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Study of the heterosexual transmission of HIV has shifted focus from the behavioral and demographic risk factors associated with HIV to the biological and molecular factors. Although factors such as genetic predisposition may be immutable, others such as co-infection with sexually transmitted diseases are modifiable by the use of treatment. The effect of antiretroviral treatment is also promising but deserves more study, as does the use of contraception and microbicides (chemical barriers meant for intravaginal use).

This is a follow-up paper of Tan and Zhu [1] in which we have considered a large population consisting of single males, single females, married couples, and prostitutes. For assessing effects of risk factors on the HIV epidemic by heterosexual transmission and the role of prostitutes in this paper, we have developed chain multinomial models for the HIV epidemic in these populations. Through Monte Carlo studies, we have shown that prostitutes form a stepping stone for the HIV epidemic by heterosexual transmission. Among the risk factors affecting HIV prevalence, our numerical results have indicated that the frequency of condom use is the most important factor followed by the number of sexual partners per unit time. Thus, promoting condom use among prostitutes may serve as a major avenue to control the spread of HIV through heterosexual transmission.

Heterosexual intercourse has become a significant means of HIV transmission, even in countries where this was previously not the case. Consequently the promotion of safer sexual practices for heterosexual women and men is of major public health importance. We examine the risks to women of contracting HIV through heterosexual sex, and critically discuss the most commonly recommended strategies for safer sex for heterosexuals. We conclude that all safer sex strategies have limitations, and therefore a wide range of options should be promoted.Women are increasingly at risk of contracting HIV through heterosexual transmission, even in countries where this was initially not a major risk factor. Of the 30-40 million adult HIV cases expected to occur by the year 2000, more than 13 million will involve women. By 2000, 80% of HIV infections worldwide will result from heterosexual intercourse. Gender, race, and social class interact and overlap to render many women particularly vulnerable to HIV. Condom use has been presented as the primary HIV preventive strategy for heterosexuals, with varying degrees of success. Although the female condom offers women a method of protection under their control, it is not yet clear that this method will be markedly more acceptable than the male condom. Other safer sex strategies require changes in the nature of sexual relationships. These practices are limited, however, by their dependence on a certain level of interpersonal honesty and fidelity. Another strategy that deserves wider promotion among women is the practice of non-coital forms of sexual intimacy. Since no one safer sex strategy is likely to be acceptable to all heterosexual women, public health campaigns should emphasize as many choices as possible.

OBJECTIVE: Cervical ectopy has been identified as a possible risk factor for heterosexual transmission of human immunodeficiency virus. To accurately assess the importance of cervical ectopy, methods for measuring ectopy with precision need to be developed. The objective of this study was to evaluate the reliability of two methods of measuring cervical ectopy: direct visual assessment and computerized planimetry. STUDY DESIGN: Cervical photographs of 85 women without cervical disease were assessed for cervical ectopy by three raters using direct visual assessment and a computer planimetry method. Agreement between the two methods, among the three raters, and among measurements by each rater over time was calculated with use of intraclass correlation coefficients, where 1.0 represents perfect agreement and 0 represents no agreement except by chance. RESULTS: The intraclass correlation coefficient among the three raters (interrater agreement) was 0.58 for direct visual assessment without application of acetic acid to the cervix compared with 0.72 for direct visual assessment with acetic acid and 0.82 for computerized planimetry with acetic acid. The intraclass correlation coefficient among measurements by each rater over time (intrarater agreement) was 0.66 for direct visual assessment without acetic acid compared with 0.77 for direct visual assessment and 0.83 for computerized planimetry after application of acetic acid. When acetic acid was used, the intraclass correlation coefficient between the two methods was 0.69. CONCLUSIONS: Computerized planimetry of cervical photographs may provide the most consistent estimate of the percent of ectopy. However, if time and resources make the use of computer planimetry difficult, direct visual assessment after application of 5% acetic acid appears to provide comparable estimates. (Am J Obstet Gynecol 1997;176:108-11.)

We studied HIV seropositivity among a targeted sample of migrant workers who used drugs, primarily crack cocaine, and their sexual partners in rural southern Florida from 1993 to 1995. We enrolled men and women who were born in the United States (n = 369) or in other countries (n = 174). Overall, 11.2% of the sample were HIV positive, including 18% of Blacks from the United States, and about 8% of non-Hispanic whites from the United States, Blacks from the Caribbean, and persons from Central or South America. No Hispanics from the United States or the Caribbean, but 3.4% of Hispanics from Mexico, were HIV positive. In logistic regression analyses, race/ethnicity, gender, and age were most highly associated with HIV seropositivity. Immigration status, current drug use, and current sexual activity were not related to HIV seropositivity. HIV prevention programs must help reduce heterosexual transmission of HIV associated with drug use both locally and where migrants travel and work.

We report here the first novel HIV-1 second-generation intercirculating recombinant form 61_BC (inter-CRF61_BC), composed of two established CRFs (CRF07_BC and CRF08_BC), in China. CRF61_BC is the first CRF found among the heterosexual population in two different regions in China, suggesting the increasing significance of heterosexual transmission of HIV in China.

Background In 2009, 27% of the 48,100 estimated new cases of HIV were attributed to heterosexual contact with an infected or at-risk person. Sexually active adults are less likely to use condoms in relationships with main partners than with non-regular partners, despite general knowledge that condom use reduces HIV transmission. Methods The purpose of this secondary qualitative analysis was to explore and contextualize perceptions of main partnerships, HIV risk, and attitudes toward condom use within main partner relationships among a subsample of intervention-arm cocaine- and/or heroin-using patients enrolled in a negative trial of brief motivational intervention to reduce the incidence of sexually transmitted disease and unsafe sexual behaviors. The open-ended portion of these interview audiotapes consisted of questions about perceptions of risk and attitudes about condom use with main partners. Enrollees were aged 18-54, English or Spanish speaking, and included in this analysis only if they reported having a main partner. We identified codes and elaborated important themes through a standard inductive three step coding process, using HyperRESEARCH™ software. Results Among 48 interviewees, 65% were male, half were non-Hispanic white, over 60% were 20-39 years of age, 58% had intravenous drug use (IDU), and 8% were HIV-positive. Participants defined respect, support, trust, and shared child-rearing responsibility as the most valued components of main partner relationships. Condom use was viewed occasionally as a positive means of showing respect with main partners but more often as a sign of disrespect and a barrier to intimacy and affection. Enrollees appraised their partners’ HIV risk in terms of perceptions of physical health, cleanliness, and sexual and HIV testing history. They based decisions regarding condom use mainly on perceived faithfulness, length of involvement, availability of condoms, and pregnancy desirability. Conclusions Risk appraisal was commonly based on appearance and subjective factors, and condom use with main sexual partners was described most often as a demonstration of lack of trust and intimacy. Trial registration NCT01379599

