Heterosexual Transmission Of Human Immunodeficiency Virus Research Articles

2-Hydroxyisovalerate Is Produced During Bacterial Vaginosis and Boosts HIV Infection in Resting T Cells.

Human immunodeficiency virus (HIV) infection and the ensuing acquired immunodeficiency syndrome (AIDS) disproportionally affect young women, yet understanding of the factors promoting heterosexual transmission in the female genital tract is limited. Colonization with highly diverse, Lactobacillus-deficient communities (HDCs) increases a woman's risk of acquiring HIV-1 compared with colonization with Lactobacillus-dominated low diversity communities (LDCs). The polymicrobial nature of these communities has made it challenging to elucidate the microbial mechanisms responsible for modulating HIV susceptibility. Here, we analyzed conserved changes in small-molecule metabolites present in the cervicovaginal lavage fluid collected from women colonized with HDCs and LDCs with the goal of identifying possible chemicals influencing HIV infection. As in previous studies, we found that the catabolite of the branched-chain amino acid valine, 2-hydroxyisovalerate (2-HV), was a consistent component of dysbiotic HDC microbiota. Effects of 2-HV on HIV infection were assessed. In experimental infections with HIV, treatment with 2-HV increased infections of resting CD4+ T cells. To understand bacterial production of 2-HV in more detail, we cultured purified HDC and LDC bacteria and used mass spectrometry to identify two HDC bacteria that synthesize high levels of 2-HV. In contrast, protective vaginal Lactobacilli did not produce high levels of 2-HV. A genomic analysis of genes encoding 2-HV synthetic pathways showed a correlation between high-level production of 2-HV and pathways for synthesis of the immediate precursor 2-ketoisovalerate. Thus, 2-HV is a candidate mediator linking vaginal microbiome structure and heterosexual HIV transmission in women.

Parenting Desires Among Individuals Living With Human Immunodeficiency Virus in the United States.

BackgroundIn 1988, 1 of 3 women (W) and heterosexual men living with human immunodeficiency virus (HIV) reported wanting children, but little is known about parenting desires of men who have sex with men (MSM) living with HIV. We examined parenting desires among persons initiating antiretroviral therapy (ART).MethodsOf 1809 participants in the AIDS Clinical Trials Group (ACTG) Study 5257, 1425 W aged ≤45 years or men completed questionnaires about parenting desires at baseline and 96 weeks after initiating ART. Self-reported desires for children in the future (yes/unsure vs no) and associations between baseline sociodemographics and parenting desires at 96 weeks were examined using multivariable logistic regression, overall and within subgroups.ResultsThe 1425 participants were as follows: 36% white, 39% black, 22% Hispanic; median age 36 (interquartile range, 28–44); 70% MSM, 13% men reported sex only with W (MSW), 17% W. At baseline, 42% may want children in the future (42% MSM, 37% MSW, 43% W); at 96 weeks, 41% may want children (41% MSM, 37% MSW, 43% W). At follow-up, approximately 10% of responses changed in each direction. In multivariable analyses, education greater than high school, <30 years, and having no children were significantly associated with future parenting desires among all subgroups. Among MSM, being black was associated with desiring children.ConclusionsApproximately 40% of MSM, W, and MSW with HIV may want children, both at baseline and 96 weeks after ART initiation. These results highlight the need to regularly assess parenting goals, provide access to comprehensive reproductive services, and address prevention of vertical and heterosexual HIV transmission.

Careful Conversations and Careful Sex: HIV Posttesting Experiences Among African American Men in Rural Florida.

In the United States, black/African American (black) men bear the greatest burden of human immunodeficiency virus (HIV), accounting for 42% of new HIV infections in 2012 despite being 6% of the population. In Florida, heterosexual HIV transmission has increased among black men. Few studies have examined HIV testing experiences for black heterosexual men (BHM) in the rural South. This study describes the post-HIV-testing trial experiences of BHM in rural Florida. We conducted 12 focus groups (4-7 participants per group) in 3 rural Florida counties with BHM who participated in a larger randomized HIV testing trial. Interviews were professionally transcribed and data were analyzed using NVivo 10. The qualitative analysis was informed by the strengths perspective (ie, emphasis on abilities rather than risks) and used a thematic analytical approach. Sixty-seven men participated (median age 41.5 years); 39 (58%) earned a monthly income of less than $500, 38 (57%) attained education through high school or higher, 37 (55%) were unmarried, and 40 (60%) reported practicing monogamy; all who tested for HIV were negative for HIV. We identified 3 main themes based on self-reported actions: (1) risk reduction (eg, more consistent condom use, fewer sex partners), (2) sexual health communications with sex partners (eg, negotiating HIV testing with sex partners, getting to know partners better), and (3) health communications with peers and family (eg, disclosing test results, encouraging others to get tested). Among BHM, being in this HIV testing study facilitated increased protective behaviors and communications for HIV prevention. Interventions for BHM in rural areas warrant incorporating these strategies to encourage routine HIV testing.

