Non-disclosure of HIV serostatus to sexual partners: Prevalence, risk factors and clinical impact in patients with HIV.

OBJECTIVE: To determine the prevalence, risk factors and impact of non-disclosure of HIV serostatus to sexual partners among HIV-positive patients at Siriraj Hospital, Bangkok. METHODS: We conducted a prospective observational study to enrol HIV-positive adults with one or more regular sexual partners during the past 3 months. We obtained personal information via anonymous questionnaire and clinical data of those receiving antiretroviral therapy (ART) for ≥12 months via chart-review. RESULTS: A total of 328 HIV-positive participants were enrolled. Approximately half were female and in the symptomatic HIV stage at diagnosis, with an average age 44.08 ± 8.59 years. Approximately one-third of participants (35.7%) reported that they had not disclosed their HIV serostatus to their sexual partners. The non-disclosure group had a higher rate of poor ART adherence owing to fear of revealing their HIV serostatus to their partner (12.0% vs. 1.9%; P < 0.001), as compared with the disclosure group. Rates of immunological and virological failure did not differ between groups. Multivariate analysis [adjusted odds ratio (OR); 95% confidence interval (CI); P-value] revealed having an occupation as a teacher (4.08; 1.40-16.61; P = 0.01) and reporting acquisition of HIV infection through blood transfusion (4.08; 1.31-12.68; P = 0.02) were independent risk factors. Furthermore, a longer duration of the sexual relationship (0.997; 0.994-0.999; P = 0.02), having a seropositive sexual partner (0.57; 0.33-0.99; P = 0.04), living in their partner's house (0.53; 0.31-0.90; P = 0.02) and having a higher mean Pictorial Thai Self-Esteem Scale (PTSS) score (0.62; 0.38-0.99; P = 0.05) were identified as independent protective factors. CONCLUSIONS: We found a high prevalence of HIV serostatus non-disclosure, which was associated with poorer ART adherence. Appropriately focusing interventions on high-risk populations with aforementioned risk factors is important for improved HIV care.

Peru-15 (Choleragarde(®)), a live attenuated oral cholera vaccine, is safe and immunogenic in human immunodeficiency virus (HIV)-seropositive adults in Thailand.

BACKGROUND: Many areas with endemic and epidemic cholera report significant levels of HIV transmission. According to the World Health Organization (WHO), over 95% of reported cholera cases occur in Africa, which also accounts for nearly 70% of people living with HIV/AIDS globally. Peru-15, a promising single dose live attenuated oral cholera vaccine (LA-OCV), was previously found to be safe and immunogenic in cholera endemic areas. However, no data on the vaccine's safety among HIV-seropositive adults had been collected. METHODS: This study was a double-blinded, individually randomized, placebo-controlled trial enrolling HIV-seropositive adults, 18-45 years of age, conducted in Bangkok, Thailand, to assess the safety of Peru-15 in a HIV-seropositive cohort. RESULTS: 32 HIV infected subjects were randomized to receive either a single oral dose of the Peru-15 vaccine with a buffer or a placebo (buffer only). No serious adverse events were reported during the follow-up period in either group. The geometric mean fold (GMF) rise in V. cholerae O1 El Tor specific antibody titers between baseline and 7 days after dosing was 32.0 (p<0.001) in the vaccine group compared to 1.6 (p<0.14) in the placebo group. Among the 16 vaccinees,14 vaccinees (87.5%) had seroconversion compared to 1 of 16 placebo recipients (6.3%). V. cholerae was isolated from the stool of one vaccinee, and found to be genetically identical to the Peru-15 vaccine strain. There were no significant changes in HIV viral load or CD4 T-cell counts between vaccine and placebo groups. CONCLUSION: Peru-15 was shown to be safe and immunogenic in HIV-seropositive Thai adults.

Oseltamivir and inhaled zanamivir as influenza prophylaxis in Thai health workers: a randomized, double-blind, placebo-controlled safety trial over 16 weeks.