Background. Because many human papillomavirus (HPV) infections are transient, rates of transmission may be miscalculated if the interval between testing spans several months. We examined rates of concordance and transmission in heterosexual couples over short intervals. Methods. Twenty-five adult couples were enrolled and sampled for HPV DNA from the genitals, hand, and mouth 5 times over a 6-week period, including 24 hours after sexual intercourse and after 48 hours of abstinence. Concordance and transmission patterns were described. Results. Concordance between the couple’s genital sites ranged from 64% to 95% for at least 1 HPV type. The highest rates of concordance were observed 24 hours after sexual intercourse. A similar peak in concordance was not seen between genital and nongenital anatomic sites. Transmission rates for female genital to male genital ranged from 26.8 to 187.5 per 100 person-months and for male genital to female genital from 14.5 to 100 per 100 person-months. Conclusions. High rates of concordance shortly after intercourse suggest that some DNA detections in the genital area are contaminants from a partner and not established HPV infections. Female-to-male transmission appeared more common than male-to-female transmission.

International audience; This paper is devoted to assess the impact of quadrivalent Human Papillomavirus (HPV) vaccine on prevalence of non-oncogenic HPV 6/11 types in French males and females. For this purpose, a non-linear dynamic model of heterosexual transmission for HPV 6/11 types infection is developed, which accounts for immunity due to vaccination in particular. The vaccinated reproduction number Rv is derived using the approach described by Diekmann (2010) called the Next Generation Operator approach. The model proposed is analyzed, with regard to existence and uniqueness of the solution, steady-state stability. Precisely, the stability of the model is investigated depending on the sign of Rv − 1. Prevalence data are used to fit a numerical HPV model, so as to assess infection rates. Our approach suggests that 10 years after introducting vaccination, the prevalence of HPV 6/11 types in females will be halved and that in males will be reduced by one quarter, assuming a sustained vaccine coverage of 30% among females. Using the formula we derived for the vaccinated reproduction number, we show that the non-oncogenic HPV 6/11 types would be eradicated if vaccine coverage in females is kept above 12%. Human Papillomavirus, deterministic epidemic model, equilibrium, stability, reproduction number, vaccination.

Although the majority of case studies in this book center on programs for some of the populations most at risk for HIV, this portion focuses on structural interventions to reduce HIV in the general population by targeting the primary mode of transmission throughout the world—noncommercial heterosexual behaviors. Globally, 85% of HIV transmission is through heterosexual intercourse (Nettleman, 2011). Moreover, this category of HIV/AIDS cases continues to rise rapidly. In the United States, approximately one-third of new diagnoses appear to be related to heterosexual transmission, with male-to-male sexual contact still accounting for more than half of new diagnoses and intravenous drug use contributing to the majority of the remaining cases. However, because the HIV/AIDS diagnosis often occurs years after infection, it is likely that a higher proportion of recent infections in the USA are due to heterosexual transmission (Nettleman).

To assess effects of risk factors on the HIV epidemic by heterosexual transmission and the role of prostitutes, in this paper we consider four populations and derive the probabilities of HIV infection in these populations. The four populations considered are the single males, the single females, the married couples, and the prostitutes. It is shown that prostitutes form a stepping stone for the HIV epidemic by heterosexual transmission. Thus, in a society in which homosexual transmission and IV drug use are not frequent, the HIV epidemic can hardly be maintained without prostitutes.

Nineteen Brazilian HIV-infected hemophiliacs and their stable heterosexual sexual partners were studied with the aim of assessing the rate of HIV transmission in this at risk group. The mean length of relationship between couples was 7.4 years. The hemophiliac men were Class II (n=6), III (n=11) and IVa (n=2) of the CDC classification. They had decreased CD4+ and elevated CD8+ cell numbers; five had p24 antigenemia. We found 3 HIV-infected women (15.8 percent) by routine and confirmatory tests, a prevalence similar to that seen in other countries. They were asymptomatic and had no detectable p24 antigenemia. The 3 seropositive women's partners were Class II and III-CDC, and had normal CD4+ and CD8+ values and no p24 antigenemia. All seronegative women also had normal CD4+ and CD8+ numbers, except for elevated CD8+ cells in three of them, but immune abnormalities had already been seen in some seronegative partners at high risk for HIV infection. Our results reinforce previous suggestions that heterosexual transmission to stable female partners occurs preferentially early after initiation of sexual exposure, and possibly when the transmitter has high levels of viremia and regular sexual activity. INTRODUÇÃO E OBJETIVOS: Pacientes hemofílicos no Brasil apresentaram alto risco de adquirirem infecção pelo HIV devido a transfusões no período de 1980-86. Entretanto, não há relatos publicados em nosso país acerca da evolução clínica destes pacientes, nem sobre sua importância como transmitteres heterossexuais. METODOLOGIA: Foram estudados 19 pacientes hemofílicos infectados pelo HIV e suas respectivas parceiras sexuais fixas, e 15 indivíduos normais como controles. No momento do estudo, 6 dos pacientes eram do grupo II (CDC, 1986), 11 do grupo III e 2 do grupo IVa. O tempo médio de relacionamento dos casais foi de 7,4 anos. A infecção pelo HIV foi diagnosticada pelas técnicas ELISA e Western-blot e presença de antigenemia (p24) por ELISA comercial. A avaliação imunológica consistiu na determinação de linfócitos CD4 e CD8 do sangue periférico por imunoflorescência indireta com anticorpos monoclonais e na dosagem de lg total, IgA, IgG e IgM séricos por nefelometria. RESULTADOS: O grupo de pacientes apresentava medianas das contagens de células CD4 e CD8 diminuídas quando comparadas ao grupo controle; 5 dos pacientes eram p24 positivos. Da mesma forma que em outras casuísticas, 15,8 % (3/19) das parceiras eram soropositivas para o HIV, encontrando-se assintomáticas e p24 negativas. Seus respectivos parceiros eram grupo II ou III-CDC, apresentavam números normais de células CD4 e CD8, e eram p24 negativos. As parceiras soronegativas apresentavam contagens normais de células CD4 e CD8, com exceção de 3 delas que apresentavam células CD8 aumentadas. Entretanto, alterações imunológicas já foram foram descritas em parceiras sexuais soronegativas de pacientes HIV positivos. CONCLUSÕES: Nossos resultados corroboram sugestões prévias de que a transmissão heterossexual a parceiras sexuais fixas parece ocorrer precocemente após o início da exposição sexual e possivelmente quando o parceiro apresenta altos índices de viremia e atividade sexual regular.

