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Biomedical subjects

J K Maniar

Publications and source records attributed to J K Maniar.

At least 19 recordsLinked to original sources

Neural network-longitudinal assessment of the Electronic Anti-Retroviral THerapy (EARTH) cohort to follow response to HIV-treatment.

HIV infection is for the most part a chronic and asymptomatic disease. To properly monitor the health status of infected individuals it is important to use host and viral surrogate markers as well as pharmacokinetic parameters. Disease progression, assessment of the antiviral potency of the drugs and response to therapy can only be monitored by repetitive measures of viral and host parameters. To prevent the emergence of antiviral drug-resistance, long term side effects and to decide on the appropriate treatment choices, a comprehensive assessment of all contributing factors, medical and non-medical, is necessary. However, the relationship between treatment outcomes with disease markers and other contributing factors is not simple. To date, a model that accurately predicts the likelihood of disease progression or treatment failure in HIV infected patients does not exist. Extending our previous work in this area, we developed temporal Artificial Intelligence models based on Jordan-Elman networks to longitudinally follow viral surrogate markers together with demographics, biochemical and laboratory data to describe the drug-virus-host interactions in over 4000 HIV adult patients. In an international (multi-continent) study of HIV clinical and laboratory data, the profiles of drug-naïve as well as treated patients were evaluated during a 20 year follow-up. Validation of models on a subset of this cohort (n=595) estimated the sensitivity and specificity of treatment success/failure, under different management modalities for individual patients. ROC-curves predicted: virologic success from baseline (ROC=0.871) in drug-naïve previously non-treated patients, switch from virologic success/ failure to failure/success if ever and when (ROC=0.625), switch to virologic success/failure from failure/success within 6 months (ROC=0.722) following a previous switch. This tool may be helpful in the design of longitudinal clinical trials.

Adult↗

Seronegative HIV-2 carriers in India.

The discordant cases of seronegative, but culture and proviral HIV-2 DNA positive were found in Mumbai, India. This was corroborated by the successful isolation of HIV-2-RNA in culture medium, HIV-2 cDNA sequence determination and the detection of the antigen. The sequence of the isolated HIV-2 genomic RNA does not seem to be altered to the extent that the change will alter antibody binding. Furthermore, antibody from the same individual (even at 8 months from initial sampling) from whom HIV-2 was isolated did not react with the antigen of this strain. Those evidences imply that extremely low or non-production of the antibody may be due to suboptimal immune stimulation due to extremely slow HIV-2 replication. This low virus-load may be responsible for the negative antibody results in the HIV-2 carriers.

Carrier State↗

Cyclospora infection in acquired immunodeficiency syndrome.

BACKGROUND: Diarrhea is a common clinical manifestation of human immunodeficiency virus (HIV) infection. The important protozoan pathogens causing diarrhea include cryptosporidium, microsporidium, Isospora belli and cyclospora besides giardia lamblia and entamoeba histolytica. OBJECTIVE: The objective of the present study was to determine the incidence of cyclospora (a coccidian protozoan) infection in HIV infected patients. METHODOLOGY: Faecal smears were stained by modified acid fast staining method to demonstrate oocysts of cyclospora. RESULTS: Out of 334 faecal specimens which were studied, cyclospora were identified in 22 cases (6.6 percent); and in 50 percent of the patients, there was a mixed infection with another protozoan parasite namely cryptosporidium. CONCLUSION: Identification of this parasite is important because cyclosporiasis can be treated with trimethoprim-sulfamethoxazole. Outbreaks of cyclospora infection have been linked to waterborne transmission. Though adequately chlorinated water is free of coliforms, it can still contain cyclospora.

AIDS-Related Opportunistic Infections↗

Interleukin-9 receptor alpha chain mRNA formation in CD8+ T cells producing anti-human immunodeficiency virus type 1 substance(s).

A search for gene(s) associated with anti-human immunodeficiency virus type 1 (HIV-1) activity of CD8+ T cells was attempted using molecular cloning and the relation between the anti-HIV activity of CD8+ T cells and the interleukin-9 receptor alpha chain (IL-9R-alpha) mRNA expression from the cDNA clones obtained was examined. The anti-HIV-1 activity of CD8+ T cell culture supernatants was assessed by measuring the level of HIV-1 replication of a CD4+ T cell line transfected with an infectious HIV-1 DNA clone. IL-9R-alpha mRNA was assayed by reverse transcriptase-polymerase chain reaction (RT-PCR). Of 5 cases showing high level of anti-HIV-1 activity (more than 80% suppression of HIV-1 replication), the mRNA was detected in 4 cases. Of 10 cases showing low level of anti-HIV-1 activity (less than 80% suppression of HIV-1 replication), the mRNA was detected in one case. Soluble recombinant human IL-9 receptor (rhIL-9sR) did not suppress HIV-1 replication at a concentration of 1 microgram/ml. These data suggest that the IL-9R-alpha mRNA formation in CD8+ T cells may correlate with and play some role in the anti-HIV-1 activity of CD8+ T cells from HIV-1-infected individuals.

