Factors contributing to treatment success among tuberculosis patients: a prospective cohort study in Bangkok.

SETTING: Chest Clinic, Ministry of Public Health and health care centres, Bangkok Metropolitan Administration. OBJECTIVE: To determine patient factors predicting successful tuberculosis (TB) treatment. DESIGN: A prospective cohort was conducted during May 2004 to November 2005. Newly diagnosed TB patients aged > or = 15 years were recruited after giving informed consent. Three sets of questionnaires were used to collect data from the patients three times. Data were also gathered from treatment cards. RESULTS: Of 1241 patients, 81.1% were successfully treated. Bivariate analysis indicated that patients' sex, education, occupation, level of knowledge about TB and adverse effects were associated with treatment success. Unconditional logistic regression analysis showed that females had a higher success rate than males (OR = 1.9, 95%CI 1.2-2.9). Patients with regular incomes had twice the likelihood of success of the unemployed (OR = 2.0, 95%CI 1.1-3.5). Patients with high knowledge levels were more likely to complete treatment (OR = 2.0, 95%CI 1.2-3.4), while those with adverse effects were less likely to adhere (OR = 0.6, 95%CI 0.4-0.9). CONCLUSION: The current low treatment success rate may be partly due to inadequate knowledge about TB among patients. Improvements in health education and early detection and management of adverse effects should be prioritised by the National Tuberculosis Programme.

Effectiveness of DOT for tuberculosis treatment outcomes: a prospective cohort study in Bangkok, Thailand.

SETTING: All health care centres under the Department of Health, Bangkok Metropolitan Administration. OBJECTIVES: To investigate patterns of drug administration for tuberculosis (TB) patients and to determine whether these patterns affect treatment success rates. DESIGN: In a prospective cohort study conducted during May 2004 to November 2005, newly diagnosed TB patients aged > or = 15 years were enrolled after giving informed consent. The cohort was followed until treatment outcome. Structured questionnaires were used to interview patients three times: at the first visit, at the end of the intensive phase and at treatment completion. Data were also collected from treatment cards. RESULTS: Five patterns of drug administration were used in the health centres: centre-based directly observed treatment (DOT), family-based DOT, self-administered treatment (SAT), centre-based DOT + SAT and centre- + family-based DOT. The pattern of drug administration had a significant impact on treatment success (P < 0.001). Using unconditional binary multiple logistic regression controlling for confounding factors, centre- + family-based DOT had the highest success rates compared with centre-based DOT (OR 20.9, 95%CI 5.0-88.3). CONCLUSION: The pattern of drug administration impacted on treatment success. Centre- + family-based DOT, family-based DOT and centre-based DOT + SAT achieved higher rates of treatment success than the World Health Organization target. Centre-based DOT had the lowest success.

Evaluation of a sensitive/less-sensitive testing algorithm using the 3A11-LS assay for detecting recent HIV seroconversion among individuals with HIV-1 subtype B or E infection in Thailand.

The development of a serologic algorithm to determine recent HIV seroconversion, using sensitive/less-sensitive testing strategies, has generated widespread interest in applying this approach to estimate HIV-1 incidence in various populations around the world. To evaluate this approach in non-B subtypes, longitudinal specimens (n = 522) collected from 90 incident infections among injecting drug users in Bangkok (subtype B infection, n = 18; subtype E infection, n = 72) were tested by the 3A11-LS assay. Standardized optical density (SOD) was calculated, using median values, and the window period between seroconversion as determined by sensitive and less sensitive tests was estimated by a maximum-likelihood model described previously. Our results show that the mean window period of the 3A11-LS assay was 155 days (95% CI, 128-189 days) for subtype B but was 270 days (95% CI, 187-349 days) for subtype E specimens from Thailand. About 4% of individuals with incident subtype E infections remained below the threshold (SOD of 0.75), even 2 years after seroconversion. Among the patients with clinical AIDS and declining antibodies, none of the 7 individuals with subtype B, but 10 (8.7%) of 115 with subtype E infections, were misclassified as recent infections. Lowering the cutoff to an SOD of 0.45 for subtype E specimens resulted in a mean window period of 185 days (95% CI, 154-211 days), with all individuals seroconverting, and reduced the number of subtype E-infected patients with AIDS who were misclassified as having recent infection to 2.6%. Our results demonstrate that the 3A11-LS assay has different performance characteristics in detecting recent infections among individuals infected with subtypes B or E. Determining appropriate cutoffs and mean window periods for other HIV-1 subtypes will be necessary before this approach can be reliably implemented in settings where non-B subtypes are common.

