Showing papers by "Myron S. Cohen published in 2011"

Prevention of HIV-1 Infection with Early Antiretroviral Therapy

Abstract: Background Antiretroviral therapy that reduces viral replication could limit the transmission of human immunodeficiency virus type 1 (HIV-1) in serodiscordant couples. Methods In nine countries, we...

Acute HIV-1 Infection

Abstract: More than 33 million people are living with HIV-1, and more than 2.5 million additional cases are detected each year. This review addresses recent advances in our understanding of the transmission of HIV-1 and of acute HIV-1 infection.

Penetration of Tenofovir and Emtricitabine in Mucosal Tissues: Implications for Prevention of HIV-1 Transmission

Abstract: A mainstay of strategies to prevent HIV-1 transmission is to use antiretroviral therapy (ART) for pre-exposure prophylaxis (PrEP). Critical to the design and interpretation of PrEP prevention trials is the ability to make accurate pharmacological measurements of ART drugs in human genital and colorectal mucosal tissues, the principal route of HIV transmission. Here, we evaluated two drugs that are preferentially used for PrEP: tenofovir (TFV) disoproxil fumarate (TDF) and emtricitabine (FTC). A single oral dose of TDF/FTC (Truvada) was administered to 15 healthy individuals. Over the next 14 days, TFV and FTC were measured in blood plasma and genital secretions using a sensitive assay (lower level of quantification, 0.1 ng/ml). The active intracellular phosphorylated metabolites of these drugs [TFV diphospate (TFV-DP) and FTC triphosphate (FTC-TP)] were measured in homogenates prepared from rectal, vaginal, and cervical tissues. TFV and FTC were detected in blood plasma 14 days after administration of a single dose. The area under the concentration-time curve from 24 hours to 14 days (AUC(1-14d)) for FTC in genital secretions was 27-fold greater than in blood plasma, whereas the AUC(1-14d) for TFV was only 2.5-fold greater in genital secretions than in blood plasma. In rectal tissue, TFV and TFV-DP concentrations were detectable for 14 days and were 100-fold higher than the concentrations in vaginal and cervical tissues. Vaginal and cervical tissue concentrations of FTC were 10- to 15-fold higher than in rectal tissue. Despite high concentrations of FTC in vaginal and cervical tissue, FTC-TP concentrations in all tissue types were detected for only 2 days after dose. The exposure to TFV, TFV-DP, FTC, and FTC-TP was wide ranging depending on the type of mucosal tissue. These results demonstrate the need for detailed pharmacological studies to improve the application of ART for PrEP to prevent transmission of HIV.

Polyclonal B Cell Responses to Conserved Neutralization Epitopes in a Subset of HIV-1-Infected Individuals

Abstract: A small proportion of HIV-infected individuals generate a neutralizing antibody (NAb) response of exceptional magnitude and breadth. A detailed analysis of the critical epitopes targeted by broadly neutralizing antibodies should help to define optimal targets for vaccine design. HIV-1-infected subjects with potent cross-reactive serum neutralizing antibodies were identified by assaying sera from 308 subjects against a multiclade panel of 12 “tier 2” viruses (4 each of subtypes A, B, and C). Various neutralizing epitope specificities were determined for the top 9 neutralizers, including clade A-, clade B-, clade C-, and clade A/C-infected donors, by using a comprehensive set of assays. In some subjects, neutralization breadth was mediated by two or more antibody specificities. Although antibodies to the gp41 membrane-proximal external region (MPER) were identified in some subjects, the subjects with the greatest neutralization breadth targeted gp120 epitopes, including the CD4 binding site, a glycan-containing quaternary epitope formed by the V2 and V3 loops, or an outer domain epitope containing a glycan at residue N332. The broadly reactive HIV-1 neutralization observed in some subjects is mediated by antibodies targeting several conserved regions on the HIV-1 envelope glycoprotein.

HIV partner notification is effective and feasible in sub-Saharan Africa: opportunities for HIV treatment and prevention.

