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Query: UMLS:C0019693 (HIV)
 170,526 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

An increasing number of AIDS cases occur each year in West Virginia despite its small urban population. From January 1984 to March 1991 at the Marshall University based multispecialty internal medicine group (the University Physicians in Internal Medicine), 66 HIV-infected persons were treated, most of whom are native West Virginians and always resided in the state. The study group consisted of 61 men and 5 women; four-fifths of the men are homosexual/bisexual and one-seventh used intravenous illicit drugs. Four women acquired infection heterosexually and one from transfusion. Twenty-eight patients never had any opportunistic infection (OI) and 38 experienced at least one OI, usually Pneumocystis carinii Pneumonia. About two-fifths of patients had CD4 counts less than 200 cells/cmm at their initial examination. Three-fourths of patients received AZT, six ddI, and most aerosolized pentamidine. Nineteen patients have died, all of whom suffered at least one OI. The mean interval until death from HIV infection and from AIDS was about 27 and 11.5 months, respectively.
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PMID:Characteristics and outcome variables of HIV cases at a university-based medical practice. 155 6

There is considerable consensus regarding the entity, aetiology, and assessment of HIV-1-caused cognitive impairment. Early fears that this would be very common, and early in onset, have not been realized. Research and clinical criteria should reflect current statistical standards. The large cohorts, broad test batteries and repeated testing of population samples provide a special opportunity to resolve perennial questions regarding the relationship between mood, health, and cognitive functions. It appears that AZT prevents mild cognitive impairment associated with HIV-1, though there is no strong evidence that it treats frank HIV-1 dementia complex. The management of patients with dementia requires proper consideration, as even if the incidence of HIV-1 dementia complex is only 5-10%, this is still a substantial number of patients for population centres with large numbers of people with HIV and AIDS. The distressing nature of this condition, combined with the specialized management required for HIV itself, make it advisable that more nurses with psychiatric training are employed in wards or units specializing in HIV.
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PMID:Neuropsychological aspects of HIV infection. 156 30

We performed motor tests (most rapid alternating movements [MRAMs] of index fingers and most rapid contractions [MRCs] of voluntary isometric index finger extensions) in HIV-positive patients with (group 1) and without (group 2) AZT treatment over a 6-month period. Whereas MRAMs remained uninfluenced, MRCs showed a clear improvement in the treated group and a decline in the nontreated group, according to the T helper cell counts. MRCs were not only a sensitive test procedure for detecting subclinical lesions in HIV-positive patients, but also a reliable therapy control measurement.
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PMID:Improvement of motor performance of HIV-positive patients under AZT therapy. 156 49

Novel phosphate triester derivatives of 3'-acetylthymidine, and of the anti-HIV nucleoside analogue AZT have been prepared by phosphorochloridate chemistry. These materials are designed to act as membrane-soluble pro-drugs of the bio-active free nucleotides. In particular, novel glycolate and lactate phosphate derivatives have been prepared. In vitro evaluation revealed the AZT compounds to have a pronounced and selective antiviral effect, the magnitude of which varied considerably with the nature of the phosphate blocking group.
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PMID:Synthesis and anti-HIV activity of some novel lactyl and glycolyl phosphate derivatives. 156 87

Because the time from primary infection to symptoms in human immunodeficiency virus type 1 (HIV-1) infection is typically 8-10 years, the use of surrogate markers to monitor disease progression and therapeutic efficacy is of interest. An acid dissociation procedure that disrupts the p24 antigen-antibody complexes found in early HIV-1 infection has greatly increased the sensitivity of p24 detection assays. The utility of p24 antigen after acid treatment as a surrogate marker of disease progression and therapeutic effect in asymptomatic HIV-infected subjects receiving zidovudine (AZT) was determined. After acid treatment, the sensitivity of p24 antigen detection increased fivefold. The proportion of subjects who were antigenemic increased over the 48-week follow-up in the placebo group; approximately 50% of subjects who were p24 antigen-positive at entry and who received AZT showed clearance or a greater than 50% reduction in baseline p24 antigen levels at 16 and 32 weeks. Thus, acid treatment of plasma may allow the use of p24 antigen as a marker of disease progression and therapeutic response.
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PMID:Acid dissociation increases the sensitivity of p24 antigen detection for the evaluation of antiviral therapy and disease progression in asymptomatic human immunodeficiency virus-infected persons. 156 43

Ampligen, a mismatched double stranded RNA, is hypothesized to be an ideal base therapy for HIV disease to which other agents, such as the nucleoside analogue, AZT, can be advantageously added. The unique properties of Ampligen which support this hypothesis include activation of immune cells, inhibition of virus replication by inducing an antiviral cellular state and inhibition of growth of neoplastic cells. Ampligen is synergistic with other agents being used or being tested for use in HIV disease and is without toxicity.
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PMID:An hypothesis concerning optimal therapy in HIV disease. 156

