139 results on '"Timothy D. Mastro"'
Search Results
2. High HIV incidence among young women in South Africa: Data from a large prospective study
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Thesla Palanee-Phillips, Helen V. Rees, Kate B. Heller, Khatija Ahmed, Joanne Batting, Ivana Beesham, Renee Heffron, Jessica Justman, Heeran Makkan, Timothy D. Mastro, Susan A. Morrison, Nelly Mugo, Gonasagrie Nair, James Kiarie, Neena M. Philip, Melanie Pleaner, Krishnaveni Reddy, Pearl Selepe, Petrus S. Steyn, Caitlin W. Scoville, Jenni Smit, Katherine K. Thomas, Deborah Donnell, Jared M. Baeten, and for the ECHO Trial Consortium
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Medicine ,Science - Abstract
Introduction South Africa has the highest national burden of HIV globally. Understanding drivers of HIV acquisition in recently completed, prospective studies in which HIV was an endpoint may help inform the strategy and investments in national HIV prevention efforts and guide the design of future HIV prevention trials. We assessed HIV incidence and correlates of incidence among women enrolled in ECHO (Evidence for Contraceptive Options and HIV Outcomes), a large, open-label randomized clinical trial that compared three highly effective. reversible methods of contraception and rates of HIV acquisition. Methods During December 2015 to October 2018, ECHO followed sexually active, HIV-seronegative women, aged 16–35 years, seeking contraceptive services and willing to be randomized to one of three contraceptive methods (intramuscular depot medroxyprogesterone acetate, copper intrauterine device, or levonorgestrel implant) for 12–18 months at nine sites in South Africa. HIV incidence based on prospectively observed HIV seroconversion events. Cox proportional hazards regression models were used to define baseline cofactors related to incident HIV infection. Results 5768 women were enrolled and contributed 7647 woman-years of follow-up. The median age was 23 years and 62.5% were ≤24 years. A total of 345 incident HIV infections occurred, an incidence of 4.51 per 100 woman-years (95%CI 4.05–5.01). Incidence was >3 per 100 woman-years at all sites. Age ≤24 years, baseline infection with sexually transmitted infections, BMI≤30, and having new or multiple partners in the three months prior to enrollment were associated with incident HIV. Conclusions HIV incidence was high among South African women seeking contraceptive services. Integration of diagnostic management of sexually transmitted infections alongside delivery of HIV prevention options in health facilities providing contraception services are needed to mitigate ongoing risks of HIV acquisition for this vulnerable population. Clinical trial registration ClinicalTrials.gov, number NCT02550067 was the main Clinical Trial from which this secondary, non-randomized / observational analysis was derived with data limited to just South African sites.
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- 2022
3. Go Where the Virus Is: An HIV Micro-epidemic Control Approach to Stop HIV Transmission
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Timothy D Mastro, Michael M. Cassell, Reshmie Ramautarsing, Rose Wilcher, and Nittaya Phanuphak
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Acquired Immunodeficiency Syndrome ,Sexual transmission ,Transmission (medicine) ,business.industry ,virus diseases ,HIV Infections ,Viremia ,General Medicine ,medicine.disease ,Virus ,Men who have sex with men ,Social support ,Relative risk ,Commentary ,medicine ,Humans ,Epidemics ,business ,Viral load ,Demography - Abstract
Essentially all HIV transmission is from people living with HIV who are not virally suppressed. An HIV micro-epidemic control approach that differentiates treatment support and prevention services for people living with HIV and their network members according to viral burden could optimize the impact of epidemic control efforts., Key Messages Essentially all HIV transmission is from people living with HIV (PLHIV) who do not know their infection status or have not yet achieved viral suppression, making support for these individuals and their risk contacts a priority for treatment and prevention efforts.Proven approaches exist to reduce viral burden and interrupt HIV transmission from PLHIV who are not yet virally suppressed, but these approaches must be implemented with enhanced focus and scale to maximize benefit.Improved diagnostic approaches offer new opportunities to increase public health impact by prioritizing support for unserved or underserved individuals with the greatest viral burdens and among members of their risk networks.Policy makers should pursue the implementation and evaluation of diagnostic approaches that can focus services among individuals and networks with the greatest viral burdens.Program managers should treat viral burden as a primary consideration in the provision of differentiated HIV services, applying an HIV micro-epidemic control framework to prioritize and tailor services for PLHIV and their risk contacts along a continuum of progression to viral suppression.
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- 2020
4. Managing amphetamine use is critical to achieving HIV control
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Steven Shoptaw, Timothy D Mastro, and Christopher Akolo
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medicine.medical_specialty ,business.industry ,Sexual Behavior ,Immunology ,Control (management) ,Human immunodeficiency virus (HIV) ,HIV Infections ,medicine.disease_cause ,Article ,Methamphetamine ,Infectious Diseases ,Vietnam ,medicine ,Humans ,Immunology and Allergy ,Amphetamine use ,Substance Abuse, Intravenous ,Psychiatry ,business - Abstract
OBJECTIVE: We assessed the association between methamphetamine use and lack of viral suppression among a cohort of HIV seropositive persons who inject drugs (PWID) in Hai Phong, Vietnam. DESIGN: Cohort study with random effects logit modeling and mediation analysis for ART adherence. METHODS: PWID were recruited from October 2016-October 2017; HIV seropositive PWID were enrolled in a cohort to assess HIV viral loads, changes in drug use, risk behaviors, and ART adherence during 24-month follow-up. Methamphetamine use in last 30 days was divided into three categories: 0 days (no use), 1–19 days (intermediate), and 20 or more days (heavy). Bivariate and a multivariable random effects logit models were used to assess the relationship between methamphetamine use and not being virally suppressed. We also assessed self-reported ART adherence as a mediating factor. RESULTS: A total of 645 HIV seropositive PWID were included at baseline; 95% male, average age 40 (SD=6.4). At baseline, methamphetamine use in last 30 days was 64% no use, 32% intermediate use, 4% heavy use. Approximately 74% of PWID reported high/complete adherence; 76% were at viral suppression. In random effects analysis, recent methamphetamine use was associated with not being virally suppressed during follow-up (AOR: 1.84, 95% CI: 1.06, 3.17); the effect was not explained by a mediating effect of self-reported adherence to ART. CONCLUSIONS: Recent methamphetamine use is associated with not being virally suppressed among PWID. The results of this study indicate the need for targeted interventions for methamphetamine use with special focus on those with HIV infection.
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- 2020
5. HIV incidence among women using intramuscular depot medroxyprogesterone acetate, a copper intrauterine device, or a levonorgestrel implant for contraception: a randomised, multicentre, open-label trial
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Helen Rees, Khatija Ahmed, Katherine K. Thomas, Kate B. Heller, Kavita Nanda, Julia D Welch, Douglas Taylor, Charles S. Morrison, Cheryl Louw, James Kiarie, Gonasagrie Nair, Petrus S. Steyn, Thesla Palanee-Phillips, Peter Gichangi, Jeffrey S. A. Stringer, Zelda Nhlabatsi, Kathleen Shears, Timothy D. Mastro, Sydney Sibiya, Mandisa Singata-Madliki, Jessica Justman, G Justus Hofmeyr, Jennifer A. Smit, Mags Beksinska, Caitlin W Scoville, Raesibe Agnes Pearl Selepe, Linda-Gail Bekker, Jared M. Baeten, Deborah Donnell, Melanie Pleaner, Margaret P Kasaro, Elizabeth A. Bukusi, Maricianah Onono, and Nelly Mugo
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medicine.medical_specialty ,education.field_of_study ,business.industry ,Obstetrics ,Hazard ratio ,Population ,General Medicine ,030204 cardiovascular system & hematology ,Intrauterine device ,medicine.disease ,Discontinuation ,03 medical and health sciences ,0302 clinical medicine ,Acquired immunodeficiency syndrome (AIDS) ,Medicine ,Medroxyprogesterone acetate ,Observational study ,Levonorgestrel ,030212 general & internal medicine ,business ,education ,medicine.drug - Abstract
Summary Background Observational and laboratory studies suggest that some hormonal contraceptive methods, particularly intramuscular depot medroxyprogesterone acetate (DMPA-IM), might increase women's susceptibility to HIV acquisition. We aimed to compare DMPA-IM, a copper intrauterine device (IUD), and a levonorgestrel (LNG) implant among African women seeking effective contraception and living in areas of high HIV incidence. Methods We did a randomised, multicentre, open-label trial across 12 research sites in eSwatini, Kenya, South Africa, and Zambia. We included HIV-seronegative women aged 16–35 years who were seeking effective contraception, had no medical contraindications to the trial contraceptive methods, agreed to use the assigned method for 18 months, and reported not using injectable, intrauterine, or implantable contraception for the previous 6 months. Participants were randomly assigned (1:1:1) to receive an injection of 150 mg/mL DMPA-IM every 3 months, a copper IUD, or a LNG implant with random block sizes between 15 and 30, stratified by site. Participants were assigned using an online randomisation system, which was accessed for each randomisation by study staff at each site. The primary endpoint was incident HIV infection in the modified intention-to-treat population, including all randomised participants who were HIV negative at enrolment and who contributed at least one HIV test. The primary safety endpoint was any serious adverse event or any adverse event resulting in method discontinuation, until the trial exit visit at 18 months and was assessed in all enrolled and randomly assigned women. This study is registered with ClinicalTrials.gov, number NCT02550067. Findings Between Dec 14, 2015, and Sept 12, 2017, 7830 women were enrolled and 7829 were randomly assigned to the DMPA-IM group (n=2609), the copper IUD group (n=2607), or the LNG implant group (n=2613). 7715 (99%) participants were included in the modified intention-to-treat population (2556 in the DMPA-IM group, 2571 in the copper IUD group, and 2588 in the LNG implant group), and women used their assigned method for 9567 (92%) of 10 409 woman-years of follow-up time. 397 HIV infections occurred (incidence 3·81 per 100 woman-years [95% CI 3·45–4·21]): 143 (36%; 4·19 per 100 woman-years [3·54–4·94]) in the DMPA-IM group, 138 (35%: 3·94 per 100 woman-years [3·31–4·66]) in the copper IUD group, and 116 (29%; 3·31 per 100 woman-years [2·74–3·98]) in the LNG implant group. In the modified intention-to-treat analysis, the hazard ratios for HIV acquisition were 1·04 (96% CI 0·82–1·33, p=0·72) for DMPA-IM compared with copper IUD, 1·23 (0·95–1·59, p=0·097) for DMPA-IM compared with LNG implant, and 1·18 (0·91–1·53, p=0·19) for copper IUD compared with LNG implant. 12 women died during the study: six in the DMPA-IM group, five in the copper IUD group, and one in the LNG implant group. Serious adverse events occurred in 49 (2%) of 2609 participants in the DMPA-IM group, 92 (4%) of 2607 participants in the copper IUD group, and 78 (3%) of 2613 participants in the LNG implant group. Adverse events resulting in discontinuation of the randomly assigned method occurred in 109 (4%) women in the DMPA-IM group, 218 (8%) women in the copper IUD group, and 226 (9%) women in the LNG implant group (p Interpretation We did not find a substantial difference in HIV risk among the methods evaluated, and all methods were safe and highly effective. HIV incidence was high in this population of women seeking pregnancy prevention, emphasising the need for integration of HIV prevention within contraceptive services for African women. These results support continued and increased access to these three contraceptive methods. Funding Bill & Melinda Gates Foundation, US Agency for International Development and the President's Emergency Plan for AIDS Relief, Swedish International Development Cooperation Agency, South African Medical Research Council, and UN Population Fund. Contraceptive supplies were donated by the Government of South Africa and US Agency for International Development.
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- 2019
6. Planning for Outcomes (P4O) Modeling Tool: Estimating the Impact of Changing the Proportion of Injectable Progestins in the Contraceptive Method Mix
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Abdulmumin Saad, Timothy D Mastro, Lauren Y. Maldonado, Xiaoming Gao, Elena Lebetkin, Kavita Nanda, Douglas Taylor, Markus J. Steiner, and Laneta J. Dorflinger
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Adult ,Male ,Adolescent ,Maternal Health ,HIV Infections ,Hiv risk ,law.invention ,Condoms ,Young Adult ,03 medical and health sciences ,0302 clinical medicine ,Procurement ,Condom ,Pregnancy ,law ,Environmental health ,Health care ,Contraceptive Agents, Female ,Humans ,Medicine ,Infant Health ,030212 general & internal medicine ,Pregnancy Complications, Infectious ,Contraception Behavior ,Africa South of the Sahara ,030219 obstetrics & reproductive medicine ,Transmission (medicine) ,business.industry ,Hazard ratio ,Child Health ,Infant ,General Medicine ,Middle Aged ,medicine.disease ,Infectious Disease Transmission, Vertical ,Health Planning ,Contraception ,Policy ,Family Planning Services ,Female ,Observational study ,Technical Notes ,Progestins ,business - Abstract
The interactive deterministic online modeling tool P4O allows users to estimate how changing the proportion of injectable progestins in the contraceptive method mix might affect HIV and maternal and child health outcomes. With careful consideration for women's individual choices, policy makers and program planners may use country-specific results to help inform programming and policy decisions., Background: Observational studies raise concern about a potential link between injectable progestin contraceptive use and HIV acquisition risk. This possible link is particularly relevant in sub-Saharan Africa where HIV risk is high and the method mix is skewed toward injectables. We developed the Planning for Outcomes (P4O) model (https://planning4outcomes.ctiexchange.org/) to predict changes in maternal and child health (MCH) and HIV outcomes that could occur if the proportion of injectables in the method mix is changed. Methods: P4O incorporates evidence-based assumptions to predict yearly changes in unintended pregnancies, morbidity/mortality, HIV infections (women and infants), and anticipated health care costs associated with changing the proportions of injectable users in 22 selected countries. Users of this model designate all countries or a subset and adjust inputs including percentage of injectable users who discontinue, percentage of discontinuers who begin use of an alternative method, hazard ratio for HIV infection with injectable use, method mix used by injectable discontinuers, annual probabilities of method-specific pregnancy and mother-to-child transmission of HIV, condom effectiveness against HIV, risk of HIV during pregnancy, and HIV incidence among women of reproductive age. Results: Illustrative results from all sub-Saharan African countries combined and from selected countries demonstrate the potential of P4O to inform program planning and procurement decisions. In countries with high use of long-acting reversible contraception, the removal of injectables from the method mix is associated with improvement in MCH and HIV indicators if most injectable users switch to more effective methods (e.g., implants). In countries with high use of short-acting methods (e.g., condoms), the model predicts mostly negative MCH outcomes. Conclusions: Policy makers and program planners may use P4O to inform programming and policy decisions. In all scenarios, programmatic preparation to accommodate changes to the contraceptive method mix, considerations of how the individual desires of women will be addressed, and potential burden of anticipated MCH-related costs warrant advanced consideration.
