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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.

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.

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.

Background: Progress in gender equity can improve health at the individual and country levels. Objectives: This study’s objective was to analyze recent trends in gender equity and identify historical and contextual factors that contributed to changes in gender equity in three countries: China, Nepal, and Nicaragua. Methods: To assess gender equity trends, we used the Gender Gap Index (GGI) from the World Economic Forum’s Global Gender Gap Report (2006–2017). The GGI incorporated data on economic participation, educational attainment, health, and political empowerment for almost 150 countries. We selected China, Nepal, and Nicaragua because of their major changes in GGI and diversity in geographical location and economic status. We reviewed major social, economic, and political events during 2006–2017, and identified key events in each country. We compared countries’ GGI with matched controls average using interrupted time-series analysis. Results: Nepal and Nicaragua both had dramatic increases in GGI (improvement in equity), Nepal (β = 0.029; 95% CI: 0.003, 0.056) and Nicaragua (β = 0.035; 95% CI: 0.005, 0.065). This was strongly influenced by political empowerment, which likely impacted access to education and employment opportunities. Despite major economic growth and new policies to address gender inequities (e.g. the One-Child Policy), China saw a significant decline in GGI between 2010 and 2017 (β = −0.014; 95% CI: −0.024, −0.004), largely resulting from decreased gender equity in educational attainment, economic participation, and health/survival sub-indices. Conclusions: Key social, economic, and political events helped explain trends in countries’ gender equity. Our study suggested that supportive social and political environments would play important roles in empowering women, which would advance human rights and promote health and well-being of individuals, households, communities, and countries.

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.

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.

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.

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

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

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.

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.

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.

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.

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)

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.

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.

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.

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)

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.

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.

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.

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.

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.

From May through August 1995, a cross-sectional survey was conducted among injecting drug users (IDUs) drawn from 15 drug treatment clinics in Bangkok and who were not known to be HIV-seropositive, to determine the prevalence of HIV-1 subtypes B and E and related risk behaviors, and to offer enrollment in a prospective cohort study. IDUs who voluntarily consented were interviewed, and blood specimens were tested for the presence of HIV antibodies. HIV-1-seropositive specimens were tested for subtypes B' (Thai B) and E by using V3 loop peptide enzyme immunoassays specific for these HIV-1 genetic subtypes. Of 1674 IDUs studied, the mean age was 31.2 years (interquartile range, 25-37 years), 94.8% were men, and 29.3% were HIV-1-seropositive. On multiple logistic regression analysis, HIV-1 seropositivity was associated with older age, not being married, less education, needle sharing, and incarceration. HIV-1 subtype B' accounted for 65% of prevalent infections and subtype E, 35%. Infection with subtype E was associated with younger age and did not seem to be associated with sexual risk behaviors, which were uncommon in general. Bangkok IDUs continue to be at high risk for HIV-1 infection related to needle sharing and incarceration. Although HIV-1 subtype B' accounts for most prevalent infections, subtype E seems to be more prevalent among younger IDUs, and most infections seem likely to result from parenteral transmission.In a 3-month period in 1995, voluntary HIV counseling and testing was offered to injecting drug users (IDUs) 20-50 years of age who attended any of the 15 drug treatment centers operated by the Bangkok (Thailand) Metropolitan Administration and were not known to be HIV-positive. The long-term purpose of this screening was to enroll a cohort in which to monitor HIV trends and obtain HIV-1 strains for genetic and phenotypic characterization. 1674 predominantly male IDUs (mean age, 31.2 years) were screened. 70.1% reported having been tested for HIV in the past 3 years. In the preceding 6 months, 77.9% had injected drugs at least once a day, 39.1% had used needles or syringes used by others, and 42.5% had shared needles. HIV-1 seroprevalence was 29.3%. In multiple logistic regression analysis, the following factors were significantly and independently associated with HIV-1 positivity: older age, unmarried status, less than 7 years of education, having shared needles or syringes, incarceration in the past 6 months, and drug injection during incarceration. A convenience sample of 205 of the 490 HIV-1-positive specimens was selected for serotyping through use of V3 loop peptide enzyme immunoassays. Of the 194 for which the HIV-1 subtype could be determined, 126 (64.9%) reacted to subtype B prime ("Thai B") and 68 (35.1%) reacted to subtype E. Subtype E was significantly more common among younger IDUs. 822 of the 1184 HIV-negative IDUs were interviewed and offered enrollment in the prospective cohort study; 678 (82.5%) agreed to participate. A phase III efficacy trial of an HIV-1 vaccine may be feasible in this cohort.