Human immunodeficiency virus type 2 (HIV-2) infection is endemic in West Africa, where it is responsible for many cases of AIDS. HIV-2-infected subjects have been described in other countries, mainly African immigrants, although infection in native individuals has been reported as well. The first cases of HIV-2 infection in Spain were identified in 1988. Through December 1995, 56 HIV-2 infected individuals have been diagnosed, primarily in large urban areas (23 cases in Madrid and 18 in Barcelona). All are African immigrants, except for 12 natives (21.4%), six of whom acquired the infection in endemic areas; the remaining six (2 women with numerous sexual partners and 4 homo/bisexual men) acquired the infection in Spain. Heterosexual transmission was probable in all but seven cases: five homo/bisexual males, a subject who likely acquired infection through parenteral exposure, and a child born to an HIV-2-infected mother. Nine patients (all Spanish born) have developed AIDS (16%), six of whom have died. In conclusion, HIV-2 infection is present in Spain at a low rate, and there is little evidence supporting an emerging ongoing transmission outside the population of African immigrants.

We present a modelling approach for transmission and population dynamics of human T-cell lymphotropic-virus-type-I (HTLV-I) infection. A steady-state analysis of the model was used to estimate transmission rates for males and females. The rate of heterosexual transmission was 2.7 times higher if the carrier was male. A dynamic transmission model was developed and used to study the impact of different intervention measures in the Jamaican population. Interventions concerning horizontal (heterosexual) transmission exceeds the effect of breaking vertical (mother-to-child) transmission, although breast feeding also has an important impact on the total number of infected individuals. (C) 1996 Wiley-Liss, Inc.

Resume Les donnees epidemiologiques disponibles en France sont des donnees de prevalence, de depistage, hospitalieres et des donnees issues de la surveillance du SIDA. L'ensemble de ces donnees permet d'analyser les tendances de l'epidemie a VIH, sans pouvoir quantifier precisement l'importance actuelle des nouvelles contaminations. L'epidemie dans la population heterosexuelle n'est pas recente, mais la progression de l'infection y a ete plus lente que dans les autres groupes. Depuis 1990, la progression est par contre un peu plus forte, les heterosexuels sont donc de plus en plus representes parmi les cas de Sida ou parmi les seropositifs depistes. Cependant, la population heterosexuelle reste beaucoup moins touchee que les populations homosexuelle ou toxicomane. L'extension future de l'epidemie depend des interactions entre la population heterosexuelle et les groupes les plus touches, de l'evolution de l'infection dans ces groupes et des comportements et des pratiques a risque chez les heterosexuels. La frequence faible des pratiques et des comportements a risque chez les heterosexuels permet de predire que l'epidemie ne sera jamais explosive dans ce groupe en France.

Though the number of HIV/AIDS cases is relatively small in Japan, it has been increasing steadily especially among Japanese male. Nearly half of all HIV infections was transmitted through the transfusion of HIV-infected blood products. However, new infections have been occurring mainly through heterosexual transmission. By the end of June 1996, cumulative total of 1, 312 AIDS cases and 3, 758 HIV infections are reported. Of 682 AIDS cases, excluding those infected through the transfusion of infected blood products, heterosexual transmission accounts for 39%, homosexual/bisexual transmission accounts for 30%, the sharing of HIV-infected injection equipment by drug users accounts for 0.9% and mother-to-child transmission accounts for 1%. Of 1, 890 HIV infections, excluding those infected through blood products, heterosexual transmission, homosexual/bisexual transmission, injecting drug use and mother-to-child transmission accounts for 50%, 21 %, 0.6%, 0.6% respectively. HIV infections have been reported from all prefectures and most infected individuals now mention Japan as the place where transmission took place. Japanese National AIDS Program consists of six areas ; health care, counseling system, HIV testing, research, education and international cooperation. In 1996, the Government puts particular emphasis on improvement of health care for those who are infected. J Epidemiol, 1996 ; 6 : S133-S137.

Background: Although modification of behavioral practices among human immunodeficiency virus (HIV)-affected patients is important in decreasing HIV disease transmission, the knowledge, attitude, and perception studies about HIV infection rarely include persons living with HIV/acquired immuno deficiency syndrome (AIDS). Aims: To assess knowledge, attitude, and perceptions of persons living with HIV/AIDS for the disease and other epidemiological aspects. Materials and Methods: One-hundred and fifty consecutive persons living with HIV/AIDS were enrolled for this questionnaire-based cross-sectional, descriptive study. Results: These 150 patients comprised 93 men and 57 women, aged between 14 and 78 (mean 37.13) years. The majority, 112 (74.67%) patients were between 20 and 50 years of age and 116 (77.3%) patients were either illiterate or high-school dropouts. Drivers, laborers, and self-employed comprised 69 (74.2%) patients among affected males. Only 129 (86%) respondents had heard about HIV/AIDS and knew about its heterosexual transmission. Ninety-eight (65.3%) respondents were aware of disease transmission from infected blood or needle pricks. Interestingly, 106 (70.7%) respondents were aware of the importance of using condom in preventing disease transmission. Television/radio was the most common sources of information for 135 (90%) patients. Nearly, 69% respondents disfavored disclosing their disease to friends/colleagues fearing stigmatization. Conclusions: Information, education, and communication activities are imperative to educate persons living with HIV/AIDS about life-long nature of the disease, modes of its transmission, and significance of preventive measures to bridge the gaps in their knowledge. While improvement in individual economic status, education, and health services remains highly desirable, mass media can play a pivotal role in creating awareness among masses.

