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Background: To assess the association between the CD4 count and clinical diseases in a cohort of Thai patients.Methods: In all, 1902 patients who presented with human immunodeficiency virus (HIV) infection at the Chulalongkorn University Hospital in Bangkok were investigated.Results: At the time of presentation 295 (15.5%) patients had acquired immunodeficiency syndrome (AIDS) and there was a highly significant tendency for lower CD4 counts in this group (median 67/mm3) than in patients free of AIDS (median 369/mm3). A total of 757 patients had data available on follow-up and were free of AIDS at the first visit. During a median follow-up of 0.9 years, 110 developed AIDS or AIDS-related death (12.2/100 person years). Subjects with CD4 count < 200/mm3 at initial visit showed over a ninefold increase in risk of developing AIDS compared to subjects with levels > or = 500/mm3 (relative risk [RR] = 9.1; 95% CI: 5.4-16.0). The rate/100 person years was 47.1 compared with 6.0 in subjects with levels > or = 500/mm3. After adjusting for initial CD4 count, homosexual men showed over a twofold increase in risk of developing AIDS compared to heterosexuals (RR = 2.4; 95% CI: 1.6-4.4) and intravenous drug users (IVDU) showed nearly a twofold increase (RR = 1.8; 95% CI: 0.9-3.9). The increased risk in homosexual men persisted even after further adjustment for clinical stage (RR = 2.2; 95% CI: 1.3-3.7) but the increased risk in IVDU was attenuated (RR = 1.5; 95% CI: 0.7-3.2) although it remained increased albeit non-significantly. Men tended to progress faster to AIDS than women but the difference was not significant. However, the faster progression in homosexual men was seen even when compared to heterosexual men only.Conclusion: The rate of progression of AIDS according to CD4 count group at baseline in this Thai cohort is broadly comparable with Western cohorts. It appears that heterosexuals in Thailand show slower progression to AIDS than homosexual men. [ABSTRACT FROM AUTHOR]

Objective: To assess safety and tolerability of enfuvirtide, an antiretroviral, in Thai patients with advanced HIV-1 disease who have received antiretroviral treatment and failed on regimens that contain at least one of each antiretroviral (ARV) classes (PIs, NRTIs, and NNRTIs), or who have intolerance to previous antiretroviral regimens., Material and Method: An open-label non-comparative study of enfuvirtide used in salvage regimens along with the backbone antiretroviral therapy of choice in Thai HIV-1 experienced cases that have been treated with at least one of each available ARV classes., Results: Twenty-three patients were recruited from five participating centers. Seventeen patients (74%) completed 96 weeks of the treatment. Six patients prematurely withdrew from the present study in which three expired from HIV related complications, two withdrew consents, and one from adverse event. The most common adverse event is injection site reactions, which occurred in 22 patients. The manifestations and intensity varied from rash, erythema, edema, pain, induration, and bleeding at the injection sites, to inflammatory nodules. Most of the patients tolerated the treatment well. Enfuvirtide administered along with other antiretroviral combination provided a good control of the disease., Conclusion: Enfuvirtide was well tolerated by Thai patients who participated in the present study. The adverse events did not compromise the patient compliance.

Stavudine is a nucleoside analogue used for the treatment of HIV-1 infection, as part of highly active antiretroviral treatment. In developing countries, stavudine is used widely, owing to low cost and inclusion in generic fixed-dose combinations. In developed countries, stavudine is now rarely used, although it is highly effective. This is because newer drugs show lower rates of mitochondrial toxicities, such as lipoatrophy, peripheral neuropathy and lactic acidosis. In the development of stavudine, there was evidence that a dosage of 20-30 mg b.i.d. was effective, but the 40-mg b.i.d. dose gained regulatory approval. This review analyses the clinical trials conducted before and after the regulatory approval of stavudine, and shows that the dose of 30 mg b.i.d. has equivalent antiviral efficacy (given the caveats of meta-analysis), with some evidence of lower rates of peripheral neuropathy and lipoatrophy. With limited resources for HIV-1 treatment in developing countries, and only 25% of eligible patients receiving highly active antiretroviral treatment, low-cost treatment options such as stavudine still need to be pursued, if safety can be improved by dose optimisation.