To determine the rate of and risk factors for HIV-1 seroconversion and describe sexually transmitted disease (STD) prevalence rates for young men in northern Thailand.Data were collected from self-administered questionnaires and serologic testing at enrollment in a prospective study in 1991 and at follow-up after 6, 17, and 23 months on a cohort of 1115 men selected by lottery for military conscription.A total of 14 men seroconverted to HIV-1 envelope subtype E. The overall HIV-1 incidence rate was 1.1 (95% confidence interval [CI], 0.6-1.8) per 100 person-years (PY) of follow-up. However, the rate was 2.0/100 PY for conscripts from the upper northern subregion of Thailand compared with 0.5/100 PY from other regions (adjusted rate ratio [RR] = 2.69; 95% CI, 0.8-12.2). On multivariate analyses, the behavioral factors associated with HIV-1 seroconversion were frequency of sex with female sex workers (FSWs; p = .04), receptive anal sex (adjusted RR = 6.73; 95% CI, 1.8-21.7), and large amount of alcohol consumption (adjusted RR = 3.12; 95% CI, 1.0-10.9). Genital ulceration was the STD most strongly associated with seroconversion. The prevalence of serologic reactivity to syphilis, Haemophilus ducreyi, and herpes simplex virus type 2 increased with greater frequency of sex with FSWs and was generally higher for men from the upper north.Young men in northern Thailand are at high risk for HIV-1, primarily through sex with FSWs; and other STDs are highly associated with HIV-1 incidence. As HIV-1 infection extends into the general population, intervention programs are needed to address the problem of sexual transmission apart from commercial sex venues.Findings are presented from a prospective study conducted to determine the rate of and risk factors for HIV-1 seroconversion, and to describe sexually transmitted diseases (STD) prevalence rates for young men in northern Thailand. Study findings are based upon data collected from self-administered questionnaires and serologic testing at enrollment in 1991 and at follow-up after 6, 17, and 23 months on a cohort of 1115 young men chosen by lottery for military conscription. Men in Thailand are generally eligible for conscription in the year of their 21st birthday. 6.9% of the men were HIV-1 seropositive at enrollment; 15.3% of men from the upper northern region compared with 2.5% of men from elsewhere. 14 subjects seroconverted to HIV-1 envelope subtype E over the course of the study. The overall HIV-1 incidence rate was 1.1/100 person-years (PY) of follow-up. However, the rate was 2.0/100 PY for conscripts from the upper northern subregion of Thailand compared with 0.5/100 PY from other regions. Multivariate analyses found frequent sex with female prostitutes, receptive anal sex, and high levels of alcohol consumption to be positively associated with HIV-1 seroconversion. Genital ulceration was the STD most strongly associated with seroconversion. The prevalence of serologic reactivity to syphilis, Haemophilus ducreyi, and herpes simplex virus type 2 increased with greater frequency of sex with female prostitutes, and was generally higher for men from the upper north.

The objective of this study was to assess changes in the family situation of HIV-infected women who have recently given birth. As part of a prospective perinatal HIV transmission study, interviews were conducted with a subset of HIV-infected women at 18 to 24 months postpartum, and answers were compared with baseline information obtained during pregnancy. Standardized scales were used to assess levels of psychosocial functioning. A convenience sample of 129 HIV-infected women enrolled during pregnancy was interviewed at 18 to 24 months postpartum. At delivery, the women were young (median age, 22 years), primiparous (57%), and asymptomatic (93%). When baseline and follow-up data were compared, more women were living alone (1% versus 6%; p = 0.03), fewer women were living with their partners (98% versus 73%; p0.001), and 30% of families had reduced incomes. At follow-up, 10% of partners had died, and more partners than wives had become ill or died (21% versus 4%; p = 0.02). Most children (78%) were living with their mothers, but only 57% of the HIV-infected women were the primary caretakers. Fewer women had disclosed their HIV status to others (e.g., family, friends) than to their partners (34% versus 84%; p0.001), largely because of fear of disclosure. The women appeared to have high levels of depression and worry. The women's greatest worries were about their children's health and the family's future. Within 2 years after childbirth, substantial change within the families of HIV-infected women was evident. These were manifest by partner illness or death, family separation, reduced family income, shifting responsibilities for child care, and signs of depression and isolation. Providing family support is a major challenge in Thailand as the perinatal HIV epidemic progresses.As part of a larger prospective perinatal HIV transmission study in Bangkok, Thailand (1992-94), interviews were conducted with a subset of 129 HIV-infected women 18-24 months after delivery and the results were compared with data obtained from these women during pregnancy. The median age of women at delivery was 22 years; 57% were primiparous and 93% were asymptomatic at delivery. 25 infants (19.4%) had confirmed HIV infection and 2 had died by the time of the follow-up interview. By follow up, 21% of male partners had died or developed HIV-related functional impairments. The proportion of women living alone rose from 1% at baseline to 6% at follow up, while the proportion living with their partner declined from 98% to 73%. 30% of families had reduced incomes at follow-up compared with baseline. Although 78% of infants were living with their mothers, they were the primary caretakers in only 57% of families. Only 34% of HIV-infected mothers had disclosed their HIV status to friends or family other than their partner. 43% of women scored above the cut-off on the depression scale. Mothers worried extensively about their child's health and their family's future. However, only 37% believed they could find someone to talk to about their feelings related to HIV. 58% were interested in joining a support group for women with HIV. These findings of family disruption, reduced family income, shifting responsibilities for child care, depression, and isolation indicate an urgent need for increased social support for HIV-infected mothers in Thailand.

