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Joseph D Tucker,
Li-Gang Yang,
Bin Yang,
He-Ping Zheng,
Helena Chang,
Cheng Wang,
Song-Ying Shen,
Zheng-Jun Zhu,
Yue-Pin Yin,
S V Subramanian,
Xiang-Sheng Chen, Myron S Cohen
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ABSTRACT: 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.
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.
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 (τb = 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.
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.
JAIDS Journal of Acquired Immune Deficiency Syndromes 04/2011; 57(5):e106-11. · 4.43 Impact Factor
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Lillian B Brown,
William C Miller,
Gift Kamanga,
Naomi Nyirenda,
Pearson Mmodzi,
Audrey Pettifor,
Rosalie C Dominik,
Jay S Kaufman,
Clement Mapanje,
Francis Martinson, Myron S Cohen,
Irving F Hoffman
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ABSTRACT: 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 .
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.
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.
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.
JAIDS Journal of Acquired Immune Deficiency Syndromes 04/2011; 56(5):437-42. · 4.43 Impact Factor
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Lillian B Brown,
William C Miller,
Gift Kamanga,
Naomi Nyirenda,
Pearson Mmodzi,
Audrey Pettifor,
Rosalie C Dominik,
Jay S Kaufman,
Clement Mapanje,
Francis Martinson, Myron S Cohen,
Irving F Hoffman
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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.
JAIDS Journal of Acquired Immune Deficiency Syndromes 04/2011; 56(5):437-442. · 4.43 Impact Factor
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Myron S Cohen
JAIDS Journal of Acquired Immune Deficiency Syndromes 03/2011; 56(3):e101-2. · 4.43 Impact Factor
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ABSTRACT: 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.
Per capita syphilis burden is greatest in coastal urban China. There are a number of biological, demographic, geographic, and behavioral/social proximate determinants of syphilis spread that distinguish the Chinese syphilis epidemic. These determinants portend the need for intensified syphilis control efforts, including: comprehensive testing and treatment; integration with HIV, sexually transmitted infection, and antenatal services; scale-up of novel rapid syphilis test technology, and multisectorial support.
The Chinese central government recently announced a 10-year syphilis plan to provide clear expectations for evaluating the success of local syphilis control programs and integration with HIV testing programs. Further research is needed to understand the social and behavioral determinants driving the spread of syphilis.
Current Opinion in Infectious Diseases 02/2011; 24(1):50-5. · 4.93 Impact Factor
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Slavé Petrovski,
Jacques Fellay,
Kevin V Shianna,
Nicole Carpenetti,
Johnstone Kumwenda,
Gift Kamanga,
Deborah D Kamwendo,
Norman L Letvin,
Andrew J McMichael,
Barton F Haynes, Myron S Cohen,
David B Goldstein
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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.
We performed a genome-wide association study (GWAS) in a population of 1532 individuals from Malawi, a country with high prevalence of HIV-1 infection. Using single-nucleotide polymorphisms (SNPs) present on the genome-wide chip, we also investigated previously reported associations with HIV-1 susceptibility or acquisition. Recruitment was coordinated by the Center for HIV/AIDS Vaccine Immunology at two sexually transmitted infection clinics. HIV status was determined by HIV rapid tests and nucleic acid testing.
After quality control, the population consisted of 848 high-risk seronegative and 531 HIV-1 seropositive individuals. Logistic regression testing in an additive genetic model was performed for SNPs that passed quality control. No single SNP yielded a significant P value after correction for multiple testing. The study was sufficiently powered to detect markers with genotype relative risk 2.0 or more and minor allele frequencies 12% or more.
This is the first GWAS of host determinants of HIV-1 susceptibility, performed in an African population. The absence of any significant association can have many possible explanations: rarer genetic variants or common variants with weaker effect could be responsible for the resistance phenotype; alternatively, resistance to HIV-1 infection might be due to nongenetic parameters or to complex interactions between genes, immunity and environment.
AIDS (London, England) 02/2011; 25(4):513-8. · 4.91 Impact Factor
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Kimberly A Powers,
Irving F Hoffman,
Azra C Ghani,
Mina C Hosseinipour,
Christopher D Pilcher,
Matthew A Price,
Audrey E Pettifor,
David A Chilongozi,
Francis E A Martinson, Myron S Cohen,
William C Miller
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ABSTRACT: 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.
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.
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).
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.
Sexually transmitted diseases 02/2011; 38(7):657-66. · 2.58 Impact Factor
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ABSTRACT: 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.
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.
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.
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.
PLoS ONE 01/2011; 6(8):e23431. · 4.09 Impact Factor
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European Journal of Immunology 01/2011; 41(1):255-7. · 5.10 Impact Factor
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Adam J Ritchie,
Suzanne L Campion,
Jakub Kopycinski,
Zoe Moodie,
Z Maggie Wang,
Kruti Pandya,
Stephen Moore,
Michael K P Liu,
Simon Brackenridge,
Kristin Kuldanek,
Kenneth Legg, Myron S Cohen,
Eric L Delwart,
Barton F Haynes,
Sarah Fidler,
Andrew J McMichael,
Nilu Goonetilleke
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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.
Journal of Virology 01/2011; 85(7):3507-16. · 5.40 Impact Factor
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Cynthia Gay,
Oliver Dibben,
Jeffrey A Anderson,
Andrea Stacey,
Ashley J Mayo,
Philip J Norris,
JoAnn D Kuruc,
Jesus F Salazar-Gonzalez,
Hui Li,
Brandon F Keele,
Charles Hicks,
David Margolis,
Guido Ferrari,
Barton Haynes,
Ronald Swanstrom,
George M Shaw,
Beatrice H Hahn,
Joseph J Eron,
Persephone Borrow, Myron S Cohen
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ABSTRACT: 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.