Continued high HIV-1 incidence in a vaccine trial preparatory cohort of injection drug users in Bangkok, Thailand.

BACKGROUND: A large epidemic of HIV-1 subtype B began among injection drug users (IDUs) in Bangkok in 1988. Despite ongoing prevention efforts, HIV-1 prevalence among IDUs remained at 30-50% through the 1990s. OBJECTIVES: To measure the incidence of HIV-1 infection and related risk factors to guide prevention efforts and to evaluate the feasibility of conducting an HIV vaccine efficacy trial. DESIGN AND METHODS: A prospective cohort study in which IDUs attending methadone treatment programs in Bangkok were screened during 1995-1996 for enrollment into the study. IDUs found to be HIV-seronegative on two occasions were offered enrollment with follow-up visits every 4 months. On each visit participants were evaluated with a questionnaire and serologic testing. RESULTS: A total of 1209 HIV-negative IDUs were enrolled. Through the end of 1998, the overall HIV-1 incidence rate was 5.8 (95% confidence interval, 4.8-6.8) per 100 person-years of follow-up. HIV-1 subtypes E and B accounted for 79 and 21% of infections, respectively. On multivariate analysis, HIV-1 seroconversion was primarily associated with the frequency of heroin injection, the sharing of injection equipment, and incarceration, especially with drug injection. Sexual behavior was not associated with increased risk for HIV-1. Risk factors for infection with HIV-1 subtypes E and B were similar. CONCLUSION: HIV-1 transmission risk remains high among Bangkok IDUs despite methadone treatment and other current prevention strategies. There is an urgent need to address this ongoing epidemic, especially in jails and prisons. This study led to the initiation in 1999 of a phase III HIV-1 vaccine efficacy trial in this population.

Genetic characterization of incident HIV type 1 subtype E and B strains from a prospective cohort of injecting drug users in Bangkok, Thailand.

We obtained specimens from 128 HIV-1 seroconverters identified from 1995 through 1998 in a prospective cohort study of 1,209 HIV-negative injecting drug users (IDUs) in Bangkok, Thailand. Epidemiologic data indicated that parenteral transmission accounted for nearly all infections. HIV-1 DNA from the C2-V4 env region was sequenced, and phylogenetic analyses determined that 102 (79.7%) of the specimens were subtype E and 26 (20.3%) subtype B strains. All subtype B strains clustered with strains often referred to in previous studies as Thai B or B'. The interstrain nucleotide distance (C2-V4) within subtype E strains was low (mean, 6.8%), and pairwise comparisons with a prototype subtype E strain, CM244, showed limited divergence (mean, 5.6%). The subtype B stains showed greater interstrain divergence (mean, 9.2%) and were significantly divergent from the prototype B strain HIV-MN (mean, 13.0%; p < 0.0001). The subtype E strains had significantly lower mean V3 loop charge than did subtype B strains (p = 0.017) and, on the basis of analysis of amino acid sequences, were predicted to be predominantly (91%) non-syncytium-inducing (NSI), chemokine coreceptor CCR5-using (CCR5+) viruses. The subtype B strains had a higher mean V3 loop charge, and a smaller proportion (23%) were predicted to be NSI/CCR5+ viruses. This study demonstrates that most incident HIV1 infections among Bangkok IDUs are due to subtype E viruses, with a narrow spectrum of genetic diversity. The characterization of incident HIV-1 strains from 1995 to 1998 will provide important baseline information for comparison with any breakthrough infections that occur among IDUs in Bangkok who are participating in an HIV-1 vaccine efficacy trial initiated in 1999.

AIDSVAX (MN) in Bangkok injecting drug users: a report on safety and immunogenicity, including macrophage-tropic virus neutralization.

