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Georgia D Tomaras,
Guido Ferrari,
Xiaoying Shen,
S Munir Alam,
Hua-Xin Liao,
Justin Pollara,
Mattia Bonsignori,
M Anthony Moody,
Youyi Fong,
Xi Chen, [......],
Robert Parks, Jaranit Kaewkungwal,
Sorachai Nitayaphan,
Punnee Pitisuttithum,
Supachai Rerks-Ngarm,
Peter B Gilbert,
Jerome H Kim,
Nelson L Michael,
David C Montefiori,
Barton F Haynes
[show abstract]
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ABSTRACT: Analysis of correlates of risk of infection in the RV144 HIV-1 vaccine efficacy trial demonstrated that plasma IgG against the HIV-1 envelope (Env) variable region 1 and 2 inversely correlated with risk, whereas HIV-1 Env-specific plasma IgA responses directly correlated with risk. In the secondary analysis, antibody-dependent cellular cytotoxicity (ADCC) was another inverse correlate of risk, but only in the presence of low plasma IgA Env-specific antibodies. Thus, we investigated the hypothesis that IgA could attenuate the protective effect of IgG responses through competition for the same Env binding sites. We report that Env-specific plasma IgA/IgG ratios are higher in infected than in uninfected vaccine recipients in RV144. Moreover, Env-specific IgA antibodies from RV144 vaccinees blocked the binding of ADCC-mediating mAb to HIV-1 Env glycoprotein 120 (gp120). An Env-specific monomeric IgA mAb isolated from an RV144 vaccinee also inhibited the ability of natural killer cells to kill HIV-1-infected CD4(+) T cells coated with RV144-induced IgG antibodies. We show that monomeric Env-specific IgA, as part of postvaccination polyclonal antibody response, may modulate vaccine-induced immunity by diminishing ADCC effector function.
Proceedings of the National Academy of Sciences 05/2013; · 9.68 Impact Factor
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Pinghuang Liu,
Nicole L Yates,
Xiaoying Shen,
Mattia Bonsignori,
M Anthony Moody,
Hua-Xin Liao,
Youyi Fong,
S Munir Alam,
R Glenn Overman,
Thomas Denny, [......],
Punnee Pitisuttithum, Jaranit Kaewkungwal,
Sorachai Nitayaphan,
Supachai Rerks-Ngarm,
David C Montefiori,
Peter Gilbert,
Nelson L Michael,
Jerome H Kim,
Barton F Haynes,
Georgia D Tomaras
[show abstract]
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ABSTRACT: The detailed examination of the antibody repertoire from RV144 provides a unique template for understanding potentially protective antibody functions. Some potential immune correlates of protection were untested in the correlates analyses due to inherent assay limitations as well as the need to keep the correlates analysis focused on a limited number of endpoints to achieve statistical power. In an RV144 pilot study, we determined that RV144 vaccination elicited antibodies that could bind infectious virions (including the vaccine strains, HIV-1 CM244 and HIV-1 MN, and an HIV-1 expressing transmitted/founder Env B.WITO.c). Among those vaccinees with the highest IgG binding antibody profile, the majority (78%) captured the infectious vaccine strain virus(CM244) while a smaller proportion of vaccinees (26%) captured HIV-1 transmitted/founder Env virus. We demonstrated that vaccine-elicited HIV-1 gp120 antibodies of multiple specificities (V3, V2, conformational C1, and gp120 conformational) mediated capture of infectious virions. Although capture of infectious HIV-1 correlated with other humoral immune responses, the extent of variation between these humoral responses and virion capture indicates that virion capture antibodies occupy unique immunological space.
Journal of Virology 05/2013; · 5.40 Impact Factor
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[show abstract]
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ABSTRACT: This study aimed to describe the temporal patterns of dengue transmission in Jakarta from 2001 to 2010, using data from the national surveillance system. The Box-Jenkins forecasting technique was used to develop a seasonal autoregressive integrated moving average (SARIMA) model for the study period and subsequently applied to forecast DHF incidence in 2011 in Jakarta Utara, Jakarta Pusat, Jakarta Barat, and the municipalities of Jakarta Province. Dengue incidence in 2011, based on the forecasting model was predicted to increase from the previous year.