Policresulen vaginal suppositories are a condensation product of metacresolsulfonic acid and formaldehyde. We investigated their use by female commercial sex workers (CSW) and whether such use could facilitate HIV transmission.We interviewed female CSW in Thailand about use of the product, and we directly observed the effects of self-administration of a single suppository by each of six women.Of 200 CSW interviewed, 32% had used policresulen vaginal suppositories in the preceding year and 46% had used them at some time. Many used them for reasons not listed on the package insert, such as improving their male partners' sexual pleasure, and most did not abstain from vaginal sex following use. Among 36 brothel-based and 67 non-brothel-based CSW with known HIV infection, the use of the product was not associated with HIV-1 infection (adjusted relative risk 1.0, 95% confidence interval, 0.5-2.0). Exfoliation of the vaginal and cervical mucosa was observed in all six CSW 1 day after product use, and, although it could have been the result of repeated examinations, an increase in genital HIV-1 RNA shedding was also detected in all three HIV-seropositive women.Although there was no epidemiological association with HIV infection, policresulen vaginal suppository use did disrupt the genital mucosa and therefore may have the potential to facilitate HIV transmission. Drug licensing authorities may wish to reassess the safety of this product. If the product continues to be distributed, steps should be taken to limit its use to the specific conditions for which it is indicated and to ensure that women abstain from vaginal sex following its use.

Extensive transmission of human immunodeficiency virus type 1 (HIV-1) in Thailand began in 1988, resulting in an estimated 800,000 cumulative infections by 1994. During 1994 and 1995, we collected blood specimens from 215 asymptomatic HIV-1-infected people with various risk behaviors from nine locations in all four regions of Thailand. HIV-1 subtypes and genetic heterogeneity were determined for 214 strains by a combination of direct DNA sequencing (n = 95), subtype-specific oligonucleotide probe testing (n = 201), and V3-loop peptide enzyme immunoassay (PEIA) (n = 214). All strains were either env subtype E (175; 81.8%) or B (39; 18.2%). Of the subtype B isolates, 37 (94.9%) were B' and 2 (5.1%) were more typical North American-like B strains (most subtype B strains in Thailand are part of a distinct subcluster within the subtype B branch on phylogenetic trees, termed B'; formerly Thai B or BB). Of 149 viruses from people with sexual risk behaviors from all regions, 146 (98.0%) were subtype E. Of 65 viruses from injecting drug users (IDUs), 29 (44.6%) were subtype E and 36 (55.4%) were subtype B, including 35 B' strains. There was regional variation in the proportions of subtypes E and B' among IDUs. The intrasubtype nucleotide divergence within the V3 and flanking regions of the env gene (mid-C2 to the start of the V4 region) was low (5.7% for subtype E and 3.1% for subtype B') compared with other HIV-1 group M subtypes from different countries. These findings of two subtypes with low heterogeneity indicate that Thailand may be a desirable setting for evaluating candidate HIV-1 vaccines. The mix of subtype E and B' strains among IDUs also offers the opportunity to study phenotypic differences between the two subtypes.The extensive transmission of HIV-1 in Thailand which began in 1988 led to an estimated 800,000 cumulative infections in the country by 1994. The authors collected blood specimens during 1994 and 1995 from 215 asymptomatic HIV-1-infected people with various risk behaviors from 9 locations across Thailand. HIV-1 subtypes and genetic heterogeneity were then determined for 214 strains using a combination of direct DNA sequencing, subtype-specific oligonucleotide probe testing, and V3-loop peptide enzyme immunoassay. 175 strains were subtype E and 39 were subtype B. 37 of the subtype B isolates were B' and 2 were more typical North American-like B strains. Of 149 viruses from people with sexual risk behaviors from all regions of the country, 146 were subtype E. Of 65 viruses from IV drug users (IVDUs), 29 were subtype E and 36 were subtype B, including 35 subtype B' strains. Regional variation was observed in the proportions of subtypes E and B' among IVDUs. The intrasubtype nucleotide divergence within the V3 and flanking regions of the env gene was 5.7% for subtype E and 3.1% for subtype B'. The finding of 2 HIV-1 subtypes with low heterogeneity suggests that Thailand may be an appropriate setting in which to evaluate candidate HIV-1 vaccines. The mix of subtype E and B' strains among IVDUs will also allow the study of phenotypic differences between the 2 subtypes.