A randomized, double-blind, placebo-controlled phase I/II study of AIDSVAX (MN) was conducted among injecting drug users in Bangkok, Thailand. Four doses of vaccine (300 microg of MN-rgp120 in alum) or placebo (alum) were given at study entry and at 1, 6, and 12 months. The objectives of the study were to evaluate (1) the feasibility of conducting vaccine trials in this population; (2) the safety of this candidate AIDS vaccine; and (3) the immunogenicity of this vaccine. Thirty-three volunteers (22 vaccine and 11 placebo recipients) were recruited. None were lost to follow-up during the 18-month study. Mild reactogenicity was noted, which was similar in both vaccine and placebo recipients. The vaccine induced anti-HIV-1 antibody in all vaccine recipients. Maximal titers of binding antibodies of MN-rgp120 and the V3 domain of MN-rgp120 were induced after the third (6 month) dose while maximal neutralizing antibodies followed the fourth (12 month) dose. The vaccine-induced antibodies from several volunteers were capable of neutralizing macrophage-tropic, subtype B viruses (301660 and JRCSF) detected in a PBMC-based assay. Binding and neutralizing antibodies declined about 10-fold in the 6 months after the last boost. Two vaccinees became infected during the trial, both with subtype E viruses. A phase III efficacy trial, using a bivalent gp120 vaccine containing antigens from a subtype B virus (MN) and a subtype E virus (A244), was initiated in March 1999 in injecting drug users in Bangkok.

Cloning and characterization of a new asparagine-rich protein in Plasmodium falciparum.

A cDNA clone that encodes a Plasmodium falciparum asparagine (N)-rich protein (PfARP) was isolated through immunoscreening of an expression library. A 9.4 kb PfARP transcript was identified by Northern blot hybridization and the gene was localized on chromosome 1. The complete coding sequence (6666 bp) revealed a protein that contains clustered as well as randomly distributed N residues (24.3%), seven copies of a repeat sequence [DNT(D/N)(K/N)(V/L/M)] and multiple copies of tripeptide repeats within a 101 amino acid region containing 89 D/E residues. The PfARP was immunogenic in inbred and outbred mice and endemic sera revealed the presence of low-titer antibodies against PfARP. Anti-PfARP sera showed cytoplasmic and surface localization of apparently cross-reactive malarial antigens in different life-cycle stages (ring, trophozoite, schizont, and gametocytes). Although the biological function(s) of PfARP are not known, the observation that it is present in multiple parasite stages and that it is a target of natural immune response warrants further study of PfARP as an immune target.

Willingness of injection drug users to participate in an HIV vaccine efficacy trial in Bangkok, Thailand.

We assessed willingness to participate in an HIV recombinant gp120 bivalent subtypes B/E candidate vaccine efficacy trial among 193 injection drug users (IDUs) attending drug treatment clinics in Bangkok, Thailand. IDUs previously enrolled in a prospective cohort study were invited to group sessions describing a potential trial, then completed questionnaires assessing comprehension and willingness to participate. A week later, they completed a follow-up questionnaire that again assessed comprehension and willingness to participate, as well as barriers to and positive motives for participation, with whom (if anyone) they talked about the information, and whether others thought participation was a good, bad, or neutral idea. At baseline, 51% were definitely willing to participate, and at follow-up 54%; only 3% were not willing to participate at either time. Comprehension was high at baseline and improved at follow-up. Participants who viewed altruism, regular HIV tests, and family support for participation as important were more willing to volunteer. Frequency of incarceration and concerns about the length of the trial, possible vaccine-induced accelerated disease progression, and lack of family support were negatively associated with willingness. Overall, IDUs comprehended the information needed to make a fully informed decision about participating in an rgp120 vaccine efficacy trial and expressed a high level of willingness to participate in such a trial.

Clinical presentation of hospitalized adult patients with HIV infection and AIDS in Bangkok, Thailand.

