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OBJECTIVE: People with chronic HIV exhibit lower regional brain volumes compared to people without HIV (PWOH). Whether imaging alterations observed in chronic infection occur in acute HIV infection (AHI) remains unknown. DESIGN: Cross-sectional study of Thai participants with AHI. METHODS: One hundred and twelve Thai males with AHI (age 20-46) and 18 male Thai PWOH (age 18-40) were included. Individuals with AHI were stratified into early (Fiebig I-II; n = 32) and late (Fiebig III-V; n = 80) stages of acute infection using validated assays. T1-weighted scans were acquired using a 3 T MRI performed within five days of antiretroviral therapy (ART) initiation. Volumes for the amygdala, caudate nucleus, hippocampus, nucleus accumbens, pallidum, putamen, and thalamus were compared across groups. RESULTS: Participants in late Fiebig stages exhibited larger volumes in the nucleus accumbens (8% larger; P = 0.049) and putamen (19%; P

Much has been learnt about the role of HLA alleles during natural infection of HIV-1, but far less is known about their role in people living with HIV (PLWH) on suppressive antiretroviral therapy (ART). In this study we used variable selection to identify predictors of HIV reservoir size, as measured by total HIV DNA in 192 participants in an acute HIV infection (AHI) cohort. Baseline clinical data including pre-ART CD4 T cell counts and plasma viral load (VL) were available from all participants along with longitudinal measurements after ART initiation during AHI. Time to VL suppression, time to CD4 reconstitution and pre-ART viremia were the strongest predictors of undetectable total HIV DNA at 24 weeks after ART initiation. We next performed HLA typing in 526 participants from the same cohort and investigated associations with the three predictors of reservoir size. HLA-B*57 and B*58 both associated significantly with time to VL suppression, which was one of the predictors of the size of the HIV reservoir. These findings are significant in PLWH and have to be considered in the context of therapeutic intervention when conducting ATI studies as participants with these alleles could impact clinical findings given the small sizes of these studies.

Development of an effective HIV-1 vaccine will be facilitated by better understanding the dynamics between the founder virus and the early humoral responses. Variations between subtypes may influence the evolution of immune responses and should be considered as we strive to understand these dynamics.

Background Efavirenz (EFV)- and dolutegravir (DTG)-based antiretroviral therapy (ART) is the former and current recommended regimen for treatment-naive individuals with human immunodeficiency virus type 1 (HIV-1). Whether they impact the immunological and neuropsychiatric profile differentially remains unclear. Methods This retrospective analysis included 258 participants enrolled during acute HIV-1 infection (AHI). Participants initiated 1 of 3 ART regimens during AHI: EFV-based (n = 131), DTG-based (n = 92), or DTG intensified with maraviroc (DTG/MVC, n = 35). All regimens included 2 nucleoside reverse-transcriptase inhibitors and were maintained for 96 weeks. CD4+ and CD8+ T-cell counts, mood symptoms, and composite score on a 4-test neuropsychological battery (NPZ-4) were compared. Results At baseline, the median age was 26 years, 99% were male, and 36% were enrolled during Fiebig stage I–II. Plasma viral suppression at weeks 24 and 96 was similar between the groups. Compared with the EFV group, the DTG group showed greater increments of CD4+ (P < .001) and CD8+ (P = .015) T-cell counts but a similar increment of CD4/CD8 ratio at week 96. NPZ-4 improvement was similar between the 2 groups at week 24 but greater in the DTG group at week 96 (P = .005). Depressive mood and distress symptoms based on the Patient Health Questionnaire and distress thermometer were similar between the 2 groups at follow-up. Findings for the DTG/MVC group were comparable to those for the DTG group vs the EFV group. Conclusions Among individuals with AHI, 96 weeks of DTG-based ART was associated with greater increments of CD4+ and CD8+ T-cell counts and improvement in cognitive performance.