The Southeast Asian journal of tropical medicine and public health 03/2013; 44(2):206-17. · 0.60 Impact Factor
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Jaranit Kaewkungwal,
Punnee Pitisuttithum,
Supachai Rerks-Ngarm,
Sorachai Nitayaphan,
Chirasak Khamboonruang,
Prayura Kunasol,
Pravan Suntharasamai,
Swangjai Pungpak,
Sirivan Vanijanonta,
Valai Bussaratid,
Wirach Maek-A-Nantawat,
Jittima Dhitavat,
Prasert Thongcharoen,
Rungrawee Pawarana,
Yupa Sabmee,
Michael Benenson,
Patricia Morgan,
Robert O'Connell,
Jerome H Kim
[show abstract]
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ABSTRACT: To assess qualities and outcomes of women participating in a large, community- based HIV vaccine trial, the present study was conducted among female participants of RV 144 prime-boost trial in Thailand from 2003-2009. Qualities of participation refer to complete vaccination, retention and status change. Outcomes of participation refer to incident rate, adverse event and participation impact event. A total of 6,334 (38.6%) women participated in the trial, of whom about 50% was classified as low risk and 11% as high-risk. About 85% of participants completed four vaccinations and 76% were included in the per-protocol analysis of on-time vaccination schedule. More women (88%) completed 42 months follow-up compared with men (85%). Women aged 21 and above had more adverse events compared to younger age groups. More women (5%) compared with men (3%) reported participation impact events (PIEs). High-risk women had more PIEs and higher infection rate compared to low risk group. Complete vaccination and retention on last follow-up were more common in married women aged above 21, and being a housewife. Female volunteers showed the same qualities and outcomes of participation as males in HIV vaccine trial. There was no statistically significant difference in vaccine efficacy between men and women especially among the high risk and married women. The study highlighted the important behavioral, social and cultural issues that could be considered for future HIV vaccine trial design.
AIDS research and human retroviruses 01/2013; · 2.18 Impact Factor
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Hua-Xin Liao,
Mattia Bonsignori,
S Munir Alam,
Jason S McLellan,
Georgia D Tomaras,
M Anthony Moody,
Daniel M Kozink,
Kwan-Ki Hwang,
Xi Chen,
Chun-Yen Tsao, [......],
Faruk Sinangil,
Jerome H Kim,
Nelson L Michael,
Thomas B Kepler,
Peter D Kwong,
John R Mascola,
Gary J Nabel,
Abraham Pinter,
Susan Zolla-Pazner,
Barton F Haynes
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ABSTRACT: The RV144 HIV-1 trial of the canary pox vector (ALVAC-HIV) plus the gp120 AIDSVAX B/E vaccine demonstrated an estimated efficacy of 31%, which correlated directly with antibodies to HIV-1 envelope variable regions 1 and 2 (V1-V2). Genetic analysis of trial viruses revealed increased vaccine efficacy against viruses matching the vaccine strain at V2 residue 169. Here, we isolated four V2 monoclonal antibodies from RV144 vaccinees that recognize residue 169, neutralize laboratory-adapted HIV-1, and mediate killing of field-isolate HIV-1-infected CD4(+) T cells. Crystal structures of two of the V2 antibodies demonstrated that residue 169 can exist within divergent helical and loop conformations, which contrasted dramatically with the β strand conformation previously observed with a broadly neutralizing antibody PG9. Thus, RV144 vaccine-induced immune pressure appears to target a region that may be both sequence variable and structurally polymorphic. Variation may signal sites of HIV-1 envelope vulnerability, providing vaccine designers with new options.
Immunity 01/2013; · 21.64 Impact Factor
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S Munir Alam,
Hua-Xin Liao,
Georgia D Tomaras,
Mattia Bonsignori,
Chun-Yen Tsao,
Kwan-Ki Hwang,
Haiyan Chen,
Krissey E Lloyd,
Cindy Bowman,
Laura Sutherland, [......],
Sorachai Nitayaphan,
Nicos Karasavva,
Supachai Rerks-Ngarm,
Jerome H Kim,
Nelson L Michael,
Susan Zolla-Pazner,
Sampa Santra,
Norman L Letvin,
Stephen C Harrison,
Barton F Haynes
[show abstract]
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ABSTRACT: An immune correlates analysis of the RV144 HIV-1 vaccine trial revealed that antibody responses to the gp120 V1V2 region correlated inversely with infection risk. The RV144 protein immunogens (A244-rp120, MN-rgp120) were modified by an N-terminal 11 amino-acid deletion (Δ11) and addition of a HSV (Herpes simplex virus)-gD protein derived tag (gD). We investigated the effects of these modifications on gp120 expression, antigenicity and immunogenicity by comparing unmodified A244 gp120 with both Δ11 deletion and gD tag and with Δ11 only. Analysis of A244 gp120, with or without Δ11 or gD, demonstrated that the Δ11 deletion, without the addition of gD, was sufficient for enhanced antigenicity to gp120 C1 region, conformational V2 and V1/V2 gp120 conformational epitopes. RV144- vaccinee sera IgG bound more avidly to A244 gp120 Δ11 than to the unmodified gp120 and their binding was blocked by C1, V2 and V1/V2 antibodies. Rhesus macaques immunized with the three different forms of A244 gp120 proteins gave similar levels of gp120 antibody titers, although higher antibody titers developed earlier in A244 Δ11 gp120 immunized animals. Conformational V1/V2 mAbs gave significantly higher levels of blocking of plasma IgG from A244 Δ11 gp120 immunized animals than IgG from animals immunized with unmodified A244 gp120, thus indicating a qualitative difference in the V1/V2 antibodies induced by A244 Δ11 gp120. These results demonstrate that deletion of N-terminal residues in the RV144 A244 gp120 immunogen improves both envelope antigenicity and immunogenicity.
