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PubMed1997

Progression of human immunodeficiency virus infection in patients with tuberculosis disease. A cohort study in Bordeaux, France, 1988-1994. The Groupe d'Epidémiologie Clinique du Sida en Aquitaine (GECSA).

To assess the role of Mycobacterium tuberculosis disease in human immunodeficiency virus (HIV) infection, the authors compared survival of tuberculosis patients and controls matched on year of HIV diagnosis and CD4+ lymphocyte count. Patients were selected in the Aquitaine Cohort, which follows, since 1985, all patients infected with HIV, aged more than 13 years, in five hospitals. Time of inclusion of controls was the date of diagnosis of tuberculosis for the corresponding tuberculosis patient. Patients who had received primary prophylaxis against mycobacteria other than tuberculosis were excluded. As of June 30, 1994, 104 tuberculosis patients and 620 controls were selected; they were similar, except for history of intravenous drug use (tuberculosis patients, 51%, vs. controls, 31%) and AIDS-defining opportunistic infection (40 vs. 29%). Survival was shorter in tuberculosis patients than in controls (risk ratio 1.5, 95% confidence interval 1.2-2.1) even after controlling for differences at entry. The risk of AIDS-defining opportunistic infection or a decrease to fewer than 50 CD4+ cells/mm3 was slightly but not statistically greater in tuberculosis patients than in controls. Tuberculosis disease affected survival but not occurrence of subsequent opportunistic infections or rate of CD4+ count decline. Tuberculosis may be a marker of advanced HIV and may accelerate its course of infection.

AIDS-Related Opportunistic Infections↗

PubMed1997

Lack of detection of human immunodeficiency virus type 1 in the saliva of infected children and adolescents.

OBJECTIVE: To determine the prevalence of human immunodeficiency virus type 1 (HIV-1) in the saliva of infected children and adolescents. METHODS: Saliva and blood samples were collected from 13 patients (age range, 1-15 years) with HIV-1 infection. Eleven were taking antiretroviral agents. The presence of HIV-1 was determined by polymerase chain reaction analysis of RNA and DNA as well as by viral culture of the saliva samples and by culture of peripheral blood mononuclear cells. RESULTS: Although HIV-1 was cultured from peripheral blood mononuclear cells of 12 patients, it was not cultured from their saliva. Only 1 of 13 saliva samples yielded positive test results for HIV-1 RNA, and none did so for HIV-1 DNA. The specimen containing HIV-1 RNA was from an untreated 10-year-old asymptomatic boy with a CD4+ lymphocyte count of 0.91 x 10(9)/L (913 cells/microL) and no infectious virus detected in plasma. CONCLUSION: The prevalence of HIV-1 in the saliva of HIV-1-infected children and adolescents is low and may not be infectious.

Adolescent↗

PubMed1997

Detection of Epstein-Barr virus in transformations of low-grade B-cell lymphomas after fludarabine treatment.

Fludarabine is a highly effective chemotherapeutic agent for chronic lymphocytic leukemia/small lymphocytic lymphoma and is also active in other B-cell lymphoproliferative disorders. Although highly efficacious in destroying the malignant B-cells, fludarabine also causes T-cell lymphopenia and immunosuppression. We present five patients given fludarabine for low-grade B-cell lymphoproliferative disorders who showed transformation of the primary neoplasm to a higher grade tumor. Immunohistologic antibody studies were performed on paraffin-embedded tissue sections of the initial tissue (when available) and on the follow-up biopsy specimens for CD20, CD3, CD45RO, CD43, CD30, CD15, and latent membrane protein (LMP-1) for Epstein-Barr virus (EBV). The initial diagnoses in these five patients included chronic lymphocytic leukemia/small lymphocytic lymphoma (three cases), follicle center lymphoma (one case), and Waldenstrom's macroglobulinemia (one case). All of the follow-up biopsy specimens showed scattered Hodgkin's-like cells, and two of the five also showed foci of large-cell transformation. The Hodgkin's-like cells showed CD30 immunoreactivity in four of the five cases and CD15 immunoreactivity in three of the five. Strong immunoreactivity of the large, atypical, Hodgkin's-like cells for LMP-1 of EBV was noted in four cases; in the remaining case, this finding was equivocal. In situ hybridization for EBV-encoded RNA was positive in four of the five cases. Molecular studies by polymerase chain reaction (PCR) showed the presence of EBV in three of the five cases. PCR for detection of immunoglobulin heavy chain demonstrated identical monoclonal rearrangements in the original lymphoma and transformation in one case with available material. The CD4 lymphocyte count in each patient was less than 550/microL, indicating cellular dysfunction. Transformation of low-grade non-Hodgkin's lymphomas after fludarabine therapy might be associated with EBV and severe immunosuppression.

