Prevalence of R5 and X4 HIV variants in antiretroviral treatment experienced patients with virologic failure.

BACKGROUND: Antiretroviral therapy (ART) inhibits virus replication. Nevertheless, ART has the disadvantage of generate selective resistance and adverse events. Coreceptor antagonists are a family of antiretroviral drugs that are used with the prior knowledge of patients HIV tropism. OBJECTIVES: The purpose of this work was to estimate the prevalence of R5 and X4 variants among Chilean patients under antiretroviral therapy and virological failure and investigate variables such as plasma viral load (pVL) and CD4 cell count in the population studied. STUDY DESIGN: HIV RNA or proviral DNA was extracted from 454 consecutives patients and tropism testing was performed using a genotypic method performed with Geno2pheno setting a cutoff value for FPR 5.75%. RESULTS: Among 454 individuals analyzed, 299 (66%) harbouring exclusively R5 variants. They not displayed a better clinical profile than individuals harbouring X4 strains (22%). For R5 patients the median of pVL and CD4 cell count were 268,000copies/mL, and 223cells/µL respectively. For X4 samples the values were 368,000copies/mL and 214cells/µL [P>0.05]). Only, 53 patients (12%) could not be analyzed and were categorized as non-reportable. CONCLUSIONS: The genotypic method confirmed that R5 strains were more prevalent despite the fact that patients were treatment-experienced for several years. The genotypic strategy proved to be a faster and cost-effective option as compared to phenotypic assays. According to our results, two of every three patients under antiretroviral therapy and with virologic failure harbour R5 strains, and may be candidates for use of a CCR5 antagonist.

Frequency of CCR5 gene 32-basepair deletion in Chilean HIV-1 infected and non-infected individuals.

A 32-basepair deletion polymorphism in the CCR5 chemokine receptor gene (CCR5Delta32) has been identified and shown to have functional significance in determining susceptibility to infection by human immunodeficiency virus type 1 (HIV-1) and possibly in influencing disease progression in HIV-1 positive individuals. These findings led to an interest in studies of DeltaCCR5 allele geographical distribution in human population, for complete understanding of the role of CCR5 in HIV-1 epidemiology. Inter-population variation in CCR5Delta32 frequency may be a significant factor in the prediction of AIDS endemicity. In this report we assessed the frequency of DeltaCCR5 in a Chilean population (63 HIV-1 infected and 62 non-infected individuals). No homozygous CCR5Delta32 individual was identified, and no significant difference was observed between HIV-1 infected (3/63) and non-infected (3/62) individuals for the heterozygote CCR5Delta32 state. This is the first evidence of the contribution of DeltaCCR5 allele to the genetic background of the Chilean population, which is characterized by intense ethnic admixture and by gene flow from the European Spanish gene pool.

[Meningitis in subjects with human immunodeficiency virus infection]. / Meningitis en sujetos infectados con el virus de la inmunodeficiencia humana.

BACKGROUND: Neurological complications are frequently observed in HIV-1 patients. Lumbar puncture (LP) and LSF analysis are two key diagnostic procedures. AIM: To describe the etiology meningeal syndromes in a hospital series of HIV patients. RESULTS: In this study, we present the different meningeal complications from 198 HIV-1 patients referred, for the last five years, to the HIV Center of the Hospital of University of Chile. The diagnosis of HIV-1 was done clinically plus a positive ELISA test, and confirmed by Western blot and/or PCR. In all cases with a possible neurological complication (52/198), a LP was performed. Cytochemical and microbiological studies, were done in each CSF sample. Serum CD4/CD8 lymphocytes number were determined by flow cytometry, and brain CT scan and/or MRI were obtained. From the 52 patients in whom a LP was done, 24 showed an abnormal CSF, compatible with the diagnosis of meningitis. The most frequent etiology (11/24) was infection by Cryptococcus neoformans, followed by Treponema pallidum (7/24). There were 3 cases of HIV-1 meningitis, and 3 other cases with lymphoma, varicella zoster and cytomegalovirus meningitis. The frequency of cryptococcal infection was similar to that reported in the literature, but two interesting observations were the high frequency of neurosyphilis and the absence of TBC meningitis. In our country, the VDRL/FTA-ABS serum tests are mandatory in HIV patients. If these tests were positive a LP was performed, and this could partially explain the high number of cases coinfected with neurosyphilis. There is an important prevalence of lung TBC in our country, and as a consequence there is a policy of immunization to all newborn. It is possible that the high prevalence of TBC "promotes" a more actively search for TBC infection, with an early diagnosis and treatment of pulmonary TBC, and so a more frequent prophylaxis therapy in HIV patients, without the development of TBC meningitis.

Complement-dependent cytotoxic antibodies to human T lymphotropic virus type I (HTLV-I)-infected cells in the sera of HTLV-I-infected individuals.

To investigate whether HTLV-I induces the development of complement-dependent cytotoxic antibodies in humans, sera of asymptomatic HTLV-I carriers and of patients suffering from tropical spastic paraparesis/HTLV-I-associated myelopathy (TSP/HAM) or adult T cell leukaemia (ATL) were used in a cytotoxicity assay against a panel of target cells. This panel included uninfected cell lines (CEM, Jurkat, Molt and H9), cell lines chronically infected with HTLV-I (MT2, MT4, C9IPL and HUT102), as well as lines H36 (H9 infected with HTLV-I), H9-IIIB (H9 infected with HIVms) and H9-MN (H9 infected with HIMVMN). HTLV-I+ sera induced lysis of H36 and of lines expressing HTLV-I antigens in the presence of rabbit complement, but did not lyse cells in presence of human complement. The HTLV-I+ sera also failed to lyse the HTLV-I- lines and H9 cells, suggesting that lysis was specific for HTLV-I. H36 cell lysis was prevented by IgG depletion of the sera and by dialysis of rabbit complement against EGTA or EDTA. Rabbit complement-dependent cytotoxic antibodies were present in the sera of 14/14 HTLV-I-infected individuals; the highest titres were predominantly found in the sera of the TSP/HAM patients. Such antibodies were also detected in 5/5 individuals coinfected with HIV-1 and HTLV-I, although no cytotoxic antibody could be found against HIV-infected cells. Vice versa, sera of HIV-1-infected individuals did not exert a lytic effect in the presence of complement (of human or rabbit origin) against HIV-1- or HTLV-I-infected cells. Incubation of the sera of four HTLV-I-infected patients with HTLV-I env-specific synthetic peptides demonstrated that some of the complement-dependent cytotoxic antibodies recognized epitopes located on gp46 between amino acids 190 and 209. There is no correlation of rabbit complement-dependent cytotoxic HTLV-I antibodies with the development of disease.

Behavioral effects of intracerebral administration of luteinizing hormone releasing hormone (LHRH) in rats.

The effects of LHRH intracerebrally infused on acquisition of conditioned avoidance responses (CARs) and spontaneous motility were studied in adult male rats. The results were the following: 1) LHRH (1 and 2.5 micrograms/rat) administered through a cannula stereotaxically implanted into the lateral ventricle induced an impairment in the acquisition of CARs along with an increase in global motility, rearing, head shaking and grooming behavior; 2) LHRH 1 microgram/rat injected into the hippocampus or nucleus accumbens induced also an impairment in acquisition which is evident 15 min after treatment. In contrast, intrastriatal injection induced an immediate disruption of this behavior; and 3) there is a good dose-response relationship for intrastriatal LHRH between 7.8 and 62.5 ng/rat. The results suggest that the estriatum could be the locus of the LHRH-induced inhibition of CARs. Then the possibility of an involvement of the dopamine nigrostriatal system is discussed.