To determine the prevalence and risk factors associated with cervicitis caused by Chlamydia trachomatis and Neisseria gonorrhoeae in human immunodeficiency virus (HIV) type 1-seropositive and HIV-seronegative pregnant women in Bangkok, and the relation to perinatal HIV transmission.As part of a multicenter perinatal HIV transmission study in an antenatal population with 2% HIV seroprevalence, endocervical swabs obtained at mid-pregnancy from a consecutive sample of 222 HIV-seropositive and 219 HIV-seronegative pregnant women at two large hospitals in Bangkok were tested for the presence of C. trachomatis and N. gonorrhoeae by DNA hybridization probe (Gen-Probe). Clinical risk factors and DNA probe results were analyzed in relation to the women's and newborns' HIV infection status.The prevalence of C. trachomatis was 16.2% in HIV-seropositive pregnant women and 9.1% in HIV-seronegative pregnant women (P = 0.03). The prevalence of N. gonorrhoeae was 2.7% in HIV-seropositive pregnant women and 1.4% in HIV-seronegative pregnant women (P = 0.5). The overall population prevalence estimate was 9.2% for C. trachomatis and 1.4% for N. gonorrhoeae. Women with gonococcal infection were more likely to be positive for C. trachomatis (RR(MH) = 5.2, P0.01). Young age (21 years) and primigravid status were associated with C. trachomatis infection among HIV-seropositive women; history of multiple sex partners (1) were associated with C. trachomatis infection among HIV-seronegative women. For HIV-seropositive women, primigravida status also was associated with C. trachomatis infection. The perinatal HIV transmission rates were similar for those with and without C. trachomatis (24.1% and 23.2%, P = 0.9) and among those with and without N. gonorrhoeae (20% and 23.5%, P = 1.0).Among pregnant women in Bangkok, C. trachomatis infection was considerably more common than N. gonorrhoeae infection and was associated with HIV infection, young age and first pregnancy (HIV-seropositive women), and multiple partners (HIV-seronegative women). Our data do not suggest an association between perinatal HIV transmission and maternal C. trachomatis or N. gonorrhoeae infection identified and treated during pregnancy. The high prevalence of C. trachomatis found using a test not readily available in Thailand emphasizes the need for improved, inexpensive ways to screen for and diagnose these sexually transmitted infections in developing countries.Numerous studies have suggested that Chlamydia trachomatis and Neisseria gonorrhoeae facilitate heterosexual HIV transmission; the impact of these sexually transmitted diseases (STDs) on perinatal HIV transmission is unknown, however, due to the expense of routine screening for STDs during pregnancy in developing countries. As part of a multicenter perinatal HIV transmission study, 222 HIV-positive and 219 HIV-negative women presenting for prenatal care at 2 hospitals in Bangkok, Thailand, during 1993-94 were enrolled. At mid-pregnancy, endocervical swabs were obtained and tested for the presence of C. trachomatis and N. gonorrhoeae by DNA hybridization probe. There were 36 cases (16.2%) of C. trachomatis infection among HIV-positive women and 20 cases (9.1%) among HIV-negative women. There were 6 cases (2.7%) of N. gonorrhoeae among HIV-positive women and 3 cases (1.4%) among HIV-negative women. Based on an estimated antenatal HIV seroprevalence of 2%, these findings imply a general antenatal prevalence of 9.2% for C. trachomatis and 1.4% for N. gonorrhoeae. Women with gonococcal infection were more likely (relative risk, 5.2) to be positive for C. trachomatis as well. C. trachomatis infection among HIV-infected pregnant women was associated with age under 21 years and primigravidity. The overall perinatal HIV transmission rate was 24.2%, with no significant difference according to STD infection status. However, since all women diagnosed with STDs received treatment by the mid-third trimester of pregnancy, it remains possible that untreated STDs facilitate perinatal HIV transmission. The high prevalence of C. trachomatis detected in this study through use of a test not readily available in Thailand emphasizes the need for inexpensive, reliable methods to screen for STDs among pregnant women in developing countries.

The epidemic of Human Immunodeficiency Virus (HIV) infection led blood banks to initiate donation deferral criteria based on self-reported risk factors. However little information is available on the differences in reporting risk factors before and after HIV status is known.Between April and July 1994, blood donors in a provincial hospital in northern. Thailand were interviewed at the time of donation, about their demographic characteristics and risk factors. All donors had agreed to learn their test results and were called back for post-test counselling and reinterview.HIV-positive blood donors were more likely to change from 'denying' to 'acknowledging' risk factors while HIV-negatives were more likely to change from 'acknowledging' to 'denying'. The differences between risk factors obtained before and after test results were known resulted in stronger, weaker or even opposite risk measures.The study results raise questions about the impact of the differences in reporting HIV-related risk factors by the donors on how effective donation deferral criteria can be developed.The widespread prevalence of HIV infection in countries and regions around the world has led blood banks to refuse blood donations from donors who are at high risk of being infected with HIV. Low-risk donors are instead recruited and all donors are tested for infection with HIV. The criteria for donor deferral are based mainly upon the epidemiology of HIV infection among the donors. The authors investigated the differences in reporting risk factors before and after HIV status is known. During April-July 1994, blood donors at a hospital in Chiangrai province were interviewed at the time of donation about their demographic characteristics and risk factors. 134 of the 175 HIV-positive donors returned for post-HIV-test counseling and reinterview. 423 of the 1062 HIV-negative donors returned. The donors were of median age 32 years. HIV-positive donors were more likely to change from denying to acknowledging risk factors, while HIV-seronegative donors were more likely to change from acknowledging to denying. The differences between risk factors observed before and after test results were known resulted in stronger, weaker, or even opposite risk measures.