Heterosexual transmission of HIV from men to women is the main route of contamination by this agent worldwide. This mode of transmission involves the contact between infected semen and healthy female genital mucosa, and then the crossing of cell-free or cell-associated viruses through the mucosa. The mechanisms involved in HIV transmission from men to women as well as the role of seminal plasma in selective transmission of R5-tropic viruses stay partially unknown. During the course of my PhD we visualized the crossing of cell-associated and cell-free virus through the endocervical genital mucosa. Initially, the study focused on the transmigration of infected immune cells through an in vitro model of endocervical mucosa, as well as on the role of seminal plasma in HIV transmission and selection of R5-tropic strains. Afterwards, we developed a fluorescent, replicative competent, infectious chimeric virus allowing its detection by confocal microscopy after several replication cycles. After contact of the endocervical mucosa with X4- or R5-tropic chimeric viruses, we visualized by confocal microscopy the infection of endocervical epithelial cells and the transmission of HIV to immune cells placed in the basal compartment. The use of a mathematical model allowed standardizing and quantifying the detection of infected cells in the mucosa. My PhD work describes as a first step the importance of the crossing of cell-associated HIV particles in the heterosexual transmission, as well as the involvement of seminal plasma in the selection of R5-tropic strains. Moreover, the virological model developed herein allows the direct visualization of HIV transmission through the female genital mucosa. I have thus demonstrated that it is possible to localize and quantify viral particles within the mucosa. This virological tool help to better understand the mechanisms involved in HIV heterosexual transmission and the selection of R5-tropic strains, La transmission hétérosexuelle de HIV de l’homme vers la femme est le principal mode de contamination dans le monde. Il implique la mise en contact du sperme infecté avec la muqueuse génitale féminine saine, puis le passage du virus libre ou associé aux cellules à travers la muqueuse. Les mécanismes impliqués dans la transmission de HIV de l’homme vers la femme ainsi que l’impact du plasma séminal sur la transmission sélective des virus à tropisme R5 sont encore mal connus. Au cours de mon séjour doctoral nous avons visualisé le passage du virus associé aux cellules ainsi que du virus libre à travers la muqueuse génitale endocervicale. Dans un premier temps l’étude s’est focalisée sur la transmigration de cellules immunitaires infectées par HIV à travers un modèle in vitro de muqueuse endocervicale reconstruite, ainsi que sur le rôle du plasma séminal dans la transmission de HIV et la sélection des virus à tropisme R5. Par la suite, un virus chimérique fluorescent, réplicatif et infectieux, permettant sa détection par microscopie confocale sur plusieurs cycles de réplication, a été développé. Après mise en contact de ce virus chimérique, à tropisme X4 ou R5, avec la muqueuse endocervicale, nous avons visualisé par microscopie confocale l’infection des cellules épithéliales endocervicales et la transmission de HIV à des cellules immunitaires disposées au pôle basal. L’utilisation d’un modèle mathématique nous a permis de standardiser et quantifier la détection de cellules infectées dans la muqueuse. Mes travaux de thèse décrivent dans un premier temps l’importance du passage de HIV associé aux cellules dans la transmission hétérosexuelle, ainsi que l’implication du plasma séminal dans la sélection des virus à tropisme R5. De plus, le modèle virologique développé permet de visualiser directement la transmission hétérosexuelle de HIV à travers la muqueuse génitale féminine. J’ai ainsi démontré qu’il est possible de visualiser directement, de localiser et de quantifier la présence du virus au sein de la muqueuse. Cet outil virologique permettra d’approfondir les connaissances et la compréhension des mécanismes impliqués dans la transmission hétérosexuelle de HIV et dans la sélection des virus à tropisme R5

The molecular epidemiology of HIV-1 in Brazil is complex and heterogeneous because several subtypes co-circulate with some important regional differences. This study evaluated HIV-1 subtypes amongst pregnant women living in the metropolitan area and in the interior cities from central western Brazil. From June 2008 to June 2010, 86.9% of confirmed cases of HIV-1 infection amongst pregnant women (172 out of 198 cases) were recruited in Goiania/Goias state. The HIV-1 pol gene was sequenced after nested-PCR. HIV-1 subtypes were assigned by REGA, phylogenetic, and bootscan analyses. The median age of participants was 26 years (15–41 years range); 58.7% of participants were diagnosed during prenatal care and 51.7% of participants came from >50 interior cities within Goias state. Amongst the 131 HIV-1 pol sequences, 64.9% were subtype B, 13.0% were BF1 recombinant, 11.4% were subtype C, 7.6% were subtype F1, and 2.3% were BC recombinant. According to the HIV-1 diagnosis date (1994–2010), a significant increase in subtype C and a decrease of BF1 mosaics were observed over time. All subtype C patients lived in interior cities where the highest prevalence of subtype C outside southern Brazil was observed (18.4%). Phylogenetic analysis revealed multiple independent introductions of the Brazilian subtype C clade from the southern/ southeastern regions of Brazil. The HIV-1 epidemic in women from central western Brazil infected by the heterosexual route is characterized by an unexpectedly high prevalence of subtype C viruses highly related to those circulating in southern/southeastern Brazil. These findings highlight the importance of molecular surveillance programs outside large metropolitan regions in Brazil.

HIV is a master at evading the human immune system. Every day, every single base-pair changes, making the virus virtually unrecognizable. This massive diversity in HIV strains makes vaccine development challenging because the optimal target is ever-changing. HIV vaccine design has focused on conserved regions of the virus, but these are usually tucked away inside the virus, protecting them from immune cells. In a recent paper, Redd and colleagues demonstrated that previously transmitted HIV strains are preferentially selected during heterosexual transmission, opening the door to new avenues of vaccine design. In a study among couples followed in the Rakai Community Cohort Study in Uganda between 1994 and 2002, interhost and intrahost HIV diversity was analyzed by using HIV sequencing. The authors were able to compare the diversity within an individual over time and identify the strain with which his or her partner was infected. The diversity was greater intrahost than interhost. Further, for the majority of couples, the newly infected partner’s HIV strain was more closely related to HIV found earlier in the infectious partner as compared with those strains circulating at the time of infection. The authors’ findings suggest that, at a population level, ancestral strains of HIV are preferentially transmitted compared with contemporary circulating strains. This work by Redd et al. has important implications for HIV prevention, specifically HIV vaccine development. Once it is confirmed that ancestral strains are preferentially transmitted, further studies can identify molecular determinants for HIV transmission, and vaccine development can focus on a narrower range of targets. A. D. Redd et al . , Previously transmitted HIV-1 strains are preferentially selected during subsequent sexual transmissions. J. Infect. Dis . 206 , 1433–1442 (2012). [[Abstract]][1] [1]: http://jid.oxfordjournals.org/content/206/9/1433.abstract