Time to Improve the Global Human Immunodeficiency Virus/AIDS Care Continuum for Adolescents: A Generation at Stake.

Time to Improve the Global Human Immunodeficiency Virus/AIDS Care Continuum for Adolescents: A Generation at Stake.

Analysis of Social and Genetic Factors Influencing Heterosexual Transmission of HIV within Serodiscordant Couples in the Henan Cohort.

There is considerable variability between individuals in susceptibility to infection by human immunodeficiency virus (HIV). Many social, clinical and genetic factors are known to contribute to the likelihood of HIV transmission, but there is little consensus on the relative importance and potential interaction of these factors. Additionally, recent studies of several variants in chemokine receptors have identified alleles that may be predictive of HIV transmission and disease progression; however the strengths and directions of the associations of these genetic markers with HIV transmission have markedly varied between studies. To better identify factors that predict HIV transmission in a Chinese population, 180 cohabiting serodiscordant couples were enrolled for study by the Henan Center for Disease Prevention and Control, and transmission and progression of HIV infection were regularly measured. We found that anti-retroviral therapy, education level, and condom use were the most significant factors in determining likelihood of HIV transmission in this study. We also assessed ten variants in three genes (CXCL12, CCR2, and CCR5) that have been shown to influence HIV transmission. We found two tightly linked variants in CCR2 and CCR5, rs1799864 and rs1800024, have a significant positive association with transmission as recessive models (OR>10, P value=0.011). Mixed effects models showed that these genetic variants both retained significance when assessed with either treatment or condom use. These markers of transmission susceptibility may therefore serve to help stratify individuals by risk for HIV transmission.

Transmission of chimeric HIV by mating in conventional mice: prevention by pre-exposure antiretroviral therapy and reduced susceptibility during estrus

SUMMARYHeterosexual transmission accounts for the majority of new human immunodeficiency virus (HIV) cases worldwide. The current approach to investigate HIV heterosexual transmission in animals involves application of virus stock to the vaginal surface, a method that does not reproduce the physiological conditions of vaginal intercourse that influence the rate of transmission. We have previously described efficient infection of conventional mice using EcoHIV/NL4-3 and EcoHIV/NDK, chimeric HIV molecular clones constructed to express all HIV structural and regulatory genes except envelope, which is replaced by a rodent-tropic envelope gene. Here we investigated whether EcoHIV/NDK-infected male mice transmit virus to females during coitus, and the sensitivity of this transmission to HIV pre-exposure prophylaxis and the estrus state. Our general approach was to allow mating between EcoHIV/NDK-infected male mice and uninfected females for 1–7 nights. At 1–6 weeks after mating, mice were euthanized and virus burdens were measured by quantitative PCR (qPCR) amplification of HIV RNA or DNA in peritoneal macrophages, inguinal lymph node cells, spleen cells or vas deferens, or by ELISA for antibodies to HIV Gag. We found that 70–100% of female mice mated to EcoHIV/NDK-infected males acquired infection. Pericoital treatment of females with either 2′,3′-dideoxcytidine (ddC) or tenofovir largely prevented their EcoHIV/NDK infection by mating (P<0.05 and P<0.003, respectively). In males, T cells were dispensable for virus transmission. The rate of EcoHIV/NDK sexual transmission to females in estrus declined sharply (P=0.003) but their infection by injection was unaffected, indicating that the local environment in the female reproductive tract influences susceptibility to HIV. We conclude that this system of EcoHIV/NDK transmission during mouse mating reproduces key features of heterosexual transmission of HIV in humans and can be used to investigate its biology and control.