This study sought to evaluate the sensitivity and specificity of peptide-binding enzyme immunoassay (PEIA) and heteroduplex mobility assay (HMA) for the determination of HIV-1 subtypes B and E; to determine the proportions of infections due to subtypes B and E over time; and to generate data on DNA sequences of the C2-V3 region of the env genes. HIV-1 subtyping was conducted by PEIA and HMA on blood specimens obtained from 97 injecting drug users (IDU) infected with HIV between 1988 and 1993. Genetic sequencing was performed on 84 specimens. Both laboratory methods were highly sensitive and specific for the determination of HIV-1 subtypes B and E. The two tests were complementary; samples which could not be typed by HMA were correctly typed by PEIA and vice versa. While subtype B accounted for 80.4% (78 out of 97) of infections overall the proportion of new infections due to subtype E increased from 2.6% (1 out of 38) in 1988-1989 to 25.6% (11 out of 43) in 1990-1991 and to 43.8% (7 out of 16) in 1992-1993 (chi squared for linear trend p < 0.001). HMA and PEIA are practical sensitive and specific laboratory methods for the determination of HIV-1 subtypes in Thailand and may be useful in other geographic areas to define the molecular epidemiology of the global HIV-1 pandemic. Data suggest that the proportion subtype E infections have increased among Bangkok IDU from 1988 through 1993. (authors)

We have entered a new era in which antiretroviral agents have been demonstrated to be highly effective in preventing HIV-1 infection, especially in serodiscordant couples. The HPTN-052 randomized, controlled trial (RCT) of early versus delayed antiretroviral therapy (ART) for the HIV-1-infected persons in sexual partnerships with HIV-negative persons demonstrated at least a 96% reduction in HIV-1 transmission in the 1763 couples studied in Africa, Asia and South America [1]. The Partners PrEP RCT, conducted among 4758 HIV-1serodiscordant couples in Kenya and Uganda, showed that when used as preexposure prophylaxis (PrEP) by the HIV-negative partner, daily tenofovir disproxil fumerate (TDF) and daily TDF/emtricitabine (FTC) were 62 and 73% effective, respectively, in preventing HIV-1 acquisition [2]. These robust effectiveness findings provide a strong basis for the use of antiretroviral agents for prevention, both to reduce the infectiousness of HIV-1infected persons and to reduce the susceptibility of HIVnegative persons.

Background Project Accept is a community randomized, controlled trial to evaluate the efficacy of community mobilization, mobile testing, same-day results, and post-test support for the prevention of HIV infection in Thailand, Tanzania, Zimbabwe, and South Africa. We evaluated the accuracy of in-country HIV rapid testing and determined HIV prevalence in the Project Accept pilot study. Methods Two HIV rapid tests were performed in parallel in local laboratories. If the first two rapid tests were discordant (one reactive, one non-reactive), a third HIV rapid test or enzyme immunoassay was performed. Samples were designated HIV NEG if the first two tests were non-reactive, HIV DISC if the first two tests were discordant, and HIV POS if the first two tests were reactive. Samples were re-analyzed in the United States using a panel of laboratory tests. Results HIV infection status was correctly determined based on-in country testing for 2,236 (99.5%) of 2,247 participants [7 (0.37%) of 1,907 HIV NEG samples were HIV-positive; 2 (0.63%) of 317 HIV POS samples were HIV-negative; 2 (8.3%) of 24 HIV DISC samples were incorrectly identified as HIV-positive based on the in-country tie-breaker test]. HIV prevalence was: Thailand: 0.6%, Tanzania: 5.0%, Zimbabwe 14.7%, Soweto South Africa: 19.4%, Vulindlela, South Africa: 24.4%, (overall prevalence: 14.4%). Conclusions In-country testing based on two HIV rapid tests correctly identified the HIV infection status for 99.5% of study participants; most participants with discordant HIV rapid tests were not infected. HIV prevalence varied considerably across the study sites (range: 0.6% to 24.4%). Trial Registration ClinicalTrials.gov registry number NCT00203749.