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- 2019
7. Estimating HIV incidence in the Akwa Ibom AIDS indicator survey (AKAIS), Nigeria using the limiting antigen avidity recency assay
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Oluseyi Balogun, Timothy D Mastro, Akan Etuk, Edward Adekola Oladele, Kwasi Torpey, Olubunmi Ruth Negedu-Momoh, Ibrahim Dafa, Hadiza Khamofu, Janet Robinson, Ezekiel James, Oluwasanmi Adedokun, Titi Badru, and Satish Raj Pandey
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Adult ,Male ,Adolescent ,Anti-HIV Agents ,HIV Antigens ,Population ,Antibody Affinity ,Psychological intervention ,Nigeria ,HIV Infections ,HIV Antibodies ,recent infection ,Immunoenzyme Techniques ,Young Adult ,03 medical and health sciences ,0302 clinical medicine ,Acquired immunodeficiency syndrome (AIDS) ,Antigen ,Surveys and Questionnaires ,HIV Seropositivity ,Humans ,Medicine ,Avidity ,030212 general & internal medicine ,Young adult ,education ,Research Articles ,education.field_of_study ,030505 public health ,business.industry ,Incidence ,Incidence (epidemiology) ,HIV‐1 ,Infant, Newborn ,Public Health, Environmental and Occupational Health ,Middle Aged ,Viral Load ,medicine.disease ,limiting antigen avidity ,Cross-Sectional Studies ,Infectious Diseases ,HIV-1 ,Female ,0305 other medical science ,business ,Viral load ,Research Article ,Demography - Abstract
Introduction HIV incidence estimates are important to characterize the status of an epidemic, identify locations and populations at high risk and to guide and evaluate HIV prevention interventions. We used the limiting antigen avidity assay (LAg) as part of a recent infection testing algorithm to estimate HIV incidence in the Akwa Ibom AIDS Indicator Survey (AKAIS), Nigeria. Methods In 2017, AKAIS, a cross‐sectional population‐based study was conducted at the household (HH) level in 31 local government areas (LGAs) of Akwa Ibom state. Of the 8963 participants aged ≥15 years who were administered questionnaires for demographic and behavioural data, 8306 consented to HIV rapid testing. Whole‐blood specimens were collected from 394 preliminary HIV‐seropositive individuals for CD4+ cell count determination and plasma storage. Samples were shipped to a central quality laboratory for HIV confirmatory testing and viral load determination. A total of 370 HIV‐positive specimens were tested for the recent HIV infection using the LAg assay. Results Of the 8306 consenting adults, the HIV prevalence was 4.8%. Of the 370 HIV‐positive samples tested for HIV recency, the median age was 35 years, 48.8% had CD4+ cell count >500/mm3 and 81.3% was not virally suppressed. Viral suppression was greater among females (21%) than for males (13%). A total of 11 specimens were classified as recent based on the LAg assay and HIV viral load ≥1000 copies/mL. The weighted, adjusted HIV‐1 incidence was 0.41/100 person‐years (95% CI 0.16 to 0.66); translating to 13,000 new cases of HIV infections annually in Akwa Ibom, a state with a population of 5.5 million. The HIV incidence rate was similar in females and males (0.41% and 0.42% respectively). The incidence rate was the highest among participants aged 15 to 49 years (0.44%, 95% CI 0.15 to 0.74) translating to 11,000 new infections annually, about 85% of all new infections in the state. Conclusions The finding of the high HIV incidence among the 15 to 49‐year age group calls for renewed and innovative efforts to prevent HIV infection among young adults in Akwa Ibom state.
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- 2021
8. The Need to Optimize Human Immunodeficiency Virus Test-and-Treat Programs in Africa
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Moses Bateganya, Hally Mahler, and Timothy D Mastro
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2019-20 coronavirus outbreak ,Coronavirus disease 2019 (COVID-19) ,business.industry ,Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) ,Human immunodeficiency virus test ,MEDLINE ,HIV ,HIV Infections ,Virology ,Infectious Diseases ,Africa ,Immunology and Allergy ,Medicine ,Humans ,business ,Developing Countries - Published
- 2021
9. Incorporating oral PrEP into standard prevention services for South African women: a nested interrupted time-series study
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Katherine K. Thomas, Jessica Justman, Margaret P Kasaro, James Kiarie, Joanne Batting, Charles S. Morrison, Kate B. Heller, Elizabeth A. Bukusi, Kathleen Shears, Mookho Malahleha, Cheryl Louw, Jared M. Baeten, Deborah Donnell, Lara Kidoguchi, Nelly Mugo, Veronique C Bailey, Raesibe Agnes Pearl Selepe, Julia D Welch, Timothy D Mastro, Sydney Sibiya, G Justus Hofmeyr, Zelda Nhlabatsi, Renee Heffron, Gonasagrie Nair, Linda-Gail Bekker, Khatija Ahmed, Kavita Nanda, Thesla Palanee-Phillips, Ivana Beesham, Petrus S. Steyn, Deborah Baron, Mandisa Singata-Madliki, Douglas Taylor, Helen Rees, Caitlin W Scoville, Nomthandazo Mbandazayo, Jeffrey S. A. Stringer, Peter Gichangi, Mags Beksinska, Melanie Pleaner, and Jennifer A. Smit
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0301 basic medicine ,Adult ,Adolescent ,Epidemiology ,Immunology ,Population ,Psychological intervention ,Administration, Oral ,HIV Infections ,Rate ratio ,03 medical and health sciences ,South Africa ,Young Adult ,0302 clinical medicine ,Acquired immunodeficiency syndrome (AIDS) ,Virology ,medicine ,Humans ,030212 general & internal medicine ,education ,education.field_of_study ,business.industry ,Incidence (epidemiology) ,Incidence ,Interrupted time series ,Emergency plan ,Articles ,medicine.disease ,030112 virology ,Clinical trial ,Infectious Diseases ,Female ,Pre-Exposure Prophylaxis ,business ,Demography - Abstract
Summary Background As oral pre-exposure prophylaxis (PrEP) becomes the standard of prevention globally, its potential effect on HIV incidence in clinical trials of new prevention interventions is unknown, particularly for trials among women. In a trial measuring HIV incidence in African women, oral PrEP was incorporated into the standard of prevention in the trial's last year. We assessed the effect of on-site access to PrEP on HIV incidence in this natural experiment. Methods We did a nested interrupted time-series study using data from the ECHO trial. At 12 sites in four countries (Eswatini, Kenya, South Africa, and Zambia), women (aged 16–35 years) were randomly assigned to receive one of three contraceptives between Dec 14, 2015, and Sept 12, 2017, and followed up quarterly for up to 18 months to determine the effect of contraceptive method on HIV acquisition. Women were eligible if they wanted long-acting contraception, were medically qualified to receive study contraceptives, and had not used any of the study contraceptives in the past 6 months. The present analyses are limited to nine South African sites where on-site access to oral PrEP was implemented between March 13 and June 12, 2018. Using an interrupted time-series design, we compared HIV incidence before versus after PrEP access, limited to quarterly study visits at which on-site PrEP access was available to at least some participants and, in a sensitivity analysis, to the 180 days before and after access. The outcome was incident HIV infection, detected using two rapid HIV tests done in parallel for each participant at every scheduled follow-up visit. This study is registered on ClinicalTrials.gov, NCT02550067. Findings 2124 women were followed up after on-site PrEP access began, of whom 543 (26%) reported PrEP use. A total of 12 HIV seroconversions were observed in 556 person-years (incidence 2·16%) after on-site PrEP access, compared with 133 HIV seroconversions in 2860 person-years (4·65%) before PrEP access (adjusted incidence rate ratio [IRR] 0·45, 95% CI 0·25–0·82, p=0·0085). Similar results were also observed when limiting the analysis to 180 days before versus after PrEP access. A total of 46 HIV seroconversions were observed in 919 person-years within 180 days before PrEP access, compared with 11 seroconversions in 481 person-years in the 180 days following PrEP access (incidence 5·00 vs 2·29 per 100 person-years; IRR 0·43, 95% CI 0·22–0·88, p=0·012). Interpretation On-site access to PrEP as part of standard of prevention in a clinical trial among women in South Africa was associated with halving HIV incidence, when approximately a quarter of women started PrEP. Providing access to on-site PrEP could decrease incidence in HIV prevention trials. These data are also among the first to show in any setting that access to PrEP is associated with decreased HIV acquisition among South African women. Funding Bill & Melinda Gates Foundation, United States Agency for International Development, President's Emergency Plan for AIDS Relief, the Swedish International Development Cooperation Agency, South African Medical Research Council, and United Nations Population Fund.
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- 2020
10. Sexually transmitted infections among women randomised to depot medroxyprogesterone acetate, a copper intrauterine device or a levonorgestrel implant
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Helen Rees, Kavita Nanda, Khatija Ahmed, Margaret Lind, Nelly Mugo, Maricianah Onono, Neena M. Philip, Joanne Batting, Cheryl Louw, Jared M. Baeten, Deborah Donnell, Mags Beksinska, Charles S. Morrison, Jennifer A. Smit, Thesla Palanee-Phillips, Jennifer Deese, Vinodh A. Edward, and Timothy D Mastro
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Adult ,medicine.medical_specialty ,Adolescent ,chlamydia trachomatis ,Context (language use) ,Dermatology ,Levonorgestrel ,Medroxyprogesterone Acetate ,Lower risk ,medicine.disease_cause ,Intrauterine device ,urologic and male genital diseases ,03 medical and health sciences ,Gonorrhea ,Young Adult ,Clinical ,0302 clinical medicine ,medicine ,Contraceptive Agents, Female ,Prevalence ,Medroxyprogesterone acetate ,Humans ,030212 general & internal medicine ,Drug Implants ,Pregnancy ,clinical trials ,030219 obstetrics & reproductive medicine ,Chlamydia ,business.industry ,Obstetrics ,Chlamydia Infections ,medicine.disease ,Intrauterine Devices, Copper ,female genital diseases and pregnancy complications ,neisseria gonorrhoeae ,Infectious Diseases ,Contraception ,Delayed-Action Preparations ,Africa ,Female ,Disease Susceptibility ,Chlamydia trachomatis ,business ,medicine.drug - Abstract
ObjectivesReproductive aged women are at risk of pregnancy and sexually transmitted infections (STI). Understanding drivers of STI acquisition, including any association with widely used contraceptives, could help us to reduce STI prevalence and comorbidities. We compared the risk of STI among women randomised to three contraceptive methods.MethodsWe conducted a secondary analysis to assess the risk of chlamydia and gonorrhoea in a clinical trial evaluating HIV risk among 7829 women aged 16–35 randomised to intramuscular depot medroxyprogesterone acetate (DMPA-IM), a copper intrauterine device (IUD) or a levonorgestrel (LNG) implant. We estimated chlamydia and gonorrhoea prevalences by contraceptive group and prevalence ratios (PR) using log-binomial regression.ResultsAt baseline, chlamydia and gonorrhoea prevalences were 18% and 5%, respectively. Final visit chlamydia prevalence did not differ significantly between DMPA-IM and copper IUD groups or between copper IUD and LNG implant groups. The DMPA-IM group had significantly lower risk of chlamydia compared with the LNG implant group (PR 0.83, 95% CI 0.72 to 0.95). Final visit gonorrhoea prevalence differed significantly only between the DMPA-IM and the copper IUD groups (PR 0.67, 95% CI 0.52 to 0.87).ConclusionsThe findings suggest that chlamydia and gonorrhoea risk may vary with contraceptive method use. Further investigation is warranted to better understand the mechanisms of chlamydia and gonorrhoea susceptibility in the context of contraceptive use.
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- 2020
11. Development and deployment of COVID-19 vaccines for those most vulnerable
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Ted M. Ross, Gabriele Neumann, Matthew B. Friemann, Jaap Goudsmit, Julia T. Ostrowsky, Adrian B. McDermott, Timothy D Mastro, Michael T. Osterholm, Alyson A. Kelvin, Ralph S. Baric, Kristine A. Moore, Theodore Schenkelberg, Yoshihiro Kawaoka, Mark J. Cameron, Cheryl M. Cameron, Frances Priddy, Stacey Schultz-Cherry, Tere Williams, and Wayne C. Koff
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0301 basic medicine ,medicine.medical_specialty ,2019-20 coronavirus outbreak ,COVID-19 Vaccines ,Coronavirus disease 2019 (COVID-19) ,Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) ,Immune senescence ,medicine.disease_cause ,03 medical and health sciences ,Disease susceptibility ,0302 clinical medicine ,Pandemic ,medicine ,Animals ,Humans ,030212 general & internal medicine ,Intensive care medicine ,Phylogeny ,business.industry ,SARS-CoV-2 ,COVID-19 ,General Medicine ,Immune dysregulation ,Disease Models, Animal ,030104 developmental biology ,Software deployment ,Disease Susceptibility ,business - Abstract
Development of safe and effective COVID-19 vaccines is a global priority and the best hope for ending the COVID-19 pandemic. Remarkably, in less than 1 year, vaccines have been developed and shown to be efficacious and are already being deployed worldwide. Yet, many challenges remain. Immune senescence and comorbidities in aging populations and immune dysregulation in populations living in low-resource settings may impede vaccine effectiveness. Distribution of vaccines among these populations where vaccine access is historically low remains challenging. In this Review, we address these challenges and provide strategies for ensuring that vaccines are developed and deployed for those most vulnerable.