Racial/ethnic and gender differences among older adults in nonmonogamous partnerships, time spent single, and human immunodeficiency virus testing.

A higher frequency of nonmonogamy, due in part to lower marriage prevalence, may contribute to elevated human immunodeficiency virus (HIV)/sexually transmitted disease rates among older blacks. To examine race and gender differences in nonmonogamy, time spent single (i.e., not married or cohabiting), and HIV testing in older adults, we analyzed US population-based data from the 2005-2006 National Social Life, Health, and Aging Project for 2825 heterosexual participants ages 57 to 85 years. Blacks spent greater portions of their adult lives single than did Hispanics or whites and were far more likely to report recent nonmonogamous partnerships (23.4% vs. 10.0% and 8.2%). Among individuals reporting sex in the prior 5 years, nonmonogamous partnerships were strongly associated with time spent single during the period. Control for time spent single and other covariates reduced the association of black race with nonmonogamous partnerships for men, but increased it for women. Less than 20% reported ever testing for HIV; less than 6% had been recommended testing by a provider. Testing rates, highest in black men and white women, differed little by history of nonmonogamous partnerships within gender strata. Singlehood helps to explain higher nonmonogamous partnership rates in older black men but not in older black women. Older adults rarely receive or are recommended HIV testing, a key strategy for reducing heterosexual HIV transmission.

Prevention of vaginal SHIV transmission in macaques by a live recombinant Lactobacillus

AbstractMost human immunodeficiency virus (HIV) transmissions in women occur through the cervicovaginal mucosa, which is coated by a bacterial biofilm including Lactobacillus. This commensal bacterium has a role in maintaining a healthy mucosa and can be genetically engineered to produce antiviral peptides. Here, we report a 63% reduction in transmission of a chimeric simian/HIV (SHIVSF162P3) after repeated vaginal challenges of macaques treated with Lactobacillus jensenii expressing the HIV-1 entry inhibitor cyanovirin-N. Furthermore, peak viral loads in colonized macaques with breakthrough infection were reduced sixfold. Colonization and prolonged antiviral protein secretion by the genetically engineered lactobacilli did not cause any increase in proinflammatory markers. These findings lay the foundation for an accessible and durable approach to reduce heterosexual transmission of HIV in women, which is coitally independent, inexpensive, and enhances the natural protective effects of the vaginal microflora.

Neisseria gonorrhoeae and Chlamydia trachomatis among human immunodeficiency virus-infected women.

Neisseria gonorrhoeae and Chlamydia trachomatis among human immunodeficiency virus-infected women.

Intimate Partner Violence and HIV Infection Among Married Indian Women

Despite reductions in prevalence of human immunodeficiency virus (HIV) infection among the general population of India, women account for a rising percentage of all HIV cases with husbands' risk behavior described as the major source of women's infection. Intimate partner violence (IPV) has been described as being associated with heterosexual transmission of HIV to women in India and elsewhere. To assess the relationship between experiencing IPV and the occurrence of HIV infection in a nationally representative sample of married Indian women tested for HIV. The Indian National Family Health Survey 3 was conducted across all Indian states in 2005 through 2006. The nationally representative sample included 124,385 married women; analyses conducted in 2007 and 2008 were limited to 28,139 married women who provided IPV data and HIV test results via systematic selection into respective subsamples. Prevalence estimates of lifetime IPV and HIV infection were calculated and demographic differences assessed. Intimate partner violence was conceptualized as physical violence with or without sexual violence and then was further categorized as physical violence only vs physical and sexual violence. Regression models were used to estimate the odds ratios (ORs) and 95% confidence intervals (CIs) for HIV infection among Indian women based on experiences of IPV after adjusting for demographics and women's HIV risk behaviors. One-third of married Indian women (35.49%) reported experiencing physical IPV with or without sexual violence from their husbands; 7.68% reported both physical and sexual IPV, and 27.80% reported experiencing physical IPV in the absence of sexual violence. Approximately 1 in 450 women (0.22%) tested positive for HIV. In adjusted models, married Indian women experiencing both physical and sexual violence from husbands demonstrated elevated HIV infection prevalence vs those not experiencing IPV (0.73% vs 0.19%; adjusted OR, 3.92; 95% CI, 1.41-10.94; P = .01). Physical IPV alone was not associated with risk of HIV infection. Women's personal sexual risk behaviors were not associated with HIV infection. Among married Indian women, physical violence combined with sexual violence from husbands was associated with an increased prevalence of HIV infection. Prevention of IPV may augment efforts to reduce the spread of HIV/AIDS.

