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At least 19 recordsLinked to original sources
PubMed1997

Human immunodeficiency virus (HIV) type-1 GP120-specific cell-mediated cytotoxicity (CMC) and natural killer (NK) activity in HIV-infected (HIV+) subjects: enhancement with interleukin-2(IL-2), IL-12, and IL-15.

Cell-mediated cytotoxicity (CMC), as mediated by cytophilic antibody to human immunodeficiency virus (HIV) antigens, may be an important defense in HIV-infected (HIV+) patients in response to the virus. In this study the ability of interleukin (IL)-2, IL-12, and IL-15 to enhance natural killer (NK) and gp120-specific CMC of mononuclear cells (MNCs) from HIV+ children and adults was examined. NK activity against K562 cells was deficient in HIV+ patients compared to controls and could be enhanced by IL-2, IL-12, or IL-15, with the combinations of IL-2 + IL-12 and IL-12 + IL-15 producing more cytotoxicity than individual cytokines. Gp120-specific CMC was significantly higher in patients than in controls. It could be increased by IL-2, IL-12, and IL-15 and further by combining IL-2 and IL-12. When an exogenous source of antibody in the form of hyperimmune HIV-specific immunoglobulin (HIVIG) was present, the response of control MNCs was much higher than that of patients, although gp120-specific cytotoxicity of patients' MNCs was significantly enhanced (two- to threefold) by the addition of HIVIG. This increment in cytotoxicity due to HIVIG, however, could not be further augmented by cytokines in controls or patients. Our findings suggest multiple cytokine administration to boost NK cell function, together with passive immunotherapy, might offer a new therapeutic approach to benefit HIV+ patients.

Adolescent↗
PubMed2004

CD40 ligand dysregulation in HIV infection: HIV glycoprotein 120 inhibits signaling cascades upstream of CD40 ligand transcription.

IL-12 production and up-regulation of CD40 ligand (CD40L) expression are impaired in the PBMC of HIV-infected donors, and exogenous CD40L rescues IL-12 production by such cells. In this study, we implicate dysregulation of CD40L expression in the IL-12 defect associated with HIV by demonstrating that induction of CD40L expression by anti-CD3/CD28 stimulation was directly correlated with the IL-12 productive capacity of PBMC. Further, we demonstrate marked decreases in the induction of CD40L protein and mRNA following anti-CD3/CD28 stimulation in HIV-infected donors compared with uninfected donors, with a tight association between these two levels. Inhibition of CD40L up-regulation was selective, as induction of CD69 or OX40 was not as severely affected. Increased instability of CD40L mRNA did not constitute a major mechanism in CD40L dysregulation, thus suggesting a potential defect in the signaling cascades upstream of transcription. The mechanisms by which HIV infection affects the induction of CD40L expression appear to involve HIV gp120-mediated engagement of CD4. Indeed, anti-CD4 mAb or inactivated HIV virions that harbor a conformationally intact gp120 significantly inhibited CD40L up-regulation at both the protein and mRNA levels. This inhibition was due to the native, virion-associated gp120, as coculture with soluble CD4 or heat treatment of inactivated HIV abolished their effect. These in vitro models mirror the CD40L defect seen in cells from HIV-infected donors and thus provide a suitable model to investigate HIV-induced CD40L dysregulation. Clear elucidation of mechanism(s) may well lead to the development of novel immunotherapeutic approaches to HIV infection.

Adult↗
PubMed2000

Discontinuation of chemoprophylaxis against Pneumocystis carinii pneumonia in patients with HIV infection. HIV Outpatient Study (HOPS) Investigators.

BACKGROUND: HIV-infected patients with sustained immunologic improvement from antiretroviral therapy may be able to discontinue chemoprophylaxis against Pneumocystis carinii pneumonia (PCP). OBJECTIVE: To compare PCP incidence in HIV-infected patients who had sustained CD4+ lymphocyte counts greater than 200 cells/mm3 and who either discontinued or continued PCP prophylaxis. DESIGN: Nonrandomized prospective cohort study. SETTING: 10 HIV clinics in eight U.S. cities. PATIENTS: 146 patients had follow-up visits for a mean of 18.2 months after discontinuation of PCP prophylaxis, and 345 patients who continued PCP prophylaxis had follow-up visits for a mean of 14.0 months. MEASUREMENTS: Incidence of PCP. RESULTS: Patients who discontinued PCP prophylaxis had higher maximum and minimum CD4+ cell counts and lower vira loads than patients who continued PCP prophylaxis. Pneumocystis carinii pneumonia did not develop in either group (upper 95% exact binomial confidence limit of incidence for those who discontinued PCP prophylaxis, 2.3/100 person-years). CONCLUSIONS: Discontinuation of PCP chemoprophylaxis may be appropriate for some HIV-infected ambulatory patients.

