Reevaluation of possible outcomes of infections with human immunodeficiency virus.

Several lines of evidence indicate that HIV infection can result in several possible incomes, including a very small proportion of individuals whose HIV replication is controlled after treatment interruption (known as HIV posttreatment controllers) or spontaneously without any treatment (known as HIV elite controllers). Both types of individuals are HIV RNA negative but HIV DNA positive, with living virus which can be stimulated ex vivo. A review was conducted to assess the literature on yet rarer cases with detectable integrated HIV DNA without HIV infectious virus in HIV-seropositive or -negative individuals. Three categories of patients were identified: (a) HIV-seropositive individuals with apparent spontaneous cure from their HIV infection, (b) HIV-seronegative children born to HIV-infected mothers and (c) highly exposed seronegative adults. Validity criteria were proposed to assess the presence of integrated HIV DNA as possible or unquestionable in these three categories. Only three articles among the 22 ultimately selected fulfilled these criteria. Among the highly exposed seronegative subjects, some individuals were described as being without integrated HIV DNA, probably because these subjects were not investigated using relevant, highly sensitive methods. Finally, we propose a definition of spontaneous cure of HIV infection based on clinical, immunologic and virologic criteria.

Cellular and plasma viral load in patients infected with HIV-2.

OBJECTIVE: To determine circulating viral load in HIV-2-infected individuals. METHODS: Viral load was determined in 40 HIV-2-infected adults using standardized quantitative cell and qualitative plasma viraemia assays. We also tested for proviral HIV-2 DNA using single and nested polymerase chain reaction (PCR) in fresh lymphocytes from 27 subjects. The results were compared, on the basis of the CD4+ lymphocyte count, with our published data for HIV-1 infection. RESULTS: HIV-2 was isolated from peripheral blood mononuclear cells (PBMC) from 19 individuals and plasma from four patients. The rate of cell and plasma viraemia positivity correlated with the CD4+ cell count and HIV-2 virus load increased as the CD4+ cell count fell. The cellular HIV-2 load in the patients with a CD4+ count < 200 x 10(6)/l was similar to reported values for HIV-1, but the HIV-2 isolation rate from the plasma of these individuals was significantly lower than for HIV-1. When the CD4+ count was between 200 and 500 x 10(6)/l, the rate of HIV-2 isolation from plasma and the cellular virus load were both significantly lower than for HIV-1. When the CD4+ count was > 500 x 10(6)/l, HIV-1 and HIV-2 were undetectable in plasma and HIV-1 was isolated from PBMC in significantly more cases than HIV-2. By single PCR, amplification were positive in 14 out of 27 subjects and there was a correlation between positivity and CD4+ cell count. By nested PCR, only four of the 27 subjects, all with a high CD4+ count, remained negative. CONCLUSIONS: Differences in viral load between individuals infected with HIV-2 and those infected with HIV-1 could partly account for reported differences in the pathogenicity of the two viruses.

Pilot phase I study using zidovudine in association with a 10-day course of anti-CD4 monoclonal antibody in seven AIDS patients.

Experimental evidence has demonstrated that monoclonal antibody (MAb) 13B8.2, a workshop-qualified anti-CD4 MAb, (1) inhibits in vitro syncytium formation as well as in vitro HIV infection of CD4+ T cells; (2) delivers negative signals to T cells, thus preventing T-cell activation and viral replication; (3) contributes to CD4+ T-cell clearance by its Fc portion, and (4) induces an immune response by the patient, contributing potentially to an anti-idiotypic response of interest for the control of the immune parameters of the disease. On this basis a phase I study combining zidovudine treatment and a 10-day course of anti-CD4 MAb was performed in seven AIDS patients (Centers for Disease Control group IV). The treatment was well tolerated. MAb dosage and schedule were adjusted on the basis of circulating CD4+ cells and MAb pharmacokinetics; immunological and virological parameters were also monitored. One patient presented a transient increment in CD4+ T cells associated with augmented T-cell function, the suppression of p24 in the serum and a negative RT assay. A second patient had a steady increment of CD4+ T cells after completion of the treatment, with a transient decrease of serum p24 5 days after completion of the anti-CD4 protocol.