Engineering of a Human Vaginal Lactobacillus Strain for Surface Expression of Two-Domain CD4 Molecules

Women are at significant risk of heterosexually transmitted human immunodeficiency virus (HIV) infection, with the mucosal epithelium of the cervix and vagina serving as a major portal of entry. The cervicovaginal mucosa naturally harbors dynamic microflora composed predominantly of lactobacilli, which may be genetically modified to serve as a more efficient protective barrier against the heterosexual transmission of HIV. We selected a vaginal strain of Lactobacillus, L. jensenii 1153, for genetic modification to display surface-anchored anti-HIV proteins. Genomic sequencing analyses revealed that L. jensenii 1153 encodes several unique high-molecular-weight cell wall-anchored proteins with a C-terminal cell wall sorting LPQTG motif. In this report, we employed these proteins to express a surface-anchored two-domain CD4 (2D CD4) molecule in L. jensenii 1153. Our studies indicated that the C-terminal cell wall sorting signal LPQTG motif alone is insufficient to drive the surface expression of heterologous proteins, and the display of surface-anchored 2D CD4 molecules required native sequences of a defined length upstream of the unique C-terminal LPQTG cell wall sorting signal and the positively charged C terminus in a Lactobacillus-based expression system. The modified L. jensenii strain displayed 2D CD4 molecules that were uniformly distributed on bacterial surfaces. The surface-anchored 2D CD4 molecule was recognized by a conformation-dependent anti-CD4 antibody, suggesting that the expressed proteins adopted a native conformation. The establishment of this Lactobacillus-based surface expression system, with potential broad applicability, represents a major step toward developing an inexpensive yet durable approach to topical microbicides for the mitigation of heterosexual transmission of HIV and other mucosally transmitted viral pathogens.

Engineered VaginalLactobacillusStrain for Mucosal Delivery of the Human Immunodeficiency Virus Inhibitor Cyanovirin-N

Women are at significant risk of human immunodeficiency virus (HIV) infection, with the cervicovaginal mucosa serving as a major portal for virus entry. Female-initiated preventatives, including topical microbicides, are urgently needed to help curtail the HIV/AIDS pandemic. Here we report on the development of a novel, live microbicide that employs a natural vaginal strain of Lactobacillus jensenii engineered to deliver the potent HIV inhibitor cyanovirin-N (CV-N). To facilitate efficient expression of CV-N by this bacterium, the L. jensenii 1153 genome was sequenced, allowing identification of native regulatory elements and sites for the chromosomal integration of heterologous genes. A CV-N expression cassette was optimized and shown to produce high levels of structurally intact CV-N when expressed in L. jensenii. Lactobacillus-derived CV-N was capable of inhibiting CCR5-tropic HIV(BaL) infectivity in vitro with a 50% inhibitory concentration of 0.3 nM. The CV-N expression cassette was stably integrated as a single copy into the bacterial chromosome and resolved from extraneous plasmid DNA without adversely affecting the bacterial phenotype. This bacterial strain was capable of colonizing the vagina and producing full-length CV-N when administered intravaginally to mice during estrus phase. The CV-N-producing Lactobacillus was genetically stable when propagated in vitro and in vivo. This work represents a major step towards the development of an inexpensive yet durable protein-based microbicide to block the heterosexual transmission of HIV in women.

O-57: An in-vitro reconstructed vaginal mucosa integrating langerhans cells to evaluate the immuno-inflammatory potential of novel anti-HIV microbicides and spermicides

Heterosexual human immunodeficiency virus (HIV) transmission requires the dissemination of virus from the vaginal mucosa to T cell zones, potentially using Langerhans cells (LCs) as transporters. Repeated topical application of current vaginal spermicides and potential microbicides can increase the production of local inflammatory mediators leading to subclinical inflammation, which is associated with increased risk for HIV transmission. We assessed the effect of novel spermicidal and nonspermicidal anti-HIV microbicides on the production of mucosal cytokines, chemokines, and growth factors using an in vitro reconstructed vaginal mucosa integrating LCs.