OBJECTIVES: Long-term chemoprophylaxis using neuraminidase inhibitors may be needed during influenza epidemics but safety data are limited to several weeks. We sought to assess the tolerability of oseltamivir and zanamivir as primary prophylaxis over 16 weeks. METHODS: We conducted a parallel group, double blind, 2 (active drug) :1 (placebo) randomized trial of oral oseltamivir/placebo or inhaled zanamivir/placebo over 16 weeks in healthy, Thai hospital professionals at two Bangkok hospitals. The primary endpoint was study withdrawal due to drug-related (possibly, probably, definitely) serious or adverse events (AEs) graded ≥ 2. RESULTS: Recruited subjects numbered 129 oseltamivir/65 placebo and 131 zanamivir/65 placebo. A total of 102 grade ≥ 2 AEs were reported or detected in 69 subjects: 23/129 (17.8%) versus 15/65 (23.1%) (P=0.26), and 23/131 (17.6%) versus 8/65 (12.3%) (P=0.28). Intercurrent infections/fevers [26/102 (25.5%)], abnormal biochemistry [25/102 (24.5%)] and gastrointestinal symptoms [18/102 (17.6%)] were the most frequently reported AEs. There were no drug-related study withdrawals. Eight serious AEs were all due to intercurrent illnesses. Laboratory, lung function and ECG parameters were similar between drugs and placebos. CONCLUSIONS: Oseltamivir and zanamivir were well tolerated in healthy hospital professionals. Both drugs can be recommended for primary influenza prophylaxis for up to 16 weeks.

Predictors of poor clinical outcome of cryptococcal meningitis in HIV-infected patients.

The aim of this study was to identify baseline prognostic factors for poor clinical outcome of HIV-associated cryptococcal meningitis. We conducted a trial in Thailand and the USA comparing low- and high-dose concomitant use of amphotericin B and fluconazole for HIV-associated cryptococcal meningitis to amphotericin B followed by fluconazole. Subjects who were either alive and cerebrospinal fluid (CSF) culture-positive or dead were considered to have a poor outcome. At day 14, baseline characteristics associated with poor outcome included: low weight, high CSF cryptococcal antigen (CrAg) titre and low CSF white blood cell (WBC) count. At day 70, the associated baseline characteristics included: CSF CrAg titre >1:1024 and low Karnofsky performance status. Overall, consistent with published findings, low weight, high CSF CrAg titre and low CSF WBC counts at baseline were predictors for poor clinical outcome. In addition, we found that low Karnofsky performance status was predictive of poor outcome. Prompt management with appropriate antifungal therapy for this particular group of patients may improve the outcomes.

Nevirapine-associated hepatotoxicity was not predicted by CD4 count ≥250 cells/µL among women in Zambia, Thailand and Kenya.

OBJECTIVE: The aim of the study was to determine risk factors for developing severe hepatotoxicity (grade 3 or 4 hepatotoxicity) and rash-associated hepatotoxicity (rash with ≥ grade 2 hepatotoxicity) among women initiating nevirapine-based antiretroviral therapy (ART). METHODS: The Non-Nucleoside Reverse Transcriptase Inhibitor Response Study was a prospective cohort study carried out in Zambia, Thailand and Kenya. Between May 2005 and January 2007, we enrolled antiretroviral-naïve HIV-infected women initiating nevirapine-based ART. At enrollment and at weeks 2, 4, 8, 16 and 24, participants had serum alanine transferase (ALT) and aspartate transaminase (AST) measured and were evaluated clinically for hepatitis and rash. RESULTS: Nevirapine-based ART was initiated in 820 women and baseline ALT or AST results were abnormal (≥ grade 1) in 113 (14%) women. After initiating nevirapine-based ART, severe hepatotoxicity occurred in 41 (5%) women and rash-associated hepatotoxicity occurred in 27 (3%) women. In a multivariate logistic regression model, severe hepatotoxicity and rash-associated hepatotoxicity were both associated with baseline abnormal (≥ grade 1) ALT or AST results, but not with a baseline CD4 cell count ≥250 cells/µL. Three participants (0.4%) died with symptoms suggestive of fatal hepatotoxicity; all three women had baseline CD4 count <100 cells/µL and were receiving anti-tuberculosis therapy. CONCLUSION: Among women taking nevirapine-based ART, severe hepatotoxicity and rash-associated hepatotoxicity were predicted by abnormal baseline ALT or AST results, but not by a CD4 count ≥250 cells/µL. In resource-limited settings where transaminase testing is available, testing should focus on early time-points and on women with abnormal baseline ALT or AST results.