Abstract: BACKGROUND: Sexual partners of persons with newly diagnosed HIV infection require HIV counseling testing and if necessary evaluation for therapy. However many African countries do not have a standardized protocol for partner notification and the effectiveness of partner notification has not been evaluated in developing countries . METHODS: Individuals with newly diagnosed HIV infection presenting to sexually transmitted infection clinics in Lilongwe Malawi were randomized to 1 of 3 methods of partner notification: passive referral contract referral or provider referral. The passive referral group was responsible for notifying their partners themselves. The contract referral group was given seven days to notify their partners after which a health care provider contacted partners who had not reported for counseling and testing. In the provider referral group a health care provider notified partners directly. RESULTS: Two hundred forty-five index patients named 302 sexual partners and provided locator information for 252. Among locatable partners 107 returned for HIV counseling and testing; 20 of 82 [24%; 95% confidence interval (CI): 15% to 34%] partners returned in the passive referral arm 45 of 88 (51%; 95% CI: 41% to 62%) in the contract referral arm and 42 of 82 (51%; 95% CI: 40% to 62%) in the provider referral arm (P < 0.001). Among returning partners (n = 107) 67 (64%) of were HIV infected with 54 (81%) newly diagnosed. DISCUSSION: This study provides the first evidence of the effectiveness of partner notification in sub-Saharan Africa. Active partner notification was feasible acceptable and effective among sexually transmitted infections clinic patients. Partner notification will increase early referral to care and facilitate risk reduction among high-risk uninfected partners.

Recurrent Signature Patterns in HIV-1 B Clade Envelope Glycoproteins Associated with either Early or Chronic Infections

Abstract: Here we have identified HIV-1 B clade Envelope (Env) amino acid signatures from early in infection that may be favored at transmission, as well as patterns of recurrent mutation in chronic infection that may reflect common pathways of immune evasion. To accomplish this, we compared thousands of sequences derived by single genome amplification from several hundred individuals that were sampled either early in infection or were chronically infected. Samples were divided at the outset into hypothesis-forming and validation sets, and we used phylogenetically corrected statistical strategies to identify signatures, systematically scanning all of Env. Signatures included single amino acids, glycosylation motifs, and multi-site patterns based on functional or structural groupings of amino acids. We identified signatures near the CCR5 co-receptor-binding region, near the CD4 binding site, and in the signal peptide and cytoplasmic domain, which may influence Env expression and processing. Two signatures patterns associated with transmission were particularly interesting. The first was the most statistically robust signature, located in position 12 in the signal peptide. The second was the loss of an N-linked glycosylation site at positions 413–415; the presence of this site has been recently found to be associated with escape from potent and broad neutralizing antibodies, consistent with enabling a common pathway for immune escape during chronic infection. Its recurrent loss in early infection suggests it may impact fitness at the time of transmission or during early viral expansion. The signature patterns we identified implicate Env expression levels in selection at viral transmission or in early expansion, and suggest that immune evasion patterns that recur in many individuals during chronic infection when antibodies are present can be selected against when the infection is being established prior to the adaptive immune response.

Experimental Gonococcal Infection in Male Volunteers: Cumulative Experience with Neisseria gonorrhoeae Strains FA1090 and MS11mkC

Abstract: Experimental infection of male volunteers with Neisseria gonorrhoeae is safe and reproduces the clinical features of naturally acquired gonococcal urethritis. Human inoculation studies have helped define the natural history of experimental infection with two well-characterized strains of N. gonorrhoeae, FA1090 and MS11mkC. The human model has proved useful for testing the importance of putative gonococcal virulence factors for urethral infection in men. Studies with isogenic mutants have improved our understanding of the requirements for gonococcal LOS structures, pili, opacity proteins, IgA1 protease, and the ability of infecting organisms to obtain iron from human transferrin and lactoferrin during uncomplicated urethritis. The model also presents opportunities to examine innate host immune responses that may be exploited or improved in development and testing of gonococcal vaccines. Here we review results to date with human experimental gonorrhea.