OBJECTIVE: To characterize the clinical spectrum of disease and immune status of adult HIV-1-infected patients in Bangkok. DESIGN: Cross-sectional survey of hospital admissions. METHODS: From November 1993 through June 1996, demographic, clinical, and laboratory data were collected from HIV-infected inpatients (> or =14 years old) at an infectious diseases hospital. RESULTS: Of 16,717 persons admitted, 3112 (18.6%) were HIV-seropositive, 2261 of whom were admitted for the first time. Of 2261, 1926 (85.2%) were male, 1942 (85.9%) had been infected heterosexually or by means not related to drug use, 319 (14.1%) were injection drug users (IDUs), and 1553 (68.7%) had AIDS. The most common AIDS-defining conditions were extrapulmonary cryptococcosis (EPC; 38.4%), tuberculosis (TB; 37.4%), and wasting syndrome (WS; 8.1%). IDUs were more likely (p < .05) to have TB or WS but less likely (p < .05) to have EPC or Pneumocystis carinii pneumonia than patients with no history of injection drug use. Lymphocyte counts were measured for 2047 (90.5%) patients; 81.8% had < or =1500 lymphocytes/microl. CONCLUSION: These HIV-infected patients were admitted with severe immunosuppression. Cryptococcosis and TB are major problems and differ in prevalence among IDUs and persons infected sexually. Clinical and immunologic information is critical in improving the lives of HIV-infected persons in Asia through prevention, treatment, and prophylaxis.

Cost-effectiveness analysis of artesunate and quinine + tetracycline for the treatment of uncomplicated falciparum malaria in Chanthaburi, Thailand.

A randomized, controlled, malaria-clinic-based field trial was carried out to compare the cost-effectiveness of a 5-day 700-mg oral artesunate and a 7-day quinine + tetracycline regimen for the treatment of uncomplicated falciparum malaria in Thailand. Cost-effectiveness was determined from the providers' perspective and based on curative effectiveness. A total of 137 patients, aged 15-60 years, attending a malaria clinic were followed for 28 days, 60 of them received quinine + tetracycline and 77 received artesunate. Cure rates were assessed on day 5 (artesunate) and day 7 (quinine + tetracycline), using the intention-to-treat approach. Cost-effectiveness and sensitivity analyses were performed by varying the day 5/day 7 curative effectiveness and cost of artesunate. The cure rate with artesunate (100%) was significantly higher than with quinine + tetracycline (77.4%) (relative risk adjusted for sex (aRR) = 1.32, 95% confidence interval (CI) = 1.12-1.55; referent quinine + tetracycline). Artesunate was more cost-effective than quinine + tetracycline at the following costs: artesunate, < or = US$0.36 per 50-mg tablet; quinine, US$0.06 per 300-mg tablet; tetracycline, US$0.02 per 250-mg capsule; and services per case found, < or = US$11.49. Because of the higher cure rate and higher cost-effectiveness of the artesunate regimen compared with quinine + tetracycline, we recommend its use for the treatment of uncomplicated falciparum malaria in malaria clinics in Thailand.

PIP: Findings are presented from a randomized, controlled, malaria clinic-based field trial conducted to compare the cost-effectiveness of a 5-day 700 mg oral artesunate and a 7-day quinine and tetracycline regimen to treat uncomplicated falciparum malaria in Thailand. Cost-effectiveness was determined from the providers' perspective and based upon curative effectiveness. 137 patients, aged 15-60 years, attending a malaria clinic were followed for 28 days. 60 received quinine and tetracycline, while 77 received artesunate. Cure rates were assessed on day 5 (artesunate) and day 7 (quinine and tetracycline). The cure rate with artesunate was 100%, significantly higher than the 77.4% rate with quinine and tetracycline. Artesunate was more cost-effective than quinine and tetracycline, with artesunate costing a maximum of US$0.36 per 50 mg tablet, quinine at US$0.06 per 300 mg tablet, tetracycline at US$0.02 per 250 mg capsule, and services per case found no higher than US$11.49.

Infection with HIV-1 subtypes B and E in injecting drug users screened for enrollment into a prospective cohort in Bangkok, Thailand.

From May through August 1995, a cross-sectional survey was conducted among injecting drug users (IDUs) drawn from 15 drug treatment clinics in Bangkok and who were not known to be HIV-seropositive, to determine the prevalence of HIV-1 subtypes B and E and related risk behaviors, and to offer enrollment in a prospective cohort study. IDUs who voluntarily consented were interviewed, and blood specimens were tested for the presence of HIV antibodies. HIV-1-seropositive specimens were tested for subtypes B' (Thai B) and E by using V3 loop peptide enzyme immunoassays specific for these HIV-1 genetic subtypes. Of 1674 IDUs studied, the mean age was 31.2 years (interquartile range, 25-37 years), 94.8% were men, and 29.3% were HIV-1-seropositive. On multiple logistic regression analysis, HIV-1 seropositivity was associated with older age, not being married, less education, needle sharing, and incarceration. HIV-1 subtype B' accounted for 65% of prevalent infections and subtype E, 35%. Infection with subtype E was associated with younger age and did not seem to be associated with sexual risk behaviors, which were uncommon in general. Bangkok IDUs continue to be at high risk for HIV-1 infection related to needle sharing and incarceration. Although HIV-1 subtype B' accounts for most prevalent infections, subtype E seems to be more prevalent among younger IDUs, and most infections seem likely to result from parenteral transmission.

