The duration of human immunodeficiency virus (HIV-1) infection prior to the development of AIDS is variable, and for most patients the exact time of infection is not known. A group of 38 ...HIV-1-infected subjects was tested while asymptomatic for comparative cytotoxic lymphocyte responses to the Gag and envelope antigens of HIV-1. Twenty of the 38 patients had no detectable primary cytotoxic T lymphocyte (CTL) response to Gag, and this was associated with a relative risk of 1.89 for progression to ARC or AIDS during the subsequent 3 to 40 months of observation when compared with patients who had Gag-specific CTL activity at the beginning of the observation period. In contrast, no significant association was observed between envelope-specific cytotoxic activity and disease progression. Other patient characteristics, including CD4+ T lymphocyte counts and antibody levels to the p24gag protein, measured at the start of observation, did not correlate with disease progression during the observation period. This suggests that the anti-Gag CTL response may be protective during HIV-1 infection.
A retrovirus belonging to the family of recently discovered human T-cell leukemia viruses (HTLV), but clearly distinct from each previous isolate, has been isolated from a Caucasian patient with ...signs and symptoms that often precede the acquired immune deficiency syndrome (AIDS). This virus is a typical type-C RNA tumor virus, buds from the cell membrane, prefers magnesium for reverse transcriptase activity, and has an internal antigen (p25) similar to HTLV p24. Antibodies from serum of this patient react with proteins from viruses of the HTLV-I subgroup, but type-specific antisera to HTLV-I do not precipitate proteins of the new isolate. The virus from this patient has been transmitted into cord blood lymphocytes, and the virus produced by these cells is similar to the original isolate. From these studies it is concluded that this virus as well as the previous HTLV isolates belong to a general family of T-lymphotropic retroviruses that are horizontally transmitted in humans and may be involved in several pathological syndromes, including AIDS.
The objective of the present study was to compare the efficacy and safety of two doses of SPV
30 in HIV asymptomatic patients. The study was designed as a randomized double-blind multicentre trial of ...two doses of SPV
30 (990 mg/d and 1980 mg/d) versus placebo. 145 previously untreated subjects with asymptomatic HIV infection (CDC group IV) and CD4 cell counts between 250 and 500 × 10
6/1 were recruited. There was a statistically significant difference in therapeutic failures between groups in favor of SPV
30 990 mg including decreases of CD4 cell count < 200 × 10
6/1 and/or number of clinical aggravations (progression to AIDS or AIDS related complex). The treatment groups differed statistically in the rate of disease progression also in favor of SPV
30 990 mg/d. Fewer patients receiving SPV
30 990 mg/d had at the end an increase of viral load greater than 0.5 log (
P = 0.029). No severe side-effects were reported in the 3 groups. From these results we conclude that SPV
30 990 mg/d has beneficial effects in HIV asymptomatic patients and appears to delay the progression of HIV disease.
A strain of lymphadenopathy associated retrovirus (LAV) passaged in vitro was used to infect a lymphoblastoid cell line obtained by transformation with Epstein-Barr virus of B lymphocytes from a ...healthy donor. The virus produced from this line (B-LAV) was also able to grow at a high rate in some other lymphoblastoid lines and in a Burkitt lymphoma line. This adapted strain retained the biochemical, ultrastructural, and antigenic characteristics of the original strain, as well as its tropism for normal T4$^{+}$ lymphocytes. It is thus possible to grow LAV in large quantities that can be used for the preparation of diagnostic reagents. The interaction between such a human retrovirus and Epstein-Barr virus, a DNA virus, may have some implication for the pathology of the acquired immunodeficiency syndrome and related diseases.
Objective: To report on the unexpected improvement in major biological surrogate markers (CD4 T‐cell count, HIV RNA viral load, and apoptosis level) during the periods of ‘brown sugar’ heroin ...intoxication (BSI) in 12 HIV‐1‐infected intravenous drug users, independently of their antiretroviral therapy, compared to the period of ‘brown sugar’ heroin withdrawal (BSW).
Methods: The patients were followed prospectively for a total of 417 months over 4 years. Twenty‐four episodes of BSI and 24 periods of BSW were analyzed.