AIDS-Related Opportunistic Infections↗
PubMed1992

Human papillomavirus (HPV) infection, HIV infection and cervical cancer in Tanzania, east Africa.

The presence of HPV-DNA was determined in tumor biopsies of cervical-cancer patients and in cervical swabs of non-cancer patients from Tanzania, East Africa, by Southern blot hybridization and/or PCR. HPV types 16 and 18 were detected in 38% and 32%, respectively, of 50 cervical-carcinoma biopsies. A consensus primer PCR capable of detecting a broad spectrum of HPV types revealed the presence of HPV-DNA in 59% of 359 cervical swabs of non-cancer patients. Type-specific PCR showed that types 16 and 18 accounted for 13.2% and 17.5%, respectively, of all HPV infections. Therefore we concluded that HPV 18 is more prevalent in Tanzania than in any other geographical location so far reported. The strongest risk factors for the presence of any HPV-DNA in the 359 female non-cancer patients were young age and HIV infection. The epidemiology of HPV types 16 and 18 was found to differ from that of other HPV types, being associated in univariate analysis with trichomonas vaginalis infection, martial status (single/divorced), age at first intercourse, and young age at menarche. However, young age at menarche accounted for most of the effects of all other, variables in multivariate analysis. Of the non-cancer patients, 12.8% had antibodies against HIV I (no patient being severely symptomatic), and HIV infection was highly correlated with the presence of HPV-DNA, especially types 16 and 18. While HPV-DNA of any type was detectable 1.4-fold more often in HIV-positive patients than in HIV-negative patients, evidence of an infection with HPV types 16 or 18 was found 2.2-fold more often in the HIV-positive patients. The HIV-positive women did not show an increased rate of cervical cytological abnormalities as assessed by PAP staining of a single cervical smear, the overall rate of abnormalities being 2.8%. Furthermore, the age-adjusted prevalence of HIV antibodies was found to be considerably lower in 270 cervical-carcinoma patients (3% HIV-positive) in comparison with non-cancer patients. Thus there was no association observable between the prevalence of HIV infections and the frequency of cervical cytological abnormalities or cervical cancer in the setting of this cross-sectional study.

Cervix Uteri↗
PubMed1999

Criteria for assessing cutaneous anergy in women with or at risk for HIV infection. HIV Epidemiologic Research Study Group.

BACKGROUND: Controversy exists about both the clinical utility of anergy testing and the optimal criteria for defining anergy. OBJECTIVE: We sought to assess various definitions of cutaneous anergy for ability to distinguish HIV status, level of immunodeficiency, and ability to mount a tuberculin reaction among women with or at risk for HIV infection. METHODS: HIV-seropositive (n = 721) and HIV-seronegative (n = 358) at-risk women at academic medical centers in Baltimore, Detroit, New York, and Providence had cutaneous testing with mumps, Candida, tetanus toxoid, and tuberculin antigens. Associations with HIV status and CD4+ lymphocyte levels were analyzed. RESULTS: Candida, mumps, and tetanus antigens alone or in combination elicited reactions significantly less often in HIV-seropositive than in HIV-seronegative women and less often in seropositive women with lower CD4+ counts, regardless of induration cutpoint chosen to define a positive reaction. The best antigen combinations for distinguishing groups included tetanus and mumps. Some women nonreactive to the 3 antigens ("anergic") had positive tuberculin reactions among both seropositive subjects (range, 1.1% to 2.9% depending on induration cutpoint for defining anergy) and seronegative subjects (range, 8.9% to 14%). CONCLUSION: Absence of reactions to Candida, mumps, and tetanus antigens alone or in combination and at any induration cutpoint is associated with HIV status and with CD4+ level. Combinations, including tetanus and mumps antigens with an induration cutpoint of less than 2 mm, may be the best for defining anergy.