In April 2007, the Centers for Disease Control and Prevention (CDC) held a two-day consultation with a broad spectrum of stakeholders to obtain input on the potential role of male circumcision (MC) in preventing transmission of human immunodeficiency virus (HIV) in the U.S. Working groups summarized data and discussed issues about the use of MC for prevention of HIV and other sexually transmitted infections among men who have sex with women, men who have sex with men (MSM), and newborn males. Consultants suggested that ( 1) sufficient evidence exists to propose that heterosexually active males be informed about the significant but partial efficacy of MC in reducing risk for HIV acquisition and be provided with affordable access to voluntary, high-quality surgical and risk-reduction counseling services; ( 2) information about the potential health benefits and risks of MC should be presented to parents considering infant circumcision, and financial barriers to accessing MC should be removed; and ( 3) insufficient data exist about the impact (if any) of MC on HIV acquisition by MSM, and additional research is warranted. If MC is recommended as a public health method, information will be required on its acceptability and uptake. Especially critical will be efforts to understand how to develop effective, culturally appropriate public health messages to mitigate increases in sexual risk behavior among men, both those already circumcised and those who may elect MC to reduce their risk of acquiring HIV.

More than half a million Americans became newly infected with human immunodeficiency virus (HIV) in the first decade of the new millennium. The domestic epidemic has had the heaviest impact on men who have sex with men and persons from racial and ethnic minority populations, particularly black persons. For example, black men who have sex with men represent

87 strains of Streptococcus pneumoniae isolated during three winter seasons (1986-89) from the blood of children with acute lower respiratory tract infection (ALRI) in Pakistan were serotyped and tested for susceptibility to a range of antimicrobial agents. 97% of isolates were resistant to at least one antimicrobial drug. 62% had decreased susceptibility to co-trimoxazole (trimethoprim/ sulphamethoxazole) (31% were fully resistant) and 39% were resistant to chloramphenicol. All isolates were susceptible to erythromycin, cefaclor, cephalothin, ceftriaxone, cefuroxime, rifampicin, vancomycin, and clindamycin. 29% of isolates were neither vaccine types nor vaccine-related types. Serotype distribution and antimicrobial susceptibility varied significantly during the three winter seasons. No single serotype was found in all three winters. The findings highlight the need for surveillance of antimicrobial resistance and serotype distribution of S pneumoniae in developing countries as a guide both to the choice of agent for treatment of pneumococcal infections, especially ALRI, and to the formulation of new pneumococcal conjugate vaccines for use in young children.

GROUP A β-hemolytic streptococcus is an uncommon but serious cause of postoperative wound infection. Group A streptococcus is isolated from less than 1 percent of all surgical-wound infections and causes less than 1 incisional-wound infection per 10,000 operations (National Nosocomial Infections Surveillance System, Centers for Disease Control: unpublished data). Clusters of group A streptococcal postoperative wound infections can usually he associated with a carrier who has direct patient-care responsibilities in the operating room. A carrier was identified in 10 of the 12 outbreaks reported since 1965.1 2 3 4 5 6 7 8 9 10 11 12 13 Eight carriers were operating-room personnel with group A streptococcus in their rectums or vaginas. . . .

Epidemiologic studies have suggested that legionnaires' disease can be transmitted to susceptible hosts by contaminated aerosolized water from cooling towers and evaporative condensers; however, epidemic strains of Legionella have not been isolated by air sampling at such sites during epidemiologic investigations. An outbreak of legionnaires' disease occurred at a retirement hotel; Legionella pneumophila serogroup 1 was isolated from an evaporative condenser and from potable water. A case-control study showed that the only significant exposure risk was in area A. L. pneumophila serogroup 1 was isolated during air sampling near the evaporative condenser exhaust site, the air conditioning intake vent, and an air vent in area A, but not in shower stalls. Monoclonal antibody subtype patterns of L. pneumophila serogroup 1 isolates from patients matched those from the evaporative condenser but not from shower water. Air sampling and monoclonal antibody subtyping results support epidemiologic evidence that the evaporative condenser was the source of this outbreak.

Recent clinical trials in Africa found that male circumcision reduces the risk of acquiring HIV from heterosexual sex--what are the implications of these studies for the United States?

In northern Thailand, where substantial male-to-female transmission of HIV has occurred in stable partnerships, the relationships between counseling, communication, and HIV-preventive behaviors in married couples have not been well studied. In a study of HIV incidence among women in northern Thailand, each participant was advised to learn her husband's HIV-infection status and was asked to bring him for an interview at the final 12-month follow-up visit. Of the 337 men interviewed, 58% reported having ever had an HIV test. More men reported testing following their wives' enrollment: 12% in the year prior to enrollment vs 22% during the 1-year study (p0.001). In the univariate analysis, men's HIV testing during the 6 months before being interviewed was associated with communication about HIV testing with their wife and extra marital sex with non-FSW while married. Testing following their wife's request was the most common reason reported. Agreement between husband's and wife's reports was poor for most issues, such as whether HIV-related communication had occurred, but agreement as to whether the husband had ever been tested for HIV was relatively high (kappa = 0.62). However, in the logistic regression analysis, only sex with non-FSW while married remained associated with HIV testing (p = 0.02). The results suggest a relationship between counseling, communication, and husband HIV testing. Better communication by couples may result in more effective use of HIV testing, which is already prevalent in this population, to prevent HIV transmission.