CD4-Positive T-Lymphocytes↗

The epidemiology of HIV in India.

India is the first country outside Africa where an HIV-2 epidemic is running in parallel to an HIV-1 epidemic, resulting in a significant proportion of double infections. HIV is spreading rapidly, mainly by heterosexual contact, but also among intravenous drug users. Genetic analyses of the HIV variants circulating in India point towards HIV-1 and HIV-2 having been introduced into the country recently.

Adult↗

Genetic analysis of human immunodeficiency virus type 1 and 2 (HIV-1 and HIV-2) mixed infections in India reveals a recent spread of HIV-1 and HIV-2 from a single ancestor for each of these viruses.

DNA sequences encoding the surface envelope glycoproteins of human immunodeficiency virus type 1 (HIV-1) and type 2 (HIV-2) were amplified by PCR from uncultured peripheral blood mononuclear cells obtained from patients with serologically defined HIV-1/HIV-2 mixed infections from Bombay, India. HIV-1-specific PCR products were obtained in seven of seven randomly chosen doubly reactive cases, while HIV-2-specific sequences were detected in five of seven cases (71%). DNA sequence analysis showed that the HIV-1 gp120 coding sequences were closely related to each other (nucleotide sequence divergence of between 3.1 and 6.8%). Phylogenetic tree analysis placed the Indian strains within the C subtype of HIV-1, being most similar to sequences previously found in East and South Africa. The HIV-2 sequences were also closely related to each other, with an overall sequence divergence of between 5.6 and 10.5%. The low level of nucleotide divergence among Indian HIV-1 and HIV-2 sequences suggests a fairly recent introduction of each virus into this population from a single point of entry in each case. The HIV-2 sequences reported here represent the first analysis of Asian HIV-2 strains and confirm the serological pattern previously detected in India. These data show that a substantial spread of HIV-2, together with HIV-1, has appeared outside Africa in a population hitherto unexposed to HIV. These findings imply that further spread of HIV-2 worldwide is to be expected and have important implications for future vaccine and therapy development.

Acquired Immunodeficiency Syndrome↗

Sequence analysis of V3 loop region of HIV-1 strains prevalent in India.

The third variable (V3) domain of human immunodeficiency virus type 1 (HIV-1) env gene has been found to elicit type-specific neutralizing antibodies as well as a cytotoxic and helper T-cell response in both humans and animals. We analyzed the V3 domain of 8 HIV-1 isolates from India by using polymerase chain reactions. The V3 loops of 7 Indian isolates contained the apical tetra peptide GPGQ, while the V3 loop of one Indian isolate carried the apical tetra peptide GPGK. The amino acid sequences of the seven Indian isolates were closely related to each other, with an average of the nucleotide sequence homology of 96.0% (94.6 to 97.6%). The marked relatedness of the amino acid sequences among the seven Indian HIV-1 isolates indicated a recent and very rapid spread of this HIV-1 variant in Bombay. The amino acid sequence of the C2/V3 region of env gene of the 7 Indian isolates were homologous to the C subtype reported by Meyers et al. These findings could be useful in assessing the sources of infection and developing an AIDS vaccine.

Amino Acid Sequence↗

HIV-1 and HIV-2 infections in a high-risk population in Bombay, India: evidence for the spread of HIV-2 and presence of a divergent HIV-1 subtype.

A high-risk population (patients of a sexually transmitted disease clinic and the GT hospital in Bombay) was tested for antibodies against HIV-1 and HIV-2. Among 405 serum samples, 226 had previously been classified HIV-positive in India using different locally available enzyme-linked immunosorbent assay (ELISA) tests. The serology of 179 samples was unknown. All 405 samples were tested at the Georg-Speyer-Haus (GSH) with the Pasteur HIV-1/2-Combi-ELISA. Positive samples were further analyzed with HIV-1 and HIV-2 Western blot kits from Dupont and Pasteur, respectively. A very high seroprevalence of HIV was found in this population. Among the 179 unscreened samples, 69 (38.5%) were positive in the ELISAs as well as the Western blots for HIV-1 or HIV-2. Among the prescreened samples, only 174 (77%) were confirmed HIV-positive. Altogether, 243 of 405 sera were HIV-positive. Of these, 184 (76%) were reactive with HIV-1, 10 (4%) were reactive with HIV-2, and 49 (20%) had dual reactivity to HIV-1 and HIV-2. Previous data from the Indian Council of Medical Research had already suggested a possible high prevalence of HIV-1 in India. Our results confirm this view. The finding of a substantial spread of HIV-2 infection was, however, totally unexpected in India, but confirms our previous study which had already demonstrated the existence of HIV-2 in this country. Asia can thus no longer be considered free of HIV-2, and testing for HIV-2 appears mandatory, at least in India.(ABSTRACT TRUNCATED AT 250 WORDS)

Acquired Immunodeficiency Syndrome↗