China's syphilis epidemic: epidemiology, proximate determinants of spread, and control responses

Abstract: Purpose of review China has experienced an increase in the incidence and prevalence of syphilis that is especially remarkable since this infection was virtually eradicated in the country 50 years ago. The purpose of this analysis is to provide an overview of recent literature on syphilis proximate determinants and potential public health responses.

Analysis of Genetic Linkage of HIV From Couples Enrolled in the HIV Prevention Trials Network 052 Trial

Abstract: Background. The HIV Prevention Trials Network (HPTN) 052 trial demonstrated that early initiation of antiretroviral therapy (ART) reduces human immunodeficiency virus (HIV) transmission from HIV-infected adults (index participants) to their HIV-uninfected sexual partners. We analyzed HIV from 38 index-partner pairs and 80 unrelated index participants (controls) to assess the linkage of seroconversion events. Methods. Linkage was assessed using phylogenetic analysis of HIV pol sequences and Bayesian analysis of genetic distances between pol sequences from index-partner pairs and controls. Selected samples were also analyzed using next-generation sequencing (env region). Results. In 29 of the 38 (76.3%) cases analyzed, the index was the likely source of the partner’s HIV infection (linked). In 7 cases (18.4%), the partner was most likely infected from a source other than the index participant (unlinked). In 2 cases (5.3%), linkage status could not be definitively established. Conclusions. Nearly one-fifth of the seroconversion events in HPTN 052 were unlinked. The association of early ART and reduced HIV transmission was stronger when the analysis included only linked events. This underscores the importance of assessing the genetic linkage of HIV seroconversion events in HIV prevention studies involving serodiscordant couples.

Pre-Exposure Prophylaxis and Antiretroviral Resistance: HIV Prevention at a Cost?

Abstract: Pre-exposure prophylaxis (PrEP), the use of antiretrovirals (ARVs) by human immunodeficiency virus (HIV)‐ uninfected individuals to prevent acquisition of the virus during high-risk sexual encounters, enjoyed its first 2 major successes with the Centre for the AIDS Programme of Research in South Africa (CAPRISA) 004 and the Pre-Exposure Prophylaxis Initiative (iPrEx) These successes were buoyed by additional positive results from the TDF2 and Partners PrEP trials Although no seroconverters in either arm of CAPRISA developed resistance to tenofovir, 2 participants in iPrEx with undetected, seronegative acute HIV infection were randomized to receive daily oral tenofovir-emtricitabine and resistance to emtricitabine was later discovered in both men A similar case in the TDF2 study resulted in resistance to both ARVs These cases prompted us to examine existing literature on the nature of resistance mutations elicited by ARVs used for PrEP Here, we discuss the impact of signature mutations selected by PrEP, how rapidly these emerge with daily ARV exposure, and the individual-level and public health consequences of ARV resistance

Single and Multiple Dose Pharmacokinetics of Maraviroc in Saliva, Semen, and Rectal Tissue of Healthy HIV-Negative Men

