < 0.01; r = 0.49, P < 0.001, respectively), while only sVCAM-1 correlated strongly to CD4+ lymphocyte count (r = -0.46, P < 0.001). Patients infected with Mycobacterium avium intracellular complex had significantly higher levels of sVCAM-1 and sICAM-1 than other AIDS patients (P < 0.05), while patients with cytomegalovirus disease had significantly lower levels both of sE-selectin and sICAM-1 (P < 0.05) than other AIDS patients. In conclusion, we found abnormal levels of circulating adhesion molecules in both symptomatic and asymptomatic HIV-1 infection including AIDS. The correlation to other parameters and clinical events may implicate involvement of circulating adhesion molecules in the immunopathogenesis of HIV-1 infection.

AIDS-Related Opportunistic Infections↗
PubMed1993

Transmission of human immunodeficiency virus type 1 (HIV-1) from mother to child correlates with viral phenotype.

The aim of this study was to investigate if the risk of mother-to-child transmission of human immunodeficiency virus type 1 (HIV-1) is influenced by the biological phenotype of the mother's virus. Virus isolates from 30 HIV-1 infected mothers and 12 infected children born to these mothers were analyzed for replication on several cell lines (Jurkat-tat, Jurkat, CEM, U937 clone 2, and MT-2). We show that mothers who harbor virus able to replicate in cell lines (rapid/high virus) have a significantly higher risk to infect their children than mothers with slow/low virus (P = 0.017). Children born to mothers with rapid/high viruses can be infected by slow/low as well as rapid/high viruses, while mothers with slow/low virus appear to transmit slow/low virus in every case. Our study shows that the biological phenotype of the mother's virus may serve as a complementary marker to CD4+ lymphocyte counts and p24 antigenemia in predicting the risk of transmission of HIV-1 to the child.

Cell Line↗
PubMed1994

The biological phenotype of HIV-1 is usually retained during and after sexual transmission.

The biological phenotype of HIV-1 isolates from 21 subjects with primary HIV-1 infection was determined in primary lymphocytes and monocyte-derived macrophages as well as in three T-cell lines (MT-2, HUT78, and C8166). Seven isolates (33%) replicated on at least one cell line and were classified as rapid/high (n = 6) or intermediate (n = 1), while 14 isolates (67%) did not replicate in cell lines and were classified as slow/low. All isolates replicated in primary monocyte-derived macrophage cultures. Studies on 10 pairs consisting of index case and seroconverting sexual partner showed that the biological phenotype of HIV-1 was unchanged in nine transmissions, including 5 pairs where a rapid/high virus was transmitted. Most individuals (5 of 6) infected by a rapid/high virus retained this phenotype after seroconversion. These individuals also had significantly lower CD4 lymphocyte counts 1-3 years after infection. Thus, in contrast to what has been suggested by others, we found that HIV-1 variants with rapid/high phenotype were usually not suppressed, neither during sexual transmission nor after seroconversion in the new host. These findings have important implications for the understanding of HIV-1 transmission and pathogenesis as well as for vaccine design.

Cell Line↗
PubMed1995

Intestinal and extraintestinal cryptosporidiosis in AIDS patients.

In a prospective study in AIDS patients with chronic diarrhea, the overall prevalence of intestinal cryptosporidiosis was 15.6% (43/275). The prevalence was higher in homosexual patients (33.3%) than in intravenous drug abusers (10.6%) (p < 0.001). Extraintestinal infection was present in 30% (13/43) of the patients with known intestinal cryptosporidiosis. Eight of the 13 (61.5%) patients with extraintestinal cryptosporidiosis had Cryptosporidium in the bile and 7 of 13 (16.28%) had it in the sputum. Of the seven patients with Cryptosporidium in the sputum, four had respiratory symptoms and an abnormal chest radiograph, although another pulmonary pathogen was isolated simultaneously. Two other patients from whom Cryptosporidium was the sole respiratory pathogen isolated had no respiratory symptoms and normal chest radiographs. The seventh patient had pulmonary symptoms, interstitial infiltrate on chest radiograph and excessive activity on a pulmonary Gallium scan; Cryptosporidium was the only organism detected in induced sputum and bronchoalveolar lavage specimens. The mean CD4+ lymphocyte count in patients with extraintestinal cryptosporidiosis was 55 cells/mm3.

AIDS-Related Opportunistic Infections↗