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.

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.

Hepatitis E virus as a newly identified cause of acute viral hepatitis during human immunodeficiency virus infection.

The recent description of chronic hepatitis E in organ transplant recipients deserves increased awareness in the context of hepatitis E virus (HEV) infection in immunocompromised individuals. Reported here is what is apparently the first PCR-documented case of acute hepatitis E in a human immunodeficiency virus (HIV)-1-infected patient. The CD4(+) T-lymphocyte count was 246/mm(3). The IgM anti-HEV antibody and HEV RNA tests results from serum were positive. Hepatitis was benign, and chronic HEV infection was ruled out. The HEV genotype was 3f. The patient did not report recent travel abroad. HEV should be tested in HIV-infected individuals presenting with acute hepatitis. HEV RNA detection is useful in diagnosing HEV infection and in monitoring recovery.

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.

Multidrug resistance genotypes (insertions in the beta3-beta4 finger subdomain and MDR mutations) of HIV-1 reverse transcriptase from extensively treated patients: incidence and association with other resistance mutations.

Multiple nucleoside resistance involves specific mutational patterns of the HIV-1 pol gene that are independent of the classic mutations conferring resistance to individual dideoxynucleosides. These include a cluster of five mutations in the reverse-transcriptase (RT) coding region (A62V, V75I, F77L, F116Y, and Q151M) generally referred to as multidrug resistance (MDR) mutations, and insertions of one or several amino acid residues between codons 67 and 70 of RT, a flexible region joining two antiparrallel beta sheets (beta3-beta4 insertions). The objectives of this study were (i) to determine the prevalence of multidrug resistance genotypes (MDR mutations and beta3-beta4 insertions) in a cohort of 632 patients who were extensively pretreated with anti-HIV drugs and not responding to their current antiretroviral therapy, and (ii) to analyze the association of multidrug resistance genotypes with other resistance mutations in the RT and protease genes. Among viruses sequenced from these patients, 15 (2.4%) of them contained an insertion and 2 (0.3%) contained a deletion in the beta3-beta4 finger subdomain of RT. In 9 cases, the insertion was associated with a D67S, G, or E mutation. In addition, we identified 13 (2.1%) viruses harboring specific MDR mutations (mainly Q151M and/or A62V, V75I, F116Y). Interestingly, the A62V mutation was found in 6 of the 15 strains with an insertion, whereas the other MDR mutations were not observed in insertion mutant strains. Especially high levels of resistance to zidovudine were observed for viruses with a beta3-beta4 insertion in the background of A62V, L210W, and T215Y. Otherwise, MDR mutations and beta3-beta4 insertions were found in association with the classic mutations conferring resistance to zidovudine, lamivudine, nonnucleoside RT inhibitors, and protease inhibitors, according to treatment history. Finally, we observed a genome with a deletion of codon 70 associated with a Q151M MDR mutation. These data suggest that the emergence of HIV-1 multidrug resistance, which may occur in various genetic contexts, poses a challenging problem in formulating treatment strategies.

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.

Monoblastic leukemia in an HIV-infected patient: absence of viral expression in RNA blasts.

A small number of patients seropositive for the human immunodeficiency virus (HIV) have been reported as developing acute non-lymphoblastic leukemia (ANLL). In the cases previously published, the authors never reported a study of the link joining HIV infection and leukemia. We describe here the case of a 41-year-old HIV positive patient who developed ANLL (FAB classification M5). Using molecular techniques, we looked for a direct link between these two co-existing diseases. We showed the absence of HIV expression in the malignant clone, suggesting that the association of ANLL and Acquired Immune Deficiency Syndrome is not a direct consequence of the myeloid precursors infection. Nevertheless a relationship may exist through a disorganization of the bone marrow micro-environment.

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.

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.

[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.

Localized brain proton MRS metabolic patterns in HIV-related encephalopathies.

We have examined 9 healthy volunteers and 63 HIV-patients (16 asymptomatic patients and 47 patients with clinical AIDS-dementia complex, ADC) by magnetic resonance spectroscopy (MRS) and imaging (MRI) on a Siemens Magnetom SP63 (1.5 T). Proton MRS of the brain was performed at 63 MHz using the PRESS sequence (echo time = 135 ms, TR = 1.6 s). Four main results have been found: (1) HIV-related encephalopathy induces significant modifications of brain metabolism analyzed by MRS and the most sensitive metabolic parameter is the N-acetyl-aspartate/Choline ratio, (2) the correlation between MRS and MRI is good in 75% of patients, (3) in 4 of the 16 neuro-asymptomatic patients (i.e. 25%) a metabolic encephalopathy was found while MRI was still normal, and (4) MR spectra describe 3 different pathological metabolic patterns in the brain of HIV patients. Two patterns might correspond to the two entities of HIV-induced lesions i.e. HIV encephalitis and HIV-related progressive leukoencephalopathy.

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.