Isolated, chronic, epilepsia partialis continua in an HIV-infected patient.

BACKGROUND: The characteristic clinical feature of epilepsia partialis continua (EPC) is chronic focal myoclonus, usually involving the distal part of one extremity. A variety of pathogenetic factors have been implicated in EPC. In children, the most common cause is Rasmussen encephalitis; in adults, it is vascular disease or tumor involving the sensorimotor cortex. Epileptic seizures are a relatively common manifestation of central nervous system involvement in patients infected with human immunodeficiency virus (HIV), but, to our knowledge, isolated, chronic EPC has not been previously reported. OBJECTIVE: To describe a case of typical EPC in a patient infected with HIV. DESIGN AND SETTING: Case report from an epilepsy center. PATIENT: A 58-year-old man infected with HIV had continuous myoclonus that involved the right arm and was associated with intermittent motor seizures. The electroencephalographic findings were normal at the onset of the symptoms, but left central theta rhythm appeared later. Serial magnetic resonance imaging scans obtained over a 3-month period showed a progressively increasing left rolandic T2-weighted hypersignal. Histologic study of a stereotactic biopsy specimen demonstrated inflammation characterized by perivascular mononuclear cell infiltration. The only detectable cause was HIV infection. Immunocytochemical tests ruled out JC virus. Neuropsychological testing showed no evidence of cognitive impairment. An electroencephalographic-electromyographic "back-averaging" study showed a reproducible transient left biphasic complex preceding the bursts by about 30 milliseconds on the C3 and F3 electrodes, thus demonstrating that the myoclonus was of cortical origin. High-dose corticosteroid (prednisone, 100 mg/d) and anti-HIV- 1 therapy led to marked radiological and clinical improvement. Infection with HIV enhances the risk of seizures, but, to our knowledge, this is the first reported case of "inflammatory" EPC. CONCLUSIONS: The present case suggests that the possibility of central nervous system involvement by HIV-1 should be taken into account in the diagnostic workup of patients with EPC. This case also indicates that treatment can be effective.

A multicenter proton magnetic resonance spectroscopy study of neurological complications of AIDS.

Human immunodeficiency virus (HIV) infection as seen in Europe and the United States has predominantly been contracted through male homosexual sex or intravenous drug abuse. In infected subjects, the brain is frequently affected both clinically and neuropathologically. The aim of this multicenter study has been to evaluate the value of single-voxel proton magnetic resonance spectroscopy (MRS) in the assessment of the neurological complications of acquired immunodeficiency syndrome (AIDS). MRS (voxel size = 8 ml, TR/TE = 1600/135 msec) was performed in 137 HIV-1-seropositive patients and 64 healthy controls without risk factors at three clinical MR sites operating at 1.5 T. The first result of this multicenter trial is that good reproducibility of results among participating sites was found. This demonstrates the reliability and robustness of MRS in the study of in vivo brain metabolism. In HIV patients, there was no significant correlation between metabolite ratios of brain detected by MRS and CDC grouping of patients or CD4 count. In contrast, the variations of brain metabolite ratios (NA/Cr, NA/Cho, and Cho/Cr) were related to the occurrence of encephalopathy, brain atrophy, or diffuse white matter lesions. There was no significant difference in brain metabolites between male homosexual AIDS patients and male intravenous drug user AIDS patients, whatever their neurological status (neurosymptomatic or neuroasymptomatic). Thus, the mode of transmission of HIV infection does not appear to affect the cerebral changes observed in the proton spectra from AIDS patients. Because of its ease of implementation and high information content, single-voxel proton MRS is likely to play a significant role in the evaluation of HIV-related encephalopathies.

TT virus infection: prevalence of elevated viraemia and arguments for the immune control of viral load.