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- 2020
12. National nutrition strategies that focus on maternal, infant, and young child nutrition in Southeast Asia do not consistently align with regional and international recommendations
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Tuan T Nguyen, Mellissa Withers, Karin Lapping, Edward A. Frongillo, Timothy D Mastro, Amy Weissman, Jennifer Cashin, Roger Mathisen, and Ashley Darnell
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0301 basic medicine ,Philippines ,Psychological intervention ,Breastfeeding ,Context (language use) ,Myanmar ,Southeast asian ,03 medical and health sciences ,0302 clinical medicine ,Pregnancy ,Environmental health ,Medicine ,Humans ,030212 general & internal medicine ,Child ,Wasting ,Asia, Southeastern ,Breastfeeding promotion ,030109 nutrition & dietetics ,Nutrition and Dietetics ,plan of action for nutrition ,business.industry ,Public Health, Environmental and Occupational Health ,Infant, Newborn ,Obstetrics and Gynecology ,Infant ,Monitoring and evaluation ,Southeast Asia ,maternal, infant, and young child nutrition (MIYCN) ,Breast Feeding ,Community mobilization ,Indonesia ,Child, Preschool ,Pediatrics, Perinatology and Child Health ,Supplement Article ,Female ,medicine.symptom ,business ,national nutrition strategy ,Child Nutritional Physiological Phenomena ,ASEAN - Abstract
We examined the consistency of national nutrition strategies and action plans (NNS) focusing on maternal, infant, and young child nutrition in Southeast Asia with regional and international recommendations. Between July and December 2017, we identified and extracted information on context, objectives, interventions, indicators, strategies, and coordination mechanisms from the most recent NNS in nine Southeast Asian countries. All NNS described context, objectives, and the following interventions: antenatal care, micronutrient supplementation during pregnancy, breastfeeding promotion, improved complementary feeding, nutrition in emergencies, and food fortification or dietary diversity. Micronutrient supplementation for young children was included in eight NNS; breastfeeding promotion during pregnancy and support at birth in seven; and school feeding, deworming, and treatment of severe acute malnutrition in six. All NNS contained programme monitoring and evaluation plans with measurable indicators and targets. Not all NNS covered wasting, exclusive breastfeeding, low birthweight, and childhood overweight. Strategies for achieving NNS goals and objectives were health system strengthening (nine), social and behaviour change communication (nine), targeting vulnerable groups (eight), and social or community mobilization (four). All addressed involvement, roles and responsibilities, and collaboration mechanisms among sectors and stakeholders. There was a delay in releasing NNS in Indonesia, Myanmar, and the Philippines. In conclusion, although Southeast Asian NNS have similarities in structure and contents, some interventions and indicators vary by country and do not consistently align with regional and international recommendations. A database with regularly updated information on NNS components would facilitate cross‐checking completeness within a country, comparison across countries, and knowledge sharing and learning.
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- 2020
13. Effects of Depot Medroxyprogesterone Acetate, Copper Intrauterine Devices, and Levonorgestrel Implants on Early HIV Disease Progression
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Mags Beksinska, Khatija Ahmed, Maricianah Onono, Renee Heffron, Maggie Lind, Jen Deese, Jeffrey S. A. Stringer, Ivana Beesham, Echo Trial Team, Charles S. Morrison, Kavita Nanda, Helen Rees, Vinodh A. Edward, Katherine K. Thomas, Thesla Palanee-Phillips, Jared M. Baeten, G Justus Hofmeyr, Neena M. Philip, Timothy D Mastro, and Gonasagrie Nair
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0301 basic medicine ,Adult ,viral suppression ,Adolescent ,Depot ,Immunology ,implants ,Physiology ,HIV Infections ,Levonorgestrel ,Medroxyprogesterone Acetate ,Intrauterine device ,03 medical and health sciences ,Young Adult ,0302 clinical medicine ,disease progression ,Virology ,Medicine ,Medroxyprogesterone acetate ,Humans ,030212 general & internal medicine ,Viral suppression ,Clinical Trials/Clinical Studies ,Proportional Hazards Models ,business.industry ,hormonal contraception ,Disease progression ,HIV ,Viral Load ,intrauterine device ,Intrauterine Devices, Copper ,CD4 Lymphocyte Count ,DMPA ,030104 developmental biology ,Infectious Diseases ,Hormonal contraception ,Female ,business ,Hiv disease ,medicine.drug - Abstract
Limited data exist on the effects of contraceptives on HIV disease progression. We studied the association between intramuscular injectable depot medroxyprogesterone acetate (DMPA-IM), the copper intrauterine device (IUD), and the levonorgestrel (LNG) implant on markers of HIV disease progression at the time of HIV detection and 3 months postdetection and time from detection to CD4 count
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- 2020
14. Integrating oral PrEP delivery among African women in a large HIV endpoint‐driven clinical trial
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Mags Beksinska, Veronique C Bailey, Deborah Baron, Thesla Palanee-Phillips, Jared M. Baeten, Deborah Donnell, Cheryl Louw, Joanne Batting, Elizabeth A. Bukusi, Mookho Malahleha, Jennifer A. Smit, Renee Heffron, Julia D Welch, Timothy D Mastro, Ivana Beesham, Lara Kidoguchi, Khatija Ahmed, and Melanie Pleaner
- Subjects
Adult ,medicine.medical_specialty ,Multiple Partners ,Referral ,Adolescent ,Anti-HIV Agents ,Human immunodeficiency virus (HIV) ,Administration, Oral ,Zambia ,HIV Infections ,Hiv risk ,medicine.disease_cause ,law.invention ,03 medical and health sciences ,Pre-exposure prophylaxis ,symbols.namesake ,South Africa ,Young Adult ,0302 clinical medicine ,Randomized controlled trial ,law ,medicine ,Humans ,030212 general & internal medicine ,Poisson regression ,Research Articles ,pre‐exposure prophylaxis ,clinical trials ,030505 public health ,business.industry ,Incidence ,Public Health, Environmental and Occupational Health ,HIV ,Kenya ,Clinical trial ,Infectious Diseases ,Sexual Partners ,standard of care ,Family medicine ,symbols ,Female ,Pre-Exposure Prophylaxis ,women ,0305 other medical science ,business ,Eswatini ,Research Article - Abstract
Introduction Global guidelines emphasize the ethical obligation of investigators to help participants in HIV‐endpoint trials reduce HIV risk by offering an optimal HIV prevention package. Oral pre‐exposure prophylaxis (PrEP) has increasingly become part of state‐of‐the‐art HIV prevention. Here we describe the process of integrating oral PrEP delivery into the HIV prevention package of the Evidence for Contraceptive Options and HIV Outcomes (ECHO) Trial. Methods ECHO was an open‐label randomized clinical trial that compared HIV incidence among women randomized to one of three effective contraceptives. In total, 7830 women aged 16 to 35 years from 12 sites in four African countries (Eswatini, Kenya, South Africa and Zambia) were enrolled and followed for 12 to 18 months, from 2015 to 2018. Part‐way through the course of the trial, oral PrEP was provided to study participants either off‐site via referral or on site via trained trial staff. PrEP uptake was compared between different contraceptive users using Chi‐squared tests or t‐tests. HIV seroincidence rates were compared between participants who never versus ever initiated PrEP using exact Poisson regression. Results PrEP access in ECHO began through public availability in Kenya in May 2017 and was available at all sites by June 2018. When PrEP became available, 3626 (46.3%) eligible women were still in follow‐up in the study, and of these, 622 (17.2%) initiated PrEP. Women initiating PrEP were slightly older; more likely to be unmarried, not living with their partner, having multiple partners; and less likely to be earning their own income and receiving financial support from partners (all p
- Published
- 2020
15. HIV comprehensive knowledge and prevalence among young adolescents in Nigeria: evidence from Akwa Ibom AIDS indicator survey, 2017
- Author
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Chinedu Agbakwuru, Timothy D Mastro, Ezekiel James, Patrick Essiet, Jefferson Mwaisaka, Annie Chen-Carrington, Satish Raj Pandey, Titilope Badru, Kwasi Torpey, Sani H. Aliyu, Hadiza Khamofu, and Oluwasanmi Adedokun
- Subjects
Comprehensive HIV knowledge ,Male ,medicine.medical_specialty ,Health Knowledge, Attitudes, Practice ,Risk perceptions ,Adolescent ,Psychological intervention ,Nigeria ,HIV Infections ,Logistic regression ,Social issues ,03 medical and health sciences ,0302 clinical medicine ,Acquired immunodeficiency syndrome (AIDS) ,Environmental health ,Surveys and Questionnaires ,Epidemiology ,medicine ,Prevalence ,Humans ,030212 general & internal medicine ,Child ,030505 public health ,Descriptive statistics ,business.industry ,lcsh:Public aspects of medicine ,Public health ,Public Health, Environmental and Occupational Health ,lcsh:RA1-1270 ,medicine.disease ,Stigma ,Cross-Sectional Studies ,Young adolescents ,Female ,Biostatistics ,0305 other medical science ,business ,Research Article - Abstract
Background Despite the recent increase in HIV infections among adolescents, little is known about their HIV knowledge and perceptions. This study, therefore, sought to examine the factors associated with comprehensive HIV knowledge, stigma, and HIV risk perceptions among young adolescents aged 10–14 years in Akwa Ibom State, Nigeria. Additionally, consenting parents and assenting young adolescents were tested for HIV. Methods We used cross-sectional data from the 2017 Akwa Ibom AIDS Indicator Survey to analyze comprehensive HIV knowledge, stigma, and HIV risk perceptions among young adolescents. Demographic characteristics of young adolescents were summarized using descriptive statistics. Chi-square test (or Fisher’s exact test in cases of small subgroup sample sizes) was used to elicit associations between demographics and study outcomes. Separate multivariable logistic regression models were then conducted to determine associations with the study outcomes. Sampling weights were calculated in order to adjust for the sample design. P-values less than 0.05 were considered to be significant. Results A total of 1818 young adolescents were interviewed. The survey highlighted significant low levels of comprehensive HIV knowledge (9.4%) among young adolescents. Adolescent-parent discussions [AOR = 2.19, 95% C.I (1.10–4.38), p = 0.03], schools as sources of HIV information [AOR = 8.06, 95% C.I (1.70–38.33), p p = 0.02] were associated with comprehensive HIV knowledge. Majority (93%) of young adolescents perceived themselves not to be at risk of HIV. Overall, 81.5% of young adolescents reported stigmatizing tendencies towards people living with HIV. HIV prevalence among young adolescents was 0.6%. Conclusions Results indicate low comprehensive HIV knowledge among young adolescents. Our findings suggest that there is a need for increased attention towards young adolescents particularly in the provision of comprehensive, functional sexuality education, including HIV at the family- and school-levels. Consequently, age appropriate interventions are needed to address the epidemiological risks of young adolescents that are influenced by a myriad of social issues.