The objective was to determine the safety and acceptability of vaginal application of Carraguard a carrageenan-derived candidate microbicide gel. A randomized placebo-controlled triple-blinded clinical trial was conducted in Chiang Rai northern Thailand. Women were asked to insert one applicator of study gel vaginally at least three times per week (with or without sex) and to use gel with condoms every time they had sex. Safety was assessed by visual inspection of the vagina and cervix changes in vaginal flora and self-reported symptoms at day 14 month 1 and then monthly for up to 1 year. Acceptability was assessed through reported use of the gel return of used and unused applicators and quarterly interviews. One hundred sixty-five women were randomized: 83 to Carraguard and 82 to the placebo (methylcellulose gel) group. Study gel use was similarly high in both groups throughout the trial with an average of four applicators per week. Carraguard use was not associated with abnormal genital clinical findings abnormal vaginal flora Pap smear abnormalities or other abnormal clinical signs or symptoms. Adverse events were mostly mild not attributed to gel use and similarly distributed between groups. Participants in both groups reported high acceptability. Carraguard can safely be used an average of four times per week with or without sex and is acceptable to Thai women. A Phase III efficacy trial of Carraguard is warranted and is currently ongoing in South Africa. (authors)

Some candidate HIV-1 vaccines may not prevent HIV-1 infection but may alter the course of disease. Surrogate endpoints based on early laboratory makers in HIV-1-infected persons who are antiretroviral therapy (ART)-naive will be useful for evaluating vaccine efficacy in slowing disease progression (VEp). We examined pretreatment HIV-1 viral loads and CD4 cell counts in recent HIV-1 seroconverters to inform selection of these endpoints.We studied 130 newly HIV-1-infected injection drug users identified from a prospective cohort of initially uninfected persons in Bangkok during 1995 through 1998. We analyzed trends in HIV-1 viral loads and CD4 cell counts as well as progression to the surrogate endpoint, defined as 2 consecutive CD4 cell counts of fewer than 350 cells/mm, during 24 months after the first HIV-1 seropositive (FP) visit.Median HIV-1 RNA copies/mL with interquartile ranges were 43,693 (14,320-94,767) at the FP visit, 46,924 (16,273-104,314) at 6 months, 28,446 (11,292-54,325) at 12 months, and 18,080 (8713-54,059) at 18 months. HIV-1 viral loads at the FP visit and at 18 months were positively correlated (r = 0.53, P0.0001). Of 130 participants, 12% reached the surrogate endpoint by 6 months, 16% by 12 months, and 27% by 18 months. In Cox regression analyses, HIV-1 viral loads of more than 50,000 copies/mL at the FP visit (hazard ratio [HR] = 2.3, 95% confidence interval [CI]: 1.1-4.8) and first CD4 cell count of 500 or fewer cells/mm (HR = 7.6, 95% CI: 3.2-17.6) were independently associated with faster progression to the surrogate endpoint.Participants with high HIV-1 RNA levels and low CD4 cell counts close to the time of seroconversion were more likely to experience early immunologic progression. Approximately one quarter of seroconverters reached the surrogate immunologic endpoint within 18 months of their FP visit and before starting ART, suggesting the utility of this endpoint for analyses of VEp in some ongoing and planned HIV-1 vaccine efficacy trials.

Homo- or bisexual (HB) adolescents may have greater and different health risks than the population of heterosexual adolescents. We assessed sexual orientation and health risk behaviors in 1,725 consenting 15- to 21-year-old vocational school students in northern Thailand. Data were collected using audio-computer-assisted self-interviewing. Nine percent of males and 11.2% of females identified themselves as homo- or bisexual. HB males had an earlier mean age at sexual debut (14.7 years) and a higher mean number of lifetime sexual partners (7.9) than did heterosexual males (16.8 years and 5.8 partners, respectively). HB males (25.9%) and females (32.2%) were sexually coerced more often than were heterosexual males (4.6%) and females (19.6%). Drug use was reported significantly more frequently by HB females and significantly less frequently by HB males than by their heterosexual counterparts. HB males showed more signs of social isolation and depression than did heterosexual males. We conclude that HB adolescents in northern Thailand are at greater and different health risks than are their heterosexual counterparts. Differential health education messages for HB and heterosexual youth are warranted.