INH preventive therapy (IPT) has been shown in several randomized controlled trials to reduce the risk of developing active TB in tuberculin skin test (TST) or purified protein derivative (PPD) positive HIV infected individuals. Detection of latent tuberculosis by TST and determination of factors associated with the PPD positivity in HIV-infected persons are important for the targeting of chemoprophylaxis. Six hundred asymptomatic and early symptomatic HIV-infected subjects attending the AIDS Clinic of the Chulalongkorn University Hospital, Bangkok, Thailand were enrolled in two randomized clinical trials of chemoprophylaxis against TB from December 1994 to December 1996. The availability of baseline characteristics, including TST reactivity, among these participants enabled a cross-sectional analysis of factors associated with PPD positivity. The results showed that 117 (19.5%) were PPD positive and 483 (80.5%) were PPD negative with ages 18-65 years (median 29 years). HIV exposure category was 46.2%, 34.5%, and 6.7% for heterosexual contact, commercial sex work, and homosexual and bisexual male contact respectively. The median CD4 cell count was 315/mm3 (range, 5-1,074/mm3). HIV exposure category and CD4 cell count were significantly associated with PPD status. Homosexual/bisexual contact had 3 times higher risk of PPD positivity than heterosexual contact (adjusted OR=2.9; 95% CI, 1.4-6.1) and risk of PPD positivity was higher among patients with CD4 cell counts of 200-500/ mm3 (adjusted OR=1.8; 95% CI, 1.0-3.1) and above 500/mm3 (adjusted OR=3.4; 95% CI, 1.7-6.7) when compared to patients with CD4 cell counts of less than 200/mm3. The HIV-infected persons in Bangkok with homosexual/bisexual contact are at higher risk for latent TB. Population-based tuberculin screening without accompanying HIV testing cannot be used to estimate the prevalence of actual latent TB in a population where HIV infection is widespread, such as in Thailand.

Only a small minority of people in the world infected with HIV will receive the benefits of the current advances in medical treatment. Planning is required to ensure that each country provides the best possible care allowed by its health resources. Relatively small amounts of money, if well spent, can go a long way towards reducing suffering and assisting death with dignity.

Objective: To evaluate the usefulness of T-cell subsets, beta-microglobulin (B2M), p24 antigen and anti-p24 antibodies as differentiating and prognostic markers in HIV-infected Thai patients., Design: Sixty-one HIV-infected patients in various stages of disease (six AIDS, three AIDS-related complex, 34 persistent generalized lymphadenopathy and 18 HIV-asymptomatic) were followed prospectively for 2 years. Patients were examined and immunological markers assessed every 6 months at least. Any HIV-related complications were treated symptomatically and clinical staging was re-evaluated at each visit. Due to financial constraints, none of the patients were given antiretroviral drugs., Methods: T-cell subsets were enumerated by indirect immunofluorescence using OKT4 or OKT8 for T-helper and T-suppressor cells, respectively. beta 2M and p24 antigen were quantified by enzyme-linked immunosorbent assay and anti-p24 antibodies were by immunoblot assay., Results: Our preliminary study revealed that the decrease in CD4+ T-cells or anti-p24 titre and the increase in p24 antigen or beta 2M correlated well with disease staging, as defined by the Centers for Disease Control. Absolute number and percentage of CD4+ T-cells, absolute number of CD8+ T-cells, beta 2M level and p24 antigen and anti-p24 antibody levels at entry could be used as reliable prognostic markers for HIV progression. The combination of p24 antigen with the number of CD4+ T-cells substantially increased the prognostic value, compared with either used alone., Conclusions: The annual rate of clinical progression from asymptomatic to symptomatic HIV infection in our study was 6.8%. The results we obtained in this preliminary study may be used as baseline data for planning future therapeutic interventions in Asian patients.

A 32-year-old homosexual man presented with headache and progressive right hemiparesis. CT scan revealed a heterogeneous ring-enhancing mass in the left parietooccipital lobe which proved to be astrocytoma. Clinicians should be aware of this new and unusual association of a cerebral glioma and acquired immune deficiency syndrome. Tissue examination is essential for proper diagnosis.

Strictly enforced antibiotic formulary restriction in combination with formulation of agreed guidelines for antibiotic use in common infection problems such as septicemia, febrile neutropenia, urinary tract infection, biliary sepsis, liver abscess, peritonitis, nosocomial pneumonia, soft tissue infection and purulent meningitis, generated a combined savings of 307,748.5 bahts or 13.5 per cent cost reduction over a 6 month period, and improved quality of use, appropriate 54.8 vs 67.5 per cent, statistically significance (P less than 0.002). Although this saving was offset in part by increased spending of unrestricted antibiotics, such as Penicillin and Gentamicin, an overall cost saving remained. In the months during the restrictions, no significant changes occurred regarding patients response and mortality. However, after the onset of the controls, it was revealed that antibiotics were more appropriately used afterwards. This study has shown, most importantly, that savings were achieved with no negative effect on good patient care. Moreover, the antibiotic use control was operationally successful, most house-staff and attending physicians, not only antibiotic evaluating team, have accepted the program in a very positive way. Overall, this program successfully achieved its initial goal, cost saving without compromising good medical practice. We are now continuing our program and also trying to modify so that it will be useful to all departments in the hospital.