Antigens, Fungal↗
PubMed1999

Stability of cutaneous anergy in women with or at risk for HIV infection. HIV Epidemiology Research Study Group.

OBJECTIVE: To study the stability of cutaneous anergy in women with or at risk for HIV infection. DESIGN: Prospective multicenter cohort study METHODS: Interviews, CD4+ lymphocyte counts, and intradermal skin testing with mumps, Candida, and tetanus toxoid antigens were performed on two occasions at a median interval of 74 weeks in 436 HIV-seropositive and 252 seronegative at-risk women; only 10 (2%) HIV-seropositive women were taking highly active antiretroviral therapy at the time of delayed-type hypersensitivity (DTH) testing. Anergy was defined as induration <2 mm to all three antigens. RESULTS: Skin test reactivity at repeat testing was seen in 202 of 233 (87%) HIV-seronegative women who were not anergic at baseline, compared with 10 (53%) of 19 seronegative women who were anergic at baseline (relative risk [RR], 1.7; 95% confidence interval [CI], 1.07-2.5). Anergy at retesting was seen in 108 of 169 (64%) HIV-seropositive women who were previously anergic, compared with 77 of 267 (29%) who were not previously anergic (RR, 2.2; 95% CI, 1.8-2.8). Among initially anergic seropositive women, CD4+ lymphocyte counts were lower at both initial and follow-up testing in those who remained anergic than in those who reacted at follow-up (p < .001). The relative risks for anergy at retesting of initially anergic seropositive women, compared with initially reactive seropositive women, were related to CD4+ level; 2.5 (95% CI, 1.4-4.3) for CD4+ counts < 200 cells/mm3, 2.0 (95% CI, 1.5-1.7) for CD4+ counts 200-500 cells/mm3, and 1.6 (95% CI, 0.9-2.8) for CD4+ counts >500 cells/mm3. CONCLUSIONS: Although anergic HIV-seropositive women may become reactive, cutaneous anergy predicts a higher likelihood of anergy at retesting as well as lower CD4+ counts. Stability of anergy is greatest in HIV-seropositive women with low CD4+ counts.

CD4 Lymphocyte Count↗
PubMed1999

Phase II, randomized, open-label, community-based trial to compare the safety and activity of combination therapy with recombinant interferon-alpha2b and zidovudine versus zidovudine alone in patients with asymptomatic to mildly symptomatic HIV infection. HIV Protocol C91-253 Study Team.

OBJECTIVES: To compare, in a community-based therapeutic setting, the safety, tolerance, and efficacy of combination therapy with recombinant interferon-alpha2b (rIFN-alpha2b) and zidovudine (ZDV) to ZDV monotherapy. DESIGN: Open-label, two-armed, randomized study. PATIENTS AND METHODS: Asymptomatic or minimally symptomatic HIV-infected adults without an AIDS-defining illness, a CD4 count of 200 to 500 cells/microl, and < or = 6 months of prior ZDV therapy received ZDV 100 mg orally five times daily. Patients randomized to rIFN-alpha2b received 3 million IU subcutaneously three times weekly for 2 weeks and 5 million IU three times weekly thereafter. The groups were compared with respect to adverse events (AEs), dosing modifications, treatment discontinuation, clinical endpoints and changes in CD4 count. A virology substudy compared the treatments with respect to HIV viral load and development of ZDV resistance. RESULTS: Between October, 1991 and January, 1993, 139 patients were randomized to combination therapy and 117 to ZDV alone. Of AEs reported at any grade, fatigue, myalgias, and sweating occurred significantly more often with combination therapy (p < .001). Study subjects receiving combination therapy showed modest but significantly greater weight loss (p = .0001), a significantly higher frequency of any abnormal laboratory test result (p = .002), neutropenia (p = .002), and leukopenia (p = .02), and also required dosage reduction for hematologic toxicity significantly more often (p < .05) than those in the ZDV monotherapy arm. No statistically significant differences were found between the groups with respect to development of specific AIDS-defining events, overall event rate, time to events, or change in performance status or CD4+ counts, or percentages or development of ZDV resistance. Viral burden, reflected by serum p24 antigen and quantitative peripheral blood mononuclear cell (PBMC) microcultures, was greater at baseline in the combination therapy group. Baseline SI phenotype predicted progression to AIDS (p = .004, chi2), whereas intermediate susceptibility to ZDV predicted development of ZDV resistance (p < .005, chi2). The annual rate of development of phenotypic resistance to ZDV was 16.8% and was not affected by administration of rIFN-alpha2b. CONCLUSIONS: At the doses and schedule used in this study, the combination of ZDV with rIFN-alpha2b was not therapeutically superior to ZDV alone and was less well tolerated. The addition of rIFN-alpha2b to ZDV did not prevent or delay the development of ZDV resistance.