BACKGROUND: The most recent polymerase chain reaction (PCR) detection protocols for the TT virus (TTV) permit one to identify the presence of viral DNA in the serum of a majority of healthy individuals, in the absence of any particular risk factor. This is in contrast with previous epidemiological studies that reported a higher prevalence of TTV infection in populations such as haemodialysis patients (HD), haemophiliacs, intravenous drug users or diabetics. OBJECTIVES: To show that these discrepant results were due to the different sensitivity (number of viral copies detected) of the detection protocols used in initial and more recent epidemiological studies. STUDY DESIGN AND RESULTS: We designed a standardised primary PCR assay that detects only viraemia >5x10(3) to 5x10(4) copies/ml for genotypes 1, 2 and 3, and compared the results of this test with those of a nested PCR assay which is 100-fold more sensitive. Viraemia >5x10(3) to 5x10(4) copies/ml were statistically more frequent in HD patients (54.3%), diabetics (54.7%), and HIV-infected patients with CD4 cells <200/mm(3) (69%) than in blood donors (37%) or HIV-infected patients with CD4 cells >500/mm(3) (33%). CONCLUSIONS: These data suggest a possible relationship between the prevalence of elevated viral loads and the level of immunocompetence of the populations studied, and therefore that of an immune control of TTV viraemia. This corroborates previous findings showing that the stimulation of the immune system by an interferon treatment was able to clear TTV viraemia.

Correlations Between Gene Rearrangements and Immunoreactivity of Reed-Sternberg Cells in Paraffin Sections: A Genotypic and Phenotypic Study of 14 Cases of Hodgkin's Disease.

Recent immunohistological analyses using monoclonal antibodies (MAbs) in paraffin sections have shown that Reed-Sternberg cells (RSC) sometimes express B-cell markers, thereby suggesting a lymphoid origin in at least some cases of Hodgkin's disease (HD). In order to clarify the meaning of RSC immunoreactivities in paraffin sections, 14 cases of HD selected on the basis of a minimal RSC content of 5% (6 with mixed cellularity and 8 with nodular sclerosing HD) were B5 fixed, paraffin embedded and analysed by immunophenotyping with a panel of MAbs (LCA, MB1, MB2, L26, LN2, UCHL1, MT1, MT2, LeuM1, Ber-H2). Prior to fixation, a part of each specimen was frozen and submitted to genotypic analysis using immunoglobulin (Ig), T-cell receptor (TCR) gamma and TCR beta genes probes. RSC were strongly positive with LeuM1, BerH2 and LN2 in all cases and weakly positive with L26 in 4 cases and MB2 in 1 case. Many MT1-UCHL1 positive small lymphocytes were densely distributed close to RSC in all cases. The 14 cases retained a germline configuration with all enzyme-probe combinations tested. This finding cannot only be explained by the low number of RSC, which represented at least 5% of the cell population. Thus, neither the clonal nor the lymphoid nature of our HD cases could be determined unequivocally. LN2, L26 and MB2 expression do not correlate with Ig gene rearrangements and therefore cannot be considered as an argument supporting the B-cell derivation of RSC.

[Study of sensory involvement and dysautonomia in HIV infected patients. A prospective study of 55 cases]. / Recherche d'une atteinte sensitive et dysautonomique chez des sujets infectés par le VIH. Etude prospective de 55 cas.

Subclinical impairment of the peripheral nervous system (PNS) is frequent during HIV infection. Nevertheless, little attention has been given to the autonomic nervous system (ANS). We undertook a prospective study of the ANS, exploring 55 HIV+ subjects with non-invasive functional tests for the cardiac ANS. We also made a quantitative study of thermic (small fibers) and vibratory (large fibers) sensibilities. The results do not show any statistically significant difference between HIV+ subjects and control subjects or between HIV+ subjects of groups I, II and III and those of group IV of the CDC classification. However, an individual analysis comparing the results of the infected subjects with those of the control group indicated the presence of functional abnormalities of the ANS (small fibers) in 34.5% of HIV+ patients with an equally frequent impairment of the thermic perception (small fibers) and of the vibratory perception (large fibers). Moreover, the signs of subclinical dysautonomia were more frequent in group IV (48.3%) than in groups I, II and III (19%) showing a progressive accentuation of the troubles during the course of the infection.