Human papillomavirus (HPV) 16 and 18 are found to be involved in 80% of anal cancers. Two vaccines against HPV infections are currently available, and vaccination policies aim to decrease mainly, incidence of cervical cancers. Moreover, an impact of HPV vaccination on the incidence of anal cancer can also be expected. Our aim was to assess the potential benefits of HPV vaccination on the occurrence of female anal cancer in France. We developed a dynamic model for the heterosexual transmission of HPV and its progression to anal cancer in women. The model was calibrated using French data of anal cancer incidence. Considering vaccine coverage observed at the launch of vaccination campaign in France, reductions of 55 and 85% in the incidence of anal cancers due to HPV 16/18 are to be expected in French women 30 and 50 years after vaccine introduction, respectively. In case of a significant decrease in vaccine coverage, a dramatic reduction in the impact of HPV vaccination on female anal cancers would be observed. The number of anal cancer cases in French women is therefore expected to decrease significantly in 30 years, assuming sustained HPV vaccine coverage. Key words: Dynamic model, human papillomavirus, vaccine, anal cancer.

The latest Portuguese report from the national monitoring center of sexually transmitted diseases (CVEDT, 2009) states that the total number of cumulative cases of HIV/AIDS was about 35 thousand with about 15 thousand of these being cases of AIDS. From the analysis of the distribution of the cases of AIDS according to the transmission categories, it appears that 40% are cases associated with heterosexual transmission. In fact, statistics suggest that the cases of AIDS confirm the epidemiological pattern recorded annually since 2000, that is, there is a proportional increase in the number of cases of heterosexual transmission.

Sexual transmission is the most common route of spread of human immunodeficiency virus (HIV), with heterosexual transmission of HIV infection accounting for 90% of those infected in 1992 and over 75% of the 10–12 million of those infected to date worldwide. Yet, heterosexual transmission is poorly understood. Since HIV can be transmitted from HIV-infected people who are asymptomatic as well as from those who have the acquired immunodeficiency syndrome (AIDS), we must better define the potential for transmission of HIV from HIV-infected individuals as well as the factors which influence the susceptibility of HIV-uninfected individuals.

In order to describe the changing patterns of risk factors for HIV-1 transmission of patients using hospital services at an AIDS referral centre in Porto Alegre, southern Brazil, data on demographic characteristics, referral patterns and risk factors at time of first presentation were collected prospectively on 405 patients between October 1985 and September 1991. Overall HIV-related patient workload increased during the study period, as did the proportion of infected female patients seen (P0.05). Of all patients, 147 (36%) presented with symptomatic HIV disease and 77 (19%) presented with an AIDS defining condition; men were more likely to present with symptomatic disease than women. Approximately 156 (44%) of men were self-referred compared with 4 (8%) of the women (P0.0001). Of the 357 infected men, 82 (23%) were bisexuals; of the 26 heterosexually infected women, 7 (24%) had bisexual male partners. These data suggest the increasing importance of heterosexual HIV transmission in this hitherto 'low' prevalence area, with male bisexuals constituting an important route through which heterosexual females are being infected in this area. The data also suggest that heterosexual women in Southern Brazil do not perceive themselves to be at risk for HIV-1 infection.Unprotected homosexual intercourse and IV drug use were originally described as the predominant routes of HIV transmission in South America. Recent data, however, indicate that heterosexual transmission is becoming increasingly important in the region. With the goal of describing the changing patterns of risk factors for HIV-1 transmission, the authors collected prospectively data on demographic characteristics, referral patterns, and risk factors of patients at the time of first presentation to hospital services at an AIDS referral center in Porto Alegre, southern Brazil. The 357 male and 48 female patients presented over the period October 1985-September 1991. The overall HIV-related patient workload increased during the study period, as did the proportion of infected female patients. 44% of the men and 8% of women were self-referred. 36% of patients presented with symptomatic HIV disease and 19% with an AIDS-defining condition, with the men more likely than women to present with symptomatic disease. 23% of the infected men were bisexual; 24% of the heterosexually infected women had bisexual male partners. These findings suggest the importance of heterosexual HIV transmission in this area, with male bisexuals serving as an important route through which heterosexual females are being infected in the area. The data also suggest that heterosexual women in southern Brazil do not perceive themselves as being at risk for HIV-1 infection.

Background Injecting drug use continues to be a primary driver of HIV epidemics in many parts of the world. Many people who inject drugs (PWID) are sexually active, so it is possible that high-seroprevalence HIV epidemics among PWID may initiate self-sustaining heterosexual transmission epidemics. Methods Fourteen countries that had experienced high seroprevalence (

A local outbreak of infectious syphilis among heterosexual men and women was noted among residents of a National Health Services board in central Scotland in 2009. This is the first, and remains the only, such outbreak in Scotland reporting transmission in the heterosexual population. It was characterized by the young age of those infected. This highlights the need for increasing knowledge and awareness of syphilis infection among this group.

More than 7000 new HIV infections are documented each day worldwide. In this Perspective, we dissect new results from a large clinical trial showing that genital and plasma HIV-1 RNA loads predict the risk of heterosexual transmission and that genital tract viral RNA load does so independently of plasma viral load. Furthermore, beyond its defined study end points, this well-conducted trial identified new research directions that should be pursued in smaller intensive basic and translational studies.

Despite recent advances in testing and treatment, the incidence of HIV/AIDS in the United States has remained stagnant with an estimated 56,300 new infections every year. Women account for an increasing proportion of the epidemic. The vulnerability of women to HIV stems from both increased biologic susceptibility to heterosexual transmission and also the social, economic, and structural disadvantages they often confront. This review describes the main reasons for the increased vulnerability of U.S. women to HIV transmission with particular emphasis on specific high-risk groups including: non-Hispanic blacks, women who use drugs, women with a history of incarceration, and victims of intimate partner violence. Although behavioral approaches to HIV prevention may be effective, pragmatic implementation is often difficult, especially for women who lack sociocultural capital to negotiate condoms with their male partners. Recent advances in HIV prevention show promise in terms of female-initiated interventions. These notably include female condoms, non-specific vaginal microbicides, and antiretroviral oral and vaginal pre-exposure prophylaxis. In this review, we will present evidence in support of these new female-initiated interventions while also emphasizing the importance of advocacy and the political support for these scientific advances to be successful.

