Life expectancy of patients with newly-diagnosed HIV infection in the era of highly active antiretroviral therapy.

BACKGROUND: Limited data are available on the life expectancy of patients with newly-diagnosed HIV infection in the era of highly active antiretroviral therapy (HAART). AIM: To provide such an estimate using a semi-parametric projection. DESIGN: Statistical analysis. METHODS: Follow-up data for patients newly diagnosed with HIV infection in Taiwan (HIV/AIDS Cohort) from 1 May 1997 to 30 April 2003 (n = 3351, only 1% are injecting drug users) were analysed using the Kaplan-Meier method. The survival function for an age- and gender-matched reference population was generated by the Monte Carlo method from the life-table of the general population. A constant excess hazard model was used to project long-term survival of HIV-infected patients, with linear extrapolation of a logit-transformed curve of survival ratio between HIV-infected patients and the reference population. RESULTS: The 5-year survival rate was 58% in patients who had already developed AIDS at diagnosis (AIDS group), and 89% in those who had not (non-AIDS group). Extrapolation yielded an expected mean survival time of 10.6 years after diagnosis for the AIDS group, and 21.5 years after diagnosis for the non-AIDS group. DISCUSSION: Our results support the expansion of HIV screening programs to minimize delay in diagnosis. With continuing advances in HAART, this estimate of survival in initially asymptomatic patients may be conservative. Their long life expectancy raises questions about what kind of preventive heath services should be offered. These should be addressed through further analysis of overall benefit and cost-effectiveness.

Re-emergence of meningococcal disease in Taiwan: circulation of domestic clones of Neisseria meningitidis in the 2001 outbreak.

The annual incidence of meningococcal disease (meningitis and septicaemia) in Taiwan was 0.94/10(5) population in 1953. It then declined to below 0.001 from 1980 to 1987, and re-emerged in 2000 with a rate of 0.07/10(5) population. In 2001 there was a further increase in incidence (43 cases, 0.19/10(5)). Of 43 isolates of Neisseria meningitidis available for this study, including 41 from patients treated in 2001, three (7.0%) were penicillin insensitive (MIC > or = 0.12 microg/ml), though all were beta-lactamase negative: 16 (37.2%) were resistant to trimethoprim-sulphamethoxazole (MIC > or = 4/76 microg/ml). Serogrouping and genotype analysis revealed nine domestic clones. None of the 43 patients had any relationship (travel or contact history) with the 2000 or 2001 Hajj pilgrimage. Epidemiological information and typing results suggested wide dissemination of a limited number of domestic clones of N. meningitidis, manifesting as serogroups W-135, B and Y. Two clones of serogroup W-135 involved in the outbreak were genetically distinct from the 2000 or 2001 Hajj-related W-135 clone.

Subtyping HIV-1 infections in Taiwan using peptide-enzyme immunoassay, reverse transcription-polymerase chain reaction, and sequencing.

BACKGROUND AND PURPOSE: There are important questions about epidemiologic transmission patterns as well as the possibility that genetic and phenotypic differences in human immunodeficiency virus type 1 (HIV-1) affect transmissibility, infectivity, pathogenicity, and response to therapy and vaccines. To delinate the genetic heterogeneity of HIV-1 and the association of subtypes with risk factors and location of residence in Taiwan, subtypes of HIV-1 in Taiwanese patients were identified and a phylogenetic study was performed. In addition, the accuracy of peptide-enzyme immunoassay (EIA) using serum samples from Taiwanese patients infected with HIV-1 was investigated. METHODS: Peptide-EIA was used to give a preliminary subtype of HIV-1-positive serum samples collected from different areas of Taiwan. Reverse transcription (RT)-polymerase chain reaction (PCR) and genetic sequencing were used to confirm the peptide-EIA results and to construct a phylogenetic tree. RESULTS: Among the 149 serum samples, 98 were subtype B (66%), 38 subtype E (25%), two subtype Thai-B (1.3%), one subtype G (0.7%), and one subtype C (0.7%). Comparison of risk factors for HIV-1 infection and subtype revealed that most B subtype infections (59/98) occurred in homosexual or heterosexual patients, whereas 28 of 38 E subtype infections occurred in heterosexual patients. The B/E ratio was significantly different (p < 0.05) in Taipei than in other areas of Taiwan. CONCLUSIONS: These results suggest that the predominant subtype of HIV-1 infection in Taiwan is B, followed by E, and that the distribution of HIV-1 subtypes in Taiwan is similar to that of Thailand, although the genetic sequences are distinct. Homosexuality, heterosexuality, bisexuality, and intravenous drug use behaviors affect the distribution of different subtypes of HIV-1 infection. Peptide-EIA in conjunction with RT-PCR and sequencing can provide accurate subtyping of HIV-1 infection.

