Human Immunodeficiency Virus-1 Viral Load Is Elevated in Individuals With Reverse-Transcriptase Mutation M184V/I During Virological Failure of First-Line Antiretroviral Therapy and Is Associated With Compensatory Mutation L74I.

BACKGROUND: M184V/I cause high-level lamivudine (3TC) and emtricitabine (FTC) resistance and increased tenofovir disoproxil fumarate (TDF) susceptibility. Nonetheless, 3TC and FTC (collectively referred to as XTC) appear to retain modest activity against human immunodeficiency virus-1 with these mutations possibly as a result of reduced replication capacity. In this study, we determined how M184V/I impacts virus load (VL) in patients failing therapy on a TDF/XTC plus nonnucleoside reverse-transcriptase inhibitor (NNRTI)-containing regimen. METHODS: We compared VL in the absence and presence of M184V/I across studies using random effects meta-analysis. The effect of mutations on virus reverse-transcriptase activity and infectiousness was analyzed in vitro. RESULTS: M184I/V was present in 817 (56.5%) of 1445 individuals with virologic failure (VF). Virus load was similar in individuals with or without M184I/V (difference in log10 VL, 0.18; 95% confidence interval, .05-.31). CD4 count was lower both at initiation of antiretroviral therapy and at VF in participants who went on to develop M184V/I. L74I was present in 10.2% of persons with M184V/I but absent in persons without M184V/I (P < .0001). In vitro, L74I compensated for defective replication of M184V-mutated virus. CONCLUSIONS: Virus loads were similar in persons with and without M184V/I during VF on a TDF/XTC/NNRTI-containing regimen. Therefore, we did not find evidence for a benefit of XTC in the context of first-line failure on this combination.

Osteonecrosis of the jaw induced by arsenic trioxide therapy in a leukemia patient: A rare case report and literature review.

A patient suffering from acute promyelocytic leukemia (APL) was referred to the dental department before introduction of chemotherapy by all-trans retinoic acid and arsenic trioxide (ATO). A panoramic radiography showed his third upper maxillary left tooth included into the maxillary bone. The patient presented with a febrile episode. Consequently, the infectious gateway was researched. A left maxillary sinus migration of his third upper left tooth together with a bony sequestrum has been observed on a CT-scan. A surgery was then performed to remove the bony sequestrum and the tooth. The first hypothesis of tooth migration could be that the patient had an infection prior to introduction of chemotherapy. However, neither clinical or radiographic signs were observed during the initial check-up. The second hypothesis is that ATO caused osteonecrosis of the jaw (ONJ) induced the formation of a bony sequestrum associated to the tooth migration into the sinus. ONJ could be a potential adverse of ATO chemotherapy.

[Retroviral restriction factors : from Fv1 to TRIM5α]. / Les facteurs de restriction rétrovirale : de Fv1 à TRIM5α.

During their evolution, mammals have developed cellular factors interfering with retroviral replication, known as « restriction factors ¼. The prototype of these factors, Fv1, was characterized in the late 60's and blocks MLV infection. Some Fv1-like factors interfering with complex retroviruses, including HIV, have recently been discovered in primate cells. These restriction factors are referred to as Ref1, which blocksMLVreplication in human cells, and Lv1, which blocks the infection of non-human primate cells by various retroviruses, including MLV and HIV. These factors are all saturable by an excess of virus, target the viral capsid and interfere with an early step of viral replication. Lv1 and Ref1 have recently been found to be species-specific variants of a single protein called TRIM5α, a member of the TRIM protein family. The mechanism of action of these factors is still unknown. The existence of natural inhibitors of retroviral infection raises new hopes for the development of therapeutic tools against HIV infection.

[Pseudohypoaldosteronisme type I: a rare cause of failure to thrive]. / Une cause rare de stagnation pondérale à la naissance : le pseudohypoaldostéronisme de type I.

We report on a boy, born on term, presenting with a weight loss and a persistent failure to thrive after 10 days despite a normal behavior under bottle-feeding. The clinical examination was normal and biological assessment revealed hyponatremia with hyponatriuria, normal kaliemia and elevated aldosterone values, leading to type I pseudohypoaldosteronism diagnosis. Treatment with salt supplementation allowed growth improvement. The diagnosis was confirmed by the identification of a mutation in the mineralocorticoid receptor. This change was also found in several family members.

Comparison of two genotypic algorithms to determine HIV-1 tropism.

OBJECTIVES: One or both of two co-receptors, CCR5 (R5) and CXCR4 (X4), are used by HIV-1 to enter into host cells. The glycoprotein 120 (gp120) V3 sequence is correlated with the R5 and X4 phenotype. CCR5 inhibitors are specifically active against R5 viruses, suggesting the need to determine tropism before the use of these antagonists. A comparison of the position-specific scoring matrices (PSSM) and Geno2pheno algorithms based on the V3 loop gp120 sequences and previously described to be correlated to the R5 or X4 phenotype was carried out. METHODS: V3 envelope (env) genes from 83 plasma samples were amplified and sequenced, and 69 sequences were analysed with the PSSM and Geno2pheno algorithms. RESULTS: These two algorithms were concordant in 86.5% of cases. The Geno2pheno algorithm gave a tropism result more frequently than the PSSM algorithm, but R5X4 or X4 viruses were less frequently detected by the Geno2pheno algorithm. R5X4 or X4 tropism was predicted in 29.9% of samples. There was more R5X4 co-receptor use in the antiretroviral-treated group than in the antiretroviral-naïve group. CONCLUSIONS: It is advisable to run a validated co-receptor use prediction tool before using co-receptor antagonists. If genotyping methods are considered, the PSSM and Geno2pheno algorithms are complementary and both are necessary. The association between predicted co-receptor use and virological response to co-receptor antagonists needs to be thoroughly evaluated.