Human Immunodeficiency Virus-type 1 (HIV- 1) binds to CD4 and CCR5 receptors on target cells in the human female reproductive tract. We sought to determine whether reducing levels of messenger RNA (mRNA) transcripts that encode these receptors in female reproductive tract cells could protect mucosal tissue explants from HIV- 1 infection. Explants prepared from the endometrium, endocervix, and ectocervix of hysterectomy tissues from HIV-1 sero-negative women were exposed to nanoparticles containing CD4- and CCR5-specific short-interfering RNA (siRNA) sequences. Explants were then exposed two days later to HIV-1, and HIV-1 reverse transcripts were measured five days post-infection. Explants treated with nanoparticles containing CD4- and CCR5-specific siRNA showed reduced levels of CD4 and CCR5 transcripts, and significantly lower levels of HIV-1 reverse transcripts compared to those treated with an irrelevant siRNA. In female reproductive tract explants and in peripheral blood cell cultures, siRNA transfection induced the secretion of IFN-alpha (IFN-α), a potent antiviral cytokine. In female mice, murine-specific Cd4-siRNA nanoparticles instilled within the uterus significantly reduced murine Cd4 transcripts by day 3. Our findings demonstrate that siRNA nanoparticles reduce expression of HIV-1 infectivity receptors in human female reproductive tract tissues and also inhibit HIV-1 infection. Murine studies demonstrate that nanoparticles can penetrate the reproductive tract tissues in vivo and silence gene expression. The induction of IFN-α after siRNA transfection can potentially contribute to the antiviral effect. These findings support the therapeutic development of nanoparticles to deliver siRNA molecules to silence host cell receptors in the female reproductive tract as a novel microbicide to inhibit mucosal HIV-1 transmission.

The HIV epidemic in Eastern Europe has continued to evolve since the early 1980s, and it is now one of the fastest growing in the world. From 1987 through 1995, the number of people living with HIV in the region grew slowly, and transmission was predominantly through male-to-male sex. The situation changed dramatically in 1998, when the number of newly reported cases of HIV among injecting drug users began growing explosively. Since 2002, there has also been a gradual increase in the percentage of cases reported as being heterosexually transmitted, although many of the individuals infected also practiced unsafe injecting behavior. Ignorance of one’s HIV status, particularly for risk-group members, represents a major challenge for the countries of Eastern Europe. Other significant challenges include ensuring equitable access to HIV treatment and making key prevention interventions available, including needle- and syringe-exchange programs and opioid-substitution therapy.

This paper focuses on heterosexual transmission the largest and fastest growing component of HIV spread. Its properties associated risk factors and the effects of societal context on these factors are reviewed. The methodological difficulties involved in establishing causal links between potential risk factors and HIV transmission and in evaluating the efficacy and population impact of alternative prevention and control strategies are summarized and a consideration of available strategies for the prevention and control of heterosexually transmitted HIV is outlined. (excerpt)

Os autores historiam a evolução da epidemia de AIDS no Brasil do ponto de vista da construção de representações sociais acerca dos segmentos envolvidos na transmissão da doença. Enfatizam a necessidade de desmistificar a correlação simplista AIDS- transmissão homossexual. Procuram retirar do relativo esquecimento o papel dos usuários de drogas injetáveis e da transmissão heterossexual na disseminação da doença, "segmentos" cuja relevância epidemiológica, crescente em nosso meio, não se tem feito acompanhar da devida atenção, seja por parte dos meios de comunicação, seja pelos órgãos formuladores de políticas de saúde. The authors report on the evolution of the AIDS epidemic in Brazil from the point of view of the construction of social representations about "risk groups" involved in the spread of the disease. They emphasize the need to demystify the immediate correlation between AIDS and homosexual transmission. They highlight the role of intravenous drug users and of heterosexual transmission in new AIDS cases in Brazil - groups and behaviours that are not included in the priorities of local health authorities.

INTRODUÇÃO: A transmissão do HIV e de outras doenças transmissíveis, de pessoa a pessoa, pode ser associada à mobilidade humana. Este trabalho avaliou a incidência de doenças oportunistas transmissíveis entre os casos de AIDS, nos municípios da faixa de fronteira brasileira. MÉTODOS: Os municípios da faixa de fronteira brasileira foram agrupados em três regiões culturais; foram consideradas as notificações feitas ao Ministério da Saúde, entre 1990 e 2003, que tenham sido feitas com os critérios de definição CDC adaptado, Rio de Janeiro/Caracas e óbito; as doenças oportunistas detectadas foram agrupadas de acordo com o tipo de transmissão: 1) inalação do agente; 2) ingestão de água/alimento contaminado e 3) contato interpessoal. A análise descritiva considerou regiões culturais, anos de escolaridade, categoria de transmissão, sexo e faixa etária. RESULTADOS: Houve diferentes padrões de incidência de AIDS nos grupos de doenças oportunistas em cada região cultural. A região extremo-sul apresentou a maior incidência de AIDS; o número de casos de AIDS do sexo feminino foi maior na categoria heterossexual; o número de casos de AIDS do sexo masculino foi maior entre usuários de drogas injetáveis; as doenças transmitidas pelo contato interpessoal foram as mais frequentes, destacando a incidência de monilíases; a tuberculose e a pneumonia foram as mais frequentes dentre as doenças transmitidas pela inalação do agente; as doenças transmitidas pela ingestão de água/alimentos contaminados mostraram um padrão de incidência estável. CONCLUSÕES: A fronteira brasileira é um espaço geográfico importante e heterogêneo; o enfrentamento da AIDS deve reconhecer as diferentes geografias culturais. INTRODUCTION: Person-to-person transmission of HIV and other communicable diseases may be associated with human geographic mobility. This article evaluated the incidence of transmissible opportunistic diseases among AIDS cases that had been reported by municipalities in the Brazilian border area. METHODS: Brazilian border area municipalities were grouped into three cultural regions; the source data was AIDS cases registered with the Ministry of Health from 1990 to 2003, which were classified according to CDC-adapted, Rio de Janeiro/Caracas and death criteria; detected communicable opportunistic diseases were categorized into groups according to transmission: 1) inhalation agent; 2) contaminated water and/or food ingestion, and 3) interpersonal contact. The descriptive evaluation considered cultural region, years of schooling, sex and age group. RESULTS: Different AIDS incidence patterns were observed among groups of opportunistic diseases in each cultural region. The extreme southern region showed the greatest incidence of AIDS; the absolute incidence of female cases was greatest in the category of heterosexual transmission; the number of male cases was greatest among intravenous drug users; transmission was most frequent in the interpersonal contact group, particularly incidences of candidiasis; tuberculoses and pneumonias were most frequent in the inhalation agent transmission group; the contaminated water/food ingestion transmission group showed an unchanged pattern of absolute incidence. CONCLUSIONS: The Brazilian border area is a very important and heterogeneous geographic phenomenon; AIDS programs must recognize different cultural geographies.