Journal of Virology 11/2012; · 5.40 Impact Factor
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Nicos Karasavvas,
Erik Billings,
Mangala Rao,
Constance Williams,
Susan Zolla-Pazner,
Robert T Bailer,
Richard A Koup,
Sirinan Madnote,
Duangnapa Arworn,
Xiaoying Shen, [......],
Faruk Sinangil,
Bette T Korber,
David C Montefiori,
John R Mascola,
Merlin L Robb,
Barton F Haynes,
Viseth Ngauy,
Nelson L Michael,
Jerome H Kim,
Mark S de Souza For The Moph Taveg Collaboration
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ABSTRACT: Abstract The Thai Phase III clinical trial (RV144) showed modest efficacy in preventing HIV-1 acquisition. Plasma collected from HIV-1-uninfected trial participants completing all injections with ALVAC-HIV (vCP1521) prime and AIDSVAX B/E boost were tested for antibody responses against HIV-1 gp120 envelope (Env). Peptide microarray analysis from six HIV-1 subtypes and group M consensus showed that vaccination induced antibody responses to the second variable (V2) loop of gp120 of multiple subtypes. We further evaluated V2 responses by ELISA and surface plasmon resonance using cyclic (Cyc) and linear V2 loop peptides. Thirty-one of 32 vaccine recipients tested (97%) had antibody responses against Cyc V2 at 2 weeks postimmunization with a reciprocal geometric mean titer (GMT) of 1100 (range: 200-3200). The frequency of detecting plasma V2 antibodies declined to 19% at 28 weeks post-last injection (GMT: 110, range: 100-200). Antibody responses targeted the mid-region of the V2 loop that contains conserved epitopes and has the amino acid sequence KQKVHALFYKLDIVPI (HXB2 Numbering sequence 169-184). Valine at position 172 was critical for antibody binding. The frequency of V3 responses at 2 weeks postimmunization was modest (18/32, 56%) with a GMT of 185 (range: 100-800). In contrast, naturally infected HIV-1 individuals had a lower frequency of antibody responses to V2 (10/20, 50%; p=0.003) and a higher frequency of responses to V3 (19/20, 95%), with GMTs of 400 (range: 100-3200) and 3570 (range: 200-12,800), respectively. RV144 vaccination induced antibodies that targeted a region of the V2 loop that contains conserved epitopes. Early HIV-1 transmission events involve V2 loop interactions, raising the possibility that anti-V2 antibodies in RV144 may have contributed to viral inhibition.
AIDS research and human retroviruses 10/2012; · 2.18 Impact Factor
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Wichai Satimai,
Prayuth Sudathip,
Saowanit Vijaykadga,
Amnat Khamsiriwatchara,
Surasak Sawang,
Thanapon Potithavoranan,
Aumnuyphan Sangvichean,
Charles Delacollette,
Pratap Singhasivanon, Jaranit Kaewkungwal,
Saranath Lawpoolsri
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ABSTRACT: The area along the Thai-Cambodian border is considered an epicenter of anti-malarial drug resistance. Recently, parasite resistance to artemisinin-based therapies has been reported in the area. The artemisinin resistance containment project was initiated in November 2008, with the aim to limit resistant parasites and eliminate malaria in this region. This study describes the response to artemisinin-based therapy among falciparum malaria patients in the area, using data from the malaria surveillance programmed under the containment project.
The study was conducted in seven provinces of Thailand along the Thai-Cambodian border. Data of Plasmodium falciparum-positive patients during January 2009 to December 2011 were obtained from the electronic malaria information system (eMIS) Web-based reporting system. All P. falciparum cases were followed for 42 days, as the routine case follow-up protocol. The demographic characteristics of the patients were described. Statistical analysis was performed to determine the cure rate of the current standard anti-malarial drug regimen--mefloquine-artesunate combination therapy (MAS). The proportion of patients who remained parasite-positive at each follow-up day was calculated. In addition, factors related to the delayed parasite clearance on day-3 post-treatment, were explored.