Adult↗

PubMed1997

Infection due to fluconazole-resistant Candida in patients with AIDS: prevalence and microbiology.

A cross-sectional study was conducted to assess the prevalence and microbiology of oral infection due to fluconazole-resistant Candida in patients with AIDS. Oral swab specimens for fungal cultures were obtained from 100 consecutive outpatients with CD4 lymphocyte counts of < 200/mm3. At least one fungal organism demonstrating in vitro resistance to fluconazole (minimum inhibitory concentration, > or = 8 micrograms/mL) was isolated from 26 (41%) of 64 patients for whom cultures were positive. When fluconazole-resistant C. albicans was isolated, in vitro resistance correlated with clinical thrush. None of 10 patients from whom only non-albicans species of Candida were isolated had active thrush. The patients from whom fluconazole-resistant Candida albicans was isolated had lower CD4 cell counts (median, 9/mm3), a greater number of treated episodes of thrush (median, 4.5), and a greater median duration of prior fluconazole treatment (231 days) than did patients from whom fluconazole-susceptible C. albicans was isolated (median CD4 cell count, 58/mm3 [P = .004]; median number of treated episodes of thrush, 2.0 [P = .001]; and median duration of prior fluconazole treatment, 10 days [P = .01]; respectively). In a multivariate analysis, the number of episodes and duration of fluconazole therapy were independent predictors of resistance.

Acquired Immunodeficiency Syndrome↗

PubMed1999

Immunological predictors of HIV-related survival.

While the prognostic role of CD4 lymphocyte count is well established, little is known about how other immunological factors are associated with HIV-related survivorship. CD8 lymphocyte count is reported to inhibit growth of HIV in vitro and to deter the development of cytomeglovirus infections. Scarce information exists, however, on its association with HIV-related survivorship. The objective of the present study therefore was to assess whether survival estimation could be improved by including CD8 lymphocyte count as a prognostic factor. The study sample consisted of 904 adult HIV-infected patients who were treated between 1992 and 1997 at a large southwestern academic medical centre in the US. Survival analysis using proportional hazards modelling showed that baseline CD4 lymphocyte was highly and positively predictive of HIV-related survival. By contrast, baseline CD8 count was not predictive of survival in the study cohort. While the interaction between CD4 and CD8 was not statistically significant in the present study sample, decomposition of this effect indicates that these factors may operate synergistically to predict survival. In conclusion, these findings suggest that clinicians may improve their prognostic accuracy by relying on both CD4 and CD8 lymphocyte counts rather than relying exclusively on CD4 counts.

Acquired Immunodeficiency Syndrome↗

PubMed2001

Pilot study of interferon-alpha with and without amantadine for the treatment of hepatitis C in HIV coinfected individuals on antiretroviral therapy.