We analyzed HLA-G 3777G > C, HLA-G 14 bp deletion/insertion and HLA-G*0105N polymorphisms in HIV-positive white adult participants, infected through horizontal heterosexual transmission, and unexposed uninfected individuals, all from north eastern Italy. We report a new association between the HLA-G*0105N allele and HIV infection in adult white female participants, being HLA-G*0105N null allele correlated with an augmented risk (odds ratio = 4.35, 95% confidence interval = 1.38-18.07, P = 0.005) for HIV infection.

This second edition of the book provides up-to-date information on new drugs, new proven HIV prevention interventions, a new chapter on positive prevention, and current HIV epidemiology. This definitive text covers all aspects of HIV/AIDS in South Africa, from basic science to medicine, sociology, economics and politics. It has been written by a highly respected team of South African HIV/AIDS experts and provides a thoroughly researched account of the epidemic in the region.

Objective To estimate the risk and probability of heterosexual transmission of HIV-1 from infected people taking combined antiretroviral treatment. Design Cross sectional and prospective cohort studies. Setting HIV clinic in Madrid, Spain. Participants Stable heterosexual couples with one partner with HIV-1 infection (index partner) and the other reporting this sexual relationship as the only risk exposure. Main outcome measures HIV seroprevalence in non-index partners at enrolment and seroconversions in follow-up according to antiretroviral treatment taken by the index partner. Results In 476 couples in which the index partner was not taking antiretroviral treatment, HIV seroprevalence at enrolment in non-index partners was 9.2% (n=44), whereas in 149 couples in which the index partner was taking combined antiretroviral therapy no partner was infected (P

Results The HIV epidemic started in SETIF in 1986 with the first diagnosed AIDS cases. The number of cases slowly but steadily increased, to reach, by 2009, 152 cases. The median age of infected persons was 39,77 years. 40.8% were WOMEN; The most frequent mode of transmission is sexual (76,9% of all cases; with mainly heterosexual transmission 77.9 percnt; with a strong correlation to travel and migration 37.20%). the proportion of persons diagnosed late (within 12 months before AIDS diagnosis) was 82,3%; 91.4% of married men (36) have sexual relationships outside marriage as compared to 0.0% of married women(27). We report also 13.60% discordant couples among married patients, Among documented HIV-positive mothers (36), their children were screend in 61.10%, and 95.5% of them were seronegatif, 55,9% of all cases were treated with ARV. HIV/ AIDS deaths 36,2% decreased markedly from 2002, associated with the advent of HAART.

In Brazil, as elsewhere, the transmission of HIV has taken place above all else through sexual contacts. For a variety of reasons that have already been examined (see, for example, Chapters 1 and 4 in this volume), heterosexual transmission, in particular, has increased rapidly in recent years. At the same time, same-sex relations between men have nonetheless continued to be central to the epidemiology of AIDS in Brazil, accounting for nearly half of the total number of AIDS cases reported in the country as a whole. And although the relative importance of homosexual transmission, visa-vis heterosexual transmission, has fallen rapidly, the incidence of HIV infection, as well as cases of AIDS, among men who have sex with men in Brazil, have nonetheless continued to climb (Ministerio da Saude, 1992).

Living with aids: profile of hiv/aids patients in northwestern Parana, 1989-2005. Over the last 27 years of the AIDS epidemic, crucial changes have taken place in the trends of HIV transmission and in the disease's epidemiological profile. This study analyzed the profiles of people enrolled in the STD/AIDS Control Program of a regional health division in the state of Parana, Brazil, between 1989 and 2005. Data were collected from the regional database of the Notifiable Diseases Information System (SINAWN), at the Epidemiology Sector of the 14 th Regional Health Division. The studied variables were: patient gender, age, occupation and city of residence; how the disease was transmitted, date of diagnosis and notification; and date of death. During the study period, 241 AIDS cases were diagnosed in the region, with a 53% concentration in the county seat; however, in six towns in the region, there were no notifications in the 17 years of the study, which can mean a real absence of cases or sub-notification/exportation of cases. The cases occurred primarily in men, between the ages of 25 and 49, through sexual transmission. However, in the period between 2001 and 2005, an increase was observed in the number of infected women, with a 1.6 male:female ratio; also, there was an increase in heterosexual transmission, affecting homemakers and self-employed individuals. The study detected an expressive number of cases with epidemiological notification of diseases resulting from AIDS on the date of diagnosis or soon thereafter, suggesting the late identification of the disease on individuals who were already in the terminal stages of the disease.

Background The human immunodeficiency virus (HIV) infectiousness of anal intercourse (AI) has not been systematically reviewed, despite its role driving HIV epidemics among men who have sex with men (MSM) and its potential contribution to heterosexual spread. We assessed the per-act and per-partner HIV transmission risk from AI exposure for heterosexuals and MSM and its implications for HIV prevention. Methods Systematic review and meta-analysis of the literature on HIV-1 infectiousness through AI was conducted. PubMed was searched to September 2008. A binomial model explored the individual risk of HIV infection with and without highly active antiretroviral therapy (HAART). Results A total of 62 643 titles were searched; four publications reporting per-act and 12 reporting per-partner transmission estimates were included. Overall, random effects model summary estimates were 1.4% [95% confidence interval (CI) 0.2–2.5)] and 40.4% (95% CI 6.0–74.9) for per-act and per-partner unprotected receptive AI (URAI), respectively. There was no significant difference between per-act risks of URAI for heterosexuals and MSM. Per-partner unprotected insertive AI (UIAI) and combined URAI–UIAI risk were 21.7% (95% CI 0.2–43.3) and 39.9% (95% CI 22.5–57.4), respectively, with no available per-act estimates. Per-partner combined URAI–UIAI summary estimates, which adjusted for additional exposures other than AI with a ‘main’ partner [7.9% (95% CI 1.2–14.5)], were lower than crude (unadjusted) estimates [48.1% (95% CI 35.3–60.8)]. Our modelling demonstrated that it would require unreasonably low numbers of AI HIV exposures per partnership to reconcile the summary per-act and per-partner estimates, suggesting considerable variability in AI infectiousness between and within partnerships over time. AI may substantially increase HIV transmission risk even if the infected partner is receiving HAART; however, predictions are highly sensitive to infectiousness assumptions based on viral load. Conclusions Unprotected AI is a high-risk practice for HIV transmission, probably with substantial variation in infectiousness. The significant heterogeneity between infectiousness estimates means that pooled AI HIV transmission probabilities should be used with caution. Recent reported rises in AI among heterosexuals suggest a greater understanding of the role AI plays in heterosexual sex lives may be increasingly important for HIV prevention.