Plasma levels of soluble CD14 and tumor necrosis factor-alpha type II receptor correlate with cognitive dysfunction during human immunodeficiency virus type 1 infection.

The relationship between monocyte immune responses and cognitive impairment during progressive human immunodeficiency virus type 1 (HIV-1) infection was investigated in 28 subjects receiving highly active antiretroviral therapy. The mean+/-SEM CD4(+) T lymphocyte count and virus load for all patients were 237+/-41 cells/mm(3) and 77,091+/-195,372 HIV-1 RNA copies/mL, respectively. Levels of soluble tumor necrosis factor-alpha type II receptor (sTNF-RII) and soluble CD14 (sCD14) were measured in plasma by ELISA and were correlated with results from neuropsychological, magnetic resonance imaging, and magnetic resonance spectroscopy tests. Plasma sCD14 and sTNF-RII levels were elevated in subjects with cognitive impairment and in those with brain atrophy. Furthermore, both factors were correlated with spectroscopic choline:creatine ratios. These findings support the idea that peripheral immune responses are linked to cognitive dysfunction during advanced HIV-1 disease.

The efficacy of potent anti-retroviral drug combinations tested in a murine model of HIV-1 encephalitis.

Development of anti-retroviral regimens with enhanced efficacy against brain HIV-1 is essential if viral eradication is to be achieved. To address this, a severe combined immune deficiency mouse model of HIV-1 encephalitis was used to assay the effect of protease-containing and protease-sparing drug regimens on viral replication in brain macrophages. Here, HIV-1-infected human monocyte-derived macrophages (MDM) are inoculated into basal ganglia, causing a multinucleated giant cell encephalitis reminiscent of human disease. Drugs were administered at the time of MDM inoculation and continued until sacrifice. Immunohistochemical tests evaluated ongoing viral replication, glial immunity, and neuronal survival. Treatment with ddI/d4T decreased the numbers of infected cells by 75%, while ddI/d4T/amprenavir or ZDV/3TC/ABC diminished infection by 98%. Triple drug regimens decreased astrogliosis by > or = 25%. This small-animal model may be used to screen drug regimens that affect ongoing HIV-1 replication within its brain sanctuary.

A comparison of two dosing regimens of zidovudine in Thai adults with early symptomatic HIV infection. Conducting clinical HIV trials in South-East Asia.

AIM: To compare the clinical and immunological efficacy, and tolerance of two dosage regimens of zidovudine (ZDV) in an adult Thai population with early symptomatic human immunodeficiency virus (HIV) disease and to identify important clinical issues associated with conducting HIV trials in South-East Asia. METHODS: HIV-infected Thai adults, with early symptomatic HIV disease and CD4 lymphocyte counts less than 400/mm3, who were managed in the infectious diseases clinics at two university teaching hospitals in Bangkok, Thailand, were enrolled in a randomised, open-label, dose-regimen comparison trial of ZDV. Two oral ZDV dosing regimens: regimen A, 100 mg tid+200 mg nocte (ZDV-A) vs regimen B, 250 mg bid (ZDV-B) were compared. The main outcome measures were: 1. Clinical efficacy: rate of progression to acquired immunodeficiency syndrome (AIDS) or death. 2. Immunologic efficacy: changes in CD4 lymphocyte numbers compared to baseline; rate of decline of CD4 lymphocyte numbers to less than 100/mm3. 3. Toxicity, as defined by clinical symptomatology and laboratory parameters. RESULTS: Two hundred and four patients were enrolled (103 ZDV-A; 101 ZDV-B) of whom 195 were followed beyond baseline. Patients were typical of those encountered with HIV in Thailand: mean age 33 years; 89% male; 88% heterosexual HIV acquisition; mean baseline CD4 lymphocyte count 241/mm3. Follow-up while on therapy was comparable for the two groups (mean+/-SD): 533+/-236 days (ZDV-A) vs 592+/-210 days (ZDV-B). One hundred and eleven patients (57%; 51 ZDV-A; 60 ZDV-B) were treated for at least 22 months (669+/-30 days). Clinical and immunological outcomes for ZDV-A and ZDV-B, including rate of progression to AIDS or death, development of non-AIDS-defining opportunistic infections, mean changes in CD4 lymphocyte numbers/mm3, difference in area under the CD4:time distribution curve and difference in the rate of decline of CD4 lymphocyte numbers to less than 100/mm3, were not significantly different. The presence of oral hairy leukoplakia or unintentional weight loss of 10-20% at enrollment were significantly associated with the later development of AIDS (p=0.03 and 0.04, respectively). ZDV-associated toxicity was similar for both regimens. Maintaining protocol adherence and appropriate clinical follow-up emerged as important practical issues. CONCLUSION: In Thai adults, ZDV 100 mg tid+200 mg nocte and ZDV 250 mg bid have similar clinical and immunological efficacy. Rates of ZDV toxicity are comparable to those reported in non-Asian populations. Despite limitations in medical care access and maintaining long-term follow-up, successful trials of antiretroviral agents are feasible in South-East Asia and multi-drug treatment trials should be pursued in appropriate institutions.