A series of nucleosides were synthesized in which the 4'-hydrogen was substituted with either an azido or a methoxy group. The key steps in the syntheses of the 4'-azido analogues were the stereo- and regioselective addition of iodine azide to a 4'-unsaturated nucleoside precursor followed by an oxidatively assisted displacement of the 5'-iodo group. The 4'-methoxynucleosides were made via epoxidation of 4'-unsaturated nucleosides with in suit epoxide opening by methanol. Reaction-mechanism considerations, empirical conformation rules, NMR-based conformational calculations, and NOE experiments suggest that the 4'-azidonucleosides prefer a 3'-endo (N-type) conformation of the furanose moiety. When evaluated for their inhibitory effect on HIV in A3.01 cell culture, all the 4'-azido-2'-deoxy-beta-D-nucleosides exhibited potent activity. IC50's ranged from 0.80 microM for 4'-azido-2'-deoxyuridine (6c) to 0.003 microM for 4'-azido-2'-deoxyguanosine (6e). Cytotoxicity was detected at 50-1500 times the IC50's in this series. The 4'-methoxy-2'-deoxy-beta-D-nucleosides were 2-3 orders of magnitude less active and less toxic than their azido counterparts. Modifications at the 2'- or 3'-position of the 4'-substituted-2'-deoxynucleosides tended to diminish activity. Further evaluation of 4'-azidothymidine (6a) in H9, PBL, and MT-2 cells infected with HIV demonstrated a similar inhibitory profile to that of AZT. However, 4'-azidothymidine (6a) retained its activity against HIV mutants which were resistant to AZT.
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PMID:Synthesis and anti-HIV activity of 4'-azido- and 4'-methoxynucleosides. 157 38

In order to study the structure-activity relationships of dioxolane nucleosides as potential anti-HIV agents, various enantiomerically pure dioxolane-pyrimidine nucleosides have been synthesized and evaluated against HIV-1 in human peripheral blood mononuclear cells. The enantiomerically pure key intermediate 8 has been synthesized in nine steps from 1,6-anhydro-D-mannose (1), which was condensed with 5-substituted pyrimidines to obtain various dioxolane-pyrimidine nucleosides. Upon evaluation of these compounds, cytosine derivative 19 was found to exhibit the most potent anti-HIV agent although it is the most toxic. The order of anti-HIV potency was as follows: cytosine (beta-isomer) greater than thymine greater than cytosine (alpha-isomer) greater than 5-chlorouracil greater than 5-bromouracil greater than 5-fluorouracil derivatives. Uracil, 5-methylcytosine, and 5-iodouracil derivatives were found to be inactive. Interestingly, alpha-isomer 20 showed good anti-HIV activity without cytotoxicity. As expected, other alpha-isomers did not exhibit any significant antiviral activity. (-)-Dioxolane-T was 5-fold less effective against AZT-resistant virus than AZT-sensitive virus.
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PMID:Asymmetric synthesis of 1,3-dioxolane-pyrimidine nucleosides and their anti-HIV activity. 159 54

Several laboratories have shown that AZT-resistant variants of HIV-1 can be isolated from patients who have received prolonged therapy with this drug. Our laboratory has now been able to generate HIV-1 variants resistant to both AZT and ddI, in tissue culture, by using step-wise increases in the concentrations of each of these compounds over a 10-week period. This work has been performed by culturing wild-type clinical strains of HIV-1 as well as the HIV-3b laboratory strain of this virus under such conditions. The ID50 values obtained for the resistant viruses thus generated vary between 50-100 times above those of the parental wild-type strains in each case. Furthermore, we have identified several new mutation sites in the HIV-1 pol gene that are responsible for the observed resistance to AZT and ddI. We have not succeeded, however, in generating drug-resistant strains of HIV-1, under conditions in which several compounds or anti-viral agents were simultaneously present during the in vitro selection process. Combinations of drugs which failed to yield drug-resistant variants included AZT plus ddI, AZT plus alpha-interferon, and ddI plus alpha-interferon. These findings indicate that HIV drug resistance is less likely to occur in tissue culture when combinations of drugs are used, and provide rationale for the development of combination clinical trials for treatment of HIV-associated disease.
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PMID:Generation of nucleoside-resistant variants of HIV-1 by in vitro selection in the presence of AZT or DDI but no by combinations. 160 23

The effect of AZT on serum HIV p24 antigen and endogenous serum alpha interferon levels was studied in AIDS and ARC patients. Following administration of AZT there was a rapid decline in the serum levels of both HIV p24 antigen and alpha interferon. When AZT treatment was interrupted, the levels of both HIV p24 antigen and of interferon rapidly increased. These findings suggest that HIV or some other AZT sensitive microorganism is the inducer of interferon which is characteristically found in the serum of AIDS and symptomatic HIV infected patients. They also suggest that the rapid decline in interferon levels may underlie some of the symptomatic benefit that follows administration of AZT.
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PMID:Modulation of alpha interferon levels by AZT treatment in HIV-seropositive patients. 162 38


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