Abstract: Between 2004 and 2007, the incidence of HIV/AIDS increased 15% in the United States [1]. In men who have sex with men (MSM), this increase was 26%. The highest risk of HIV acquisition occurs with receptive anal intercourse [2], as the rectal mucosa is rich in lymphoid tissue and has a thin epithelium [3]. Data from the Phase III CAPRISA 004 study, which evaluated a topical tenofovir gel formulation for prevention of HIV acquisition in women, not only provide the proof of concept for microbicides but also further evidence that antiretroviral-based prevention strategies can be effective [4]. To date, topical rectal microbicide and vaccine trials have not demonstrated compelling benefit in HIV prevention; therefore, investigations using orally administered antiretrovirals are still necessary [5, 6]. Antiretrovirals can be used for both primary and secondary HIV prevention. Primary prophylaxis prevents acquisition of HIV in an uninfected individual, and secondary prophylaxis reduces the likelihood of an HIV-infected individual transmitting HIV. Primary prevention can be further separated into pre-exposure prophylaxis (PrEP) and post-exposure prophylaxis (PEP). PrEP requires administering antiretrovirals to at-risk individuals prior to a potential HIV exposure, and PEP involves administering antiretrovirals to an HIV-negative individual after a suspected exposure to HIV. Measuring antiretroviral exposure in rectal tissue could assist in selecting drugs and dosing regimens for PrEP and PEP. HIV transmission modeling has correlated increasing concentrations of HIV RNA in semen to an increasing probability of infection [7]. Despite suppression of HIV RNA in blood, HIV RNA can still be detected in genital secretions of up to 8% of HIV-infected men on antiretroviral therapy [8]. Using selected antiretrovirals to target the genital tract and decrease HIV replication in genital secretions has implications for transmission. If semen drug concentrations are high enough, it might be also be possible to deliver a protective amount of drug to a receptive mucosal surface through this route [9]. The ability to monitor drug concentrations has allowed clinicians to make important decisions regarding adherence to antiretroviral regimens. Under most conditions, concentration monitoring requires a blood sample. Saliva sampling has been explored as an alternative to blood sampling and has the advantages of being less invasive and requiring less processing time upon collection [10]. Within the female genital tract, the CCR5 antagonist maraviroc (Celsentri/Selzentry; Pfizer, Inc) achieves very high exposure [11]. The current study was designed to understand exposure of maraviroc in the saliva, seminal fluid, and rectal tissue following single and multiple doses.

HIV-1 treatment as prevention: the good, the bad, and the challenges

Abstract: Purpose of review This work focuses on the use of antiretroviral agents to prevent the sexual transmission of HIV-1. Recent findings Two randomized clinical trials demonstrated that antiretroviral agents provided before exposure to HIV-1 offer substantial protection, ostensibly directly proportional to the concentration of antiretroviral therapy (ART) in the genital secretions. Intense focus on the use of HIV treatment as prevention has led to publication of modeling exercises, ecological studies, and observational studies, most of which support the potential benefits of ART. However, the logistical requirements for successful use of ART for prevention are considerable. Summary ART will serve as a cornerstone of combination prevention of HIV-1. Continued research will be essential to measure anticipated benefits and to detect implementation barriers and untoward consequences of such a program, especially increases in primary ART resistance.

HIV incidence among men who have sex with men in China: a meta-analysis of published studies.

Abstract: BACKGROUND: Men who have sex with men (MSM) have now become one of the priority populations for prevention and control of HIV pandemic in China. Information of HIV incidence among MSM is important to describe the spreading of the infection and predict its trends in this population. We reviewed the published literature on the incidence of HIV infection among MSM in China. METHODS: We identified relevant studies by use of a comprehensive strategy including searches of Medline and two Chinese electronic publication databases from January 2005 to September 2010. Point estimate of random effects incidence with corresponding 95% confidence intervals (CI) of HIV infection was carried out using the Comprehensive Meta-Analysis software. Subgroup analyses were examined separately stratified by study design and geographic location. RESULTS: Twelve studies were identified including three cohort studies and nine cross-sectional studies. The subgroup analyses revealed that the sub-overall incidence estimates were 3.5% (95% CI 1.7%-5.3%) and 6.7% (95% CI 4.8%-8.6%) for cohort and cross-sectional studies respectively (difference between the sub-overalls Q = 5.54 p = 0.02); and 8.3% (95% CI 6.9%-9.7%) and 4.6% (95% CI 2.4%-6.9%) for studies in Chongqing and other areas respectively (difference between the sub-overalls Q = 7.58 p<0.01). Syphilis infection (RR = 3.33 p<0.001) multiple sex partnerships (RR = 2.81 p<0.001) and unprotected receptive anal intercourse in the past six months (RR = 3.88 p = 0.007) represented significant risk for HIV seroconversion. CONCLUSIONS: Findings from this meta-analysis indicate that HIV incidence is substantial in MSM in China. High incidence of HIV infection and unique patterns of sexual risk behaviors in this population serve as a call for action that should be answered with the innovative social and public health intervention strategies and development of biological prevention strategies.

