To study the V beta T-cell repertoire in peripheral blood lymphocytes (PBL) during acute HIV syndrome by using several anti-V beta monoclonal antibodies (MAb) and to analyse its functionality by ...stimulating PBL with superantigens (SAg) such as Staphylococcus aureus enterotoxins.
Cytofluorimetric analysis of V beta T-cell-receptor expression was performed on PBL from eight patients with symptomatic, acute HIV-1 primary infection, showing a dramatic decrease of CD4+ PBL accompanied by a marked increase in activated/memory CD8+ T cells, and on 12 age- and sex-matched healthy controls. PBL were then isolated, stimulated with different SAg, anti-CD3 MAb or phytohaemagglutinin and cultured for 3 days. PBL capability to progress through cell cycle was studied by the classic cytofluorimetric method of bromodeoxyuridine incorporation and DNA staining with propidium iodide.
Despite the presence of a few expansions of some V beta families among CD8+ T lymphocytes, no gross alterations in T-cell repertoire were present in patients with acute HIV syndrome. Its functionality was maintained overall, as PBL responsiveness to SAg was well preserved. Interestingly, all CD8+ T cells, although bearing different V beta T-cell receptors, expressed marked signs of activation, i.e., CD45R0, CD38 and major histocompatibility complex class II molecules, and also high amounts of CD11a and CD18.
Our data suggest, at least in the early phases and in the acute form of the infection, that HIV is not likely to act as a SAg. However, further studies are needed to analyse other sites, such as lymph nodes, where HIV could exert other, significant effects, and to study the expression of other V beta families than those investigated here.
A vast majority of HIV-infected subjects who experience HIV acute seroconversion actually receive treatment. Open questions are how can we identify patients who will be slow progressors or long-term ...non progressors, and, as a consequence, do not require treatment.
An observational retrospective study on patients who experienced acute HIV seroconversion from August 1995 to June 2001, who are still alive and followed as outpatients at the Clinic of Infectious Diseases of Modena, Italy.
Twelve patients were studied. Five patients (45.4%) were treated during acute seroconversion, while 7 were not treated. Two of these seven subjects received antiretroviral treatment 12 and 26 weeks after acute seroconversion. All the untreated patients were in good viro-immunological condition 6 months after seroconversion, and 2 of them also after 3 and 7 years. Patients who were treated showed a significant daily increase in CD4/CD8 T cell ratio with longer time spent on therapy (0.04% increase per day longer on antiretroviral therapy, p=0.02).
This study suggests that treatment during primary HIV infection should not be considered in all patients. Randomized clinical trials enrolling patients with an asymptomatic primary HIV infection, with a high CD4 count and low HIV plasma viremia are needed to evaluate the indications for treatment in this subgroup of patients. On the other hand, this study confirms the good viro-immunological response obtained after treating patients during primary HIV infection.
Life expectancy of people with human immunodeficiency virus (HIV) is now estimated to approach that of the general population in some successfully treated subgroups. However, to attain these life ...expectancies, viral suppression must be maintained for decades.
We studied the rate of triple-class virologic failure (TCVF) in patients within the Collaboration of Observational HIV Epidemiological Research Europe (COHERE) who started antiretroviral therapy (ART) that included a nonnucleoside reverse-transcriptase inhibitor (NNRTI) or a ritonavir-boosted protease inhibitor (PI/r) from 1998 onwards. We also focused on TCVF in patients who started a PI/r-containing regimen after a first-line NNRTI-containing regimen failed.
Of 45 937 patients followed up for a median (interquartile range) of 3.0 (1.5-5.0) years, 980 developed TCVF (2.1%). By 5 and 9 years after starting ART, an estimated 3.4% (95% confidence interval CI, 3.1%-3.6%) and 8.6% (95% CI, 7.5%-9.8%) of patients, respectively, had developed TCVF. The incidence of TCVF rose during the first 3 to 4 years on ART but plateaued thereafter. There was no significant difference in the risk of TCVF according to whether the initial regimen was NNRTI or PI/r based (P = .11). By 5 years after starting a PI/r regimen as second-line therapy, 46% of patients had developed TCVF.
The rate of virologic failure of the 3 original drug classes is low, but not negligible, and does not appear to diminish over time from starting ART. If this trend continues, many patients are likely to need newer drugs to maintain viral suppression. The rate of TCVF from the start of a PI/r regimen after NNRTI failure provides a comparator for studies of response to second-line regimens in resource-limited settings.
The effect of amrinone on cardiac mitochondria of guinea pig was studied. It was found that amrinone does not change the respiratory function of cardiac mitochondria in the presence of ...α-ketoglutarate, whereas it inhibits glutamate oxidation. It was also found that amrinone strongly inhibits the activity of glutamic dehydrogenase of both crude extract from sonicated heart mitochondria and of purified preparation from bovine liver. This inhibition may explain the effect of amrinone on the oxidation of glutamate in mitochondria. These results are discussed in view of the contradictory effects of amrinone on cardiac and other tissues.
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