Repeated Intravaginal Inoculation with Cell‐Associated Simian Immunodeficiency Virus Results in Persistent Infection of Nonhuman Primates

The goal of the present study was to develop a nonhuman primate model of intravaginal human immunodeficiency virus (HIV) transmission with cell-associated virus. Reproductively mature, cycling cynomolgus macaques with or without chemically induced, transient ulcers of the lower female reproductive tract repeatedly received challenge with a variable amount of in vitro simian immunodeficiency virus mac239-infected peripheral blood mononuclear cells. Persistent viremia was established with surprisingly few infectious lymphocytes containing physiologically relevant quantities of cell-associated virus. This model will be indispensable for the testing of vaccines and topical agents that are aimed toward the prevention of heterosexual transmission of HIV.

Prevalencia de VIH entre las personas de ocho ciudades españolas que se realizan la serología tras exposiciones heterosexuales, 1992-2003

The human immunodeficiency virus (HIV) epidemic in Spain was characterized throughout the first few years by the predominance of infections among injected drug users (IDU's), but everything currently points to a progressive predominance of sexual transmission. This study is aimed at describing the trend in HIV infection among several heterosexual populations groups and at characterizing the situations in which the infections occurred. Descriptive study of the individualls who had the test conducted for the first time at nine HIV diagnosis centres within the 1992-2003 period due to high-risk heterosexual exposures, not including injected drug users. A total of 47,870 individuals had serology performed during the period under study. The HIV prevalence among the population under study dropped from 3.2% to 1.0% (p< 0.001). Among the individuals with an HIV infected partners, the prevalence remained at around 10%, the male users of prostitution having dropped from 1.9% to 1.0% (p=0.049); among women involved in prostitution, from 1.4% to 0.7% (p=0.008); and among all other heterosexuals, having dropped from 1.6% to 1.0% among males (p=0.014) and from 1.1% to 0.7% among women (p=0.012). The results indicate advances in the control of heterosexual human immunodeficiency virus transmission, mainly among women, although it is necessary to still continue stressing prevention.

Heterosexual Transmission of HIV—29 States, 1999-2002

Worldwide, the majority of human immunodeficiency virus (HIV) infections result from heterosexual transmission. To characterize heterosexual transmission of HIV infections in the United States, CDC analyzed data for 1999-2002 from the 29 states that have met CDC standards for name-based HIV/acquired immunodeficiency syndrome (AIDS) reporting for > or =4 years. This report summarizes the results of that analysis, which indicated that heterosexually acquired HIV infections represented 35% of all new HIV cases; 64% of heterosexually acquired HIV infections occurred in females, and 74% occurred in non-Hispanic blacks. To decrease the number of new heterosexually acquired HIV infections, especially among certain minority populations, culturally targeted education and prevention programs should be provided, and barriers to HIV care and prevention services should be removed.

Modelling the social dynamics of a sex industry: its implications for spread of HIV/AIDS

A theoretical model is proposed for a community which has the structure of two classes (direct and indirect) of commercial sex workers (CSW), and two classes of sexually active male customers with different levels of sexual activity. The direct CSW’s work in brothels while the indirect CSW’s are based in commercial establishments such as bars, cafes, and massage parlours where sex can be bought on request and conducted elsewhere. Behaviour change and the resulting change of activity class occurs between the two classes of CSW’s and two classes of males under the setting of the proliferation of human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome epidemic and the subsequent intervention programmes. In recently years, this phenomenon has been observed in several countries in Asia. Given the lower levels of condom use and higher HIV prevalence of the indirect CSW’s, ascertaining the impact of this change in the structure of the sex industry on the spread of HIV is the main focus of this paper. The complete analysis of the disease-free model is given. For the full model, local analysis will be performed for the case of preferred mixing without activity class change, as well as the case with activity class change and restricted mixing. The basic reproduction number for the spread of epidemic will be derived for each case. Results of biological significance include: (i) the change of behaviour by the CSW’s has a more direct effect on the spread of HIV than that of the male customers; (ii) the basic reproduction number is obtained by considering all possible infection cycles of the heterosexual transmission of HIV which indicates the importance of understanding the sexual networking in heterosexual transmission of HIV; (iii) the social dynamics of the sex industry is not just a simple ‘supply and demand’ mechanism driven by the demand of the customers, hence highlighting the need for further understanding of the changing structure of the sex industry. The main points of this work will be illustrated with numerical examples using the HIV data of Thailand.