- Published
- 2020
16. Trends in Prevalence of Advanced HIV Disease at Antiretroviral Therapy Enrollment — 10 Countries, 2004–2015
- Author
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Adebobola Bashorun, Jonathan E. Kaplan, Yen Ngoc Le, Deborah Carpenter, Peter Preko, Beth A. Tippett Barr, Gideon Kwesigabo, Hank Tomlinson, Mahesh Swaminathan, Henry Debem, Fred Wabwire-Mangen, Joelle D eas Van Onacker, Solomon Odafe, Ermane G. Robin, Eduardo Samo Gudo, Nhan T Do, Modest Mulenga, Sheryl B. Lyss, Mayer Antoine, Shirish Balachandra, Chris Delcher, E. Kainne Dokubo, Alice Namale, Kwasi Torpey, Thomas J. Spira, Gram Mutandi, Eric van Praag, Elizabeth Gonese, Francisco Mbofana, Jean Wysler Domercant, Elliot Raizes, Carla Xavier, Sebastian Hachizovu, Timothy D Mastro, Mark Griswold, Helen Chun, Nirva Duval, Oseni Abiri, Christine Ross, Owen Mugurungi, George Bicego, Velephi Okello, Kesner Francois, Julie A. Denison, Isaac Zulu, Angela A Ramadhani, Duncan A. MacKellar, Robert Colebunders, Olivier Koole, Moses Bateganya, Kiren Mitruka, Harriet Nuwagaba-Biribonwoha, Simon Agolory, Kahemele Ng'wangu, Ramadhani Gongo, David W. Lowrance, Tedd V. Ellerbrock, Caroline Ryan, Charity Alfredo, Julius N Kalamya, Melissa Briggs, Carol Dukes Hamilton, Ikwo Oboho, Gracia Desforges, Spencer Lloyd, Ibrahim Dalhatu, Mohamed Mfaume, Sundeep Gupta, Dennis Onotu, Harrison Kamiru, Souleymane Sawadogo, Trista Bingham, Trong Ao, Varough M. Deyde, Bridget Mugisa, Andrew F. Auld, Yrvel Desir, Ndapewa Hamunime, Tsitsi Mutasa-Apollo, Naemi Shoopala, Andrew L. Baughman, Seymour G. Williams, Rituparna Pati, Michelle R. Adler, Aleny Couto, Nadjy Joseph, Valerie Pelletier, Alfredo Vergara, Jacob Dee, Ishani Pathmanathan, Ray W. Shiraishi, Peter Ehrenkranz, Abu S. Abdul-Quader, Patrick Swai, Stephanie Behel, Duc B. Nguyen, and Sharon Tsui
- Subjects
medicine.medical_specialty ,Health (social science) ,Epidemiology ,Health, Toxicology and Mutagenesis ,Art initiation ,030231 tropical medicine ,MEDLINE ,HIV Infections ,Disease ,Hiv testing ,World health ,03 medical and health sciences ,0302 clinical medicine ,Health Information Management ,Advanced disease ,Prevalence ,Medicine ,Humans ,030212 general & internal medicine ,Full Report ,business.industry ,General Medicine ,Antiretroviral therapy ,Haiti ,CD4 Lymphocyte Count ,Anti-Retroviral Agents ,Vietnam ,Africa ,Physical therapy ,business ,Demography ,Hiv disease - Abstract
Monitoring prevalence of advanced human immunodeficiency virus (HIV) disease (i.e., CD4+ T-cell count
- Published
- 2017
17. ECHO: context and limitations - Authors' reply
- Author
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Nelly Mugo, Helen Rees, Timothy D Mastro, James Kiarie, and Jared M. Baeten
- Subjects
business.industry ,Speech recognition ,Echo (computing) ,Medicine ,Context (language use) ,General Medicine ,business - Published
- 2019
18. HIV Incidence and Risk Behaviours of People Who Inject Drugs in Bangkok, 1995-2012
- Author
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Suphak Vanichseni, Manoj Leethochawalit, Philip A. Mock, Sithisat Chiamwongpaet, Somyot Kittimunkong, Jordan W. Tappero, Janet M. McNicholl, Kachit Choopanya, Frits van Griensven, Udomsak Sangkum, Punnee Pitisuttithum, Jaranit Kaewkungwal, Timothy D. Mastro, and Michael Martin
- Subjects
Placebo ,01 natural sciences ,03 medical and health sciences ,symbols.namesake ,0302 clinical medicine ,Acquired immunodeficiency syndrome (AIDS) ,Environmental health ,medicine ,030212 general & internal medicine ,Poisson regression ,0101 mathematics ,Prospective cohort study ,Tenofovir ,business.industry ,Incidence (epidemiology) ,010102 general mathematics ,Vaccine trial ,Hiv incidence ,virus diseases ,HIV ,General Medicine ,medicine.disease ,Thailand ,HIV pre-exposure prophylaxis ,symbols ,business ,People who inject drugs ,Cohort study ,Research Paper - Abstract
Background Three consecutive prospective studies were conducted among people who inject drugs (PWID) from May 1995 through June 2012 in Bangkok, Thailand. We examined data from these studies to evaluate HIV incidence and explore trends in risk behaviours. Methods We used data from a 1995–1998 cohort study, a 1999–2004 HIV vaccine trial, and a 2005–2012 HIV pre-exposure prophylaxis (PrEP) study to examine per-quarter trends in HIV incidence, using a restricted cubic spline function for time in a Poisson regression. We also examined temporal trends in HIV-associated risk behaviours. Findings HIV incidence declined from 5.7 per 100 person-years during the cohort study, to 2.7 per 100 person-years in the vaccine trial, to 0.7 per 100 person-years among PrEP study placebo recipients. Incidence peaked at 12.1 per 100 person-years in 1996 and declined to
- Published
- 2018
19. Assays for estimating HIV incidence: updated global market assessment and estimated economic value
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Stefano Ongarello, Natasha Mack, Peter Dailey, Neil Parkin, Jennifer Osborn, E. Megan Davidson Averill, Rick Homan, Jamilah Taylor, Charles S. Morrison, Pairin Seepolmuang, and Timothy D Mastro
- Subjects
0301 basic medicine ,Cross-sectional study ,Cost-Benefit Analysis ,Population ,HIV Infections ,Global Health ,HIV incidence ,03 medical and health sciences ,0302 clinical medicine ,surveys ,Market analysis ,Environmental health ,laboratory assays ,Global health ,Humans ,Medicine ,030212 general & internal medicine ,Epidemics ,education ,Research Articles ,Estimation ,education.field_of_study ,Cost–benefit analysis ,business.industry ,Incidence ,Incidence (epidemiology) ,Public Health, Environmental and Occupational Health ,HIV ,030112 virology ,HIV testing ,Cross-Sectional Studies ,Infectious Diseases ,Sample size determination ,surveillance ,business ,Forecasting ,Research Article - Abstract
Introduction Accurate incidence estimates are needed to characterize the HIV epidemic and guide prevention efforts. HIV Incidence assays are cost-effective laboratory assays that provide incidence estimates from cross-sectional surveys. We conducted a global market assessment of HIV incidence assays under three market scenarios and estimated the economic value of improved incidence assays. Methods We interviewed 27 stakeholders, and reviewed journal articles, working group proceedings, and manufacturers’ sales figures. We determined HIV incidence assay use in 2014, and estimated use in 2015 to 2017 and in 5 to 10-years under three market scenarios, as well as the cost of conducting national and key population surveys using an HIV incidence assay with improved performance. Results Global 2014 HIV incidence assay use was 308,900 tests, highest in Asia and mostly for case- and population-based surveillance. Estimated 2015 to 2017 use was 94,475 annually, with declines due to China and the United States discontinuing incidence assay use for domestic surveillance. Annual projected 5 to 10 year use under scenario 1 – no change in technology – was 94,475. For scenario 2 – a moderately improved incidence assay – projected annual use was 286,031. Projected annual use for scenario 3 – game-changing technologies with an HIV incidence assay part of (a) standard confirmatory testing, and (b) standard rapid testing, were 500,000 and 180 million, respectively. As HIV incidence assay precision increases, decreased sample sizes required for incidence estimation resulted in $5 to 23 million annual reductions in survey costs and easily offset the approximately $3 million required to develop a new assay. Conclusions Improved HIV incidence assays could substantially reduce HIV incidence estimation costs. Continued development of HIV incidence assays with improved performance is required to realize these cost benefits.
- Published
- 2017
20. Blood and Seminal Plasma HIV-1 RNA Levels Among HIV-1-Infected Injecting Drug Users Participating in the AIDSVAX B/E Efficacy Trial in Bangkok, Thailand
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Jordan W. Tappero, Janet M. McNicholl, Michael Martin, Wanitchaya Kittikraisak, Timothy D Mastro, Dale J. Hu, Peter B. Gilbert, Ruengpung Sutthent, Marc Gurwith, Rutt Chuachoowong, Suphak Vanichseni, Udomsak Sangkum, Dwip Kitayaporn, Frits van Griensven, and Kachit Choopanya
- Subjects
Adult ,Male ,HIV Infections ,Article ,Double-Blind Method ,Acquired immunodeficiency syndrome (AIDS) ,Semen ,Blood plasma ,Humans ,Medicine ,Pharmacology (medical) ,Substance Abuse, Intravenous ,Sida ,AIDS Vaccines ,biology ,business.industry ,Thailand ,biology.organism_classification ,medicine.disease ,Virology ,Vaccination ,Infectious Diseases ,AIDSVAX ,Lentivirus ,Immunology ,HIV-1 ,Linear Models ,RNA, Viral ,Female ,Viral disease ,business ,Viral load - Abstract
We investigated effects of vaccination with AIDSVAX B/E HIV-1 candidate vaccine on blood and seminal plasma HIV-1 RNA viral loads (BVL and SVL, respectively) in vaccine recipients (VRs) and placebo recipients (PRs) who acquired infection.Linear mixed models were fitted for repeated measurements of BVL. Generalized estimating equations were used to assess the difference in SVL detectability between VRs and PRs.A total of 196 participants became HIV-1 infected during the trial. Thirty-two (16%) became infected with HIV-1 subtype B and 164 (84%) with HIV-1 subtype CRF01_AE. Per protocol-specified analysis, there were no differences in BVL levels between VRs and PRs. When stratified by HIV-1-infecting subtype, vaccination with AIDSVAX B/E was initially associated with higher BVL among HIV-1 CRF01_AE-infected VRs compared with HIV-1 CRF01_AE-infected PRs; however, this difference did not persist over time. HIV-1 subtype B-infected VRs had slightly higher BVL levels and were more likely to have detectable SVL during the follow-up period than HIV-1 subtype B-infected PRs.Subtle differences in BVL and SVL were detected between VRs and PRs. These results may help to further understand the dynamics between HIV-1 vaccination, HIV-1-infecting subtypes, and subsequent viral expression in different body compartments.
- Published
- 2009
21. Epidemiology of HIV in the United States and Canada: Current Status and Ongoing Challenges
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Chris P. Archibald, Jennifer Geduld, Timothy D. Mastro, Philip Rhodes, Robert S. Janssen, H. Irene Hall, Qian An, and David Boulos
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Adult ,Male ,Canada ,medicine.medical_specialty ,Sexual transmission ,Adolescent ,Sexual Behavior ,media_common.quotation_subject ,MEDLINE ,Ethnic group ,HIV Infections ,Young Adult ,Acquired immunodeficiency syndrome (AIDS) ,Risk Factors ,Environmental health ,Epidemiology ,Ethnicity ,Humans ,Medicine ,Pharmacology (medical) ,Homosexuality ,Young adult ,Child ,Aged ,media_common ,Aged, 80 and over ,business.industry ,Incidence ,Incidence (epidemiology) ,Infant, Newborn ,Infant ,virus diseases ,Middle Aged ,medicine.disease ,United States ,Infectious Diseases ,Child, Preschool ,Immunology ,Female ,business - Abstract
To determine the status of the HIV epidemic in the United States and Canada.We used data on AIDS and HIV diagnoses for 1996-2005 reported to the United States and Canadian national surveillance systems to determine trends in AIDS and HIV (33 US states only) diagnoses and to identify population groups most affected by HIV. HIV incidence for Canada was determined using back-calculation methods. We also determined the proportion of persons diagnosed late (HIV diagnosis within 12 months before AIDS diagnosis).AIDS diagnosis rates were higher in 2005 among blacks (54.1 per 100,000) and Hispanics (18.0) compared with whites (5.9) in the United States and among blacks (4.7) and aboriginal peoples (4.9) compared with whites (0.7) in Canada. Since 2001, HIV diagnoses increased among men who have sex with men in both countries and in Canada, increased among persons from HIV-endemic countries and where heterosexual contact was the only identified risk of transmission. Overall, HIV incidence remained relatively stable in Canada during that period. A large proportion of persons were diagnosed late in the disease process (United States, 54.3%; Canada, 64.2%).Rates of HIV transmission remain a challenge in both the United States and Canada as overall diagnosis rates have not decreased in recent years. Renewed prevention efforts are needed to further reduce the high HIV diagnosis rates among racial/ethnic minorities and to decrease HIV transmission among men who have sex with men.
- Published
- 2009
22. Advancing HIV Prevention Demonstration Projects: New Strategies for a Changing Epidemic
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Patrick S. Sullivan, David W. Purcell, Robert S. Janssen, Timothy D. Mastro, Raul A. Romaguera, Bernard M. Branson, James D. Heffelfinger, and Sean D. Griffiths
- Subjects
medicine.medical_specialty ,Human immunodeficiency virus (HIV) ,HIV Infections ,Context (language use) ,medicine.disease_cause ,Acquired immunodeficiency syndrome (AIDS) ,Epidemiology ,medicine ,Humans ,Sida ,biology ,business.industry ,Incidence ,Public health ,Incidence (epidemiology) ,Public Health, Environmental and Occupational Health ,AIDS Serodiagnosis ,biology.organism_classification ,medicine.disease ,Virology ,United States ,Family medicine ,Public Health ,Viral disease ,Centers for Disease Control and Prevention, U.S ,business ,Perspectives - Abstract
New approaches are needed to fight the human immunodeficiency virus (HIV) epidemic, now in its third decade in the United States. The epidemiology of HIV in the past decades illustrates these new challenges. Annual incident cases of acquired immunodeficiency syndrome (AIDS) declined 38% and deaths from AIDs declined 63% between 1995 and 1998, due primarily to the introduction of combination antiretroviral therapy (ART).1,2 However, the annual number of incident AIDS cases and deaths remained stable from 1999 through 2006, and the estimated number of new HIV infections occurring annually in the U.S. has remained stable since 2000.1,3 This article seeks to put the current emphasis of the Centers for Disease Control and Prevention (CDC) on HIV testing programs in the context of the epidemiology of the U.S. HIV epidemic; to describe major CDC prevention initiatives that involve HIV testing, focusing on the Advancing HIV Prevention (AHP) initiative;4 and to describe what has been learned in the first five years since new strategies for preventing HIV infection were outlined in the AHP initiative.