PIP: In a 3-month period in 1995, voluntary HIV counseling and testing was offered to injecting drug users (IDUs) 20-50 years of age who attended any of the 15 drug treatment centers operated by the Bangkok (Thailand) Metropolitan Administration and were not known to be HIV-positive. The long-term purpose of this screening was to enroll a cohort in which to monitor HIV trends and obtain HIV-1 strains for genetic and phenotypic characterization. 1674 predominantly male IDUs (mean age, 31.2 years) were screened. 70.1% reported having been tested for HIV in the past 3 years. In the preceding 6 months, 77.9% had injected drugs at least once a day, 39.1% had used needles or syringes used by others, and 42.5% had shared needles. HIV-1 seroprevalence was 29.3%. In multiple logistic regression analysis, the following factors were significantly and independently associated with HIV-1 positivity: older age, unmarried status, less than 7 years of education, having shared needles or syringes, incarceration in the past 6 months, and drug injection during incarceration. A convenience sample of 205 of the 490 HIV-1-positive specimens was selected for serotyping through use of V3 loop peptide enzyme immunoassays. Of the 194 for which the HIV-1 subtype could be determined, 126 (64.9%) reacted to subtype B prime ("Thai B") and 68 (35.1%) reacted to subtype E. Subtype E was significantly more common among younger IDUs. 822 of the 1184 HIV-negative IDUs were interviewed and offered enrollment in the prospective cohort study; 678 (82.5%) agreed to participate. A phase III efficacy trial of an HIV-1 vaccine may be feasible in this cohort.

Advancing AIDSVAX to phase 3. Safety, immunogenicity, and plans for phase 3.

AIDSVAX (VaxGen, Inc., South San Francisco, CA), a possible vaccine to protect against human immunodeficiency virus type 1 (HIV-1) infection, is being tested for efficacy in phase 3 studies. It has been tested for potential efficacy in chimpanzees, and tested for safety and immunogenicity in human clinical studies. Four candidate vaccines, each with a different envelope protein antigen or combination of antigens, have been produced in alum formulations. In both design and clinical testing, AIDSVAX has an excellent safety profile. Because these highly purified proteins were prepared using recombinant DNA technology, there is no possibility of these vaccines causing HIV infection. Having been administered to over 1200 people, the only side effects attributable to AIDSVAX have been local pain and inflammation at the injection site. After immunization, essentially all recipients developed a robust antibody response, including binding and neutralizing antibodies. The neutralizing antibodies peaked after a 12-month boost. Excellent memory is induced. Two phase 3 trials of two bivalent formulations will evaluate their efficacy. One trial will use a bivalent subtype B formulation. This trial in North America will involve 5000 men who have sex with men and heterosexual women at high risk. The other study will use a bivalent subtype B/subtype E formulation. This trial in Thailand and will involve 2500 intravenous drug users. Both studies will be randomized, double-blinded and placebo controlled. The volunteers will be followed for 3 years. The end points of the studies are infection, as defined by seroconversion to standard diagnostic tests, and viral load, as defined by commercial polymerase chain reaction (PCR) tests.

Compliance with artesunate and quinine + tetracycline treatment of uncomplicated falciparum malaria in Thailand.