Evaluation of antiretroviral drug efficacy for HIV-1 encephalitis in SCID mice.

OBJECTIVES: To compare the efficacy of the nucleoside reverse transcriptase inhibitors (NRTIs) abacavir, zidovudine (AZT), lamivudine (3TC), didanosine (ddI), and stavudine (d4T) to inhibit viral replication in brain macrophages. A severe combined immunodeficiency (SCID) mouse model of HIV-1 encephalitis (HIVE) was used to monitor spreading viral infection in the CNS. BACKGROUND: The development of antiretroviral therapies with CNS efficacy against neuroinvasive virus is important if eradication of HIV-1 can be achieved within critical "hidden reservoirs." METHODS: HIV-1-infected human monocyte-derived macrophages (MDMs) (after a single round of viral replication) were inoculated into the caudate and putamen of SCID mice. This resulted in the spreading of viral infection with a concomitant multinucleated giant cell encephalitis (astrogliosis, microglial activation, and neuronal injury). NRTIs were administered to animals at the time of intracerebral MDM inoculations and continued until the time of sacrifice. Antiretroviral effects were assessed by viral load and percentages of infected MDMs. RESULTS: In brains of SCID mice with HIVE, abacavir and lamivudine reduced HIV-1 p24 antigen-positive cells by 80% and 95%, respectively, whereas both decreased viral load by approximately 1 log. Zidovudine, didanosine, and stavudine showed variable effects. CONCLUSION: Abacavir and lamivudine showed significant antiretroviral activity in SCID mice with HIVE when compared with other NRTIs. The extrapolation of these results to humans with HIV-1 dementia awaits future investigations.

The mounting medical care cost for adult AIDS patients at the Faculty of Medicine, Siriraj Hospital: consideration for management.

From January 1993 to December 1995, case records of adult AIDS and HIV symptomatic patients admitted in the Department of Medicine, observation room and HIV Counseling Clinic were reviewed for the medical care cost of the patients based on the 1995 value of the Thai baht. In the three years, a total of 196, 227 and 182 adult AIDS case were admitted as in-patients respectively. The median duration of admission was 14 days. The leading causes of admission were tuberculosis, cryptococcal meningitis, Pneumocystis carinii pneumonia, diarrhea, salmonellosis and toxoplasmosis. An increase in the number of AIDS patients in the observation room was observed: from 572 cases in 1993 to 1,205 cases in 1995. In addition, approximately 600 AIDS cases were followed up at four to eight week intervals. The analysis of the data found an average medical care cost for hospitalized patients to be 1,452 baht per day while in the observation room it was 1,509 baht per day and 1,132 baht per month for the patients attending the HIV and Counseling Clinic. Because of the higher number of cases and the limited number of admission beds, only 15 per cent of AIDS patients in the observation room could be admitted as hospitalized patients. At present, it is urgent that a referral network be established among all university hospitals, all government hospitals and health centers. In this way, the more advanced medical facilities can serve as a primary diagnostic center which can refer patients for care and follow-up based on an established referral system. In addition, the development of a hospice service and community care is needed for cases in the terminal stage of the illness.

