Human immunodeficiency virus type 1 Vpr interacts with antiapoptotic mitochondrial protein HAX-1.

Human immunodeficiency virus type 1 viral protein R (Vpr) is required for viral pathogenesis and has been implicated in T-cell apoptosis through its activation of caspase 3 and caspase 9 and perturbation of mitochondrial membrane potential. To understand better Vpr-mitochondria interaction, we report here the identification of antiapoptotic mitochondrial protein HAX-1 as a novel Vpr target. We show that Vpr and HAX-1 physically associate with each other. Overexpression of Vpr in cells dislocates HAX-1 from its normal residence in mitochondria and creates mitochondrion instability and cell death. Conversely, overexpression of HAX-1 suppressed the proapoptotic activity of Vpr.

Clinical course of children of human immunodeficiency virus-infected mothers in Taiwan.

The objective of this study was to describe the clinical courses of infants born to human immunodeficiency virus (HIV)-infected mothers in Taiwan. Eleven children, including 1 set of twins, born to 10 HIV-infected mothers were included in the study. HIV antibodies were assayed and HIV-1 polymerase chain reaction (HIV-PCR) or virus cultures were performed; HIV infection was established when there were at least 2 separate positive results of HIV-PCR or culture. Three sets of primers detecting LTR-gag, pol and env were used. The viral load of HIV RNA was measured and used as an indicator of the treatment response. Two of the children were HIV-infected and received combination therapy, including 2 kinds of nucleoside analogue reverse transcriptase inhibitors plus 1 protease inhibitor. Neither of these children exhibited HIV-related symptoms or signs during the study period. Both mothers of the infected children were Taiwanese and their HIV infection status was not known during pregnancy. In contrast, HIV infection was found in early pregnancy in the 4 women living in Taiwan who were from other countries, all of whom received prophylactic therapy. The other 4 mothers who did not transmit the infection to the infant were Taiwanese, 3 of whom were known to be HIV-seropositive during pregnancy. Based on these results, the vertical rate of transmission was 18% (2/11). Early detection of HIV-infected pregnancy is vital to reduce the incidence of HIV-infected births.

Decreased HIV transmission after a policy of providing free access to highly active antiretroviral therapy in Taiwan.

BACKGROUND: Taiwan established a nationwide surveillance system for human immunodeficiency virus (HIV) infection in 1989 and adopted a policy to provide all HIV-infected citizens with free access to highly active antiretroviral therapy (HAART) beginning in April 1997. This provided an opportunity to determine the effect of the widespread use of HAART on the evolution of the HIV epidemic. METHODS: We analyzed national HIV surveillance data. The HIV transmission rate was estimated by use of an exponential model of HIV epidemic evolution, with statistical projection over the interval between infection and detection to fit the surveillance data. RESULTS: By the end of 2002, the cumulative number of HIV-infected citizens in Taiwan had reached 4390 (0.019% of the total population). After free access to HAART was established, the estimated HIV transmission rate decreased by 53% (0.391 vs. 0.184 new cases/prevalent case-year [95% confidence interval, 31%-65%]). There was no statistically significant change in the incidence of syphilis, in the general population or among HIV-positive patients, during the same period. CONCLUSION: Providing free HAART to all HIV-infected citizens was associated with a 53% decrease in the HIV transmission rate and contributed to the control of the HIV epidemic in Taiwan.

Left ventricular dysfunction is associated with CD4 lymphocyte count rather than opportunistic infection in human immunodeficiency virus infection.

BACKGROUND AND PURPOSE: Left ventricular (LV) dysfunction is often found in the early stage of human immunodeficiency virus (HIV) infection and deteriorates with disease progression. CD4 lymphocyte count and opportunistic infection are the major indicators for the clinical staging of HIV infection. This study investigated the association of these indicators with LV dysfunction in the clinical course of HIV infection. METHODS: HIV-positive patients without cardiac manifestations consecutively admitted from May 1998 to April 1999 were enrolled in the study. Echocardiographic LV function evaluation and measurement of CD4 lymphocyte count were performed. Parameters for LV systolic and diastolic functions were compared between patients with CD4 lymphocyte count >or= 200/microL and those with CD4 < 200/microL. In patients with CD4 < 200/microL, LV function was further correlated with the presence or absence of opportunistic infections. RESULTS: Ninety eight HIV-positive patients including 52 with CD4 >or= 200/microL and 46 with CD4 < 200/microL were studied. One half of the 46 patients with CD4 < 200/microL had active opportunistic infections. We found that LV fractional shortening, ejection fraction, and isovolumic relaxation time were all significantly lower in the patients with CD4 < 200/microL compared with those with CD4 >or= 200/microL. Moreover, these LV systolic and diastolic dysfunctions were positively correlated with decreased CD4 lymphocyte count. In contrast, no difference was found in these parameters between patients with and without opportunistic infections. In multiple regression analysis, CD4 lymphocyte count was found to be the only factor for predicting the LV systolic and diastolic dysfunction. CONCLUSIONS: Both LV systolic and diastolic function deteriorate as the CD4 lymphocyte count decreases in HIV infection. Opportunistic infection seems to have a limited role in the pathogenesis of LV dysfunction in advanced HIV infection.

Current state of HIV/AIDS in Taiwan and reappraisal of early diagnostic value of serial and comparative analyses of western blot patterns of HIV infection.

Since Taiwan is not a member of the World Health Organization (WHO), the problems of human immunodeficiency virus (HIV) and acquired immunodeficiency syndrome (AIDS) in Taiwan are not well known to the world. In this report we summarize the trend and current status of HIV/AIDS in Taiwan and also analyze Western blot (WB) patterns. The application of serial and comparative WB analyses is important in establishing an early diagnosis of neonatal HIV infection. These analyses will be useful as well in evaluating the clinical status of adults infected with HIV in developing countries. When there are "indeterminate" WBs in adults with recent HIV infection, it is imperative to perform a WB weekly to attain the earliest possible diagnosis and treatment. Usually anti-gag antibodies, most frequently the anti-p24, are followed by anti-env and anti-pol antibodies. When the set point is attained, WB studies may also be repeated if the clinical status changes or if the patients are receiving highly active antiretroviral therapy (HAART). In the advanced stages of HIV infection, usually the anti-gag antibodies will fade first and then disappear, this occurs next in the anti-pol and in the anti-env antibodies. During HAART, viral replication is usually controlled and there will thus be a partial restoration of the immunological function that will induce changes in the antigen-antibody ratio and, in the end, this will result in changes in the WB patterns. In the mid 1980s all the hepatitis B immunoglobulin (HBIG) used in Taiwan was anti-HIV positive. However, follow-up ELISA and WB studies of the HBIG injected newborns proved that HBIG was anti-HIV positive but that there was no replicable HIV in HBIG. Monthly WB tests of newborns and anti-HIV positive mothers were used to differentiate HIV infection from the passive placental transference by comparing their WB patterns. Comparative WB analyses was also done between blood donors and recipients, and also between husbands and wives. In this 21st century there are probably more than 36 million people infected with HIV in the world and over 95% of them are in developing countries. In these countries people are much less able to respond to HIV/AIDS crisis. Not only are they unable to obtain such expensive anti-retroviral therapies they are also unable to carry out CD4 and viral load quantitative analyses. However, we believe that each country can afford to carry out WB studies. With experience, the reaction patterns can be interpreted easily and correlated with any clinical changes (Fig. 1).