A total of 1,709 P. falciparum-positive cases were reported during the study period. Almost 70% of falciparum cases received MAS therapy (n = 1,174). The majority of cases were males, aged between 31 and 50 years. The overall MAS cure rate was >90% over the three-year period. Almost all patients were able to clear the parasite within 7 to 14 days post-treatment. Approximately 14% of patients undergoing MAS remained parasite-positive on day-3. Delayed parasite clearance was not significantly associated with patient gender, age, or citizenship. However, delayed parasite clearance varied across the study area.
Anti-malarial drug-resistant parasites should be closely monitored in the area along the Thai-Cambodian border. Although the MAS cure rate in this study area was above 90%, an increasing trend of treatment failure has been reported in neighboring parts. Effective malaria surveillance is an important component to monitor drug-resistance in the malaria containment project.
Malaria Journal 08/2012; 11:300. · 3.19 Impact Factor
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Mattia Bonsignori,
Justin Pollara,
M Anthony Moody,
Michael D Alpert,
Xi Chen,
Kwan-Ki Hwang,
Peter B Gilbert,
Ying Huang,
Thaddeus C Gurley,
Daniel M Kozink, [......],
Jerome H Kim,
Nelson L Michael,
Georgia D Tomaras,
David C Montefiori,
George K Lewis,
Anthony Devico,
David T Evans,
Guido Ferrari,
Hua-Xin Liao,
Barton F Haynes
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ABSTRACT: The ALVAC-HIV/AIDSVAX-B/E RV144 vaccine trial showed an estimated efficacy of 31%. RV144 secondary immune correlate analysis demonstrated that the combination of low plasma anti-HIV-1 Env IgA antibodies and high levels of antibody-dependent cellular cytotoxicity (ADCC) inversely correlate with infection risk. One hypothesis is that the observed protection in RV144 is partially due to ADCC-mediating antibodies. We found that the majority (73 to 90%) of a representative group of vaccinees displayed plasma ADCC activity, usually (96.2%) blocked by competition with the C1 region-specific A32 Fab fragment. Using memory B-cell cultures and antigen-specific B-cell sorting, we isolated 23 ADCC-mediating nonclonally related antibodies from 6 vaccine recipients. These antibodies targeted A32-blockable conformational epitopes (n = 19), a non-A32-blockable conformational epitope (n = 1), and the gp120 Env variable loops (n = 3). Fourteen antibodies mediated cross-clade target cell killing. ADCC-mediating antibodies displayed modest levels of V-heavy (VH) chain somatic mutation (0.5 to 1.5%) and also displayed a disproportionate usage of VH1 family genes (74%), a phenomenon recently described for CD4-binding site broadly neutralizing antibodies (bNAbs). Maximal ADCC activity of VH1 antibodies correlated with mutation frequency. The polyclonality and low mutation frequency of these VH1 antibodies reveal fundamental differences in the regulation and maturation of these ADCC-mediating responses compared to VH1 bNAbs.
Journal of Virology 08/2012; 86(21):11521-32. · 5.40 Impact Factor
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Amnat Khamsiriwatchara,
Prayuth Sudathip,
Surasak Sawang,
Saowanit Vijakadge,
Thanapon Potithavoranan,
Aumnuyphan Sangvichean,
Wichai Satimai,
Charles Delacollette,
Pratap Singhasivanon,
Saranath Lawpoolsri, Jaranit Kaewkungwal
[show abstract]
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ABSTRACT: The Bureau of Vector-borne Diseases, Ministry of Public Health, Thailand, has implemented an electronic Malaria Information System (eMIS) as part of a strategy to contain artemisinin resistance. The attempt corresponds to the WHO initiative, funded by the Bill & Melinda Gates Foundation, to contain anti-malarial drug resistance in Southeast Asia. The main objective of this study was to demonstrate the eMIS' functionality and outputs after implementation for use in the Thailand artemisinin-resistance containment project.
The eMIS had been functioning since 2009 in seven Thai-Cambodian border provinces. The eMIS has covered 61 malaria posts/clinics, 27 Vector-borne Disease Units covering 12,508 hamlets at risk of malaria infections. The eMIS was designed as an evidence-based and near real-time system to capture data for early case detection, intensive case investigation, monitoring drug compliance and on/off-site tracking of malarial patients, as well as collecting data indicating potential drug resistance among patients. Data captured by the eMIS in 2008-2011 were extracted and presented.
The core functionalities of the eMIS have been utilized by malaria staff at all levels, from local operational units to ministerial management. The eMIS case detection module suggested decreasing trends during 2009-2011; the number of malaria cases detected in the project areas over the years studied were 3818, 2695, and 2566, with sero-positive rates of 1.24, 0.98, and 1.16%, respectively. The eMIS case investigation module revealed different trends in weekly Plasmodium falciparum case numbers, when classified by responsible operational unit, local and migrant status, and case-detection type. It was shown that most Thai patients were infected within their own residential district, while migrants were infected either at their working village or from across the border. The data mapped in the system suggested that P. falciparum-infected cases and potential drug-resistant cases were scattered mostly along the border villages. The mobile technology application has detected different follow-up rates, with particularly low rates among seasonal and cross-border migrants.