- Published
- 2008
23. Executive summary and recommendations from the WHO/UNAIDS/IAVI expert group consultation on ‘Phase IIB-TOC trials as a novel strategy for evaluation of preventive HIV vaccines’, 31 January–2 February 2006, IAVI, New York, USA
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Margaret I. Johnston, Dean Follmann, Mitchell Warren, Eric Sandström, Frances Priddy, Saladin Osmanov, Deborah L. Birx, Jim Ackland, Bonnie J. Mathieson, Susan Allen, Barry Peters, Ronald H. Gray, Siobhan Malone, Judith N. Wasserheit, David A. Cooper, Abhay Indrayan, Helen Rees, Patricia E. Fast, Ibou Thior, Shuigao Jin, Georges Thiry, Pontiano Kaleebu, Pete Smith, Timothy D. Mastro, Punnee Pitisuttithum, John G. McNeil, Wasima Rida, Steven G. Self, Elwyn Chomba, Raymond Hutubessy, Jonathan Levin, R. Ramakrishnan, Etienne Karita, Alan Fix, Gavin J. Churchyard, Daniel Barth-Jones, C. Schmidt, Mary A. Foulkes, Yuhua Ruan, Ruth Macklin, Michael N. Robertson, Ann Duerr, and Godfrey B. Tangwa
- Subjects
AIDS Vaccines ,Licensure ,medicine.medical_specialty ,Executive summary ,business.industry ,International Cooperation ,Clinical study design ,Immunology ,Alternative medicine ,HIV Infections ,Vaccine efficacy ,medicine.disease ,Test (assessment) ,Clinical Trials, Phase II as Topic ,Infectious Diseases ,Acquired immunodeficiency syndrome (AIDS) ,Evaluation Studies as Topic ,Research Design ,Family medicine ,medicine ,Humans ,Immunology and Allergy ,HIV vaccine ,business - Abstract
This report summarizes the discussions and recommendations from a consultation held in New York City, USA (31 January-2 February 2006) organized by the joint World Health Organization-United Nations Programme on HIV/AIDS HIV Vaccine Initiative and the International AIDS Vaccine Initiative. The consultation discussed issues related to the design and implementation of phase IIB 'test of concept' trials (phase IIB-TOC), also referred to as 'proof of concept' trials, in evaluating candidate HIV vaccines and their implications for future approval and licensure. The results of a single phase IIB-TOC trial would not be expected to provide sufficient evidence of safety or efficacy required for licensure. In many instances, phase IIB-TOC trials may be undertaken relatively early in development, before manufacturing processes and capacity are developed sufficiently to distribute the vaccine on a large scale. However, experts at this meeting considered the pressure that could arise, particularly in regions hardest hit by AIDS, if a phase IIB-TOC trial showed high levels of efficacy. The group largely agreed that full-scale phase III trials would still be necessary to demonstrate that the vaccine candidate was safe and effective, but emphasized that governments and organizations conducting trials should consider these issues in advance. The recommendations from this meeting should be helpful for all organizations involved in HIV vaccine trials, in particular for the national regulatory authorities in assessing the utility of phase IIB-TOC trials in the overall HIV vaccine research and development process. (c) 2007 Lippincott Williams & Wilkins.
- Published
- 2007
24. The evolving HIV epidemic among people who inject drugs in India and the need for a heightened response
- Author
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Bitra George, Timothy D Mastro, and Kevin Osborne
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Male ,medicine.medical_specialty ,business.industry ,Immunology ,Hiv epidemic ,HIV Infections ,Virology ,Article ,Infectious Diseases ,Family medicine ,medicine ,Immunology and Allergy ,Humans ,Female ,business ,Substance Abuse, Intravenous - Published
- 2015
25. Frequent Human Leukocyte Antigen Class I Alleles Are Associated With Higher Viral Load Among HIV Type 1 Seroconverters in Thailand
- Author
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Dale J. Hu, Frits van Griensven, Thomas W. Hodge, Lily Nguyen, Kachit Choopanya, Timothy D. Mastro, Philip A. Mock, Jordan W. Tappero, Robert Nelson, Suphak Vanichseni, Thanyanan Chaowanachan, and Janet M. McNicholl
- Subjects
Genes, MHC Class I ,HIV Infections ,Viremia ,Human leukocyte antigen ,HIV Antibodies ,HIV Seropositivity ,medicine ,Humans ,Pharmacology (medical) ,Seroconversion ,Substance Abuse, Intravenous ,Alleles ,biology ,Odds ratio ,Viral Load ,Thailand ,medicine.disease ,biology.organism_classification ,Virology ,Infectious Diseases ,Haplotypes ,HLA-B Antigens ,Viral evolution ,Immunology ,Lentivirus ,HIV-1 ,Viral disease ,Viral load - Abstract
The loss of viral control by the host may be due to the evolution of viruses with mutations that limit presentation by human leukocyte antigen (HLA) to cytotoxic T cells. The authors hypothesized that the consequence of such evolution might be that persons with common HLA class I alleles would be less able to control viremia, on average, than would those with rare alleles. HLA class I typing was completed for 128 injection drug users who seroconverted in a prospective cohort study in Bangkok, Thailand. Logistic regression was used to model viral load (greater than or equal to the median) at 9 and 12 months after seroconversion with an HLA score that profiled the relative prevalence of each individual's alleles. At 12 months after seroconversion, injection drug users with the most common HLA alleles (highest quartile HLA score) had an almost 4-fold increased risk for higher viral load (> or = 32,055 copies/mL) than injection drug users with less common HLA alleles (adjusted odds ratio, 3.92; 95% confidence interval, 1.3-11.8). These findings support the importance of frequency-dependent effects of host genes on HIV type 1 evolution in different populations and suggest that HLA-driven viral evolution critically influences control of viremia in early HIV type 1 infection.
- Published
- 2004
26. Sexual Risk Reduction in a Cohort of Injecting Drug Users in Bangkok, Thailand
- Author
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Kachit Choopanya, Don C. Des Jarlais, Suphak Vanichseni, Dwip Kitayaporn, Jordan W. Tappero, Frits van Griensven, Timothy D. Mastro, Boonrawd Prasithiphol, Udomsak Sangkhum, Philip A. Mock, and Krit Hiranrus
- Subjects
Adult ,Counseling ,Male ,Safe Sex ,medicine.medical_specialty ,Methadone maintenance ,Sexual Behavior ,HIV Infections ,Cohort Studies ,Condoms ,Acquired immunodeficiency syndrome (AIDS) ,Risk Factors ,Humans ,Medicine ,Pharmacology (medical) ,Risk factor ,Substance Abuse, Intravenous ,Prospective cohort study ,Needle sharing ,business.industry ,Middle Aged ,Thailand ,medicine.disease ,Surgery ,Substance abuse ,Infectious Diseases ,Cohort ,Female ,business ,Risk Reduction Behavior ,Demography ,Cohort study - Abstract
Objective To determine changes in risk behavior in relation to study participation among injecting drug users (IDUs) in Bangkok, Thailand. Methods During 1995-1996, 1,209 HIV-seronegative IDUs were recruited from Bangkok Metropolitan Administration drug abuse treatment programs to participate in a prospective cohort study. Study visits occurred every 4 months, at which the participants underwent an interview to assess risk behavior and HIV counseling and testing. Eight hundred nine of the IDUs were considered "long-term" participants, who remained in the study through at least the first four scheduled follow-up visits (16 months). Injection risk behavior at each study visit was measured on a four-point scale strongly associated with incident HIV infections in the cohort. Individual regression slopes were used to assess changes in injection risk behavior (risk increase, no change, or risk reduction). Results Of the 806 long-term study participants, 79% showed declines, 4% showed no change, and 17% showed increases in injection risk behavior. The percentage of participants in the highest-risk category (injecting daily or more frequently and sharing needles and syringes) declined from 42% at baseline to 3% at the final follow-up visit. Being in methadone maintenance treatment was associated with stable low rates of injection risk behavior, while recruitment from the 45-day detoxification treatment was associated with reductions in injection risk behavior. The risk reduction was independent of decline in risk behavior among IDUs in the community at large. Conclusions Participation in this cohort study was associated with substantial declines in injection risk behavior. This information is important in the evaluation of possible adverse behavioral effects of participation in future preventive HIV vaccine trials including IDUs, particularly in developing country settings.
- Published
- 2004
27. Recruitment, screening and characteristics of injection drug users participating in the AIDSVAX®B/E HIV vaccine trial, Bangkok, Thailand
- Author
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Donald P. Francis, Frits van Griensvan, Suphak Vanichseni, Timothy D. Mastro, Eiam Vimutisunthorn, Jordan W. Tappero, Punnee Pitisuttithum, Dwip Kitayaporn, William L. Heyward, and Kachit Choopanya
- Subjects
Adult ,Male ,medicine.medical_specialty ,Immunology ,Population ,HIV Infections ,law.invention ,Cohort Studies ,Risk-Taking ,Double-Blind Method ,Patient Education as Topic ,Acquired immunodeficiency syndrome (AIDS) ,Randomized controlled trial ,law ,HIV Seronegativity ,Surveys and Questionnaires ,Internal medicine ,medicine ,Humans ,Immunology and Allergy ,HIV vaccine ,Substance Abuse, Intravenous ,education ,AIDS Vaccines ,education.field_of_study ,business.industry ,Patient Selection ,Vaccine trial ,virus diseases ,Middle Aged ,Thailand ,medicine.disease ,Clinical trial ,Sexual Partners ,Infectious Diseases ,Cohort ,HIV-1 ,Female ,business ,Attitude to Health ,Cohort study - Abstract
The objective was to describe recruitment screening and baseline characteristics of injection drug users (IDU) participating in a phase III HIV vaccine (AIDSVAX1B/E; VaxGen USA) trial and to compare enrollment characteristics between trial participants and 1209 IDU from a 1995–1998 vaccine trial preparatory cohort for changes that might impact trial design assumptions. Enrollment for both studies was conducted at Bangkok narcotic treatment clinics where a standardized questionnaire was administered on demographics risk behavior and incarceration history over the previous 6 months. During 1999–2000 4943 IDU were screened for enrollment; successful sources of recruitment included clinic attendees (43.4%) an IDU referral program (20.4%) and preparatory cohort participants (14.7%). Of those screened 1689 (34%) were HIV seropositive (HIV subtype B 23.6%; subtype E 76.4%). Of the 2545 enrolled 93.4% were male. Compared with cohort IDU trial IDU were younger (mean age: 28.8 versus 31.3 years) better educated (secondary level or higher: 67.2% versus 58.7%) and less likely to inject drugs daily (39.4% versus 90.4%); they were more likely to have been incarcerated (78.4% versus 65.7%) have recently injected stimulants (14.8% versus 5.8%) and tranquilizers (11.5% versus 2.3%) and obtained needles/syringes from a source other than a pharmacist (7.2% versus 3.9%) (all P = 0.003). IDU at high risk for HIV have been successfully enrolled in the AIDSVAX1B/E efficacy trial. Only minor epidemiologic differences were found at enrollment between trial and preparatory cohort IDU. The latter has proven critical in guiding trial design; results are expected in late 2003. (authors)
- Published
- 2004
28. Determining HIV Incidence in Populations: Moving in the Right Direction
- Author
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Timothy D Mastro
- Subjects
Infectious Diseases ,Text mining ,business.industry ,Hiv incidence ,Immunology and Allergy ,Medicine ,business ,Demography - Published
- 2012
29. Determining the Incidence of Hepatitis C Virus Infection in Populations: An Important Tool for Epidemic Control
- Author
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Charles S. Morrison, Carol Dukes Hamilton, and Timothy D Mastro
- Subjects
education.field_of_study ,Incidence (epidemiology) ,Hepatitis C virus ,Population ,Psychological intervention ,Hepatitis C ,Biology ,medicine.disease_cause ,medicine.disease ,03 medical and health sciences ,0302 clinical medicine ,Infectious Diseases ,Environmental health ,Immunology ,medicine ,Immunology and Allergy ,030211 gastroenterology & hepatology ,Hcv prevalence ,030212 general & internal medicine ,Hiv treatment ,education ,Epidemic control - Abstract
persons. These logistically complicated studies often yield results that are not representative of the larger population of interest as the interventions involved may alter behaviors and subsequent HCV infection incidence. Use of mathematical models to estimate incidence on the basis of HCV prevalence has a role, but input parameters are often not available for specific locations and key populations, resulting in imprecise estimates. Accurate determinations of the incidence of HCV infection are essential to characterize and monitor the epidemic, identify populations currently at highest risk, and assess the effectiveness of interventions. Fortunately, we are in the midst of a
- Published
- 2016
30. Risk Factors for Sexually Transmitted Diseases in Northern Thai Adolescents
- Author
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Peter H. Kilmarx, Somsak Supawitkul, Timothy D. Mastro, Gabriela Paz-Bailey, Maya R. Sternberg, Thanyanan Chaowanachan, Lauri E. Markowitz, Supaporn Jeeyapant, and Frits van Griensven
- Subjects
Adult ,Male ,Microbiology (medical) ,Sexually transmitted disease ,Health Knowledge, Attitudes, Practice ,medicine.medical_specialty ,Adolescent ,Population ,Sexually Transmitted Diseases ,Dermatology ,Specimen Handling ,law.invention ,Risk-Taking ,Sex Counseling ,Sex Factors ,Condom ,law ,Surveys and Questionnaires ,Prevalence ,medicine ,Humans ,Risk factor ,education ,Gynecology ,education.field_of_study ,Audiovisual Aids ,Participation bias ,Computers ,business.industry ,Age Factors ,Public Health, Environmental and Occupational Health ,Thailand ,Health Surveys ,Sexual intercourse ,Logistic Models ,Infectious Diseases ,Specimen collection ,Adolescent Behavior ,Adolescent Health Services ,Female ,business ,Demography - Abstract
BACKGROUND: Previous studies of sexual behavior and sexually transmitted diseases (STDs) in Thai adolescents may have been limited by participation bias and underreporting of stigmatized behaviors. GOAL: The goal was to increase knowledge about risk behaviors and STDs among youths in Thailand. STUDY DESIGN: Students aged 15 to 21 years completed an audio-computer-assisted self-interview. Oral fluid was tested for HIV antibodies and urine was tested for Chlamydia trachomatis and Neisseria gonorrhoeae nucleic acids with polymerase chain reaction. RESULTS: Of 1736 invited students, 1725 (99.4%) agreed to participate. Overall, C trachomatis infection was detected in 49 (2.8%), and there were five cases (0.3%) each of infection with N gonorrhoeae and HIV. Among those who reported sexual intercourse, the prevalence of chlamydial infection was 3.7% among men and 6.1% among women. Logistic regression analysis showed age-adjusted factors associated with chlamydial infection among men to be parents' occupation in agriculture, having sold sex, having a sex partner who had been pregnant, and the number of casual sex partners during lifetime. Among women, age-adjusted factors were parents' occupation in agriculture, number of casual partners during lifetime, having an older sex partner, and perception of higher HIV infection risk. CONCLUSION: These adolescents had high rates of unprotected intercourse and are at risk for STDs. Prevention programs should emphasize use of effective contraceptive methods, including condom use; reducing the number of sex partners (stressing the risk a partner of older age may pose to female adolescents); and reducing engagement in commercial sex.