Background: Intravaginal practices are commonly used by women to manage their vaginal health and sexual life. These practices could, however, affect intravaginal mucosal integrity. The objectives of this study were to examine evidence for associations between: intravaginal practices and acquisition of HIV infection; intravaginal practices and vaginal infections; and vaginal infections and HIV acquisition. Methodology/Principal Findings: We conducted a systematic review of prospective longitudinal studies, searching 15 electronic databases of journals and abstracts from two international conferences to 31(st) January 2008. Relevant articles were selected and data extracted in duplicate. Results were examined visually in forest plots and combined using random effects meta-analysis where appropriate. Of 2120 unique references we included 22 publications from 15 different studies in sub-Saharan Africa and the USA. Seven publications from five studies examined a range of intravaginal practices and HIV infection. No specific vaginal practices showed a protective effect against HIV or vaginal infections. Insertion of products for sex was associated with HIV in unadjusted analyses; only one study gave an adjusted estimate, which showed no association (hazard ratio 1.09, 95% confidence interval, Cl 0.71, 1.67). HIV incidence was higher in women reporting intravaginal cleansing but confidence intervals were wide and heterogeneity high (adjusted hazard ratio 1.88, 95% Cl 0.53, 6.69, I-2 83.2%). HIV incidence was higher in women with bacterial vaginosis (adjusted effect 1.57, 95% Cl 1.26, 1.94, I-2 19.0%) and Trichomonas vaginalis (adjusted effect 1.64, 95% Cl 1.28, 2.09, I-2 0.0%). Conclusions/Significance: A pathway linking intravaginal cleaning practices with vaginal infections that increase susceptibility to HIV infection is plausible but conclusive evidence is lacking. Intravaginal practices do not appear to protect women from vaginal infections or HIV and some might be harmful.

Three SIVMne-infected female pigtailed macaques (Macaca nemestrina) were mated with two SIV-negative males. The females exhibited signs of SAIDS and SIVMne was readily isolated from peripheral blood mononuclear cells (PBMC). Both males became infected with SIVMne, developed SAIDS, and died. This is the first documented case of the transmission of SIVMne between adult macaques housed together. Although transmission through scratching or biting cannot be ruled out, heterosexual transmission appears the most likely mode of SIVMne transmission in this study.

In Sweden, cases of both HIV infection and AIDS are registered. By looking at the extent to which people who develop AIDS are already known to be HIV-infected, we can assess the coverage of the HIV registration. It was found that virtually all those who were infected by injecting themselves with drugs, blood transfusions, blood products or congenitally were already known to be infected when AIDS developed. However, when homosexual or heterosexual transmission had occurred, 20.5% and 33.3% respectively of these cases were not previously known. Working with different assumptions regarding the development of the epidemic, we find that the true number of sexually infected people is roughly twice the number of registered HIV-infected people in these groups. Our estimate is that between 3300 and 6300 people were infected with HIV in Sweden up till the end of 1990.

PURPOSE OF REVIEW: Over the past several years one segment of the complex field of HIV transmission dynamics - heterosexual networks - has dominated theoretical and empirical investigation. This review provides an overview of recent work on HIV risks and networks with a focus on recent findings in heterosexual network dynamics. RECENT FINDINGS: Qualitative (ethnographic) assessments have demonstrated the heterogeneity and complexity of heterosexual connections particularly in Africa where tradition official polygamy and unofficial multiperson arrangements have lead to concurrency of sexual partnerships. A large quantitative study on Likoma Island Malawi demonstrated the considerable interlocking sexual connections that arise from a high-concurrency sexual setting even with a low average number of partnerships (low degree) of long duration. Such settings as suggested by ethnographic studies may be common in Africa and coupled with newer information about transmissibility during acute and early infection may provide a plausible explanation for endemic transmission and possibly for rapid HIV propagation. SUMMARY: Recognition of high-concurrency low-degree networks is an important development for understanding HIV transmission dynamics. Their relevance to heterosexual transmission and possible extension to other epidemiologic settings reinforces the heterogeneity and complexity of HIV transmission dynamics.

International audience; OBJECTIVES: A synergy between HIV and herpes simplex virus type 2 (HSV-2) infections has been reported in observational studies. The objectives of this study were to estimate the per-sex-act female-to-male transmission probabilities (FtoMTPs) of HIV and HSV-2, the effect of each infection on the FtoMTP of the other and the effect of male circumcision on these FtoMTPs. DESIGN: We used longitudinal data collected during the male circumcision trial conducted in Orange Farm (South Africa). METHODS: Results were obtained by specific mathematical modeling of HIV and HSV-2 statuses of the men as functions of their sexual behavior and male circumcision status. The model took into account an estimation of the HIV and HSV-2 statuses of each of their female partners. Confidence intervals (CI) were estimated using a bootstrap resampling method. RESULTS: The HIV and HSV-2 FtoMTPs, during an unprotected sexual contact for an uncircumcised male in the absence of the other virus in both partners, were 0.0047 (95% CI: 0.0014-0.017) and 0.0067 (95% CI: 0.0028-0.014), respectively. HSV-2 in either partner increased HIV FtoMTP with a relative risk (RR) of 3.0 (95% CI: 1.01-7.3). Conversely, HIV in either partner increased HSV-2 FtoMTP (RR= 2.5; 95% CI: 1.1- 6.3). Male circumcision significantly decreased these probabilities with RRs of 0.24 (95% CI: 0.11-0.44) and 0.59 (95% CI: 0.36-0.91), respectively. CONCLUSION: This study gave the first estimates of HSV-2 per-sex-act FtoMTPs in Africa. It demonstrated a synergy between HIV and HSV-2 infections and a protective effect of male circumcision on HSV-2 acquisition by males.