Multiple HIV-1 specific IgG3 responses decline during acute HIV-1: implications for detection of incident HIV Infection

Abstract: Objective Different HIV-1 antigen specificities appear in sequence after HIV-1 transmission and the immunoglobulin G (IgG) subclass responses to HIV antigens are distinct from each other. The initial predominant IgG subclass response to HIV-1 infection consists of IgG1 and IgG3 antibodies with a noted decline in some IgG3 antibodies during acute HIV-1 infection. Thus, we postulate that multiple antigen-specific IgG3 responses may serve as surrogates for the relative time since HIV-1 acquisition.

Common human genetic variants and HIV-1 susceptibility: a genome-wide survey in a homogeneous African population.

Abstract: To date, CCR5 variants remain the only human genetic factors to be confirmed to impact HIV-1 acquisition. However, protective CCR5 variants are largely absent in African populations, in which sporadic resistance to HIV-1 infection is still unexplained. We investigated whether common genetic variants associate with HIV-1 susceptibility in Africans.

Cross-sectional detection of acute HIV infection: timing of transmission, inflammation and antiretroviral therapy.

Abstract: Background: Acute HIV infection (AHI) is a critical phase of infection when irreparable damage to the immune system occurs and subjects are very infectious. We studied subjects with AHI prospectively to develop better treatment and public health interventions. Methods: Cross-sectional screening was employed to detect HIV RNA positive, antibody negative subjects. Date of HIV acquisition was estimated from clinical history and correlated with sequence diversity assessed by single genome amplification (SGA). Twenty-two cytokines/chemokines were measured from enrollment through week 24. Results: Thirty-seven AHI subjects were studied. In 7 participants with limited exposure windows, the median exposure to HIV occurred 14 days before symptom onset. Lack of viral sequence diversification confirmed the short duration of infection. Transmission dates estimated by SGA/sequencing using molecular clock models correlated with transmission dates estimated by symptom onset in individuals infected with single HIV variants (mean of 28 versus 33 days). Only 10 of 22 cytokines/chemokines were significantly elevated among AHI participants at enrollment compared to uninfected controls, and only 4 participants remained seronegative at enrollment.

Dynamic Antibody Specificities and Virion Concentrations in Circulating Immune Complexes in Acute to Chronic HIV-1 Infection

Abstract: Understanding the interactions between human immunodeficiency virus type 1 (HIV-1) virions and antibodies (Ab) produced during acute HIV-1 infection (AHI) is critical for defining antibody antiviral capabilities. Antibodies that bind virions may prevent transmission by neutralization of virus or mechanically prevent HIV-1 migration through mucosal layers. In this study, we quantified circulating HIV-1 virion-immune complexes (ICs), present in approximately 90% of AHI subjects, and compared the levels and antibody specificity to those in chronic infection. Circulating HIV-1 virions coated with IgG (immune complexes) were in significantly lower levels relative to the viral load in acute infection than in chronic HIV-1 infection. The specificities of the antibodies in the immune complexes differed between acute and chronic infection (anti-gp41 Ab in acute infection and anti-gp120 in chronic infection), potentially suggesting different roles in immunopathogenesis for complexes arising at different stages of infection. We also determined the ability of circulating IgG from AHI to bind infectious versus noninfectious virions. Similar to a nonneutralizing anti-gp41 monoclonal antibody (MAb), purified plasma IgG from acute HIV-1 subjects bound both infectious and noninfectious virions. This was in contrast to the neutralizing antibody 2G12 MAb that bound predominantly infectious virions. Moreover, the initial antibody response captured acute HIV-1 virions without selection for different HIV-1 envelope sequences. In total, this study demonstrates that the composition of immune complexes are dynamic over the course of HIV-1 infection and are comprised initially of antibodies that nonselectively opsonize both infectious and noninfectious virions, likely contributing to the lack of efficacy of the antibody response during acute infection.

Continued high risk sexual behavior following diagnosis with acute HIV infection in South Africa and Malawi: implications for prevention.