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- 2003
31. Leaving sex work: Barriers, facilitating factors and consequences for female sex workers in northern Thailand
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Somsak Supawitkul, Peter H. Kilmarx, Rebecca Bunnell, Supaporn Chaikummao, Chomnad Manopaiboon, M E St Louis, Khanchit Limpakarnjanarat, and Timothy D. Mastro
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Adult ,Employment ,Safe Sex ,Gerontology ,Health (social science) ,Social Psychology ,Occupational prestige ,Population ,HIV Infections ,Cohort Studies ,Acquired immunodeficiency syndrome (AIDS) ,Interview, Psychological ,Humans ,Medicine ,Family ,education ,Life Style ,Socioeconomic status ,Sex work ,education.field_of_study ,business.industry ,Social change ,Public Health, Environmental and Occupational Health ,Social environment ,Middle Aged ,Thailand ,medicine.disease ,Sex Work ,Sexual Partners ,Socioeconomic Factors ,Income ,Female ,business ,Attitude to Health ,Cohort study - Abstract
Factors facilitating or inhibiting women's ability to leave sex work are still poorly characterized, and little is known about women's lives after they leave the profession. This paper presents findings from a qualitative study about factors affecting women's ability to leave sex work and influencing their lives after leaving. We interviewed 42 current and former female sex workers (FSWs) drawn from a cohort study of 500 FSWs in northern Thailand. All but one of the participants had quit sex work at least once. The majority experienced one or more quit-re-entry-quit cycles. Women's ability and decisions to leave sex work were determined primarily by four factors: economic situation, relationship with a steady partner, attitudes towards sex work and HIV/AIDS experience. Economic concerns, ranging from survival needs to materialistic desires, had the strongest influence. Most women perceived their risk for HIV infection to be lower after leaving sex work, but three of the 17 HIV-infected women acquired infection after having left, presumably from their steady partners. Prevention efforts should guide women as they transition out of commercial sex work. Interventions aimed at assisting women wanting to leave sex work need to address the role of economic factors.
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- 2003
32. Prevalence of and risk factors for methamphetamine use in northern Thai youth: results of an audio-computer-assisted self-interviewing survey with urine testing
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Timothy D. Mastro, Somsak Supawitkul, Supaporn Chaikummao, Timothy J. Dondero, Frits van Griensven, Martin V. Sattah, Nancy L. Young, Chomnad Manopaiboon, and Peter H. Kilmarx
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medicine.medical_specialty ,Multivariate analysis ,business.industry ,Cross-sectional study ,education ,Medicine (miscellaneous) ,Odds ratio ,Methamphetamine ,Psychiatry and Mental health ,Epidemiology ,medicine ,Peer pressure ,Risk factor ,Psychiatry ,business ,Psychosocial ,medicine.drug ,Clinical psychology - Abstract
Aims Data from drug treatment facilities, drug seizures and drug arrests suggest rapidly increasing methamphetamine use by adolescents in Thailand. However, limited quantitative data are available about the prevalence of its use or correlates of use. The purpose of our study was therefore to estimate the prevalence of methamphetamine use and to identify possible risk factors. Design Cross-sectional survey using anonymous audio-computer-assisted self-interview and urine specimen analysis. Setting Chiang Rai Province, Thailand. Participants 1725 students, 15–21 years of age (893 male and 832 female) attending one of three vocational schools in Chiang Rai Province. Findings Three hundred and fifty male and 150 female students reported a history of having ever used methamphetamine. In addition, 128 male and 49 female students had positive urine test results, indicating recent methamphetamine use; 27 of these students denied having ever used methamphetamine. According to history, urine test, or both, 41.3% of male students and 19.0% of female students used methamphetamine. In multivariate analysis, methamphetamine use was highly correlated with the use of other substances, sexual activity, peer pressure, positive attitudes toward methamphetamine, and absence of a family confidant. Conclusions Methamphetamine use is common among adolescent students in northern Thailand. Demographic, behavioral and psychosocial correlates of methamphetamine use identified in this study may be helpful for the design and implementation of preventive interventions.
- Published
- 2002
33. Higher Viral Loads and Other Risk Factors Associated With HIV-1 Seroconversion During a Period of High Incidence Among Injection Drug Users in Bangkok
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Philip A. Mock, Dwip Kitayaporn, Frits van Griensven, Robert H. Byers, Don C. Des Jarlais, Suphak Vanichseni, Lily Nguyen, Nancy L. Young, Dale J. Hu, Timothy D. Mastro, Robert Nelson, Kachit Choopanya, and Shambavi Subbarao
- Subjects
Adult ,Male ,medicine.medical_specialty ,HIV Infections ,HIV Antibodies ,Cohort Studies ,Acquired immunodeficiency syndrome (AIDS) ,Risk Factors ,Internal medicine ,HIV Seropositivity ,Humans ,Medicine ,Pharmacology (medical) ,Prospective Studies ,Risk factor ,Seroconversion ,Substance Abuse, Intravenous ,Drug injection ,business.industry ,Incidence ,Incidence (epidemiology) ,Odds ratio ,Viral Load ,Thailand ,medicine.disease ,Infectious Diseases ,Immunology ,HIV-1 ,Viral disease ,business ,Viral load - Abstract
We analyzed data from a prospective cohort study of injection drug users (IDUs) attending methadone treatment clinics in Bangkok, Thailand, during 1995-1998 to characterize factors associated with a period of high incidence (PHI) from July 1996 through January 1997 compared with periods of lower incidence. Sociobehavioral characteristics were similar for all participants during and outside the PHI except for the following: there was more reported drug injection while IDUs were incarcerated during the PHI (odds ratio, 1.67; p =.02) and significantly higher proportions of persons reported heroin injection (91% vs. 75%, respectively; p =.02) and higher frequencies of daily injection and sharing of injection equipment (40% vs. 25%, respectively; p =.05) during the PHI than outside the PHI. Through most of the first year after seroconversion, plasma HIV-1 loads were significantly higher in persons who seroconverted during the PHI than in those who seroconverted outside the PHI. Higher viral loads may potentially contribute to faster disease progression and increased infectiousness or transmissibility to subsequent contacts. Our findings suggest that prevention efforts to reduce the effective size and turnover within IDU sharing networks may have a significant impact on the epidemic by disrupting the rapid transmission of HIV-1 from recently infected, highly infectious individuals.
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- 2002
34. Subtype-specific Transmission Probabilities for Human Immunodeficiency Virus Type 1 among Injecting Drug Users in Bangkok, Thailand
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Dwip Kitayaporn, Suphak Vanichseni, Glen A. Satten, M. Elizabeth Halloran, Timothy D. Mastro, Michael G. Hudgens, Kachit Choopanya, Philip A. Mock, Ira M. Longini, and Dale J. Hu
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Adult ,Male ,medicine.medical_specialty ,Adolescent ,Epidemiology ,Population ,HIV Infections ,Statistics, Nonparametric ,Acquired immunodeficiency syndrome (AIDS) ,Risk Factors ,Humans ,Medicine ,Substance Abuse, Intravenous ,education ,Sida ,education.field_of_study ,biology ,business.industry ,Transmission (medicine) ,Incidence ,Middle Aged ,Thailand ,medicine.disease ,biology.organism_classification ,Survival Analysis ,Cohort ,Immunology ,HIV-1 ,Female ,Viral disease ,business ,Cohort study ,Demography - Abstract
The Bangkok (Thailand) Metropolitan Administration cohort of injecting drug users (IDUs) consisted of 1,209 IDUs initially seronegative for human immunodeficiency virus (HIV) who were followed from 1995 to 1998 at 15 Administration drug treatment clinics. At enrollment and approximately every 4 months thereafter, participants were assessed for HIV seropositivity. As of December 1998, there were 133 HIV type 1 seroconversions and approximately 2,300 person-years of follow-up. Of the 133 observed seroconversions, specimens from 126 persons were available for subtyping (27 subtype B, 99 subtype E). In this analysis, the authors assessed differences in subtype-specific transmission while controlling for important risk factors. The methodology used accounts for left truncation, interval censoring, and competing risks as well as for time-varying covariates such as each IDU's history of reported frequency of injection and of incarceration. Using plausible epidemiologic assumptions and controlling for behavioral risks, the authors found that a significantly higher transmission probability was associated with subtype E compared with subtype B in this population. Since many epidemiologic, virologic, and host factors can influence HIV transmission, it was difficult to conclude whether these differences in transmission probabilities were due to biologic properties associated with subtype.
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- 2002
35. Incarceration and Risk for HIV Infection Among Injection Drug Users in Bangkok
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Suphak Vanichseni, Dwip Kitayaporn, Suwanee Raktham, Kachit Choopanya, Sathit Sujarita, Philip A. Mock, Don C. Des Jarlais, Timothy D. Mastro, William L. Heyward, and Krit Hireanras
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Adult ,Male ,Multivariate analysis ,Adolescent ,Cross-sectional study ,HIV Infections ,Cohort Studies ,Risk-Taking ,Acquired immunodeficiency syndrome (AIDS) ,Environmental health ,medicine ,Humans ,Pharmacology (medical) ,Substance Abuse, Intravenous ,Drug injection ,business.industry ,Incidence ,Prisoners ,Incidence (epidemiology) ,virus diseases ,Thailand ,medicine.disease ,Substance abuse ,Infectious Diseases ,Multivariate Analysis ,Immunology ,HIV-1 ,Female ,business ,Methadone ,medicine.drug ,Cohort study - Abstract
This paper aims to assess potential multiple relationships between incarceration and HIV infection among injecting drug users (IDUs) in Bangkok. Previous cross-sectional studies have shown strong relationships between incarceration and HIV infection but have not been able to assess potential casual pathways. Injection drug users seen at methadone treatment programs in Bangkok were screened during 1995 to 1996 for enrollment into the study. With informed consent 1209 seronegative IDUs were enrolled in a cohort study to determine HIV incidence and identify factors associated with incident infections. Follow-up visits were conducted every 4 months with HIV testing and assessment of risk behaviors. Overall incidence rate was 5.8 per 100 person-years (95% confidence interval [CI] 4.8-6.8) of follow-up. A four-step "infection risk" scale was constructed that included less frequent than daily infection daily injection daily injection with reported sharing of injection equipment and injection while incarcerated. This scale was strongly related to HIV incidence with incidence approximately doubling for each step in the scale. Incidence rate for follow-up periods that contained drug injection while incarcerated was 35/100 person-years at risk. In multivariate analyses incarceration was related to incident HIV infection in multiple ways: previous incarceration and recent incarceration without drug injection and the injection risk scale were all independently predictors of incident HIV infection. Incarceration is related to incident HIV infection through multiple pathways. Previous incarcerations are likely to serve as markers for unmeasured high-risk behaviors and it is also highly likely that HIV is transmitted during periods of incarceration. Programs to reduce HIV transmission in jails and prisons including drug abuse treatment of inmates and programs to reduce the likelihood of incarceration of IDUs are needed urgently. Given the current diffusion of injecting drug use of HIV infection among drug injectors and of the common policy of incarcerating drug users it is very likely that the problem of HIV transmission in jails and prisons is increasing in many countries throughout the world. (authors)
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- 2002
36. ARV-based HIV prevention for women – where we are in 2014
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Timothy D Mastro, Nirupama Sista, and Quarraisha Abdool-Karim
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medicine.medical_specialty ,Biomedical Research ,Population level ,HIV prevention ,Human immunodeficiency virus (HIV) ,HIV Infections ,New infection ,Review Article ,medicine.disease_cause ,Women and ARV-based prevention: opportunities and challenges ,Chemoprevention ,Acquired immunodeficiency syndrome (AIDS) ,Disease Transmission, Infectious ,medicine ,HIV treatment ,Humans ,Hiv acquisition ,Transmission (medicine) ,business.industry ,Public Health, Environmental and Occupational Health ,HIV ,virus diseases ,medicine.disease ,Research findings ,Treatment as prevention ,antiretroviral agents ,PrEP ,AIDS ,Administration, Intravaginal ,Infectious Diseases ,Anti-Retroviral Agents ,Family medicine ,Immunology ,Anti-Infective Agents, Local ,Female ,Pre-Exposure Prophylaxis ,women ,business - Abstract
Women continue to be at special risk for HIV acquisition due to a complex mix of biological, behavioural, structural, cultural and social factors, with unacceptable rates of new infection. Scientific advances over the past decade have highlighted the use of antiretroviral (ARV) drugs as pre-exposure prophylaxis (PrEP) to prevent HIV acquisition (sexually, parenterally and vertically) and ARV treatment (ART) for HIV-positive patients to prevent onward transmission (treatment as prevention - TasP). This paper reviews the evidence base for PrEP and TasP, describes new products in development and the need to translate research findings into programmes with impact at the population level.