Acquired Immunodeficiency Syndrome↗
PubMed2003

[Enfuvirtide, the first representative of a new class of drugs for the treatment of HIV infection : HIV fusion inhibitors].

In March 2003, enfuvirtide was approved in the USA and the European Union for the treatment of patients with HIV infection who have experienced failure or intolerable side effects of treatment with at least one representative of each antiretroviral drug class. Enfuvirtide has a new mode of action: it binds to the viral envelope glycoprotein 41 that is involved in the fusion of the virus to the membrane of the CD4 T cell. In two large phase III studies, 90 mg of enfuvirtide administered twice daily subcutaneously in addition to a background treatment of other antiretroviral drugs, had a significant favourable effect on both the plasma viral load (decrease) and the CD4 counts (increase) compared to the background treatment alone. Disadvantages of treatment with enfuvirtide are its subcutaneous administration (98% of the patients had local adverse reactions) and the high costs involved (1500 euro per patient per month).

Anti-HIV Agents↗
PubMed1998

Oral lesions among women living with or at risk for HIV infection. HIV Epidemiology Research Study (HERS) Group.

PURPOSE: Our objectives were to compare the prevalence of oropharyngeal mucosal lesions among human immunodeficiency virus (HIV) seropositive and demographically similar seronegative women, and to determine the association of oral lesions with immunosuppression, substance abuse, use of medications, and utilization of dental services. POPULATION AND METHODS: Participants in a multicenter, longitudinal cohort study of HIV infection in women were evaluated at baseline by interview, physical examination, and laboratory studies. RESULTS: Oropharyngeal pathology was found in 40% of seropositive and 23% of seronegative women. Oral candidiasis was identified in 15% of seropositive and 3% of seronegative women. Among seropositive women, history of previous oral candidiasis, lower CD4 lymphocyte counts, and current antibiotic use were associated with oral candidiasis. Hairy leukoplakia was identified in 5% of seropositive women and was significantly associated with lower CD4 lymphocyte counts. Gingival erythema and ulcerative gingivitis were found in 23% of participants overall, but were unrelated to HIV serostatus or CD4 lymphocyte count. Substance abuse, lack of dental care, and African-American race were associated with gingival pathology. CONCLUSION: The high prevalence of oral lesions among HIV seropositive and at-risk seronegative women underscores the need for routine oral examination and targeted treatment of this population.

AIDS-Related Opportunistic Infections↗
PubMed1997

The changing distribution of HIV infection: HIV surveillance in Lazio, Italy, 1985 through 1994. Lazio HIV Surveillance Collaborative Group.

OBJECTIVES: This study sought to describe the human immunodeficiency virus (HIV) surveillance system in Lazio, Italy, and to analyze exposure patterns and time trends of HIV serodiagnoses from January 1985 to December 1994. METHODS: A linkage procedure made it possible to identify newly diagnosed HIV cases. Anonymous information was collected on demographic and exposure factors for each individual. RESULTS: Of 35,425 reports, 13,660 were newly diagnosed HIV cases, 70.9% of them in men. The proportion of women increased at the beginning of the study period (the male:female ratio declined from 3.5 in 1985 to 2.6 in 1986) and then remained stable. The proportion of subjects reporting heterosexual exposure, in men and women, respectively, increased from 1.5% and 2.0% in 1985 to 21.2% and 60.8% in 1994. Starting in 1992, heterosexual contact has become the main transmission route for women. CONCLUSIONS: A changing pattern in the HIV epidemic is emerging, with a shift in the incidence of HIV diagnosis from "core" high-risk groups (drug injectors) to the large low-risk population (the general population) exposed through heterosexual transmission. This is probably occurring in other areas (e.g., large urban centers in the United States) with a similar epidemiological situation.

AIDS Serodiagnosis↗