A randomized, controlled, malaria-clinic-based field trial was conducted to compare compliance with a 7-day quinine + tetracycline regimen and a 5-day 700-mg artesunate regimen for the treatment of uncomplicated falciparum malaria in a community in Thailand. Of 137 patients, aged 15-60 years attending a malaria clinic, 77 received artesunate and 60 received quinine + tetracycline. Compliance and cure rates were evaluated on days 5 (artesunate) and 7 (quinine + tetracycline) using patient interview/residual pill counts and peripheral blood smear, respectively. Data were analysed using the intention-to-treat approach, and the reasons for compliance and noncompliance were investigated. Compliance was significantly higher (98.4%) with artesunate than with quinine + tetracycline (71.7%) (relative risk adjusted for sex (aRR) = 1.39 (95% C.I. = 1.15-1.68); referent: quinine + tetracycline). Cure rate (100%) was higher in those receiving artesunate than quinine + tetracycline (77.4%) (aRR = 1.32 (95% C.I. = 1.12-1.55)). Reasons for compliance included the desire to be cured and to follow the advice of malaria staff/employer, and the simple dosing regimen. Noncompliance was mostly due to adverse reactions and forgetting to take the drugs. These results can serve as a baseline for designing and evaluating new interventions to improve compliance, as well as for studying cost-effectiveness to help drug policy decision-making. We recommend a strategy which integrates a short-course, once-a-day regimen (with minimal adverse reactions), a better delivery system for antimalarial drugs and health education, and an enhanced advisory role of malaria staff. Considering the higher compliance rate and curative effectiveness of artesunate, we recommend its use instead of quinine + tetracycline for the treatment of uncomplicated malaria in clinics in Thailand.

"Why I am not infected with HIV": implications for long-term HIV risk reduction and HIV vaccine trials.

OBJECTIVE: To describe beliefs about remaining HIV-seronegative in injecting drug users in two high-seroprevalence cities, and to consider implications of these beliefs for ongoing risk reduction efforts and for HIV vaccine efficacy trials. DESIGN: Cross-sectional survey with open- and closed-ended questions. SUBJECTS: 58 HIV-seronegative injecting drug users participating in HIV vaccine preparation cohort studies in New York City, New York, U.S.A., and Bangkok, Thailand. MAJOR FINDINGS: Large majorities of subjects in Bangkok (90%) and in New York (89%) believed their "own efforts" to practice safer injection methods and safer sex were very important in avoiding HIV infection. More Bangkok subjects (30%) believed that they would "probably" become infected with HIV in the future than New York subjects (4%). Three percent of Bangkok subjects and 70% of New York subjects believed "having an immune system strong enough to avoid becoming infected with HIV despite exposure to the virus" was very important in avoiding HIV infection. This belief in New York subjects was associated with having previously engaged in high-risk behaviors (i.e., sharing injection equipment, unprotected sex, or both) with partners known to be HIV-seropositive. CONCLUSIONS: Risk reduction programming for high-HIV-seroprevalence populations and within HIV vaccine trials should address not only specific HIV risk behaviors, but also the complex belief systems about avoiding HIV infection that develop within such groups. The person's "own efforts/self-efficacy" appears to be central in the psychology of risk reduction. Members of some high-risk populations may overestimate greatly the frequency of any possible natural immunity to becoming infected with HIV. Prevention programs for these populations will need to address explicitly the probabilistic nature of HIV transmission.

PIP: Both New York City and Bangkok have experienced rapid, large-scale HIV epidemics among their IV drug using populations. The authors surveyed 58 HIV-seronegative IV drug users (IVDUs) participating in HIV vaccine preparation cohort studies in the two cities to gain insight into their beliefs about remaining HIV-seronegative. The 28 IVDUs in New York City and 30 IVDUs in Bangkok were recruited from ongoing cohort studies of HIV incidence among IVDUs in these cities. The New York cohort subjects were 76% male, 30% White, 27% Black, 43% Latino, and of median age 42 years. The majority had injected both heroin and cocaine. The Bangkok cohort subjects were 94% male, 100% Thai, of mean age 32 years, and almost all had injected heroin only. 89% of the subjects in New York City and 90% in Bangkok believed that their own efforts to practice safer injection methods and safer sex were very important in avoiding HIV infection. However, 4% of New York subjects and 30% of Bangkok subjects thought that they would probably become infected with HIV in the future. 70% of New York subjects and 3% of Bangkok subjects believed that having an immune system strong enough to avoid becoming infected with HIV despite exposure was very important in avoiding HIV infection. This latter belief among New York subjects was associated with having previously engaged in high-risk behaviors with partners known to be HIV-seropositive. Risk reduction programming for such populations and within HIV vaccine trials must take into account the prevailing belief systems about avoiding HIV infection.