The eMIS demonstrated that it could capture essential data from individual malaria cases at local operational units, while effectively being used for situation and trend analysis at upper-management levels. The system provides evidence-based information that could contribute to the control and containment of resistant parasites. Currently, the eMIS is expanding beyond the Thai-Cambodian project areas to the provinces that lie along the Thai-Myanmar border.
Malaria Journal 07/2012; 11:247. · 3.19 Impact Factor
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Merlin L Robb,
Supachai Rerks-Ngarm,
Sorachai Nitayaphan,
Punnee Pitisuttithum, Jaranit Kaewkungwal,
Prayura Kunasol,
Chirasak Khamboonruang,
Prasert Thongcharoen,
Patricia Morgan,
Michael Benenson,
Robert M Paris,
Joseph Chiu,
Elizabeth Adams,
Donald Francis,
Sanjay Gurunathan,
Jim Tartaglia,
Peter Gilbert,
Don Stablein,
Nelson L Michael,
Jerome H Kim
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ABSTRACT: The Thai phase 3 HIV vaccine trial RV 144 showed modest efficacy of a vaccine against HIV acquisition. Baseline variables of age, sex, marital status, and risk did not modify vaccine efficacy. We did a post-hoc analysis of the trial's data to investigate behavioural risk and efficacy every 6 months after vaccination.
RV 144 was a randomised, multicentre, double-blind, placebo-controlled efficacy trial testing the combination of the HIV vaccines ALVAC-HIV (vCP1521) and AIDSVAX B/E to prevent HIV infection or reduce setpoint viral load. Male and female volunteers aged 18-30 years were recruited from the community. In this post-hoc analysis of the modified intention-to-treat population (16,395 participants), HIV risk behaviour was assessed with a self-administered questionnaire at the time of initial vaccination in the trial and every 6 months thereafter for 3 years. We classified participants' behaviour as low, medium, or high risk. Both the acquisition endpoint and the early viral-load endpoint were examined for interactions with risk status over time and temporal effects after vaccination. Multiple proportional hazards regression models with treatment and time-varying risk covariates were analysed.
Risk of acquisition of HIV was low in each risk group, but 9187 (58·2%) participants reported higher-risk behaviour at least once during the study. Participants classified as high or increasing risk at least once during follow-up were compared with those who maintained low-risk or medium-risk behaviour as a time-varying covariate, and the interaction of risk status and acquisition efficacy was significant (p=0·01), with greater benefit in low-risk individuals. Vaccine efficacy seemed to peak early--cumulative vaccine efficacy was estimated to be 60·5% (95% CI 22-80) through the 12 months after initial vaccination--and declined quickly. Vaccination did not seem to affect viral load in either early or late infections.
Future HIV vaccine trials should recognise potential interactions between challenge intensity and risk heterogeneity in both population and treatment effects. The regimen tested in the RV 144 phase 3 trial might benefit from extended immunisation schedules.
US Army Medical Research and Materiel Command and Division of AIDS, National Institute of Allergy and Infectious Disease, National Institutes of Health.
The Lancet Infectious Diseases 05/2012; 12(7):531-7. · 17.39 Impact Factor
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David C Montefiori,
Chitraporn Karnasuta,
Ying Huang,
Hasan Ahmed,
Peter Gilbert,
Mark S de Souza,
Robert McLinden,
Sodsai Tovanabutra,
Agnes Laurence-Chenine,
Eric Sanders-Buell, [......],
Steve G Self,
Phillip W Berman,
Donald Francis,
Faruk Sinangil,
Carter Lee,
Jim Tartaglia,
Merlin L Robb,
Barton F Haynes,
Nelson L Michael,
Jerome H Kim
[show abstract]
[hide abstract]
ABSTRACT: A recombinant canarypox vector expressing human immunodeficiency virus type 1 (HIV-1) Gag, Pro, and membrane-linked gp120 (vCP1521), combined with a bivalent gp120 protein boost (AIDSVAX B/E), provided modest protection against HIV-1 infection in a community-based population in Thailand (RV144 trial). No protection was observed in Thai injection drug users who received AIDSVAX B/E alone (Vax003 trial). We compared the neutralizing antibody response in these 2 trials.
Neutralization was assessed with tier 1 and tier 2 strains of virus in TZM-bl and A3R5 cells.