OBJECTIVE: We examined individual differences in CD4/CD8 T-cell ratio trajectories and associated risk profiles from acute HIV infection (AHI) through 144 weeks of antiretroviral therapy (ART) using a data-driven approach. METHODS: A total of 483 AHI participants began ART during Fiebig I-V and completed follow-up evaluations for 144 weeks. CD4+, CD8+, and CD4/CD8 T-cell ratio trajectories were defined followed by analyses to identify associated risk variables. RESULTS: Participants had a median viral load (VL) of 5.88 copies/ml and CD4/CD8 T-cell ratio of 0.71 at enrollment. After 144 weeks of ART, the median CD4/CD8 T-cell ratio was 1.3. Longitudinal models revealed five CD4/CD8 T-cell ratio subgroups: group 1 (3%) exhibited a ratio >1.0 at all visits; groups 2 (18%) and 3 (29%) exhibited inversion at enrollment, with normalization 4 and 12 weeks after ART, respectively; and groups 4 (31%) and 5 (18%) experienced CD4/CD8 T-cell ratio inversion due to slow CD4+ T-cell recovery (group 4) or high CD8+ T-cell count (group 5). Persistent inversion corresponded to ART onset after Fiebig II, higher VL, soluble CD27 and TIM-3, and lower eosinophil count. Individuals with slow CD4+ T-cell recovery exhibited higher VL, lower white blood cell count, lower basophil percent, and treatment with standard ART, as well as worse mental health and cognition, compared with individuals with high CD8+ T-cell count. CONCLUSIONS: Early HIV disease dynamics predict unfavorable CD4/CD8 T-cell ratio outcomes after ART. CD4+ and CD8+ T-cell trajectories contribute to inversion risk and correspond to specific viral, immune, and psychological profiles during AHI. Adjunctive strategies to achieve immune normalization merit consideration.

Efavirenz (EFV)- and Dolutegravir (DTG)-based antiretroviral therapy (ART) are the formerly and currently recommended regimen for treatment-naïve individuals with HIV-1. Whether they impact the immunological and neuropsychiatric profile differentially remains unclear.This retrospective analysis included 258 participants in the RV254 acute HIV-1 infection (AHI) cohort. Participants initiated one of three ART regimens during AHI: EFV-based (n = 131), DTG-based (n = 92), or DTG intensified with maraviroc (DTG/MVC, n = 35). All regimens included two nucleoside reverse transcriptase inhibitors and were maintained for 96 weeks. CD4 + and CD8+ T-cell counts, mood symptoms, and performance on a 4-test neuropsychological battery (NPZ-4) were compared.At baseline, the median age was 26 years; 99% were male; 36% were enrolled during Fiebig stage I-II. Plasma viral suppression at weeks 24 and 96 was similar between the groups. Compared to the EFV group, the DTG group showed greater increments of CD4+ (p 0.001) and CD8+ (p = 0.015) T-cell counts but similar increment in CD4/CD8 ratio at week 96. Improvement in NPZ-4 was similar between the two groups at week 24, but greater in the DTG group at week 96 (p = 0.005). Depressive mood and distress symptoms based on the Patient Health Questionnaire and distress thermometer were similar between the two groups at follow-up. Findings for the DTG/MVC group were comparable to those for the DTG group in comparison to the EFV group.Among individuals with AHI, 96 weeks of DTG-based ART was associated with greater increments of CD4 + and CD8+ T-cell counts, and greater improvement in cognitive performance.

Define the clinical presentation of acute human immunodeficiency virus infection (AHI) among men and women from 2 continents to create a clinical scoring algorithm.Comparison of incident sign and symptom between those with and without AHI.At-risk human immunodeficiency virus (HIV) negative men and women in Thailand, Kenya, Tanzania, and Uganda underwent twice-weekly testing for HIV. Newly diagnosed participants were evaluated twice weekly for 21 days after infection.Of the 3345 participants enrolled, 56 African females and 36 biological males from Thailand were diagnosed with AHI. Four hundred fifty-two of their encounters were compared to 18,281 HIV negative encounters. Due to a high degree of heterogeneity among incident symptoms, 2 unique subgroups based upon geography and sex were created. Among Thai males, the signs and symptoms with the greatest odds ratio (OR) between AHI and uninfected participants were nausea (OR 16.0, 95% confidence interval [CI] 3.9-60.2, P .001) and lymphatic abnormalities (OR 11.8, 95% CI 4.2-49.0, P .001); and among African females were pain behind the eyes (OR 44.4, 95% CI 12.0-158.0, P .0001) and fatigue (OR 22.7, 95% CI 11.3-44.3, P .001). The Thai male scoring algorithm had a 66% sensitivity and 84% specificity while the African female algorithm had a sensitivity of 27% and specificity of 98%.The different incident symptoms during AHI necessitated creating 2 different scoring algorithms that can guide diagnostic testing among a particular sex in the appropriate geographic setting. Further research on risk exposure, sex, and demographic specific models is warranted.