BACKGROUND: Concurrent potent therapy of hepatitis C (HCV) and HIV includes at least five antiviral drugs. Drug interactions, toxicity, tolerance and acceptance by patients of such treatment regimens are unknown. STUDY DESIGN: A prospective open randomized pilot trial was conducted to test interferon-alpha (6 million units/day for the 1st month followed by 6 million thrice weekly) and amantadine versus interferon-alpha monotherapy for tolerability and feasibility among HIV and HCV co-infected patients on stable antiretroviral combination therapy. RESULTS: 1,013 HIV-infected patients were consecutively evaluated. 314 were anti-HCV antibody positive; only eight (2.4%) were eligible. Major reasons for exclusion were: normal transaminase levels (34%), ongoing intravenous drug use (33%), or recent change in antiretroviral therapy (31%). Study drugs were stopped in all of the seven patients enrolled because of side effects and/or failure of anti-HCV therapy. CD4 lymphocyte counts and HIV-1 RNA remained stable. CONCLUSION: Among patients on highly active antiretroviral therapy, the addition of interferon-alpha with or without amantadine was inefficient and poorly tolerated, but had no negative influence on HIV infection. Eligibility for the study was unexpectedly low.

Adult↗

PubMed2005

Effectiveness of highly active antiretroviral therapy in reducing heterosexual transmission of HIV.

Highly active antiretroviral therapy (HAART) has been shown to be highly effective in reducing plasma levels of HIV RNA; therefore, these treatments could diminish the risk of transmission. We analyzed 393 steady heterosexual couples, of which one partner had been previously diagnosed with HIV infection (index case) and where the nonindex partner reported his or her sexual relationship with the index case as the unique risk exposure. These couples were consecutively enrolled in the period 1991 through 2003 when the nonindex partners took their first HIV test. HIV prevalence among partners of index cases who had not received antiretroviral therapy was 8.6%, whereas no partner was infected in couples in which the index case had been treated with HAART (P = 0.0123). HIV prevalence among nonindex partners declined from 10.3% during the pre-HAART period (1991-1995) to 1.9% during the late HAART period (1999-2003; P = 0.0061). In the multivariate analysis, this decline held (odds ratio = 0.14, 95% confidence interval: 0.03-0.66) after adjusting for length of partnership, unprotected coitus, and pregnancies as well as gender, CD4 lymphocyte count, AIDS-defining diseases, and sexually transmitted infections in the index case. When HAART became widely available, a reduction of approximately 80% in heterosexual transmission of HIV was observed, irrespective of changes in other factors that affect transmission.

Acquired Immunodeficiency Syndrome↗

PubMed1998

[Surrogate endpoints in clinical studies exemplified by HIV infection].

Surrogate endpoints are used extensively in clinical studies to evaluate the efficacy of therapy. The effect of a treatment on surrogate endpoints should predict efficacy with regard to clinical endpoints such as morbidity and death. Benefits and risks in the use of surrogate endpoints in clinical trials and daily practice are discussed using the example of HIV infection. CD4-lymphocyte counts and plasma HIV-RNA are powerful markers of disease progression in HIV infection. They are also increasingly used as surrogate endpoints to evaluate the efficacy of antiretroviral treatments. Surrogate endpoints should be biologically plausible and must be validated statistically. However, clinical endpoints are still of paramount importance in assessing the value of treatments for chronic diseases.

Anti-HIV Agents↗

PubMed2004

Comprehensive pediatric human immunodeficiency virus care and treatment in Constanta, Romania: implementation of a program of highly active antiretroviral therapy in a resource-poor setting.

BACKGROUND: Relatively few human immunodeficiency virus (HIV)-infected children worldwide have access to care and treatment. The Romanian-American Children's Center, a collaborative project of a U.S. health care institution and the Romanian government, has established a comprehensive program of highly active antiretroviral therapy for children in Constanta, Romania. OBJECTIVES: To describe the design and outcomes of a program of pediatric HIV/acquired immunodeficiency syndrome (AIDS) care and treatment in a resource-poor setting. SETTING: Outpatient center providing comprehensive primary and HIV/AIDS specialty care and treatment to all known HIV-infected children living in Constanta County, Romania. OUTCOMES: As of August 2003, a total of 452 children were receiving highly active antiretroviral therapy. Therapy has been well-tolerated, with approximately 90% of children continuing to receive treatment after a median duration of follow-up of 67 weeks. Normal weight and height growth velocities have been observed among treated children. Marked decreases have been observed in rates of hospitalization and mortality. The mean change in CD4+ lymphocyte count for 173 children who have both a baseline count and at least 1 follow-up count is +284 cells/microL (P < 0.0001). CONCLUSIONS: Highly active antiretroviral therapy can be administered safely and effectively to children in a resource-poor setting, with outcomes comparable with those observed in U.S. pediatric antiretroviral clinical trials.