Neutralization of several tier 1 viruses was detected in both RV144 and Vax003. Peak titers were higher in Vax003 and waned rapidly in both trials. The response in RV144 was targeted in part to V3 of gp120.vCP1521 priming plus 2 boosts with gp120 protein was superior to 2 gp120 protein inoculations alone, confirming a priming effect for vCP1521. Sporadic weak neutralization of tier 2 viruses was detected only in Vax003 and A3R5 cells.
The results suggest either that weak neutralizing antibody responses can be partially protective against HIV-1 in low-risk heterosexual populations or that the modest efficacy seen in RV144 was mediated by other immune responses, either alone or in combination with neutralizing antibodies.
The Journal of Infectious Diseases 05/2012; 206(3):431-41. · 6.41 Impact Factor
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ABSTRACT: Hepatitis C virus (HCV) co-infection is common among HIV-infected patients; its treatment is not affordable in resource-limited settings. This study aimed to compare the morbidity, mortality, immunological and virological outcomes of antiretroviral therapy (ART) between HIV-infected patients with and without HCV co-infection in a setting where HCV infection is rarely treated. A retrospective cohort study was conducted among HIV-infected patients attending Ramathibodi Hospital between 1998 and 2008. We studied 171 HIV-infected patients 57 with and 114 without HCV co-infection. The mean age of patients was 34.6 years and 67.3% were males. There were no differences in demographics, HIV staging, CD4 counts, ART use and ART regimens between the two groups (p>0.05). All patients who had a CD4 count <200 cells/mm3 or had an AIDS-defining illness during following-up were given ART; these consisted of 84.2% and 88.6% of patients with and without HCV co-infection, respectively. Only 4 out of 57 (7%) HCV co-infected patients were treated for HCV infection. During a median (range) follow-up time of 2.9 (1.2-9.8) years, no patients died in either group. The rates of AIDS-defining illnesses and hospitalization in the two groups were similar (p>0.05). In a resource-limited setting where HCV treatment is not affordable, HCV co-infection does not appear to affect morbidity, mortality or treatment responses to ART. ART may have a greater impact than HCV co-infection on the survival of HCV/HIV co-infected patients. Further studies are needed to assess the long-term impact of HCV co-infection on clinical outcomes in HIV-infected patients without HCV treatment.
The Southeast Asian journal of tropical medicine and public health 05/2012; 43(3):646-51. · 0.60 Impact Factor
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Mark S de Souza,
Silvia Ratto-Kim,
Weerawan Chuenarom,
Alexandra Schuetz,
Somsak Chantakulkij,
Bessara Nuntapinit,
Anais Valencia-Micolta,
Doris Thelian,
Sorachai Nitayaphan,
Punnee Pitisuttithum,
Robert M Paris, Jaranit Kaewkungwal,
Nelson L Michael,
Supachai Rerks-Ngarm,
Bonnie Mathieson,
Mary Marovich,
Jeffrey R Currier,
Jerome H Kim
[show abstract]
[hide abstract]
ABSTRACT: The Thai HIV phase III prime/boost vaccine trial (RV144) using ALVAC-HIV (vCP1521) and AIDSVAX B/E was, to our knowledge, the first to demonstrate acquisition efficacy. Vaccine-induced, cell-mediated immune responses were assessed. T cell epitope mapping studies using IFN-γ ELISPOT was performed on PBMCs from HIV-1-uninfected vaccine (n = 61) and placebo (n = 10) recipients using HIV-1 Env peptides. Positive responses were measured in 25 (41%) vaccinees and were predominantly CD4(+) T cell-mediated. Responses were targeted within the HIV Env region, with 15 of 25 (60%) of vaccinees recognizing peptides derived from the V2 region of HIV-1 Env, which includes the α(4)β(7) integrin binding site. Intracellular cytokine staining confirmed that Env responses predominated (19 of 30; 63% of vaccine recipients) and were mediated by polyfunctional effector memory CD4(+) T cells, with the majority of responders producing both IL-2 and IFN-γ (12 of 19; 63%). HIV Env Ab titers were higher in subjects with IL-2 compared with those without IL-2-secreting HIV Env-specific effector memory T cells. Proliferation assays revealed that HIV Ag-specific T cells were CD4(+), with the majority (80%) expressing CD107a. HIV-specific T cell lines obtained from vaccine recipients confirmed V2 specificity, polyfunctionality, and functional cytolytic capacity. Although the RV144 T cell responses were modest in frequency compared with humoral immune responses, the CD4(+) T cell response was directed to HIV-1 Env and more particularly the V2 region.