Background Increasing number of hepatitis C virus (HCV) infections among HIV positive men whohave sex with men (MSM) as in an acute HIV infection cohort study in Bangkok, reached an incidence of 45/1000 person-years in 2018. Direct-acting antivirals (DAAs), that cure HCV infection and thereby can prevent transmission, are expensive, their reimbursement being presently delayed to the chronic stages of liver fibrosis. The aim of this study was to determine the cost-effectiveness of immediate DAA treatment to reduce HCV transmission among HIV positive MSM in Bangkok. Methods A deterministic transmission model was calibrated to the HCV epidemic among HIV positive MSM in Bangkok. We compared the current practice of starting DAAs at METAVIR stage F2 rather than at stage F1, or immediately after diagnosis, at stage F0. Cost-effectiveness was examined from a payer's perspective, using a 3% annual discounting rate. Results Compared to the incidence in 2018, delaying DAA treatment to METAVIR stage F2 or F1, increases HCV incidence in 2030 to 63/1000 person-years and 56/1000 person-years, respectively. Conversely, immediate DAA treatment reduces the incidence to 26/1000 person-years. Compared to initiating treatment at stage F2, immediate treatment is cost saving within seven years and saves $17 million over 40 years. One-way sensitivity analysis showed that lower cost savings were achieved at a higher price of DAA treatment and at less frequent HCV screening. Conclusion Immediate DAA treatment is cost saving and increases health benefits by reducing HCV incidence among HIV-infected MSM.

To date, six vaccine strategies have been evaluated in clinical trials for their efficacy at inducing protective immune responses against HIV infection. However, only the ALVAC-HIV/AIDSVAX B/E vaccine (RV144 trial) has demonstrated protection, albeit modestly (31%; P = 0.03). One potential correlate of protection was a low-frequency HIV-specific CD4 T cell population with diverse functionality. Although CD4 T cells, particularly T follicular helper (Tfh) cells, are critical for effective antibody responses, most studies involving HIV vaccines have focused on humoral immunity or CD8 T cell effector responses, and little is known about the functionality and frequency of vaccine-induced CD4 T cells. We therefore assessed responses from several phase I/II clinical trials and compared them to responses to natural HIV-1 infection. We found that all vaccines induced a lower magnitude of HIV-specific CD4 T cell responses than that observed for chronic infection. Responses differed in functionality, with a CD40 ligand (CD40L)-dominated response and more Tfh cells after vaccination, whereas chronic HIV infection provoked tumor necrosis factor alpha (TNF-α)-dominated responses. The vaccine delivery route further impacted CD4 T cells, showing a stronger Th1 polarization after dendritic cell delivery than after intramuscular vaccination. In prime/boost regimens, the choice of prime and boost influenced the functional profile of CD4 T cells to induce more or less polyfunctionality. In summary, vaccine-induced CD4 T cell responses differ remarkably between vaccination strategies, modes of delivery, and boosts and do not resemble those induced by chronic HIV infection. Understanding the functional profiles of CD4 T cells that best facilitate protective antibody responses will be critical if CD4 T cell responses are to be considered a clinical trial go/no-go criterion. IMPORTANCE Only one HIV-1 candidate vaccine strategy has shown protection, albeit marginally (31%), against HIV-1 acquisition, and correlates of protection suggested that a multifunctional CD4 T cell immune response may be important for this protective effect. Therefore, the functional phenotypes of HIV-specific CD4 T cell responses induced by different phase I and phase II clinical trials were assessed to better show how different vaccine strategies influence the phenotype and function of HIV-specific CD4 T cell immune responses. The significance of this research lies in our comprehensive comparison of the compositions of the T cell immune responses to different HIV vaccine modalities. Specifically, our work allows for the evaluation of vaccination strategies in terms of their success at inducing Tfh cell populations.