PIP: This study examines case records of adult AIDS and HIV symptomatic patients admitted to the Siriraj Hospital's Department of Medicine during January 1993 and December 1995. The study aims to determine the medical care cost of adult AIDS patients admitted to the observation room, hospital, and HIV and Counseling Clinic and to determine which factors are the most costly. An AIDS diagnosis is determined according to the Thailand Ministry of Health protocols. Costs include medication cost, facility cost, and testing in 1995 baht prices. Government-supplied medicines are not included in the cost. AIDS cases numbered 196, 227, and 182 adult persons in the respective years 1993, 1994, and 1995. The median CD4 lymphocyte count was 59 cells/mm. The median duration of visit was 14 days. AIDS patients occupied 5.4-7% of inpatient admission beds. 17.6-18.8% of patients were readmitted during the year. 26.4% to 33.7% died before discharge. The leading cause of admission was tuberculosis cryptococcal meningitis, pneumocystis carinii pneumonia, diarrhea, salmonellosis, and toxoplasmosis. The number of AIDS cases admitted to the observation room for 2-5 days increased from 572 cases in 1993 to 1205 cases in 1995. However, due to space limitations, only 15% of AIDS patients under observation were admitted to the hospital in 1995. About 600 cases each year were followed up for complications. Medical care costs were 1452 baht/day/patient for admissions; 1509 baht/day/patient in an observation room; and 1132 baht/month/patient for HIV counseling care. The average cost for all adult AIDS patients/year rose from 18,726,176 baht to 26,812,204 baht during 1993-95. Medicine costs almost tripled for treating cryptococcoses. Treatment costs are lower in provincial hospitals. There is a need for the establishment of a referral network, hospice care, and low costs for treatment.

Evaluation of the MycoDot test for the diagnosis of tuberculosis in HIV seropositive and seronegative patients.

SETTING: Patients were recruited from Siriraj, Bamrasnaradura, and Central Chest Hospitals, the three major hospitals responsible for tuberculosis patients in Bangkok, Thailand, and vicinity. OBJECTIVE: To evaluate a new rapid serologic test, the MycoDot test, for diagnosis of tuberculosis (TB). DESIGN: The study was conducted as a cross-sectional survey. A total of 594 patients were tested with the MycoDot test. This included 142 human immunodeficiency virus (HIV) seropositive patients with active TB, 144 HIV seronegative patients with active TB, 153 HIV seropositive controls, and 155 HIV seronegative controls. RESULTS: The sensitivity of the MycoDot test for detection of TB was 40.1% in HIV seropositive patients, compared with 63.2% in HIV seronegative patients (P < 0.001). If only patients with laboratory proven TB were evaluated, the sensitivity was 40.6% in seropositive and in 70.8% seronegative patients. The sensitivity of the MycoDot test was similar in TB patients with pulmonary and extra-pulmonary disease. The sensitivity of the test in patients with CD4 counts > or = 200 cells/mm3 was significantly higher than in those with CD4 counts < 200 cells/mm3. The specificity of the test was 97.4%, and was identical in HIV seropositive and seronegative individuals. CONCLUSION: The MycoDot test had a higher sensitivity for the diagnosis of TB among HIV seronegative than HIV seropositive patients. Although the MycoDot test has a less than optimal sensitivity, the test specificity approaches 100%. It may be useful in patients with suspected TB and negative smears and in extra-pulmonary TB.

Seroprevalence of anti-HCV among HIV-infected persons and general population.

From November 1993 to December 1994, the seroprevalence of anti-HCV, HBsAg was studied among 346 HIV-infected persons (asymptomatic HIV-infected persons and AIDS patients) and 1,023 subjects from the general population (including 119 cord blood samples). The prevalence of anti-HCV, HBsAg among HIV-infected patients aged 15-45+ years was 11.0 and 11.6 per cent respectively which is significantly higher than the comparable levels for the general population (1.9% and 4.7%) in the age group 15-44 years. There was no statistically significant association of anti-HCV and HBsAg prevalence among 200 asymptomatic HIV-infected carriers and 146 AIDS patients. Assays for anti-HCV among blood donors are highly recommended to reduce the development of liver disease or cirrhosis in the immediate future.