The Journal of Immunology 04/2012; 188(10):5166-76. · 5.79 Impact Factor
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Barton F Haynes,
Peter B Gilbert,
M Juliana McElrath,
Susan Zolla-Pazner,
Georgia D Tomaras,
S Munir Alam,
David T Evans,
David C Montefiori,
Chitraporn Karnasuta,
Ruengpueng Sutthent, [......],
Michael D Alpert,
Nicole L Yates,
Xiaoying Shen,
Richard A Koup,
Punnee Pitisuttithum, Jaranit Kaewkungwal,
Sorachai Nitayaphan,
Supachai Rerks-Ngarm,
Nelson L Michael,
Jerome H Kim
[show abstract]
[hide abstract]
ABSTRACT: In the RV144 trial, the estimated efficacy of a vaccine regimen against human immunodeficiency virus type 1 (HIV-1) was 31.2%. We performed a case-control analysis to identify antibody and cellular immune correlates of infection risk.
In pilot studies conducted with RV144 blood samples, 17 antibody or cellular assays met prespecified criteria, of which 6 were chosen for primary analysis to determine the roles of T-cell, IgG antibody, and IgA antibody responses in the modulation of infection risk. Assays were performed on samples from 41 vaccinees who became infected and 205 uninfected vaccinees, obtained 2 weeks after final immunization, to evaluate whether immune-response variables predicted HIV-1 infection through 42 months of follow-up.
Of six primary variables, two correlated significantly with infection risk: the binding of IgG antibodies to variable regions 1 and 2 (V1V2) of HIV-1 envelope proteins (Env) correlated inversely with the rate of HIV-1 infection (estimated odds ratio, 0.57 per 1-SD increase; P=0.02; q=0.08), and the binding of plasma IgA antibodies to Env correlated directly with the rate of infection (estimated odds ratio, 1.54 per 1-SD increase; P=0.03; q=0.08). Neither low levels of V1V2 antibodies nor high levels of Env-specific IgA antibodies were associated with higher rates of infection than were found in the placebo group. Secondary analyses suggested that Env-specific IgA antibodies may mitigate the effects of potentially protective antibodies.
This immune-correlates study generated the hypotheses that V1V2 antibodies may have contributed to protection against HIV-1 infection, whereas high levels of Env-specific IgA antibodies may have mitigated the effects of protective antibodies. Vaccines that are designed to induce higher levels of V1V2 antibodies and lower levels of Env-specific IgA antibodies than are induced by the RV144 vaccine may have improved efficacy against HIV-1 infection.
New England Journal of Medicine 04/2012; 366(14):1275-86. · 53.30 Impact Factor
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ABSTRACT: The purpose of this study was to assess the knowledge and attitudes about human papilloma virus (HPV) and cervical cancer, and the acceptability of HPV vaccine among students, parents and teachers in secondary schools in Bangkok, Thailand. We conducted a school-based cross-sectional study at four public secondary schools in Bangkok. A total of 644 students aged 12-15 years, 664 parents and 304 teachers were recruited into the study. Data were collected by self-administered questionnaires. The percentages of students, parents and teachers who were willing to be vaccinated were 26, 49 and 43%, respectively. Forty-one percent of parents wanted their children to be vaccinated. Students, parents and teachers had a moderate knowledge of HPV, cervical cancer and the HPV vaccine with mean scores of 6.91 (SD = 1.75), 6.82 (SD = 1.88), and 6.70 (SD = 1.89), respectively. The attitudes of students, parents, and teachers were fair with scores of 3.46 (SD = 0.41), 3.52 (SD = 0.43), and 3.46 (SD = 0.47) out of 5, respectively. Twenty-nine percent of students and 36% of parents were willing to pay USD 14.3-28.5 per dose for the quadrivalent vaccine; 33% of teachers were willing to pay < USD 14.3 per dose for the quadrivalent vaccine. This study is the first study to report the knowledge, and attitudes and acceptability of HPV vaccination in Thailand. The findings suggest the willingness to pay was relatively low and related to the price, while knowledge and attitudes regarding the importance of the HPV vaccine were fair particularly among parents and teachers. Greater effort may be needed to educate people regarding the cost and benefits of HPV vaccination before it would be more acceptable to parents, teachers and students in Thailand.
The Southeast Asian journal of tropical medicine and public health 03/2012; 43(2):340-53. · 0.60 Impact Factor
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ABSTRACT: Participation in the community socially by stroke victims is an optimal outcome post-stroke. We carried out a cohort study to evaluate a model for community participation by Thai stroke victims 6 months post-stroke. Six standardized instruments were used to assess the patient's status 1, 3 and 6 months after stroke. These were the modified Rankin Scale, the National Institute of Health Stroke Scale, the Fugl-Meyer Assessment and the Berg Balance Scale. The performance of activities of daily living and community ambulation were measured using the Barthel Index and walking velocity. Participation in the community was measured by the Stroke Impact Scale. The outcomes demographics and stroke related variables were analyzed using the Generalized Estimating Equations. Of the 98 subjects who completed the follow-up assessment, 72 (86.5%) felt they had more participation in the community 6 months post-stroke. The level of disability, performance of independent activities and length of time receiving physical therapy were associated with the perceived level of participation in the community among stroke victims 6 months post-stroke. To achieve a goal of good participation in the community among stroke victims, health care planning should focus on improving the stroke victim's ability to independently perform daily activities. The average length of physical therapy ranged from 1 to 6 months, at 3 to 8 hours/month. Clinical practice guidelines should be explored to optimize participation in the community.