Cardiac beriberi among illegal mainland Chinese immigrants.

The most common symptoms of chronic beriberi due to thiamine deficiency include dyspnoea, fatigue, leg oedema, lower extremity weakness and numbness. When collapsed peripheral circulation, metabolic acidosis, or shock are present, the disease has advanced from chronic beriberi to pernicious or fulminating beriberi heart failure (Shoshin beriberi). We report two patients with fulminating beriberi; both of whom had been incarcerated at a detention centre for 5 months before hospitalization. A prolonged monotonous diet, low in thiamine, was a major risk factor in both patients. Thiamine deficiency should be considered for any patient with symptoms and signs compatible with beriberi.

Determination of human immunodeficiency virus type 1 subtypes in Taiwan by vpu gene analysis.

The genetic diversity of human immunodeficiency virus (HIV) type 1 (HIV-1) has been characterized mainly by analysis of the env and gag genes. Information on the vpu genes in the HIV sequence database is very limited. In the present study, the nucleotide sequences of the vpu genes were analyzed, and the genetic subtypes determined by analysis of the vpu gene were compared with those previously determined by analysis of the gag and env genes. The vpu genes were amplified by nested PCR of proviral DNA extracted from 363 HIV-1-infected individuals and were sequenced directly by use of the PCR products. HIV-1 subtypes were determined by sequence alignment and phylogenetic analysis with reference strains. The strains in all except one of the samples analyzed could be classified as subtype A, B, C, E, or G. The vpu subtype of one strain could not be determined. Of the strains analyzed, genetic subtypes of 247 (68.0%) were also determined by analysis of the env or gag gene. The genetic subtypes determined by vpu gene analysis were, in general, consistent with those determined by gag and/or env gene analysis except for those for two AG recombinant strains. All the strains that clustered with a Thailand subtype E strain in the vpu phylogenetic analyses were subtype E by env gene analysis and subtype A by gag gene analysis. In summary, our genetic typing revealed that subtype B strains, which constituted 73.8% of all strains analyzed, were most prevalent in Taiwan. While subtype E strains constituted about one-quarter of the viruses, they were prevalent at a higher proportion in the group infected by heterosexual transmission. Genetic analysis of vpu may provide an alternate method for determination of HIV-1 subtypes for most of the strains, excluding those in which intersubtype recombination has occurred.

An epidemic of enterovirus 71 infection in Taiwan. Taiwan Enterovirus Epidemic Working Group.

BACKGROUND: Enteroviruses can cause outbreaks of hand-foot-and-mouth disease (characterized by vesicular lesions on the hands, feet, and oral mucosa) or herpangina, usually without life-threatening manifestations. In 1998 an epidemic of enterovirus 71 infection caused hand-foot-and-mouth disease and herpangina in thousands of people in Taiwan, some of whom died. METHODS: We assessed the epidemiologic aspects of this outbreak. Cases of hand-foot-and-mouth disease or herpangina in ambulatory patients were reported to the Taiwan Department of Health by a mean of 818 sentinel physicians. Severe cases in hospitalized patients were reported by 40 medical centers and regional hospitals. Viruses were isolated by 10 hospital laboratories and the department of health. RESULTS: The sentinel physicians reported 129,106 cases of hand-foot-and-mouth disease or herpangina in two waves of the epidemic, which probably represents less than 10 percent of the estimated total number of cases. There were 405 patients with severe disease, most of whom were five years old or younger; severe disease was seen in all regions of the island. Complications included encephalitis, aseptic meningitis, pulmonary edema or hemorrhage, acute flaccid paralysis, and myocarditis. Seventy-eight patients died, 71 of whom (91 percent) were five years of age or younger. Of the patients who died, 65 (83 percent) had pulmonary edema or pulmonary hemorrhage. Among patients from whom a virus was isolated, enterovirus 71 was present in 48.7 percent of outpatients with uncomplicated hand-foot-and-mouth disease or herpangina, 75 percent of hospitalized patients who survived, and 92 percent of patients who died. CONCLUSIONS: Although several enteroviruses were circulating in Taiwan during the 1998 epidemic, enterovirus 71 infection was associated with most of the serious clinical manifestations and with nearly all the deaths. Most of those who died were young, and the majority died of pulmonary edema and pulmonary hemorrhage.