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- 2014
37. Production of a Novel Viral Suppressive Activity Associated with Resistance to Infection among Female Sex Workers Exposed to HIV Type 1
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Timothy D. Mastro, Thomas W. Hodge, Nancy L. Young, Khanchit Limpakarnjanarat, Thomas M. Folks, Tracy L. Pisell, and Salvatore T. Butera
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CD4-Positive T-Lymphocytes ,Immunology ,Human immunodeficiency virus (HIV) ,HIV Infections ,CD8-Positive T-Lymphocytes ,Biology ,Virus Replication ,medicine.disease_cause ,Monocytes ,Virus ,Cohort Studies ,Acquired immunodeficiency syndrome (AIDS) ,HIV Seronegativity ,Virology ,Immunopathology ,medicine ,Humans ,Prospective Studies ,Sida ,Cells, Cultured ,Immunity, Cellular ,Monocyte ,virus diseases ,Thailand ,biology.organism_classification ,medicine.disease ,Sex Work ,Coculture Techniques ,Infectious Diseases ,medicine.anatomical_structure ,Chemokines, CC ,Culture Media, Conditioned ,Lentivirus ,HIV-1 ,Female ,Viral disease - Abstract
To investigate mechanisms of natural resistance to human immunodeficiency virus type 1 (HIV-1), we obtained blood samples from eight women who remained HIV-1 negative after3 years of high-risk sex work in Chiang Rai, Thailand. CD4+ T lymphocytes from these highly exposed, persistently seronegative (HEPS) women were readily infectable in vitro with HIV-1 subtypes B and E. Autologous CD8+ cell suppression of both HIV-1 subtypes was evident in HEPS infection cultures, but to an extent also observed in cultures from non-HIV-exposed individuals. Furthermore, production of beta-chemokines was not enhanced in HEPS cultures. However, HEPS cultures displayed significantly enhanced production of a soluble activity that suppressed postintegrated HIV-1 replication. This activity was the unique product of CD4+ T cell and monocyte cocultures. Therefore, although HEPS individuals are apparently susceptible to infection, the production of a postintegrated HIV-1 suppressive activity during monocyte-T cell interactions might protect against the establishment of infection by limiting viral dissemination.
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- 2001
38. HIV Seroconversion During Pregnancy and Risk for Mother-to-Infant Transmission
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Chantapong Wasi, Nathan Shaffer, Sunee Singhanati, Bharat Parekh, Varaporn Sangtaweesin, Timothy D. Mastro, R. J. Simonds, Nirun Vanprapar, Nancy L. Young, Wimol Siriwasin, Anuvat Roongpisuthipong, and Philip A. Mock
- Subjects
Adult ,medicine.medical_specialty ,Time Factors ,Population ,Gestational Age ,Cohort Studies ,Acquired immunodeficiency syndrome (AIDS) ,Pregnancy ,Risk Factors ,HIV Seropositivity ,medicine ,Birth Weight ,Humans ,Pharmacology (medical) ,Prospective Studies ,Pregnancy Complications, Infectious ,Seroconversion ,Substance Abuse, Intravenous ,education ,education.field_of_study ,biology ,Cesarean Section ,Obstetrics ,Transmission (medicine) ,business.industry ,Infant, Newborn ,virus diseases ,Gestational age ,Viral Load ,Thailand ,biology.organism_classification ,medicine.disease ,Sex Work ,Infectious Disease Transmission, Vertical ,CD4 Lymphocyte Count ,Infectious Diseases ,Lentivirus ,Immunology ,HIV-1 ,RNA, Viral ,Female ,Disease Susceptibility ,business ,Viral load - Abstract
Pregnant women infected with HIV-1 were enrolled in a prospective mother-to-infant transmission study from 1992 through 1994 in Bangkok. In participating hospitals, voluntary HIV testing was routinely offered at the beginning of antenatal care and again in the middle of the third trimester of pregnancy. Women who seroconverted to HIV during pregnancy were compared with women who had tested positive on their first antenatal test. Maternal HIV RNA levels were determined during pregnancy, at delivery, and postpartum using RNA polymerase chain reaction (PCR), and infection status in infants was determined by DNA PCR. No infants were breast-fed, but prophylactic antiretroviral therapy was not yet used in Thailand to prevent transmission from mother to infant. Among enrolled women, 16 who seroconverted during pregnancy and 279 who were HIV-1-seropositive at their first antenatal test gave birth. Median plasma RNA levels at delivery were similar for the two groups (17,505 and 20,845 copies/ml, respectively; p =.8). Two (13.3%) of 15 infants born to women who seroconverted and 66 (24.8%) of 266 infants born to previously HIV-seropositive women were infected with HIV (p =.5). There was no increased risk for mother-to-infant HIV transmission and no significant difference in viral load at delivery between HIV-infected women who seroconverted to HIV during pregnancy and those who were HIV-seropositive when first tested.
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- 2001
39. Viral load differences in early infection with two HIV-1 subtypes
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La-Ong Srisuwanvilai, Chantapong Wasi, Walid Heneine, Philip A. Mock, Timothy D. Mastro, Dale J. Hu, Kachit Choopanya, Bharat Parekh, Suwanee Raktham, Shambavi Subbarao, Ruengpung Sutthent, Suphak Vanichseni, and Nancy L. Young
- Subjects
Adult ,Male ,medicine.medical_specialty ,Immunology ,HIV Infections ,CD8-Positive T-Lymphocytes ,Acquired immunodeficiency syndrome (AIDS) ,HIV Seropositivity ,Epidemiology ,medicine ,Humans ,Immunology and Allergy ,Prospective Studies ,Seroconversion ,Sida ,Prospective cohort study ,biology ,Viral Load ,Thailand ,biology.organism_classification ,medicine.disease ,Virology ,CD4 Lymphocyte Count ,Infectious Diseases ,Lentivirus ,HIV-1 ,RNA, Viral ,Female ,Viral disease ,Viral load - Abstract
Objectives Information on early HIV-1 infection has come primarily from studies of persons infected with subtype B in North America and Europe; much less is known about other subtypes. The purpose of the present study was to compare the virologic and immunologic parameters following seroconversion among recently-infected persons infected with either of two different HIV-1 subtypes. Method A prospective cohort study was carried out at methadone treatment clinics administered by the Bangkok Metropolitan Administration, Thailand. A total of 130 HIV-1-infected seroconverters (103 with HIV-1 subtype E and 27 with subtype B) were included in the study. The main outcome measures were serial HIV-1 RNA viral load, natural killer cell percentage, CD4 and CD8 lymphocyte counts since seroconversion. Results The demographic and behavioral characteristics of persons with either subtype were similar. Median RNA viral levels at the earliest time within 3 months of seroconversion were more than three times higher for persons infected with subtype E than subtype B (63 100 versus 18 050 copies/ml, P = 0.001). However, this difference decreased over time such that viral loads were similar at 12, 18, and 24 months following seroconversion. The CD4 and CD8 lymphocyte counts were similar in infections with either subtype during the entire period up to 24 months post-seroconversion. Conclusions Higher viral loads associated with subtype E may result from inter-subtype biological differences; however, the epidemiological dynamics of transmission in Bangkok may have also contributed to this phenomenon.
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- 2001
40. 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
- Author
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Suwanee Rakhtam, Suphak Vanichseni, Kachit Choopanya, Dwip Kitayaporn, La-Ong Srisuwanvilai, Dale J. Hu, Timothy D. Mastro, Glen A. Satten, Robert S. Janssen, Nancy L. Young, Bharat Parekh, and Debra Candal
- Subjects
Adult ,Male ,Time Factors ,Immunology ,HIV Infections ,Window period ,Sensitivity and Specificity ,Immunophenotyping ,Serology ,Acquired immunodeficiency syndrome (AIDS) ,Virology ,HIV Seropositivity ,Humans ,Medicine ,Longitudinal Studies ,Seroconversion ,Substance Abuse, Intravenous ,Sida ,Immunoassay ,biology ,business.industry ,Incidence (epidemiology) ,Thailand ,biology.organism_classification ,medicine.disease ,Infectious Diseases ,Lentivirus ,HIV-1 ,Viral disease ,business ,Algorithm ,Algorithms - Abstract
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.
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- 2001
41. Estimating the Transmission Probability of Human Immunodeficiency Virus in Injecting Drug Users in Thailand
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Suphak Vanichseni, Dwip Kitayaporn, Kachit Choopanya, Michael G. Hudgens, Timothy D. Mastro, Philip A. Mock, M. Elizabeth Halloran, and Ira M. Longini
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Statistics and Probability ,Needle sharing ,medicine.medical_specialty ,business.industry ,Prevalence ,Censoring (statistics) ,law.invention ,Transmission (mechanics) ,law ,Epidemiology ,Statistics ,Cohort ,medicine ,Statistics, Probability and Uncertainty ,Seroconversion ,Likelihood function ,business ,Demography - Abstract
SUMMARY We estimate the transmission probability for the human immunodeficiency virus from seroconversion data of a cohort of injecting drug users (IDUs) in Thailand. The transmission probability model developed accounts for interval censoring and incorporates each IDU’s reported frequency of needle sharing and injecting acts. Using maximum likelihood methods, the per needle sharing act transmission probability estimate between infectious and susceptible IDUs is 0.008. The effects of covariates, disease dynamics, mismeasured exposure information and the uncertainty of the disease prevalence on the transmission probability estimate are considered.
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- 2001
42. Placental Abnormalities Associated with Human Immunodeficiency Virus Type 1 Infection and Perinatal Transmission in Bangkok, Thailand
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Wendy Bhanich Supapol, Timothy D. Mastro, Tuenjai Chuangsuwanich, Suthi Sungkarat, David A. Schwartz, Nathan Shaffer, Pichai Charoenpanich, and Jirasak Laosakkitiboran
- Subjects
Adult ,medicine.medical_specialty ,Adolescent ,Placenta ,Population ,HIV Infections ,Biology ,Chorioamnionitis ,Umbilical Cord ,Placental Membrane ,Cohort Studies ,Acquired immunodeficiency syndrome (AIDS) ,Pregnancy ,Risk Factors ,Funisitis ,Decidua ,medicine ,Humans ,Immunology and Allergy ,Prospective Studies ,Pregnancy Complications, Infectious ,education ,education.field_of_study ,Obstetrics ,Infant, Newborn ,Infant ,virus diseases ,Odds ratio ,Thailand ,medicine.disease ,Infectious Disease Transmission, Vertical ,Infectious Diseases ,medicine.anatomical_structure ,Immunology ,HIV-1 ,Female ,Chorionic Villi - Abstract
The effects of human immunodeficiency virus (HIV) type 1 on the placenta and the role of the placenta in mother-to-child HIV-1 transmission are not well understood. Placentas from 78 HIV-infected and 158 HIV-uninfected women were examined as part of a prospective perinatal HIV transmission study in Bangkok. HIV-infected women were more likely than HIV-uninfected women to have chorioamnionitis (odds ratio [OR], 2.1; P=.03), placental membrane inflammation (PMI; OR, 2. 7; P=.02), and deciduitis (OR, 2.3; P=.03) and less likely to have villitis (OR, 0.3; P=.02). However, among HIV-infected women, fewer women who transmitted infection to their child had chorioamnionitis (relative risk [RR], 0.2; P=.03), funisitis (RR, 0.4; P=.1), or PMI (RR undefined; P=.03). These findings suggest that, in this population, HIV-infected women are at increased risk for placental membrane inflammatory lesions, but that placental inflammatory lesions are not associated with increased perinatal HIV transmission.
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- 2000
43. A Comparison of Full-Length Glycoprotein 120 from Incident HIV Type 1 Subtype E and B Infections in Bangkok Injecting Drug Users with Prototype E and B Strains That Are Components of a Candidate Vaccine
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Timothy D. Mastro, Shambavi Subbarao, Suphak Vanichseni, Nancy L. Young, Suwanee Raktham, Dale J. Hu, Margaret E. Callahan, Kachit Choopanya, and Kim-Oanh Phan
- Subjects
Molecular Sequence Data ,Immunology ,HIV Infections ,HIV Envelope Protein gp120 ,Virus ,Acquired immunodeficiency syndrome (AIDS) ,Virology ,Humans ,Medicine ,Amino Acid Sequence ,Substance Abuse, Intravenous ,Sida ,Phylogeny ,AIDS Vaccines ,biology ,Molecular epidemiology ,business.industry ,Vaccination ,Vaccine trial ,virus diseases ,Thailand ,biology.organism_classification ,medicine.disease ,Infectious Diseases ,Cohort ,Lentivirus ,HIV-1 ,Viral disease ,business - Abstract
Complete gp120 sequence information was obtained from eight persons with incident HIV-1 infections (four subtype E and four subtype B) who were part of a prospective injecting drug user (IDU) cohort in Bangkok, Thailand, during 1996-1998. The incident subtype E strains were similar to the prototype subtype E strain CM244 isolated in 1992 in northern Thailand. The incident subtype B strains displayed divergence, in both overall genetic distance and other significant gp120 characteristics, from the prototype North American subtype B strain HIV-MN. Recombinant gp120s derived from CM244 and HIV-MN strains are components of a vaccine that is undergoing phase III efficacy testing, begun in March 1999, among Bangkok area IDUs. The information presented here will be important in the evaluation of any breakthrough HIV-1 infections occurring among vaccinees during the vaccine trial and in ongoing vaccine development efforts in Thailand.