The Southeast Asian journal of tropical medicine and public health 07/2011; 42(4):1005-13. · 0.60 Impact Factor
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Kobkul Aunhachoke,
Valai Bussaratid,
Pornchai Chirachanakul,
Boosbun Chua-Intra,
Jittima Dhitavat,
Kanokporn Jaisathaporn, Jaranit Kaewkungwal,
Kowit Kampirapap,
Thiravud Khuhaprema,
Kulprapat Pairayayutakul,
Punnee Pitisuttithum,
Jirot Sindhvananda,
Yupin Thaipisuttikul
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ABSTRACT: This study aimed to measure the herpes zoster-associated burden of illness, healthcare utilization, and costs among Thai patients.
This prospective cohort study of 180 patients aged ≥ 50 years and healthy, or ≥ 20 years and immunosuppressed, with zoster rash, was conducted in Bangkok and its environs, Thailand, during 2007-2008. Each patient was followed for six months for zoster-associated rash, pain, quality of life (QoL), and healthcare utilization and costs.
A total of 180 subjects were enrolled in the study. Their mean ± standard deviation (SD) age was 58.9 ± 13.8 years. Of the 180 patients enrolled, 138 (76.7%), 34 (18.9%) and eight (4.4%) patients were elderly, HIV-infected, and receiving immunosuppressive agents, respectively; 35 (19.4%) had post-herpetic neuralgia (PHN), and 13 (7.2%) had zoster ophthalmicus. The severity of zoster pain was moderately highly correlated with activities of daily living (ADL), at 0.68 ≤ ρ ≤ 0.76. Most patients required only one or two outpatient visits. The mean ± SD total of direct healthcare costs was 3083.4 ± 5047.0 Thai baht or ∼ 1.1% of annual income per capita.
Herpes zoster contributes a significant burden of illness to both patients and the wider community.
International journal of dermatology 04/2011; 50(4):428-35. · 1.18 Impact Factor
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ABSTRACT: The objective of this study was to conduct a cross-sectional evaluation of pregnancy indicators, child growth failure, and the effect of antenatal care on birth outcomes in a marginalized community under the care of a health center in Suan Phung District, Ratchaburi Province. Health and socioeconomic data about children born in 2007 and their parents were obtained from the sub-district health center and district hospital were collected and analyzed by univariate and multivariate methods. Most of the residents in the study were Karen ethnic origin. Data was available for 152 children, of which 136 met study inclusion criteria. Health outcomes of the study population significantly different from the general Thai population included higher average parity (2.53 +/- 1.99 vs 1.735; p < 0.001), lower average birth weight (2,876.05 +/- 399.48 grams vs 3,200 grams, p < 0.001), and lower average height-for-age and weight-for-age (p < 0.001). The prevalences of stunting, underweight and wasting were higher than the general Thai population (p < 0.001). Having fewer than 4 antenatal care (ANC) visits was associated with low birth weight (unadjusted OR 4.88, 95% CI 1.13-21.05; adjusted OR 5.77, 95% CI 1.27-26.30).
The Southeast Asian journal of tropical medicine and public health 01/2011; 42(1):152-60. · 0.60 Impact Factor
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ABSTRACT: At the verge of elimination of malaria in Bhutan, this study was carried out to analyse the trend of malaria in the endemic districts of Bhutan and to identify malaria clusters at the sub-districts. The findings would aid in implementing the control activities. Poisson regression was performed to study the trend of malaria incidences at district level from 1994 to 2008. Spatial Empirical Bayesian smoothing was deployed to identify clusters of malaria at the sub-district level from 2004 to 2008.
Trend of the overall districts and most of the endemic districts have decreased except Pemagatshel, which has an increase in the trend. Spatial cluster-outlier analysis showed that malaria clusters were mostly concentrated in the central and eastern Bhutan in three districts of Dagana, Samdrup Jongkhar and Sarpang. The disease clusters were reported throughout the year. Clusters extended to the non-transmission areas in the eastern Bhutan.
There is significant decrease in the trend of malaria with the elimination at the sight. The decrease in the trend can be attributed to the success of the control and preventive measures. In order to realize the target of elimination of malaria, the control measure needs to be prioritized in these high-risk clusters of malaria.
Malaria Journal 01/2011; 10:89. · 3.19 Impact Factor