Absent inhibition of hepatitis B virus replication by azidothymidine in patients chronically coinfected by HIV-1 and HBV.

The effect of Azidothymidine (AZT) in vivo on the replication of the Hepatitis B Virus (HBV) was studied in a population of 25 patients chronically coinfected by HBV and Human Immunodeficiency Virus Type 1 (HIV-1), and receiving AZT at the usual dosage. The drug effect was evaluated by sequential measurement of the HBV DNA level. No significant activity at short and medium term was found on HBV replication in either homosexuals or IV drug users chronically coinfected by HIV-1 and HBV.

[Hemichorea-hemiballismus and toxoplasmosis in AIDS]. / Hémichorée-hémiballisme et toxoplasmose au cours du SIDA.

The authors report two cases of hemichorea-hemiballism revealing a toxoplasmic abscess in the subthalamic nucleus during AIDS. Despite the great frequency of this opportunistic infection such cases are exceptional. This rarity seems to be explained by the frequent association of other lesions of the basal ganglia which may prevent the movement disorders. Nevertheless an hemichorea-hemiballism in young people must suggest a cerebral toxoplasmosis. Finally a symptomatic treatment is often necessary; in these cases the use of sodium valproate must be considered, this drug being able to induce a clinical improvement.

[Value of anticardiolipin antibody assay in human immunodeficiency virus infection]. / Intérêt du dosage des anticorps anticardiolipine au cours de l'infection par le virus de l'immunodéficience humaine.

Recently published encouraging data concerning the value of anticardiolipin antibody assays in patients with HIV infection, both for prognostic purposes and to diagnose pneumocystosis, have prompted us to evaluate these assays in a series of 116 patients. We were unable to demonstrate any correlation between the levels of these antibodies and the clinical stage of the infection or the presence of thrombocytopenia. Varying levels of anticardiolipin antibodies were found in 29.3 percent of our patients. More frequent positivity and higher levels seemed to be associated only with the development of cerebral toxoplasmosis. The value and the possible physiopathological role of these antibodies in patients with HIV infection should be reconsidered.

[Cutaneo-mucosal hyperpigmentation in AIDS. 4 cases]. / Hyperpigmentation cutanéo-muqueuse au cours du SIDA. 4 observations.

Four cases of pigmentation of the skin and mucous membranes in homosexuals of the IVC1 group (CDC classification) are reported. The aetiological investigation, although incomplete, pointed to a medicinal origin which could not be formally confirmed. The drugs suspected were azidothymidine, pyrimethamine and ketoconazole. There was no clinical or laboratory evidence of adrenal insufficiency. The few published cases of cutaneo-mucosal pigmentation in HIV infection, often mimicking adrenal insufficiency, emphasize the need for thorough toxicological investigation; this may avoid prescribing an unnecessary and dangerous corticosteroid therapy which might be harmful in these deeply immunocompromized patients who often have multiple infections.

[Epilepsy seizures in HIV infection. 52 cases]. / Crises d'épilepsie au cours de l'infection par le VIH. 52 observations.

Fifty-two patients at various stages of human immunodeficiency virus (HIV) infection who had one or several epileptic seizures in the course of that disease were retrospectively studied from 1985 to 1990. Thirty-five percent of these patients were in overt clinical AIDS at the time of the seizure(s). AIDS was revealed by a seizure in 2 cases. Generalized seizures were observed in 71 percent of the patients, and partial seizures in 29 percent. Electroencephalograms showed signs of brain irritation in only 19 percent of the cases. The cause of epileptic seizure(s) could be determined in 36 patients: cerebral toxoplasmosis in 23 cases; progressive multifocal leucoencephalitis in 2 cases; HIV encephalopathy in 3 cases; iatrogenic cause in 4 cases; meningoencephalitis in 3 cases and neurosyphilis in 1 case. No cause other than HIV infection was found in 16 patients. These findings confirm those of previous studies. In about one-third of AIDS patients epileptic seizures are the only clinical manifestation of viral central nervous system infection.