Immunogenicity and reactogenicity of two recombinant hepatitis B vaccines in healthy adolescents on two-dose schedule.

This is an open, randomized study to compare the immunogenicity and reactogenicity of two recombinant hepatitis B virus (HBV) vaccines. The HBV-NF is a new formulation with a new adjuvant phenoxyethanol which replaced the conventional adjuvant of a commercially available recombinant HBV vaccine (Engerix-B). These two vaccines had the same 20 micrograms hepatitis B surface antigen (HBsAg). They were administered to the deltoid muscle of 116 healthy adolescents, aged between twelve and eighteen years, according to the 0, 6-month schedule. Serum was taken at month 0, 1, 6, and 7. Antibody to HBsAg was tested by radioimmunoassay. Geometric mean titers of both vaccines displayed no significant difference at month 1, 6, and 7. Following the second dose of vaccine, the seroprotection titer (10 mIU/ml) rates at month 7 were 90.9% in HBV-NF and 93.4% in Engerix-B, respectively (p = 0.43). The incidences of local and general adverse reactions were from 3% to 7% without significant difference between the two vaccines and the reactions were all mild and tolerable. Based on this study, regimens of this two-dose schedule proved to be safe and immunogenic, which may provide a cost-effective alternative for HBV mass vaccination program in adolescents.

HIV 10 Years Later - Where Do We Stand Now?. 10th international aids meeting, yokohama.

A wide variety of up-to-date results and knowledge were presented at the 10th International AIDS Meeting, Yokohama. Epidemiologically, most interest was focused on the discovery of a new HIV subtype O, which cannot be reliably detected by currently available ELISA kits. Clinically, it is gradually appreciated that one single most important parameter is the viral load; the extent of viral load can help explain many clinical observations. Another eye-catching finding was the report of a clinical follow-up of a group of long-term nonprogressors. If the underlying operative mechanism can be elucidated, we can learn the necessary elements for halting HIV infection progression. Therapeutically, the trend has shifted to combination therapy, preferentially 3-drug combination of 2 RT inhibitors and 1 protease inhibitor. For the vaccine development, many novel vectors were introduced, but their potentials are unknown at present. The successful application of single-cell in situ PCR has changed our perception of HIV infection. This powerful technique can detect a single viral genome inside cells and revealed that a large proportion of cells already harbor HIV genomes soon after the entry of HIV into the body. A direct viral effect may fully explain subsequent T cell depletion without invoking a lot of indirect mechanisms such as apoptosis. Copyright 1995 S. Karger AG, Basel

Molecular subtypes of env sequences around V3 region of human immunodeficiency virus type 1 in Taiwan.

Samples of peripheral blood mononuclear cells (PBMC) were collected during 1990-91 from seropositive healthy, male HIV-1 carriers visiting Taipei Venereal Disease Control Center, and a male AIDS patient admitted to a general hospital. The V3 and its flanking nucleotide (nt) sequences in their DNA were amplified by polymerase chain reaction (PCR) and compared with those of known HIV-1 prototypes. The nt sequences obtained from 21 individuals (e.g., TW92) clustered as Group A, which were highly homologous (95.6-99.5%) to that of HXB2 virus while those from 6 individuals (TW90, TW91, TW97, TW99, TW102 and TW104) were classified as Group B showing low similarities (73.2-84.2%) to those of HXB2 and moderate similarities (80.7-90.0%) to those of SC and Bangkok (BK) viruses. By comparison of their deduced amino acid sequences with those of consensus sequences for subtypes A-F as defined by Myers et al. (1993), both Groups A and B viruses (except TW102) together with those of HXB2, SC and BK viruses could be identified as members or variants of subtype B, and the TW102 virus as a member of subtype E viruses. Individuals with the Group A viruses included 4 homosexual and 17 heterosexual Taiwanese males, 2 of the latter having a history of i.v. drug abuse. Among individuals with Group B viruses, those with TW97, TW99, TW104 and TW91, who was an AIDS patient, were heterosexual Taiwanese males, whereas both TW90 and TW102 viruses were from individuals who were overseas heterosexual Chinese from Thailand, the former with a history of i.v. drug abuse and the latter without.