BackgroundAcute human immunodeficiency virus type 1 (HIV-1) infection is a major contributor to transmission of HIV-1. An understanding of acute HIV-1 infection may be important in the development of treatment strategies to eradicate HIV-1 or achieve a functional cure. MethodsWe performed twice-weekly qualitative plasma HIV-1 RNA nucleic acid testing in 2276 volunteers who were at high risk for HIV-1 infection. For participants in whom acute HIV-1 infection was detected, clinical observations, quantitative measurements of plasma HIV-1 RNA levels (to assess viremia) and HIV antibodies, and results of immunophenotyping of lymphocytes were obtained twice weekly. ResultsFifty of 112 volunteers with acute HIV-1 infection had two or more blood samples collected before HIV-1 antibodies were detected. The median peak viremia (6.7 log10 copies per milliliter) occurred 13 days after the first sample showed reactivity on nucleic acid testing. Reactivity on an enzyme immunoassay occurred at a median of 14 days. The n...

Background We examined hormonal contraceptive (HC) discontinuation and factors associated with discontinuation among HIV-uninfected women and the effect of HIV diagnosis on subsequent contraceptive use. Study Design We analyzed 4461 HIV-uninfected women from a prospective study of HC and HIV acquisition in Uganda, Zimbabwe and Thailand. Participants were ages 18–35 years, not pregnant, and using oral contraceptives (OCs) or injectable depot medroxyprogesterone acetate (DMPA) for at least 3 months before enrollment (median duration of OC and DMPA use before enrollment was 11.7 and 8.9 months, respectively). We compared the probability of OC and DMPA discontinuation using survival analysis and factors related to discontinuation using Cox regression. We also analyzed contraceptive patterns among 194 women who became infected with HIV. Results Median duration of use after study enrollment was 15.6 months for OCs and 18.5 months for DMPA. Continuation rates for both methods were highest in Thailand. Factors associated with OC discontinuation included, nausea, breast tenderness, condom use, and no sex. Factors associated with DMPA discontinuation included young age, breast tenderness, nausea, irregular bleeding, high-risk sexual behaviors, partner risk, condom use, and no sex. Following an HIV diagnosis, 135 (98.5%) of 137 hormonal users continued HC and 14 (25%) of 57 nonusers began using HC. Conclusions Contraceptive continuation for OCs and DMPA was relatively high over 2 years. Young women, those reporting side effects, and those using condoms are more likely to discontinue and need ongoing contraceptive counseling. Many women receiving HIV-positive diagnoses desire effective contraception.

Women diagnosed with cervical cancer report longer duration and more recent use of combined oral contraceptives (COCs). It is unclear whether COC use is associated with upstream events of human papillomavirus (HPV) infection prior to development of clinical disease. The objective of our study was to assess the association of contraceptive use on the risk for prevalent HPV infection in a cohort of long-term hormonal contraceptive (HC) users. One thousand and seventy (n = 1,070) HIV-negative women aged 20-37 from Thailand enrolled in a prospective study of the natural history of HPV. Baseline HPV genotype information, recency and duration of HC use, sexual behavior, other sexually transmitted infection (STI) information and cervical cytology and histology were assessed. At enrollment, 19.8% and 11.5% of women were infected with any HPV or any high-risk (HR)-HPV, respectively. After adjustment for age, current and past sexual risk behaviors, STI history and cytology, the use of COCs for >6 years was found to be associated with an increased risk of infection with any HPV [prevalence ratio (PR): 1.88 (1.21, 2.90)] and any HR-HPV [PR: 2.68 (1.47, 4.88)] as compared to never users. Recent, long-term COC use was associated with an increased risk for prevalent HPV infection independent of sexual behavior and cervical abnormalities. No similar association was observed for recent or long duration use of progestin-only contraceptives (i.e., depomedroxyprogesterone acetate). These data suggest that COC use may impact early upstream events in the natural history of HPV infection.

Background Progestin-only injectable contraceptives continue to gain in popularity, but uncertainty remains about pregnancy risk among women late for reinjection. The World Health Organization (WHO) recommends a “grace period” of 2 weeks after the scheduled 13-week reinjection. Beyond 2 weeks, however, many providers send late clients home to await menses. Study design A prospective cohort study in Uganda, Zimbabwe and Thailand followed users of depot-medroxyprogesterone acetate (DMPA) for up to 24 months. Users were tested for pregnancy at every reinjection, allowing analysis of pregnancy risk among late comers. Results The analysis consists of 2290 participants contributing 13,608 DMPA intervals. The pregnancy risks per 100 women-years for “on time” [0.6; 95% confidence interval (CI), 0.33–0.92], “2-week grace” (0.0; 95% CI, 0.0–1.88) and “4-week grace” (0.4; 95% CI, 0.01–2.29) injections were low and virtually identical. Conclusion Extending the current WHO grace period for DMPA reinjection from 2 to 4 weeks does not increase pregnancy risk and could increase contraceptive continuation.