Acquired Immunodeficiency Syndrome↗

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↗

PubMed2002

Low level viremia and high CD4% predict normal survival in a cohort of HIV type-2-infected villagers.

A community-based study of human immunodeficiency virus type 2 (HIV-2) infection was conducted in a rural village in northern Guinea Bissau, West Africa to assess the relationship between plasma HIV-2 RNA levels, CD4 lymphocyte percentage, and survival over an 8-year period. The cohort of 133 HIV-2-infected individuals and 160 HIV-uninfected controls enrolled in 1991 were followed up at home until 1998. Thirty-one (23%) HIV-2-infected and 24 (16%) HIV-uninfected individuals died over the follow-up period (mortality hazard ratio 1.7, 95% CI 1.0, 2.9; p= 0.06). In HIV-2-infected individuals, the median HIV-2 RNA level was 347 copies/ml and the mean CD4% was 28.6. Both plasma viremia and CD4% were independent predictors of survival, with hazard ratios increasing by 1.6 (95% CI, 1.1, 2.3) for each log(10) increase of plasma viremia and 1.7 (1.1, 2.6) for each 10% decrease of CD4%. Infected subjects with a plasma viral load >or= the median (347 copies/ml) and a CD4% <or= the mean (28.6%) had a mortality hazard ratio of 3.1 (95% CI 1.7, 5.8) compared to uninfected controls, whereas the remaining infected subjects had a mortality rate similar to uninfected controls, the mortality hazard ratio being 1.0 (95% CI, 0.5, 2.1.) In those who survived between 1991 and 1996, HIV-2 RNA levels were unchanged overall and CD4 lymphocyte counts remained high. In conclusion, baseline HIV-2 RNA levels predicted a normal survival for the majority, with low and stable levels of plasma viremia characterizing HIV-2 infections in this rural West African community.

Adult↗

PubMed2000

Fat malabsorption assessed by 14C-triolein breath test in HIV-positive patients in different stages of infection: is it an early event?

The aim of this study was to evaluate fat absorption in HIV-positive (HIV+) patients in different phases of HIV infection using a 14C-triolein breath test. We distributed 47 HIV+ patients according to the 1993 Centers for Disease Control Revised Classification: 20 in Group 2 (A1 or A2) and 27 in Group 3 (B1, B2, A3, B3, or C). Ten HIV-negative healthy subjects comprised the control group (Group 1). All individuals underwent a 14C-triolein breath test. Parasitic infection was evaluated through three stool exams, including Cryptosporidium and Isospora investigation. The median value of cumulative 6 hours' 14C excretion expressed as percentage of the 14C given as triolein was significantly higher in Group 1 (8.4%) than Group 2 (5.5%) or Group 3 (3.4%), p = 0.04 and p << 0.01, respectively. Fat malabsorption was found in 25% of Group 2 individuals, 52.6% of those without diarrhea in Group 3, and was correlated with CD4+ lymphocyte counts (p << 0.01). Fat malabsorption is a common feature in advanced stages of HIV infection, even in the absence of diarrhea and is also present in asymptomatic HIV+ patients. These findings suggest that malabsorption is an early event in HIV-infected individuals and is correlated with the degree of immunosuppression.

Adult↗

PubMed1995

Phase I study of atevirdine, a nonnucleoside reverse transcriptase inhibitor, in combination with zidovudine for human immunodeficiency virus type 1 infection. ACTG 199 Study Team.