The sensitivity, specificity and convenience of carrying out malaria diagnosis in acridine orange stained capillary tubes using a fluorescent microscope (the QBC system) was compared to screening for Plasmodia on conventional Giemsa stained thick smears. A dilution study revealed that the QBC is able to detect Plasmodia in as low a dilution as 5 organisms per ul. The QBC system was evaluated at a district hospital in Thailand. A preliminary study of 186 patients compared the QBC system to the routine malaria screening procedure (screening up to 30 microscopic fields on a thick smear). The sensitivity of the QBC was found to be 98.9% with a specificity of 94.4%. A second combined series of 465 febrile subjects were screened by thick smear and these results were compared to the QBC. 202 were positive for malaria on both QBC and thick smear. Sensitivity in this study was found to be 99.5% (202/203) and the specificity was 94.6% (248/262). When both series were combined, there were 14 QBC malaria positives that were not detected on thick smear, and 2 QBC malaria false negatives among the 651 patients studied. The parasite densities in these cases were between 10 and 320,000 organisms/microliters. The QBC system provided only a crude estimate of the level of parasitemia. The species of Plasmodia (P. falciparum and P. vivax) were correctly identified on QBC in 78% of cases.

Solid phase enzyme immunoassays (EIA) are widely used for the detection of infectious agents in body fluids such as stool specimens. However, we found that stool specimens contained substances which desorb from 50% to 68% of the immunoreactant from solid phase surfaces. This desorbing activity decreased the sensitivity of EIA systems for toxin A of C. difficile, rotavirus and adenovirus. The desorbing activity in stool specimens was partially heat labile at 56 degrees C for 30 min, was present in stool fractions corresponding to an estimated molecular weight of 25,000 and was shown to degrade solid phase protein. In addition, the desorbing activity was partially reversed by specific and nonspecific protease inhibitors. Thus, the desorption may reflect the enzymatic activity of stool proteases. The desorption was markedly reduced by diluting specimens in 50% fetal calf serum or an acid-protein buffer such as 0.25 M citrate buffer, pH 4.7, containing 5% bovine serum albumin. These diluents were shown to improve the recovery of toxin A of C. difficile, rotavirus and adenovirus in EIA systems for these antigens.

Complement profiles were sequentially studied in 183 Thai adults infected with Plasmodium falciparum. On the first day of admission, CH50, C1q, C4 and C3 were low in 65%, 8%, 19% and 62% of cases, respectively. All patients with low C1q or C4 also had low C3 and CH50. Simultaneous reduction of C1q, C4, C3 and CH50 were found in 10 instances. Factor B was not reduced in any of the patients indicating that only the classical pathway is activated during acute falciparum malaria infection. The incidence and the degree of hypocomplementaemia were higher in patients with cerebral, renal and hepatic complications although significant difference was seen only for C3. After 3-4 days of effective anti-malarial treatment, normalization of C1q and C4 was found in almost all instances whereas C3 and CH50 remained low in 27% and 54% of the cases, respectively. Normalization of C3 was achieved at 4 weeks after discharge while low CH50 still persisted. The reasons for the persistently low CH50 remain unknown.

Various autoantibodies were sequentially studied in 183 consecutive Thai adults infected with Plasmodium falciparum. On the first day of admission, 31.1% of the patients had positive fluorescent anti-nuclear antibodies (FANA) and 16.9% had positive smooth muscle antibodies (SMA). The incidences of positive FANA and SMA rose progressively with times when the patients returned for the 2 and 4 week follow-ups after discharge, although most of their malaria was cured. The majority of the positive FANA and SMA titres lay between 1:20 and 1:160. The positivity of the FANA and SMA did not correlate with the complications of malaria, nor the initial serum IgG or IgA levels. However, they significantly correlated with the initial hyper-IgM. More interestingly, almost all of the positive FANA were of the speckled type of nuclear staining. The antigen specificity of the speckled FANA were found not to be the double stranded DNA or the extractable nuclear antigens. The polyclonal B cell activation in active malarial infection was postulated.

The analysis of human B cell responses at the clonal level (limiting dilution assay) is still technically difficult. In the present study we report on a culture system that leads to activation, proliferation and differentiation into antibody-secreting cells (ASC) of about 90% of B cells from peripheral blood or spleen. In this system, B cells are cultured in the presence of a mutant subclone of the mouse thymoma EL4 for B cell activation and human T cell plus macrophage supernatant as source of proliferation and differentiation factors. ASC precursors generating clonal responses of IgM only, IgM plus IgG, or IgG only occurred at a ratio of about 6:3:1. The mean clone size was 380 cytoplasmic Ig+ cells; the mean amount of Ig secreted per clone was 20 ng. Furthermore, it has been found using this system that a considerable proportion of peripheral blood B cells from individuals with a history of malaria infection could generate clones of anti-malaria (Plasmodium falciparum) ASC (range of 0.1 to 1%, n = 6). In a control group of blood donors the corresponding frequencies were 10 times lower (range of 0.01 to 0.1%, n = 9). These results show that the EL4 culture system can be applied to the investigation of the human B cell specificity repertoire and of priming effects such as result from infectious disease.