PIP: During 1990-1991 in Taipei, Taiwan, health workers took peripheral blood mononuclear cells from healthy HIV-1 infected males at the Taipei Venereal Disease Control Center and from a male AIDS patient at a general hospital. Researchers used the polymerase chain reaction (PCR) to examine the env sequences around the V3 loop of HIV-1 which is critical for binding of neutralizing antibody to HIV-1 and to compare the sequences with those of known HIV-1 prototypes. They also wanted to see whether the env sequences were the North American subtype (HXB2). The nt sequences from 21 men (TW92) clustered as Group A and were very homologous (95.6-99.5%) to that of HXB2 virus. Those from the remaining six men were grouped together as Group B and were not like HXB2 virus (73.2-84.2%). The nt sequences from these six men were TW90, TW91, TW97, TW99, TW102, and TW104. They were most closely related to SC and Bangkok (BK) viruses (85.7% and 78.1%, respectively). When the researchers compared the deduced amino acid sequences with those of sequences for subtypes A-F (as defined by Myers et al.) both group A and B viruses (except TW102) and HXB2, SC, and BK were similar to subtype B (71.6-95.3% homologous). The TW102 virus was a member of subtype E viruses (95.3% homologous). The group A viruses belonged to four homosexual and 17 heterosexual Taiwanese, two of the 17 had a history of IV drug use. The group B viruses belonged to four heterosexual Taiwanese, one of whom had AIDS, and two overseas heterosexual Chinese from Thailand, one of whom had a history of IV drug use. These findings demonstrate the need for rapid, efficient methods (e.g., PCR technology) to monitor the incidence and prevalence of different HIV-1 variants so scientists can select vaccines for effective anti-HIV immunity in different geographic regions.

Relationship of hepatitis B virus infection to human immunodeficiency virus type 1 infection.

The Multicenter AIDS Cohort Study (MACS) was designed to study the natural history of human immunodeficiency virus type 1 (HIV-1) infection, including the relationship between hepatitis B virus (HBV) and HIV-1 infection. In total, 4954 homosexual men were recruited from April 1984 through March 1985 and have been followed up thereafter every 6 months. Hepatitis B surface antigen and hepatitis B core antibody were tested for at the first visit by RIA or EIA; HIV-1 antibody testing was done at each visit by ELISA and confirmed by Western blot assay. The role of HBV infection in HIV-1 seroconversion was studied by stratification for sexual behavior and disease visit by visit. The adjusted risk ratio was 2.02 for hepatitis B surface antigen carriers and 2.14 for hepatitis-immune cases compared with hepatitis B-susceptible subjects. Similar results were obtained using a logistic regression model. After taking into account changes in sexual behavior and disease over time, the authors conclude that past HBV infection remains suspect as a cofactor or as a surrogate for other factors associated with HIV-1 seroconversion.

Incidence of hepatitis among students at a university in Taiwan.

The incidence of hepatitis in a general open population of Asian adults was estimated for the first time in this study. A group of 2445 students were first tested when they enrolled at National Taiwan University in 1977; approximately one third were susceptible to hepatitis A and another third to hepatitis B. Most of these students (92%) were retested shortly before their graduation in 1981 to determine the frequency of serologic conversions and clinical hepatitis which had occurred in the 3 1/2 years since they had entered the university. Among 704 susceptible to hepatitis A, 12 (1.7%) had undergone serologic conversions, 33% of which were associated with clinical illness diagnosed as hepatitis. Among 738 susceptible to hepatitis B, 39 (5.3%) had undergone serologic conversions, 12.8% of which were associated with clinical hepatitis. The annual incidence of new infections was 0.5% for hepatitis A and 1.5% for hepatitis B. An additional eight students among the 17 who had clinical hepatitis had no associated conversion of hepatitis A or hepatitis B markers, and were considered to have non-A, non-B hepatitis. No factors could be identified which were predictive of hepatitis risk. No difference in incidence was observed according to sex, type of residence, place of food consumption, or receipt of acupuncture or blood transfusion. Among the 39 students who experienced hepatitis B infections while at the university, there were 2.7% who became hepatitis B surface antigen (HBsAg) carriers. Thus the carrier frequency following hepatitis B infection among Chinese adults is the same or lower than that among Caucasian adults.