Abstract: Understanding sexual behavior following diagnosis of acute HIV infection (AHI) is key to developing prevention programs targeting individuals diagnosed with AHI. We conducted separate qualitative and quantitative interviews with individuals newly diagnosed (n = 19) with AHI at 1-, 4- and 12-weeks post-diagnosis and one qualitative interview with individuals who had previously been diagnosed with AHI (n = 18) in Lilongwe, Malawi and Johannesburg, South Africa between October 2007 and June 2008. The majority of participants reported engaging in sexual activity following diagnosis with AHI with a significant minority reporting unprotected sex during this time. Most participants perceived to have changed their behavior following diagnosis. However, participants reported barriers to condom use and abstinence, in particular, long term relationships and the need for disclosure of sero-status. Understanding of increased infectiousness during AHI was limited. Participants reported a desire for a behavioral intervention at the time of AHI diagnosis, however, there were differences by country in the types of interventions participants found acceptable. Studies are underway to determine the feasibility, acceptability and potential effectiveness of interventions designed for individuals with AHI.

Reappraisal of the Relationship between the HIV-1-Protective Single-Nucleotide Polymorphism 35 Kilobases Upstream of the HLA-C Gene and Surface HLA-C Expression

Abstract: Previous studies have found an association between a single-nucleotide polymorphism 35 kb upstream of the HLA-C locus (−35 SNP), HLA-C expression, and HIV-1 set point viral loads. We show that the difference in HLA-C expression across −35 SNP genotypes can be attributed primarily to the very low expression of a single allelic product, HLA-Cw7, which is a common HLA type. We suggest that association of the −35 SNP and HIV-1 load manifests as a result of linkage disequilibrium of this polymorphism with both favorable and unfavorable HLA-C and -B alleles.

An expanding syphilis epidemic in China: epidemiology, behavioural risk and control strategies with a focus on low-tier female sex workers and men who have sex with men.

Abstract: Syphilis has made a dramatic resurgence in China during the past two decades. During the Cultural Revolution (1966–76), sexually transmitted infections (STI) were so uncommon that they were removed from standard Chinese medical training curricula.1 As China's market economy expanded during 1980s economic reforms, reported STI, including syphilis infection, quickly re-appeared. An evolving STI reporting infrastructure largely assembled in the 1990s has noted increasing syphilis cases, particularly during the past 5 years (figure 1).2 3 Now syphilis is among the top five reported communicable diseases in many major province-level municipalities and provinces.4 While China's syphilis case reporting system and potential determinants of spread have been outlined in other reviews,2 there have been many studies on syphilis infection among female sex workers (FSW),5 6 this review analyses syphilis in China from the perspective of two critical high-risk populations: men who have sex with men (MSM) and low-tier FSW. Here we define low-tier FSW as women who usually solicit clients on the street or public outdoor places and sell sex for less than approximately €2–10 per client. Although preventing adverse outcomes associated with syphilis in pregnancy is important,7 this review focuses …

Differences in HIV-Specific T Cell Responses between HIV-Exposed and -Unexposed HIV-Seronegative Individuals†

Abstract: HIV-1-specific T lymphocyte responses in individuals exposed to HIV-1 but who remain persistently seronegative (HESNs) have been reported in some but not all previous studies. This study was designed to resolve unequivocally the question of whether HESNs make HIV-1-specific T cell responses. We performed a blind investigation to measure HIV-1-specific T cell responses in both HIV-1-serodiscordant couples and HIV-1-unexposed seronegative controls (HUSNs). We found low-frequency HIV-1-specific T cells in both HESNs and HUSNs but show that the response rates were higher over time in the former (P = 0.01). Furthermore, the magnitudes of the HIV-1-specific T cell responses were significantly higher among responding HESNs than among HUSNs over time (P = 0.002). In both groups, responses were mediated by CD4 T cells. The responses were mapped to single peptides, which often corresponded to epitopes restricted by multiple HLA-DR types that have previously been detected in HIV-1-infected patients. HIV-1-specific T cell responses in HUSNs and some HESNs likely represent cross-reactivity to self or foreign non-HIV-1 antigens. The significantly greater T cell responses in HESNs, including in two who were homozygous for CCR5Δ32, demonstrates that HIV-1-specific T cell responses can be induced or augmented by exposure to HIV-1 without infection.