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.
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.
The results emphasize the difficulty in recruiting subjects early in AHI. Viral sequence diversity proved accurate in estimating time of infection. Regardless of aggressive screening, peak viremia and inflammation occurred before enrollment and potential intervention. Given the personal and public health importance, improved AHI detection is urgently needed.
PLoS ONE 01/2011; 6(5):e19617. · 4.09 Impact Factor
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ABSTRACT: 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.
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.
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.
PLoS ONE 01/2011; 6(5):e19648. · 4.09 Impact Factor
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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.
Journal of Virology 01/2011; 85(7):3367-74. · 5.40 Impact Factor
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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.
Frontiers in microbiology. 01/2011; 2:123.
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ABSTRACT: Azithromycin has been used to treat primary and secondary syphilis and as prophylaxis for sexual partners. We evaluated syphilis treatment failure in patients who received azithromycin therapy.
Patients who did not respond to azithromycin therapy were referred to Shanghai Skin Disease and sexually transmitted disease hospital. Treatment failure was defined as follows: (1) persistent ulcers or cutaneous or mucosal lesions 1 month after therapy; or (2) detection of spirochetes in dark-field microscopy examination of a lesion at least 1 week after treatment; or (3) failure of rapid plasma reagin titers to decrease 4-fold at 3 months after treatment.
A total of 132 patients with primary and secondary syphilis who failed azithromycin therapy were referred to our hospital between January 2001 and October 2008. Of 132 patients, 42 (31.8%) had primary syphilis and 90 (68.2%) had secondary syphilis. Twenty-six patients with primary syphilis developed multiple lesions or secondary syphilis, or persistent ulcers despite using azithromycin. The skin or mucosal lesions did not resolve in 37 patients with secondary syphilis after azithromycin treatment. Ten patients had a positive dark-field examination for Treponema pallidum (T. pallidum) after treatment. The serum rapid plasma reagin titers studied in all cases had failed to decrease 4-fold at 3 months after therapy. The doses of azithromycin used for treatment ranged from 4 to 30 g.
The failure of azithromycin to cure a substantial number of patients with primary and secondary syphilis in Shanghai suggests that azithromycin has limited therapeutic value in this setting.
Sexually transmitted diseases 11/2010; 37(11):726-9. · 2.58 Impact Factor
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ABSTRACT: Acute human immunodeficiency virus (HIV) infection (AHI) can be defined as the time from HIV acquisition until seroconversion. Incident HIV infection is less well defined but comprises the time from the acquisition of HIV (acute infection) through seroconversion (early or primary HIV infection) and the following months until infection has been well established, as characterized by a stable HIV viral load (viral load set point) and evolution of antibodies with increased concentration and affinity for HIV antigens. During AHI, a viral latent pool reservoir develops, the immune system suffers irreparable damage, and the infected (often unsuspecting) host may be most contagious. It has proved very difficult to find individuals with AHI either in longitudinal cohorts of subjects at high risk for acquiring the virus or through cross-sectional screening, and the opportunity for diagnosis is generally missed during this phase. We review the technical strategies for identifying individuals with acute or incident HIV infection. We conclude that further technical advances are essential to allow more widespread detection of patients with AHI and to affect HIV treatment outcomes and transmission prevention.
The Journal of Infectious Diseases 10/2010; 202 Suppl 2:S270-7. · 6.41 Impact Factor
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Myron S Cohen
Clinical Infectious Diseases 10/2010; 51(11):1323-4. · 9.15 Impact Factor
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Myron S Cohen
JAIDS Journal of Acquired Immune Deficiency Syndromes 10/2010; 55(2):137-8. · 4.43 Impact Factor
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Jiayin Xue,
Zenabu Mhango,
Irving F Hoffman,
Innocent Mofolo,
Esmie Kamanga,
James Campbell,
Greg Allgood, Myron S Cohen,
Francis E A Martinson,
William C Miller,
Mina C Hosseinipour
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ABSTRACT: To evaluate a pilot prevention of mother-to-child transmission post-natal programme in Lilongwe, Malawi, through observed retention and infant diarrhoeal rates.
Free fortified porridge and water hygiene packages were offered to mothers to encourage frequent post-natal visits and to reduce diarrhoeal rates in infants on replacement feeding. Participant retention and infant health outcome were assessed.
Of 474 patients enrolled, 357 (75.3%) completed 3-month follow-up visits. Ninety-nine percent of women reported hygiene package use, and only 17.7% (95% CI 13.8-22.0%) of the infants had diarrhoea at least once over the 3-month period. Being 12 months or younger, confirmed HIV positive, access to tap water, and having a mother with diarrhoea were all associated with increased risk of infant diarrhoea.
The majority of participants adhered to their scheduled visits and retention was favourable, possibly because of the introduction of hygiene and nutrition incentives. The infant diarrhoeal rate was low, suggesting benefits of regular medical care with hygiene package usage and reliable replacement feeding options. Continuation and expansion of the programme would allow further studies and improve the post-natal care of HIV-exposed infants in Malawi and in other resource-constrained countries.
Tropical Medicine & International Health 10/2010; 15(10):1156-62. · 2.80 Impact Factor
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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.
AIDS and Behavior 10/2010; 15(6):1243-50. · 3.49 Impact Factor