HIV-1 infection among low income women attending a Siriraj sexually transmitted disease clinic: sociodemographic differentials.

From August 1993 to October 1994, 322 women attended or were referred to a female sexually transmitted disease clinic, were studied for the prevalence of HIV infection. No subject had a history of commercial sex work, injection drugs use or blood transfusion within the past 8 years. The majority of women belonged to the low socioeconomic stratum. HIV-1 antibody was found in the sera of 38 women (11.8%). HIV-1 seropositivity was not associated with any type of current sexually transmitted disease such as genital ulcers, serologic markers of syphilis or other sexually transmitted disease as well as history of past sexually transmitted disease within the past 2 years. Significant differential factors were found between the HIV-1 seropositive and seronegative women for self risk assessment and ability to communicate concerns with the husband or partner regarding HIV infection/AIDS. Programs are urgently needed for HIV/AIDS prevention and control to low-income communities and to determine what factors enable the HIV-1 seronegative women to be more assertive in their relationship and whether these skills can be enhanced to eliminate future episodes of STD and transfer these skills to the more vulnerable low-income women. Early diagnosis and prevention of HIV infection among women is a priority for public health interventions both in industrialized and in developing countries.

Risk factors for HIV infection among Thai laborers during 1992-1993.

From June 1992 to May 1993, 39,939 Thai men attended the clinic for laborers going abroad at Siriraj Hospital in Bangkok for a pre-assignment physical exam and mandatory blood screen for HIV and syphylis. Of this total, 438 tested positive for HIV antibody (1.1%). Of these, 215 men returned for post test interview and physical exam and were compared with 1,348 men randomly selected HIV-1 seronegative men. None of the HIV-1 seropositive had a history of injecting drug use or had received blood transfusion in the past seven years. HIV-1 seropositivity was associated with the TPHA serological marker for syphylis > 1.160 (p = 0.015, odd ratio 1.8), history of urethritis (p = 0.009, odd ratio 1.92) (Table 4). This study found that HIV-1 seropositive men were mostly single, were likely to be from the rural northern provinces of Thailand or Bangkok. History of purchase of low-fee commercial sex and less condom use were significantly associated with HIV-1 seropositivity as was a history of STD in the year prior to interview. Information on HIV disease and pre-test/post test counselling is needed for Thai laborers who are applying for work abroad to countries which require HIV and syphylis screening. In this effort, the Ministry of Labor and Social Welfare, the Ministry of Public Health and the clinic for laborers going abroad should join forces to provide this service. This will serve to increase awareness and self-determination among an increasingly vulnerable segment of the population who also have the potential to spread HIV infection to their spouse and other sex partners.(ABSTRACT TRUNCATED AT 250 WORDS)

PIP: According to data from the Siriraj Hospital Medical School, where mandatory human immunodeficiency virus (HIV) screening is provided for Thais who travel abroad as contract laborers, the incidence of HIV infection in this population group increased from 0.25% in 1989 to 1.16% in 1992. To assess the risk factors associated with this trend, interviews were conducted with every 25th laborer out of the 39,939 men who presented to the clinic from June 1992 to May 1993. This yielded a sample of 1786 men, 438 of whom were HIV-positive. However, only 215 HIV-positive men returned to the clinic, resulting in a sample of 1563 men (average age, 31.4 years). None of the seropositive subjects had a history of intravenous drug use or blood transfusion. HIV-infected laborers were significantly more likely than their noninfected counterparts to be single, from the Northern and Central provinces, and to be less educated and unskilled. 75.3% of HIV-positive men, compared to 19.5% of seronegative men, had engaged in commercial sex in the past year and were more likely than their counterparts to have visited a low fee (under 100 baht) brothel-based prostitute. The rate of condom use during commercial sex encounters was 59.3% among seropositive men compared to 68.9% among seronegative men. 53.7% of seropositive men, compared to 33.1% of their seronegative counterparts, reported having a sexually transmitted disease (especially urethritis) in the preceding year. Given the threat that HIV-infected itinerant laborers will transmit the virus to others in their home provinces, it is recommended that HIV prevention education become a part of labor recruitment; also urged are continued efforts to promote the goal of 100% condom use in Thailand's commercial sex industry.