The objective was to estimate the probability of pregnancy for oral contraceptive pill (OCP) injectable contraceptive and condom users in Uganda Thailand and Zimbabwe. This study is a secondary analysis of 5224 women who participated in a prospective study evaluating the association between hormonal contraception and human immunodeficiency virus (HIV) acquisition. The overall 12-month cumulative probability of pregnancy of injectable contraceptive users was 0.6% (95% confidence interval [CI] 0.3-1.0) with similar risks in Uganda (0.3% 95% CI 0-0.7) Thailand (0.6% 95% CI 0-1.2) and Zimbabwe (1.0% 95% CI 0.3-1.7). The 12-month cumulative probability of pregnancy for OCP users was 9.5% (95% CI 8.1-11.0%) with similar risks of pregnancy in Uganda and Zimbabwe (14.6% 95% CI 11.7-17.4; and 10.2% 95% CI 8.0 -12.5 respectively) but substantially lower risk in Thailand (0.5% 95% CI 0-1.2). The overall 12-month cumulative probability of pregnancy for women intending to use a given method at baseline was 2.0% (95% CI 1.4-2.6%) for injectable contraceptives 15.7% (95% CI 14.1-17.3%) for OCPs and 25.8% (95% CI 23.2-28.4) for condoms. Women in Thailand experienced lower pregnancy risk with condoms (18.4% 95% CI 11.1-25.7) than in Uganda (29.5% 95% CI 25.7-33.4) and Zimbabwe (23.3% 95% CI 19.4-27.2). The overall risk of pregnancy for injectable contraceptive users was substantially lower than for oral contraceptive pill users. However Thai participants had similarly low cumulative pregnancy probabilities for both methods. Women receiving contraceptive counseling should be informed that their experience with a given method may differ from the average or typical-use pregnancy rates often discussed during contraceptive counseling. Tailored counseling is necessary for women to make informed choices. (authors)

Background Cervical cancer is the most common cancer among women of reproductive age in Thailand. However, information on the prevalence and correlates of anogenital HPV infection in Thailand is sparse. Methods HPV genotype information, reproductive factors, sexual behavior, other STI and clinical information, and cervical cytology and histology were assessed at enrollment among one thousand two hundred and fifty-six (n = 1,256) HIV negative women aged 20–37 from Thailand enrolled in a prospective study of the natural history of HPV. The type-specific prevalence of HPV was estimated using cervical swab specimens from healthy women and women with a diagnosis of CIN 2/3 at baseline. Prevalence ratios (95% CI) were estimated using Poisson regression to quantify the association of demographic, behavioral, and clinical correlates with prevalent HPV infection. Results Overall, 307 (24.6%) and 175 (14.0%) of women were positive for any HPV type and any HR-HPV type, respectively; the most common types were 72, 52, 62, and 16. Among women diagnosed with CIN 2/3 at enrollment (n = 11), the most prevalent HPV types were 52 and 16. In multivariate analysis, HPV prevalence at enrollment was higher among women with: long-term combined oral contraceptive use, a higher number of lifetime sexual partners, a prior Chlamydia infection, and a current diagnosis of Bacterial Vaginosis. Conclusion The study findings provide important information that can be used in the evaluation of primary and secondary interventions designed to reduce the burden of cervical cancer in Thailand. Electronic supplementary material The online version of this article (doi:10.1186/s12879-015-0886-z) contains supplementary material, which is available to authorized users.