Factors Associated with Utilization of a Free HIV VCT Clinic by Female Sex Workers in Jinan City, Northern China

Abstract: Based on our previous qualitative exploration, this research presents the second phase in our study of factors associated with utilization of a free HIV VCT clinic in Jinan City, Northern China, by female sex workers (FSWs). A total of 970 FSWs from entertainment venues were interviewed and prospectively followed to determine who ultimately sought and received VCT at the clinic, compared to those who did not. Simple and multiple logistic regressions were performed on factors drawn from the Ecological Perspective, hypothesized to be associated with utilization of testing at the VCT clinic. Despite 69% of FSWs expressing willingness to attend the VCT clinic, only 11% were actually tested. The multiple logistic regression model that provided best goodness of fit included the covariates of willingness to attend the VCT clinic (Adjusted OR 3.13, 95% CI: 1.62–6.59), low perceived HIV infection risk (Adjusted OR 0.64, 95% CI: 0.35–1.11), low fear of FSWs status disclosure in the clinic (Adjusted OR 0.55, 95% CI: 0.31–0.94) and influence of acquaintances (Adjusted OR 0.52, 95% CI: 0.29–0.89) and peers (Adjusted OR 2.45, 95% CI: 1.40–4.50). This is the first study in China to follow FSWs longitudinally to measure factors related to VCT utilization. The low utilization of VCT services by participants in our study is similar to prior reports throughout China. FSWs’ access to VCT service is associated with intrapersonal, institutional, and particularly, interpersonal factors. Based on these findings, we recommend emphasis on confidentiality of services, VCT education for influential peers, and introduction of HIV rapid testing on site.

Public Health Education in India and China:History, Opportunities, and Challenges

Abstract: Public health education in China and India has a long history that has been both deeply responsive to the unique needs and medical traditions of each country, and sensitive to global influences. The history of public health education in China reaches back several centuries, with substantial input from American and European organizations during the Republican Era, 1911–1949. In India, centuries-old health care traditions were influenced during the colonial period by the British Empire prior to independence in 1947. Political upheaval in both countries during the 1940s further impacted the public health systems as well as public health education. The primary goal of this review is to outline public health education in India and Mainland China, with a focus on describing the historical systems and structures that have promoted the development of formalized public health education. We examine current challenges, and analyze opportunities for improvement. Health reforms in China and India need to consider new and modern models for public health education, perhaps in independent faculties of public health, to reinvigorate public health education and strengthen the position of public health in addressing the health challenges of the 21st century.

Sexual partnership patterns in malawi: implications for HIV/STI transmission.

Abstract: Background Concurrent sexual partnerships are believed to play an important role in HIV transmission in sub-Saharan Africa, but the contributions of concurrency to HIV and sexually transmitted infection (STI) spread depend on the details of infectious periods and relationship patterns. To contribute to the understanding of sexual partnership patterns in this region, we estimated partnership lengths, temporal gaps between partners, and periods of overlap across partners at an STI clinic in Lilongwe, Malawi. Methods Participants underwent physical examinations and HIV tests, and responded to questionnaires about demographics and risk behaviors, including detailed questions about a maximum of 3 sexual partners in the previous 2 months. We calculated partnership length as the time between the first and most recent sexual contact with a partner, and gap length as the time between the most recent contact with 1 partner and the first contact with the next. We defined concurrent and consecutive partnerships as gap length ≤0 days and gap length >0 days, respectively. Results In the study population (n = 183), 86% reported 0 or 1 partner, 5% reported multiple consecutive partnerships, and 9% reported concurrency. The mean partnership length was 858 days (median = 176 days). Gaps between consecutive partnerships were short (mean = 21 days), and overlaps across concurrent partners tended to be long (mean = 246 days). Conclusions Multiple sexual partnerships were uncommon, and partnerships were long on average. Among those reporting multiple recent partners, both long-term concurrency and narrowly spaced consecutive partnerships could present substantial risk for efficient transmission of HIV and classical STIs.