[Kaposi's sarcoma in AIDS. 70 cases]. / Maladie de Kaposi au cours du SIDA. Soixante-dix observations.

Although Kaposi's sarcoma is the most frequent of malignant diseases associated with AIDS and one of the first recognized manifestations of the syndrome, its management has not yet been standardized. This study concerns 70 AIDS patients with Kaposi's sarcoma followed up in the author's hospital department between june 1985 and december 1989. Most of these patients were homosexual or bisexual males. The mean time elapsed between the finding of a positive HIV test and the discovery of Kaposi's sarcoma was 15 +/- 3.2 months. Systematic evaluation disclosed visceral lesions in 50 percent of the patients. Chemotherapy was used in 55 cases, interferon-alpha in 23 cases and radiotherapy in 13 cases. The presence of visceral lesions clearly reduced survival time, although deaths were mainly due to opportunistic infections. Atypical forms of Kaposi's sarcoma sometimes make its diagnosis difficult, but the main problem is that of treatment, in view of the underlying immunodepression. The authors advocate the setting up of multicentre trials aimed at determining the best therapeutic approach in these patients.

[Disseminated Histoplasma capsulatum histoplasmosis in African AIDS patients (3 cases)]. / Histoplasmose disséminee à Histoplasma capsulatum et SIDA chez l' africain (à propos de 3 cas).

The authors describe three cases of Histoplasma capsulatum histoplasmosis that occurred in black AIDS patients living in France but originally from Guinea and Ivory Coast. In all three cases histoplasmosis was disseminated with fever. In two cases there were cutaneous manifestations. One patient had renal insufficiency and nephrotic syndrome and another presented ulcerative colitis with histoplasma in the chorion. The outcome was favorable in two patients. These three cases are in addition to the five previously reported cases in african AIDS patients. These cases stress the need for awareness of this opportunistic infection as a complication of AIDS in patients from Black Africa.

Survival after neuroAIDS: association with antiretroviral CNS Penetration-Effectiveness score.

OBJECTIVE: We examined if the CNS Penetration-Effectiveness (CPE) score of antiretroviral drugs was associated with survival after a diagnosis of HIV-related encephalopathy, progressive multifocal leukoencephalopathy (PML), cerebral toxoplasmosis, or cryptococcal meningitis. METHODS: Using data from the FHDH-ANRS CO4, we compared the survival of 9,932 HIV-infected patients diagnosed with a first neurologic AIDS-defining event in the pre-combination antiretroviral therapy (cART) (1992-1995), early cART (1996-1998), or late cART (1999-2004) periods. Follow-up was subdivided (CPE < 1.5 and CPE ≥ 1.5), and relative rates (RR) of death were estimated using multivariable Poisson regression models. RESULTS: In the pre-cART and early cART periods, regimens with CPE ≥ 1.5 were associated with lower mortality after HIV-related encephalopathy (RR 0.64; 95% confidence interval [CI] 0.47-0.86 and RR 0.45; 95% CI 0.35-0.58) and after PML (RR 0.79; 95% CI 0.55-1.12 and RR 0.45; 95% CI 0.31-0.65), compared to regimens with CPE < 1.5, while in the late cART period there was no association between the CPE score and the mortality. A higher CPE score was also associated with a lower mortality in all periods after cerebral toxoplasmosis (RR 0.68, 95% CI 0.56-0.84) or cryptococcal meningitis (RR 0.50, 95% CI 0.34-0.74). Whatever the neurologic event, these associations were not maintained after adjustment on updated plasma HIV-RNA (missing, <500, ≥500 copies/mL) with RR ranging from 0.82 (95% CI 0.36-1.91) to 1.02 (0.69-1.52). CONCLUSION: At the beginning of the cART era, the CPE score was of importance for survival after severe neurologic event, while in the late cART period, the additional effect of CPE score vanished with more powerful antiretroviral regimens associated with plasma viral load control.