Twenty patients were enrolled in a phase I clinical trial of atevirdine, a nonnucleoside reverse transcriptase inhibitor (NNRTI), given in combination with zidovudine for treatment of human immunodeficiency virus type 1 (HIV-1) infection. Fifteen patients had received no previous antiretroviral therapy. HIV-1 isolates obtained at 6-week intervals were tested for sensitivity to atevirdine and zidovudine. Two patients developed a rash within 2 weeks of enrollment, and 1 of these developed concomitant fever and hepatitis. No hematopoietic, neurologic, or pancreatic toxicities were observed. Atevirdine had considerable initial interpatient pharmacokinetic variability. Forty-seven percent of patients treated with atevirdine plus zidovudine had increased CD4 lymphocyte counts, and HIV isolates from 62% of patients remained sensitive to atevirdine after 24 weeks of therapy. Atevirdine plus zidovudine was well-tolerated. Additional studies should be done to determine the role of atevirdine in the therapy for HIV infection.

Adult↗

PubMed2002

[Efficacy of efavirenz in a mixed population of patients. Identification of drop-out causes].

AIM: To determine drop-out causes and EFV efficacy in ARVT. MATERIALS: We examined a case-study of 106 patients (74% males, 26% females) followed for up to 23 months. 14% of the patients were naive for ARVT, 21% had already been treated with other drugs (non effective therapy), 28% were administered EFV as a supporting drug, 37% were administered EFV as a replacement drug (side-effects). The parameters used to assess efficacy are: CD4+ lymphocyte count and HIV viral load. The statistical tests used are: Student t, Fischer F, Kruskal Wallis H. RESULTS: 33 (31.1%) patients are D.O. because of: non efficacy (11%), rash (5%), psychological disorders (8%), impotence (1%), psychosis (2%), acute hepatitis (1%), abdominal pain (2%), self-suspended ARVT (2%). After the EFV introduction, in few months it has been observed a sudden fall of the viral load while the CD4+ course increases up to the 18 month of follow up, and later on it has been observed a small decrease. CONCLUSION: This study proves the efficacy of EFV in ARVT. The D.O. patients because of side-effects are only a small number.

Adult↗

PubMed1999

Mycobacterial lymphadenitis associated with the initiation of combination antiretroviral therapy.

OBJECTIVE: To characterize the impact of combination antiretroviral therapy on the clinical and laboratory features of mycobacterial lymphadenitis, we conducted a retrospective chart review of HIV-related mycobacterial lymphadenitis at St. Paul's hospital between 1989 and 1997. Among 52 evaluable patients, 12 presented within 12 weeks of initiating combination antiretroviral therapy (group 1, n = 12); the others developed lesions while receiving no antiretrovirals, monotherapy, or a stable combination regimen of >12 weeks duration (group 2, n = 40). RESULTS: Group 1 patients had higher absolute CD4 lymphocyte counts (median, 150 versus 20 cells/mm3, respectively; p = .001) and hemoglobin levels (median, 113 versus 88 g/L, respectively; p = .002) at the time of mycobacterial diagnosis. Clinical comparison showed that group 1 patients were more likely to develop a draining sinus (50% versus 0%; p < .001), but less often to have weight loss (17% versus 74%; p < .0001) or disease which was disseminated (25% versus 70%; p = .04) or caused by Mycobacterium tuberculosis (0% versus 33%; p = .04). CONCLUSIONS: Mycobacterial lymphadenitis developing within 12 weeks of initiating combination antiretroviral therapy is often localized Mycobacterium avium complex disease, associated with a relatively high CD4 count. The clinical course is often complicated by the development of a draining sinus. The close temporal association suggests that such treatment may unmask subclinical infection by enhancing the immune response to mycobacterial antigens.

AIDS-Related Opportunistic Infections↗

PubMed2002

AIDS presenting with cutaneous Kaposi's sarcoma and bacillary angiomatosis in the bone marrow mimicking Kaposi's sarcoma.