Candida infection as a risk factor for HIV transmission.

Numerous epidemiological studies have documented that ulcerative sexually transmitted diseases (STDs), such as syphilis, chancroid, and genital herpes, promote heterosexual human immunodeficiency virus (HIV) transmission. However, the role of vaginal inflammations, such as Candida infection, in HIV acquisition has not been well established, even though, like Trichomona vaginalis infection, it is rapidly emerging as a significant co-factor in HIV transmission. This study was conducted among a high-risk population of heterosexual women, cohabitating with their HIV-positive male partners, to determine if an association exists between vaginal infections, primarily Candida, and HIV seroconversion. These serodiscordant couples (i.e., one of the persons is HIV positive, and the other is HIV negative) are currently enrolled in an ongoing longitudinal heterosexual discordant couple cohort that is being prospectively followed at Project Sans Francisco (PSF), an HIV Prevention and Research Center in Lusaka, Zambia. A nested case-control study that used retrospective laboratory analyses data obtained from medical, clinical, and laboratory records at PSF was employed. The findings from this study clearly document that women who seroconverted from HIV-negative status during baseline to HIV-positive status at follow-up were significantly more likely to have vaginal Candida infections than were the correspondingly matched seronegative control women. These findings suggest that high-risk heterosexual HIV-negative women could benefit from appropriate gynecological management and care regarding the prevention and treatment of vaginal Candida infections, especially in resource-poor environments.

HIV/AIDS in Children

The incidence of human immunodeficiency virus (HIV) infection and acquired immunodeficiency syndrome (AIDS) in children has risen steadily over the years and has become an increasing cause of morbidity and mortality during childhood. More than 90% of all children with HIV infection acquired their infection at birth from HIV-infected mothers. With increasing evidence of heterosexual HIV transmission, the number of infected women and consequently their children is increasing. The transmission rate of HIV from mother to infant varies from 20% to 40%. Children can be affected directly through HIV infection and AIDS, and indirectly by the effects of their parents’ HIV infection, including being orphaned, discrimination, infant abandonment and negative impact on children’s education. Another concern regards children who are most vulnerable to HIV infection and AIDS, such as child prostitutes and children in difficult circumstances. Recommended actions include prevention of parental HIV infection, prevention of mother-to-child HIV transmission, addressing child prostitution, prevention of child labour and improving work conditions, assistance to street children, addressing discrimination, solving the problem of children orphaned by AIDS, reducing HIV-related child abandonment and creating new roles for schools in reducing negative social impact. Although the largest number of HIV-infected persons are from sub-Saharan Africa, the annual incidence of HIV infection in Asia is escalating alarmingly. As reported by the Joint United Nations Programme on HIV/AIDS (UNAIDS) and the World Health Organization in December 2001, HIV infection has already killed more than 20 million people worldwide since the beginning of the epidemic and has infected more than 40 million people; almost half of them were women. There are at least 7 million people living with HIV/AIDS in the Asia-Pacific region. The numbers of HIV-infected women and children are increasing at an alarming rate. Over 1 million children are HIV-infected; in the year 2000 alone, 600,000 children acquired HIV infection.

Assisted reproductive technology for men and women infected with human immunodeficiency virus type 1.

In 2001, the World Health Organization reported 4.3 million new human immunodeficiency virus (HIV) infections in adults globally, 41% of which were in women. During the year 2000, 27% of newly diagnosed HIV infections in the United States occurred in women. In developed countries, the perception of HIV infection has changed from an acute, lethal infection to a chronic illness; the introduction of highly active antiretroviral therapy has decreased morbidity and mortality, and new drug therapies have dramatically decreased perinatal transmission. In view of these advances, some HIV-infected individuals are considering reproduction. Following the lead of organizations in other developed countries, the American College of Obstetricians and Gynecologists has recently endorsed the use of reproductive technology in HIV-infected patients. Which patients should be offered assisted reproduction and what the optimal methods are of decreasing heterosexual and perinatal HIV transmission must be determined.