HIV-1 subtype B and CRF01_AE have been in circulation in Thailand and Southeast Asia for more than a decade. Initially separated by risk group, the two strains are increasingly intermixed, and two recombinant strains of essentially reciprocal structure have been recently reported. Here we identify additional CRF_01B recombinants and provide the evidence that HIV-1 strains now pass freely between the two high-risk populations. HIV isolates that showed discordance between CRF01_AE and subtype B in multi-region genotyping assays were selected for the study. They were drawn from 3 different cohorts in Thailand representing different risk behaviors and demographic characteristics: a drug user cohort in the north, a family planning clinic attendee cohort in the southeast, and a cohort study of the mucosal virology and immunology of HIV-1 infection in Thailand. The DNA from these isolates was PCR amplified to recover the full HIV-1 genome and subjected to sequencing and phylogenetic analysis. We establish that one particular CRF_01B recombinant, with the external envelope of subtype B and the rest of the genome from CRF01_AE, is circulating widely in Thailand. Termed CRF15_01B (also referred to as CRF15), the strain was primarily heterosexually transmitted, although injecting drug use (IDU) also played a role. In aggregate data from the studies, CRF15 constituted 1.7% of all HIV-1 infections (95% confidence interval 0.5-4.4%) and was dispersed widely in the country. The previously separate heterosexual and IDU epidemics have apparently been bridged by a new CRF. The entry of CRF15 into the mainstream of the epidemic signals new complexity in the long stable molecular picture in Thailand. These recombinants must be considered in ongoing or projected efficacy evaluations of HIV-1 vaccines and antiviral therapies.

Human immunodeficiency virus type 1 (HIV) RNA load was measured in paired samples of peripheral blood plasma and nasopharyngeal (NP) washes from 97 Thai subjects infected with subtype E or B. HIV RNA was quantifiable in 93% of peripheral blood plasma samples tested and was inversely correlated (ρ =-0.524; p < 0.001) with CD4 absolute count. HIV RNA was quantifiable in 29% of NP samples tested, and the median value was less than that of plasma viral load. HIV RNA load in NP samples was correlated (ρ = 0.388; p < 0.001) with viral load in peripheral blood. HIV RNA was not detected in NP washes from subjects with undetectable plasma viral load. Virus isolation attempts on two NP samples were negative. The results do not support local HIV production in the nasopharynx, but extend current knowledge of HIV shedding to include the NP compartment.

Women diagnosed with cervical cancer report longer duration and more recent use of combined oral contraceptives (COCs). It is unclear how COC use impacts risk of cervical carcinogenesis.We estimated the risk of new human papillomavirus (HPV) DNA detection and persistence among 1135 human immunodeficiency virus (HIV)-negative women aged 20-37 years from Thailand who were followed for 18 months at 6-month intervals. Type-specific HPV DNA, demographic information, hormonal contraceptive use, sexual behavior, genital tract coinfection, and Papanicolaou test results were assessed at baseline and each follow-up.Women who reported current COC use during follow-up were less likely to clear HPV infection compared with nonusers, independent of sexual behavior, and Papanicolaou test diagnosis (AHR: 0.67 [95% CI: .49-.93]). Similar associations were not observed among women reporting current use of depomedroxyprogesterone acetate (DMPA). Neither COC nor DMPA use was significantly associated with new HPV DNA detection.These data do not support the hypothesis that contraceptive use is associated with cervical cancer risk via increased risk of HPV acquisition. The increased risk of HPV persistence observed among current COC users suggests a possible influence of female sex hormones on host response to HPV infection.

Aim: To identify risk factors associated with and evaluate algorithms for predicting Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG) cervical infections in women attending family planning clinics in Thailand. Methods: Eligible women were recruited from family planning clinics from all regions in Thailand. The women were followed at 3-month intervals for 15-24 months. At each visit the women were interviewed for interval sexually transmitted infection (STI) history in the past 3 months recent sexual behavior and contraceptive use. Pelvic examinations were performed and endocervical specimens were collected to test for CT and NG using polymerase chain reaction. Results: Factors associated with incident CT/NG cervical infections in multivariate analyses included region of country other than the north age

Human papillomavirus type 52 is highly prevalent in Asia and Africa and accounts for 2-3% of total cervical cancer burden worldwide. The Roche Molecular Systems HPV Linear Array (RMS-LA uses multiple type (i.e. mixed) probes to detect DNA from HPV 52 infection which limits the assay's ability to determine HPV 52 status in the presence of HPV 33, 35, or 58 infection. This report presents a simple to use and highly reproducible HPV 52 type-specific quantitative real-time PCR (RT-PCR) assay based on Taqman chemistry for detection and quantification of HPV 52 DNA from cervical swab specimens. Mixed probe positive cervical swab specimens collected from rural and urban women in Thailand (n=68) were used to determine assay agreement and differences in HPV 52 DNA viral load across cytological diagnosis. Forty-eight specimens were determined to be HPV 52 positive by RMS-LA with 94% (n=45) confirmed positive by Taqman assay (kappa: 0.86, 95% CI: 0.74, 0.99). Higher median viral load was observed among women with a Pap diagnosis of >=ASCUS vs. normal/inflammation (8510 copies/1000 cell equivalents vs. 279 copies/1000 cell equivalents, p