Results: (1) BSI: the mean (±SE) duration was 9±1.8 months; at onset, the mean±SE CD4 T‐cell count was 401±88/mm3; at the end, an absolute increase of 346 CD4 T‐cells/mm3 and a CD4 T‐cell count relative variation of +131% was observed. Half of the patients showed an increase of CD4 T‐cell count of more than 90% during their follow‐up. The mean±SE of CD8 T‐cell count increased significantly by 108%. (2) BSW: the mean ±SE duration was 8.4±1.3 months; at onset, the mean ±SE CD4 T‐cell count was 695±78/mm3; at the end, an absolute decrease of 342 CD4 T‐cells/mm3 and a CD4 T‐cell count relative variation of −52% was observed. Half of the patients showed a decrease of CD4 T‐cell count of more than 51%. (3) Circulating viral load appeared to be significantly higher during BSW (median: 452000 Eq RNA/mL) than during BSI (median: 52000 Eq RNA/mL); p<0.01. (4) Similarly, the apoptotic process affecting circulating lymphocytes was significantly lower during BSI than during BSW episodes. (5) The 4‐year mortality rate was 7%, compared with 36% in HIV‐positive former drug users (p<0.001).
Conclusions: Taken together, these features suggest that ‘brown sugar’ heroin could have either immunomodulatory or antiretroviral properties. Confirmation of these findings and investigation of the role of the many substances in ‘brown sugar’ heroin are indicated.
The existence of distinct 69- and 100-kDa forms of 2-5A-synthetase in addition to the smaller (40 and 46 kDa) forms has recently been established. Using specific monoclonal antibodies we investigated ...the induction, synthesis, and activity of 69- and 100-kDa 2',5'-oligoadenylate (2-5A) synthetases in interferon-treated human Daudi cells. Although induction of these synthetases is detectable in cells treated with as little as 1-5 units/ml of human alpha-interferon, higher concentrations are required for maximum synthesis of the 100 kDa than the 69-kDa protein. At 5 units/ml of interferon, enhanced synthesis of both proteins is detectable at 4 h with maximum synthesis occurring between 8 to 12 and 12 to 16 h for 69- and 100-kDa 2-5A-synthetases, respectively. At 24 h after addition of interferon, synthesis of these synthetases declines due to a decrease of active interferon in the culture medium. The synthesis of both synthetases is blocked by actinomycin D, and the half-life of these proteins is estimated to be 8 h. The activities of immunoaffinity purified 69- and 100-kDa synthetases are dependent on double-stranded (ds)RNA but show different requirements for optimum concentration of dsRNA and pH of the reaction. The apparent Km of 69- and 100-kDa synthetases for ATP is 1.7 X 10(-3) M and 3.6 X 10(-3) M, respectively. At optimum conditions for the activity of these enzymes, the pattern of 2',5'-linked oligoadenylates synthesized are different, the 69-kDa protein synthesizing higher oligomers than the 100-kDa species. Taken together, these results indicate that the 69- and 100-kDa 2-5A-synthetases are distinct proteins each with specific characteristics of induction and enzymatic activity.
The major envelope glycoprotein of the causative agent of Acquired Immune Deficiency Syndrome (AIDS) lymphadenopathy-associated virus (LAV) has been identified and characterized. The glycoprotein has ...an apparent molecular weight of 110,000–120,000 under denaturing conditions in polyacrylamide gel electrophoresis. Upon deglycosylation by a specific endoglycosydase,its size is reduced to 80,000. Cellular precursors of this glycoprotein have been detected with apparent molecular weight of 150,000 and 135,000. Nearly all AIDS and pre-AIDS patients have detectable antibodies against this viral glycoprotein.
The neutralization properties of three independent HIV-2 isolates were examined in comparison with four diverse HIV-1 strains. Human sera containing antibodies specific to HIV-2 can cross-neutralize ...HIV-1. By contrast, HIV-1 sera are group-specific and have no neutralizing effect on HIV-2. Therefore, HIV-2 antigens may be important components for the development of broadly cross-protective AIDS vaccines.
We performed a longitudinal study (mean follow-up 19.5 months, range 3 to 42 months) in 18 consecutive children with clinical symptoms of LAV/HTLV III infection. Twelve patients were born to mothers ...infected with LAV/HTLV III, and six were infected by blood products administered during the first weeks of life. Immunologic studies included lymphocyte markers, in vitro responses to mitogens and antigens with corresponding skin tests, and antibody response with isoagglutinins, post-vaccination antibodies, and Candida. A serologic profile of antibody to GP110, P18, and P25 LAV/HTLV III antigens by radioimmunoprecipitation assay was also performed. The antigen-induced proliferative responses were normal in 10 patients who had a stable course, but were profoundly impaired in eight others who died or had poor condition with opportunistic infections. These in vitro measurements were well correlated with antigen skin tests. An abnormal antibody response to antigens, a low level of isoagglutinins, and a peculiar profile of LAV/HTLV III antibodies were also frequently observed in these eight patients. These measurements appear to be of prognostic value because they were noticed soon after onset of clinical symptoms.
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