A Twin Response to Twin Epidemics: Integrated HIV/Syphilis Testing at STI clinics in South China

Abstract: BACKGROUND: HIV testing is still stigmatized among many high-risk groups in China whereas routine syphilis testing has been widely accepted at sexually transmitted infection (STI) clinics. This project used the platform of a rapid syphilis screening test to expand HIV test uptake. The objective of this study was to use multilevel modeling to analyze determinants of syphilis and HIV-testing uptake at STI clinics in China. METHODS: 2061 STI patients at 6 clinics in Guangdong Province were offered free rapid syphilis and free rapid HIV testing. Test uptake was defined by patient receipt of results and a multilevel model was used to analyze predictors of uptake. RESULTS: This was the first syphilis or HIV test for the large majority (1388 77.7%) of participants. Syphilis test uptake and HIV test uptake were high (1681 81.6% syphilis test uptake; 1673 81.2% HIV test uptake). HIV test uptake was significantly concordant with syphilis test uptake (taub = 0.89 P < 0.001). The most parsimonious model of refusing HIV test uptake included the following variables: being married having a previous HIV test being unaccompanied and participating in the last 2 months of the study. CONCLUSIONS: STI clinic-based screening for syphilis and HIV represents an excellent opportunity for scaling up integrated services especially in South China where syphilis and sexually transmitted HIV cases are both rapidly increasing. Effective integration of HIV testing into routine clinical practice requires an understanding not only of individual test uptake but also of the broader social context of HIV testing.

Combined oral contraceptives and antiretroviral PK/PD in Malawian women: pharmacokinetics and pharmacodynamics of a combined oral contraceptive and a generic combined formulation antiretroviral in Malawi.

Abstract: This letter to the editor addresses the concern regarding women who are HIV positive and interested in oral contraceptives. HIV positive women are typically advised to avoid using combined oral contraceptives which proves difficult because COC’s are the most widely circulated contraceptives in the world. Health care professionals must understand the pharmacokinetics and pharmacodynamics between COC pills and ART treatments. This is especially important in areas with high rates of HIV positive women or where rates exceed 10% HIV positive females within the HIV population. In these areas women should be informed of the most effective treatment for their unique condition.

A spatial analysis of county-level variation in syphilis and gonorrhea in Guangdong Province, China.

Abstract: BACKGROUND: Sexually transmitted infections (STI) have made a resurgence in many rapidly developing regions of southern China but there is little understanding of the social changes that contribute to this spatial distribution of STI. This study examines county-level socio-demographic characteristics associated with syphilis and gonorrhea in Guangdong Province. METHODS/PRINCIPAL FINDINGS: This study uses linear regression and spatial lag regression to determine county-level (n = 97) socio-demographic characteristics associated with a greater burden of syphilis gonorrhea and a combined syphilis/gonorrhea index. Data were obtained from the 2005 China Population Census and published public health data. A range of socio-demographic variables including gross domestic product the Gender Empowerment Measure standard of living education level migrant population and employment are examined. Reported syphilis and gonorrhea cases are disproportionately clustered in the Pearl River Delta the central region of Guangdong Province. A higher fraction of employed men among the adult population higher fraction of divorced men among the adult population and higher standard of living (based on water availability and people per room) are significantly associated with higher STI cases across all three models. Gross domestic product and gender inequality measures are not significant predictors of reported STI in these models. CONCLUSIONS/SIGNIFICANCE: Although many ecological studies of STIs have found poverty to be associated with higher reported STI this analysis found a greater number of reported syphilis cases in counties with a higher standard of living. Spatially targeted syphilis screening measures in regions with a higher standard of living may facilitate successful control efforts. This analysis also reinforces the importance of changing male sexual behaviors as part of a comprehensive response to syphilis control in China.