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- 2000
44. Early Diagnosis of HIV-1–Infected Infants in Thailand Using RNA and DNA PCR Assays Sensitive to Non-B Subtypes
- Author
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Nirun Vanparapar, Timothy D. Mastro, Philip A. Mock, Punneeporn Wasinrapee, Thongpoon Chaowanachan, Kulkanya Chokephaibulkit, Nancy L. Young, Tawee Chotpitayasunondh, Rutt Chuachoowong, R. J. Simonds, Naris Waranawat, and Nathan Shaffer
- Subjects
Population ,HIV Infections ,Polymerase Chain Reaction ,Sensitivity and Specificity ,Virus ,law.invention ,Cohort Studies ,Immunoenzyme Techniques ,Zidovudine ,law ,Predictive Value of Tests ,medicine ,Humans ,Pharmacology (medical) ,Serotyping ,education ,Polymerase chain reaction ,Randomized Controlled Trials as Topic ,education.field_of_study ,biology ,Reverse-transcriptase inhibitor ,Age Factors ,Infant, Newborn ,RNA ,Infant ,Viral Load ,biology.organism_classification ,Thailand ,Virology ,Infectious Diseases ,Lentivirus ,DNA, Viral ,HIV-1 ,RNA, Viral ,Viral load ,medicine.drug - Abstract
The aim was to evaluate the sensitivity and specificity of RNA and DNA polymerase chain reaction (PCR) for early diagnosis of perinatal HIV-1 infection and to investigate early viral dynamics in infected infants. A cohort study of 395 non-breast-fed infants born to HIV-infected mothers was conducted in a randomized clinical trial of short-course antenatal zidovudine. Infant venous blood specimens collected at birth 2 months and 6 months of age were tested by qualitative DNA and quantitative RNA PCR (Roche Amplicor). To determine sensitivity and specificity of DNA and RNA PCR results were compared with later DNA PCR results and to antibody results at 18 months. The HIV-1 subtype of the mothers infection was determined by peptide serotyping. In the study 92% of mothers were infected with subtype E. DNA PCR sensitivity was 38% (20 of 53) at birth and 100% at 2 months (53 of 53) and 6 months (47 of 47). RNA PCR sensitivity was 47% (25 of 53) at birth and 100% (53 of 53) at 2 months. All samples that tested DNA-positive tested RNA-positive. Specificity was 100% for both DNA and RNA testing at all timepoints. For infected infants the median viral load of RNA-positive specimens was 407000 copies/ml (5.6 log 10) at birth 3700000 copies/ml (6.6 log 10) at 2 months and 1700000 copies/ml (6.2 log 10) at 6 months. Infant RNA levels at 2 and 6 months did not differ by maternal zidovudine exposure or RNA level at birth. This RNA PCR assay performed well for diagnosing perinatal HIV subtype E infection detecting nearly half of infected infants at birth and 100% at 2 and 6 months with 100% specificity. Infected infant viral RNA levels were very high at 2 and 6 months and were unaffected by maternal zidovudine treatment. (authors)
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- 2000
45. Protease sequences from HIV-1 group M subtypes A???H reveal distinct amino acid mutation patterns associated with protease resistance in protease inhibitor-naive individuals worldwide
- Author
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Mark A. Rayfield, Robert W. Downing, Timothy D Mastro, Renu B. Lal, Benon Biryahwaho, Danuta Pieniazek, Vincent Soriano, Stefan Z. Wiktor, Amilcar Tanuri, John N. Nkengasong, Timothy J. Dondero, and Dale J. Hu
- Subjects
Mutation ,Protease ,biology ,medicine.medical_treatment ,Immunology ,Drug resistance ,biology.organism_classification ,medicine.disease_cause ,Virology ,Molecular biology ,Virus ,law.invention ,Infectious Diseases ,law ,Lentivirus ,medicine ,Immunology and Allergy ,Protease inhibitor (pharmacology) ,Gene ,Polymerase chain reaction - Abstract
Background: Although numerous mutations that confer resistance to protease inhibitors (PRI) have been mapped for HIV-1 subtype B, little is known about such substitutions for the non-B viruses, which globally cause the most infections. Objectives: To determine the prevalence of PRI-associated mutations in PRI-naive individuals worldwide. Design: Using the polymerase chain reaction, protease sequences were amplified from 301 individuals infected with HIV-lsubtypes A (79), B (95), B' (19), C (12), D (26), A/E (23), F (26), A/G (11), and H (3) and unclassifiable HIV-1 (7). Amplified DNA was directly sequenced and translated to amino acids to analyze PRI-associated major and accessory mutations. Results: Of the 301 sequences, 85% contained at least one codon change giving substitution at 10, 20, 30, 36, 46, 63, 71, 77, or 82 associated with PRI resistance; the frequency of these substitutions was higher among non-B (91%) than B (75%) viruses (P 771 (19%) > 10I/V/R (6%) = 361 (6%) = 71T/V (6%) > 20R (2%), and non-B strains, 361 (83%) > 63P (17%) > 101/V/R (13%) > 20R(10%) > 771 (2%), which differed statistically at positions 20, 36, 63, 71, and 77. Conclusions: The high prevalence of PRI-associated substitutions represent natural polymorphisms occurring in PRI-naive patients infected with HIV-1 strains of subtypes A-H. The significance of distinct mutation patterns identified for subtype B and non-B strains warrants further clinical evaluation. A global HIV-1 protease database is fundamental for the investigation of novel PRI.
- Published
- 2000
46. Oral zidovudine during labor to prevent perinatal HIV transmission, Bangkok: tolerance and zidovudine concentration in cord blood
- Author
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Nathan Shaffer, C. Bhadrakom, Timothy D. Mastro, K. H. P. Moore, W. H. Hannon, Nirun Vanprapar, Nancy L. Young, R. J. Simonds, V. Sangtaweesin, Suvanna Asavapiriyanont, and J. V. Mei
- Subjects
Pregnancy ,business.industry ,Immunology ,virus diseases ,medicine.disease ,Umbilical cord ,Zidovudine ,Infectious Diseases ,medicine.anatomical_structure ,Pharmacokinetics ,immune system diseases ,Oral administration ,Cord blood ,Anesthesia ,Chemoprophylaxis ,Immunology and Allergy ,Gestation ,Medicine ,business ,medicine.drug - Abstract
The aim was to evaluate tolerance for the oral administration of zidovudine (ZDV) during labor and measure the resulting ZDV concentrations in umbilical cord blood. A cross-sectional study was conducted on women in a placebo-controlled trial of short-course ZDV (twice a day from 36 weeks gestation until labor and every 3 hours during labor) to prevent perinatal HIV transmission in Bangkok. Umbilical cord blood was collected. 60 control specimens and specimens from 372 women (182 in the ZDV group 190 in the placebo group) were tested for ZDV by radioimmunoassay (lower detection limit
- Published
- 2000
47. Analysis of Genetic Variability within the Immunodominant Epitopes of Envelope gp41 from Human Immunodeficiency Virus Type 1 (HIV-1) Group M and Its Impact on HIV-1 Antibody Detection
- Author
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Benon Biryahwaho, Jonathan Dorn, Dale J. Hu, Timothy D. Mastro, Danuta Pieniazek, Robert Downing, John N. Nkengasong, Mark A. Rayfield, Chunfu Yang, Renu B. Lal, and Silvina Masciotra
- Subjects
Microbiology (medical) ,Molecular Sequence Data ,Cross Reactions ,HIV Antibodies ,Gp41 ,medicine.disease_cause ,Polymerase Chain Reaction ,Epitope ,Virus ,Viral envelope ,Virology ,medicine ,Antigenic variation ,Humans ,Amino Acid Sequence ,Peptide sequence ,biology ,Immunodominant Epitopes ,AIDS Serodiagnosis ,Sequence Analysis, DNA ,Simian immunodeficiency virus ,Antigenic Variation ,HIV Envelope Protein gp41 ,Amino Acid Substitution ,HIV-1 ,biology.protein ,Antibody - Abstract
The serodiagnosis of human immunodeficiency virus type 1 (HIV-1) infection primarily relies on the detection of antibodies, most of which are directed against the immunodominant regions (IDR) of HIV-1 structural proteins. Among these, the N-terminal region of gp41 contains cluster I (amino acids [aa] 580 to 623), comprising the cytotoxic T-lymphocyte epitope (AVERYLKDQQLL) and the cysteine loop (CSGKLIC), and cluster II (aa 646 to 682), comprising an ectodomain region (ELDKWA). To delineate the epitope diversity within clusters I and II and to determine whether the diversity affects serologic detection by U.S. Food and Drug Administration (FDA)-licensed enzyme immunoassay (EIA) kits, gp41 Env sequences from 247 seropositive persons infected with HIV-1 group M, subtypes A ( n = 42), B ( n = 62), B′ ( n = 13), C ( n = 38), D ( n = 41), E ( n = 18), F ( n = 27), and G ( n = 6), and 6 HIV-1-infected but persistently seronegative (HIPS) persons were analyzed. While all IDR were highly conserved among both seropositive and HIPS persons, minor amino acid substitutions (n = 152) tested positive with all five FDA-licensed EIA kits. Furthermore, all specimens reacted with a group M consensus gp41 peptide (WGIKQLQARVLAVERYLKDQQLLGIWGCSGKLICTTAVPWNASW), and high degrees of cross-reactivity (>80%) were observed with an HIV-1 group N peptide, an HIV-1 group O peptide, and a peptide derived from the homologous region of gp41 from simian immunodeficiency virus from chimpanzee (SIVcpz). Taken together, these data indicate that the minor substitutions observed within the IDR of gp41 of HIV-1 group M subtypes do not affect antibody recognition and that all HIV-1-seropositive specimens containing the observed substitutions react with the FDA-licensed EIA kits regardless of viral genotype and geographic origin.
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- 2000
48. Short‐Course Antenatal Zidovudine Reduces Both Cervicovaginal Human Immunodeficiency Virus Type 1 RNA Levels and Risk of Perinatal Transmission
- Author
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Nancy L. Young, R. J. Simonds, John M. Karon, Wimol Siriwasin, Rutt Chuachoowong, Philip A. Mock, Nathan Shaffer, Thongpoon Chaowanachan, Naris Waranawat, Pongsakdi Chaisilwattana, Sanay Chearskul, and Timothy D. Mastro
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medicine.medical_specialty ,Pregnancy ,business.industry ,Obstetrics ,medicine.disease ,Placebo ,Confidence interval ,Zidovudine ,Infectious Diseases ,Immunology ,Immunology and Allergy ,Gestation ,Medicine ,Risk factor ,business ,Viral load ,Postpartum period ,medicine.drug - Abstract
Human immunodeficiency virus (HIV) levels in cervicovaginal lavage (CVL) and plasma samples were evaluated in relation to perinatal transmission in a randomized placebo-controlled trial of brief antenatal zidovudine treatment. Samples were collected at 38 weeks' gestation from 310 women and more frequently from a subset of 74 women. At 38 weeks, after a 2-week treatment period, CVL HIV-1 was quantifiable in 23% and 52% of samples in the zidovudine and placebo groups, respectively (P 10,000 copies/mL) and 1% among women without quantifiable CVL HIV-1 and with low plasma virus levels (P
- Published
- 2000
49. Maternal Virus Load and Perinatal Human Immunodeficiency Virus Type 1 Subtype E Transmission, Thailand
- Author
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Sanay Chearskul, Tawee Chotpitayasunondh, Chaiporn Bhadrakom, Bharat Parekh, Timothy D. Mastro, Shambavi Subbarao, Philip A. Mock, Timothy C. Granade, Wimol Siriwasin, Nancy L. Young, Susan Phillips, Anuvat Roongpisuthipong, Bruce G. Weniger, Marcia L. Kalish, Pratharn Chinayon, and Nathan Shaffer
- Subjects
Maternal Transmission ,Transmission (medicine) ,Biology ,medicine.disease ,biology.organism_classification ,Virology ,Virus ,Infectious Diseases ,Acquired immunodeficiency syndrome (AIDS) ,Lentivirus ,medicine ,Immunology and Allergy ,Viral disease ,Sida ,Viral load - Abstract
To determine the rate and risk factors for human immunodeficiency virus (HIV)-1 subtype E perinatal transmission, with focus on virus load, pregnant HIV-infected women and their formula-fed infants were followed prospectively in Bangkok. Of 281 infants with known outcome, 68 were infected (transmission rate, 24.2%; 95% confidence interval, 19.3%-29.6%). Transmitting mothers had a 4.3-fold higher median plasma HIV RNA level at delivery than did nontransmitters (P 10,000 copies/mL. Although risk is multifactorial, high maternal virus load at delivery strongly predicts transmission. This may have important implications for interventions designed to reduce perinatal transmission.
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- 1999
50. Short-course zidovudine for perinatal HIV-1 transmission in Bangkok, Thailand: a randomised controlled trial
- Author
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Philip A. Mock, Pratharn Chinayon, John M. Karon, Chaiporn Bhadrakom, Tawee Chotpitayasunondh, Wimol Siriwasin, Anuvat Roongpisuthipong, Nathan Shaffer, R.J. Simonds, Rutt Chuachoowong, Timothy D. Mastro, Sanay Chearskul, and Nancy L. Young
- Subjects
education.field_of_study ,medicine.medical_specialty ,Pregnancy ,Pediatrics ,business.industry ,Population ,Breastfeeding ,General Medicine ,Placebo ,medicine.disease ,Surgery ,law.invention ,Regimen ,Zidovudine ,Randomized controlled trial ,law ,medicine ,education ,business ,Viral load ,medicine.drug - Abstract
Summary Background Many developing countries have not implemented the AIDS Clinical Trials Group 076 zidovudine regimen for prevention of perinatal HIV-1 transmission because of its complexity and cost. We investigated the safety and efficacy of short-course oral zidovudine administered during late pregnancy and labour. Methods In a randomised, double-blind, placebo-controlled trial, HIV-1-infected pregnant women at two Bangkok hospitals were randomly assigned placebo or one zidovudine 300 mg tablet twice daily from 36 weeks' gestation and every 3 h from onset of labour until delivery. Mothers were given infant formula and asked not to breastfeed. The main endpoint was babies' HIV-1-infection status, tested with HIV-1-DNA PCR at birth, 2 months, and 6 months. We measured maternal plasma viral concentrations by RNA PCR. Findings Between May, 1996, and December, 1997, 397 women were enrolled; 393 gave birth to 395 live-born babies. Median duration of antenatal treatment was 25 days, and median number of doses during labour was three. 99% of women took at least 90% of scheduled antenatal doses. Adverse events were similar in the study groups. Of 392 babies with at least one PCR test, 55 tested positive: 18 in the zidovudine group and 37 in the placebo group. The estimated transmission risks were 9·4% (95% CI 5·2–13·5) on zidovudine and 18·9% (13·2–24·2) on placebo (p=0·006; efficacy 50% [15·4–70·6]). Between enrolment and delivery, women in the zidovudine group had a mean decrease in viral load of 0·56 log. About 80% of the treatment effect was explained by lowered maternal viral concentrations at delivery. Interpretation A short course of twice-daily oral zidovudine was safe and well tolerated and, in the absence of breastfeeding, can lessen the risk for mother-to-child HIV-1 transmission by half. This regimen could prevent many HIV-1 infections during late pregnancy and labour in less-developed countries unable to implement the full 076 regimen.
- Published
- 1999
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