Kaposi's sarcoma (KS) and bacillary angiomatosis (BA) may be histologically similar. A precise diagnosis is required because of the different management of these diseases. KS or BA involving bone marrow is rare in patients with and without acquired immune deficiency syndrome (AIDS). We report the case of a 40-year-old human immunodeficiency virus (HIV)-positive homosexual male who presented with small KS lesions in the skin and BA in the bone marrow that histologically were similar. Laboratory evaluation revealed anemia and thrombocytopenia; CD4 count was 103/mm3, and the viral load was 750,000 HIV-1 mRNA copies per milliliter in plasma. Bartonella henselae, the etiologic agent of BA, was isolated from a blood culture. DNA sequences of human herpesvirus-8 (HHV-8), the putative etiologic agent of KS, were identified by polymerase chain reaction (PCR) in skin and bone marrow specimens, but antibody anti-HHV-8-encoded protein ORF73, localized signals only in the skin-KS lesion. The patient received clarithromycin and cefotetan for the BA, and antiretroviral therapy for the HIV infection. The skin lesions gradually regressed, the HIV-1 mRNA copy number decreased to less than 400 per milliliter and the CD4 lymphocyte count increased to 665/mm3. In conclusion, vascular lesions of BA and KS may be clinically and histologically similar, both may be associated with advanced AIDS, and an accurate diagnosis is required because of their different management.

AIDS-Related Opportunistic Infections↗

PubMed1998

Efficacy of the acyclic nucleoside phosphonates (S)-9-(3-fluoro-2-phosphonylmethoxypropyl)adenine (FPMPA) and 9-(2-phosphonylmethoxyethyl)adenine (PMEA) against feline immunodeficiency virus.

The acyclic nucleoside phosphonates (S)-9-(3-fluoro-2-phosphonylmethoxypropyl)adenine (FPMPA) and 9-(2-phosphonylmethoxyethyl)adenine (PMEA) were evaluated for their efficacy and side effects in a double-blind placebo-controlled trial using naturally occurring feline immunodeficiency virus (FIV)-infected cats. This natural retrovirus animal model is considered highly relevant for the pathogenesis and chemotherapy of HIV in humans. Both PMEA and FPMPA proved effective in ameliorating the clinical symptoms of FIV-infected cats, as measured by several clinical parameters including the incidence and severity of stomatitis, Karnofsky's score, immunologic parameters such as relative and absolute CD4+ lymphocyte counts, and virologic parameters including proviral DNA levels in peripheral blood mononuclear cells (PBMC) of drug-treated animals. In contrast with PMEA, FPMPA showed no hematologic side effects at a dose that was 2.5-fold higher than PMEA.

Adenine↗

PubMed1992

Prevention of Pneumocystis carinii pneumonia and toxoplasmic encephalitis in human immunodeficiency virus infected patients: a clinical approach comparing aerosolized pentamidine and pyrimethamine/sulfadoxine.

The incidence of Pneumocystis carinii pneumonia (PCP) and toxoplasmic encephalitis (TE) was analyzed in 83 human immunodeficiency virus (HIV)-infected patients who inhaled aerosolized pentamidine (AP) either for primary prophylaxis (group Ia) or secondary prophylaxis (group IIa) of PCP. These cohorts were compared with two historical groups of patients who took Fansidar (pyrimethamine/sulfadoxine) for primary prophylaxis (group Ib) or secondary prophylaxis (group IIb) of PCP. The follow-up was 3-41 months (median 8 months). PCP did not occur in group Ia but was seen in 1 patient of group Ib (5%). TE was observed in 3 patients of group Ia (7.3%) and in 1 patient of group Ib (5%). PCP relapses were seen in 5 patients of group IIa (11.9%) and in 3 patients of group IIb (6.9%), whereas TE occurred in 13 patients of group IIa (30.9%) and in 1 patient of group IIb (2.3%). 20.3% of patients with CD4+ counts less than or equal to 100/microliters and only 7.7% of those with CD4+ counts greater than 100/microliters developed toxoplasmosis. In conclusion, Fansidar rather than AP prophylaxis should be recommended for patients with a history of PCP or toxoplasmosis and for all HIV-infected patients with CD4+ counts less than or equal to 100/microliters. In patients with CD4+ lymphocyte counts between 100 and 200/microliters, AP prophylaxis appears appropriate.

Adult↗