The leukocytes of rhesus monkeys contain cyclic octadecapeptides (theta;-defensins) that can protect cells from infection by HIV-1 in vitro. Although humans express mRNA from one or more theta;-defensin pseudogenes, these transcripts contain a premature stop codon that prevents formation of theta;-defensin peptides. We hypothesized that some highly exposed persistently seronegative (HEPS) individuals might have intact theta;-defensin (DEFT) genes and produce functional theta;-defensins that might account for their resistance to HIV-1 infection. We sequenced DEFT genes from 30 women in Chiang Rai, northern Thailand: 11 HEPS female sex-workers and 19 control women (10 HIV-1 infected and 9 HIV-1 uninfected). We found that theta;-defensin genes from all 11 HEPS women contained the crucial signal sequence stop codon, as did the 19 control women. Synthetic theta;-defensins based on the cDNA sequences to generate a human theta;-defensin (termed retrocyclin-1 and -2) were capable of inhibiting replication of Thai HIV-1 subtype B and CRF01_AE isolates regardless of the coreceptor utilization of the isolates. Although our study indicates that synthetic theta;-defensin peptides are effective in vitro against Thai subtype B and CRF01_AE isolates of HIV-1, the presence of premature stop codons in the DEFT genes of these HEPS women makes it unlikely that endogenous theta;-defensin production accounts for their resistance to HIV-1.

Development of serologic tests to detect recent HIV-1 infection has generated worldwide interest in applying this approach to estimate incidence. We previously devised an IgG-capture BED-EIA (or BED-CEIA) that detects increasing levels of anti-HIV IgG following seroconversion to identify recent infection and to estimate incidence among persons infected with diverse HIV-1 subtypes worldwide. Injection drug users (IDUs; n = 1969) were screened in 1996 for participation in a prospective cohort study. Serum specimens from 594 IDUs were HIV-1 seropositive (30.2%) and were tested with the BED-CEIA. The proportion of recent infections and estimated incidence by different epidemiological risk factors were compared with incidence data measured from the prospective cohort. Of 594 HIV-1-seropositive specimens, 113 (19%) were identified as recent infections. Overall, the estimated annual incidence among persons screened was 17.3%/year (95% CI, 12.8-24.2%/year) compared with 9.0%/year (95% CI, 6.7-11.9%/year) measured from the prospective cohort during the same time period. Estimated incidence was higher among younger aged and unemployed IDUs as well as among those who injected more frequently, confirming previously reported risk factors from this prospective cohort. As persons screened from a cross-sectional sampling probably have higher risk for HIV than selected uninfected individuals who choose to participate and receive risk reduction counseling in a longitudinal cohort study, use of this or other serologic testing strategies to identify populations with high incidence (such as for HIV vaccine trials) may overestimate incidence measured from prospective cohorts.

The performance of the bioMérieux Vironostika-LS EIA (less sensitive enzyme immunoassay) was assessed to detect recent seroconversion among injecting drug users (IDUs) in Bangkok, Thailand who were infected with either HIV-1 subtypes B' or E (also known as circulating recombinant form CRF01_AE). To evaluate the Vironostika-LS EIA in non-B subtypes, we collected longitudinal specimens (n = 796) from 115 IDUs (subtype B' infection, n = 24; subtype E infection, n = 91). After testing HIV-positive specimens with the Vironostika-LS EIA, standardized optical densities (SODs) were calculated using median values to determine the window period, which is the time from seroconversion on a standard EIA to seroconversion on the Vironostika-LS EIA for a given SOD, for either subtype. For an SOD cutoff of 1.0, Vironostika-LS EIA results showed a mean window period of 239 days (95% confidence interval [95% CI], 208-287 days) for subtype B' and 356 days (95% CI, 318-402 days) for subtype E in Thailand. This outcome demonstrates that the Vironostika-LS EIA has significantly different performance characteristics in detecting recent seroconversion between different HIV-1 subtypes. Accurate identification of recent infection and estimation of incidence for HIV-1 strains other than North American subtype B, using the Vironostika-LS EIA, requires knowledge of specimen subtype and use of appropriate cutoffs and mean window periods.

To investigate knowledge and perceptions of HIV transmission risk and interest in vaginal microbicides in northern Thailand, we conducted 14 focus group discussions and 80 interviews with men and women in Chiang Rai province. Women were recruited from antenatal or postpartum clinics, and men from various work sites. Participants evinced substantial knowledge about HIV, with two exceptions important for prevention campaigns: (a) confusion about the window period between a new infection and positive HIV-test result and (b) overestimation of the safety of extramarital sex with partners who are not sex workers. Most participants reported no personal HIV risk. Participants described Thai women as generally vulnerable to HIV infection because of the unlikelihood of condom use with their husbands and because women cannot control their husbands' extramarital behavior. Women apparently face particular risk after childbearing; peripartum abstinence averages 6-9 months, during which time some Thai men may have alternative sex partners. Women, and to a lesser degree, men were interested in potential microbicides, although they voiced many thoughtful questions about the products and about efficacy trials.