Objective: To determine risk factors for incident bacterial vaginosis (BV) in young Thai women. Study Design: Prospective data from a cohort of 1522 women aged 18 to 35 years, who were enrolled in a study of hormonal contraception and HIV acquisition, were used to evaluate potential risk factors for BV, as diagnosed by Amsel criteria. Results: The median prevalence of BV from 3 to 24 months of follow-up visits was 2.5%. The BV incidence was 10.0 per 100-woman years. Statistically significant factors in multivariable analysis were sex during menstruation [hazard ratio (HR), 1.80; 95% CI, 1.11–2.92], male partners having sex with other women (HR, 2.3; 95% CI, 1.45–2.98), cigarette smoking (HR, 1.79; 95% CI, 1.08–2.98), and trichomoniasis (HR, 15.68; 95% CI, 4.95–49.68). Intravaginal practices were not associated with incident BV in unadjusted or adjusted analysis. Conclusions: This study supports the association between sexual behaviors and the incident BV. Failure to detect an association between intravaginal practices and incident BV warrants further studies in high-risk populations or in women with a higher prevalence of intravaginal practices.

Molecular characterization of C2-V5 envelope sequences from maternal plasma, peripheral blood mononuclear cells (PBMC), cervical secretions and infant PBMC was performed in eight CRF01_AE-infected mother/infant pairs. Maternal viruses were relatively homogeneous within a compartment but distinct in different compartments in mothers with high CD4 cell counts. Infant viruses were almost distinct, but phylogenetically related, to maternal viruses, mostly from the maternal PBMC compartment, reflecting the frequent transmission of HIV-1 from maternal cells rather than free viruses.

CRF01_AE and subtype B are circulating in Thailand and the strains have become intermixed in some high-risk groups, establishing the possibility of intersubtype recombination. The first such recombinant, mostly B with gp120 from CRF01_AE, was recently identified. Here we report a heterosexually acquired recombinant of different structure, with most of the genome from CRF01_AE but almost the entire envelope from subtype B. Surveillance by V3 serotype and genotype in multiple regions, followed by full-genome sequencing, was used to identify this strain. Pending vaccine trials in Thailand require knowledge of the presence of such strains in the population, and these recombinants provide valuable reagents for the laboratory evaluation of cross-subtype immunity. Studies are underway to determine whether either recombinant is circulating widely.

High-resolution HIV-1 genotyping of large sample sets is crucial to define the evolving and dynamic epidemics in Asia. Here we present MHAbce v.2, a multi-region hybridization assay that individually discriminates subtypes B, C, CRF01_AE, and virtually all of their described recombinants, based on real-time PCR using subtype-specific TaqMan probes in 8 regions throughout the viral genome. In a validation panel (n=70), the assay performed with a sensitivity of 95.7% and specificity of 99.8%. The assay was field-tested on samples from a retrospective MTCT cohort (n=180; Lampang Province, Northern Thailand; 1996–1998). 177/180 of the samples were typeable, and 94.4% were typed as CRF01_AE. The remaining strains represented even proportions of subtype B and B/CRF01_AE recombinants and were confirmed by sequencing, revealing early links between the heterosexual and IDU HIV-1 epidemics in Thailand. MHAbce v.2, with an area of application including China, India, Southeast Asia, and the Pacific Rim, can be used to develop a comprehensive and detailed picture of this important component of the HIV/AIDS pandemic.

Methods 49 healthy, vaccinia-naive volunteers were enrolled in a phase I randomized, double-blind, dose-escalation, route-comparison, placebo-controlled trial to assess the safety and immunogenicity of MVA-CMDR HIV-1 vaccine. The study was divided into Part A: low-dose 106/pfu ID versus 107 pfu/IM and Part B: high-dose 107 pfu/ID vs 108 pfu/IM. Vaccinations were given at months 0, 1 and 3 with an active:placebo ratio of 10:2. Chromium-release CTL, IFNγ Elispot, and polyfunctional flow cytometry (IL2/IFNγ/TNFα/MIP-1β/CD107a), were performed on all volunteers. Synthetic peptide pools and GLP-grade MVA were used to assess insert (Gag/Pol/Env) and vector immunogenicity respectively.