Predicting differential responses to structured treatment interruptions during HAART

Highly active antiretroviral therapy (HAART) has been used clinically in various administration schemes for several years. However, due to the development of drug resistance, evolution of viral strains, serious side effects, and poor patient compliance, the combination of drugs used in HAART fails to effectively contain virus long term in a high proportion of patients. Our group and others have suggested a change to the usual regimen of continuous HAART through structured treatment interruptions (STIs). STIs may provide similar clinical benefits as continuous treatment such as reduced viral loads and reestablishment of CD4⁺ T cells while allowing patients drug holidays. We explore the use of STIs using a previously published model that accurately represents CD4⁺ T-cell counts and viral loads during both untreated HIV-1 infection and HAART therapy. We simulate the effects of different STI regimens including weekly and monthly interruptions together with variations in treatment initiation time. We predict that differential responses to STIs as observed in conflicting clinical trial data are impacted by the duration of the interruption, stage of infection at initiation of treatment, strength of the immune system in suppressing virus, or pre-therapy CD4⁺ T-cell count or virus load. Our results indicate that dynamics occurring below the limit of detection (LOD) are influenced by these factors, and contribute to reemergence or suppression of virus during interruptions. Simulations predict that short-term viral suppression with varying interruptions strategies does not guarantee long-term clinical benefit.     

Antagonistic coevolution between hosts and sexually transmitted infections

Sexually transmitted infections (STIs) are predicted to play an important role in the evolution of host mating strategies, and vice versa, yet our understanding of host-STI coevolution is limited. Previous theoretical work has shown mate choice can evolve to prevent runaway STI virulence evolution in chronic, sterilizing infections. Here, I generalize this theory to examine how a broader range of life-history traits influence coevolution; specifically, how host preferences for healthy mates and STI virulence coevolve when infections are acute and can cause mortality or sterility, and hosts do not form long-term sexual partnerships. I show that mate choice reduces both mortality and sterility virulence, with qualitatively different outcomes depending on the mode of virulence, costs associated with mate choice, recovery rates, and host lifespan. For example, fluctuating selection—a key finding in previous work—is most likely when hosts have moderate lifespans, STIs cause sterility and long infections, and costs of mate choice are low. The results reveal new insights into the coevolution of mate choice and STI virulence as different life-history traits vary, providing increased support for parasite-mediated sexual selection as a potential driver of host mate choice, and mate choice as a constraint on the evolution of virulence.     

Quantifying the stationarity and time reversibility of the nucleotide substitution process

Markov models describing the evolution of the nucleotide substitution process, widely used in phylogeny reconstruction, usually assume the hypotheses of stationarity and time reversibility. Although these models give meaningful results when applied to biological data, it is not clear if the 2 assumptions mentioned above hold and, if not, how much sequence evolution processes deviate from them. To this aim, we introduce 2 sets of indices that can be calculated from the nucleotide distribution and the substitution rates. The stationarity indices (STIs) can be used to test the validity of the equilibrium assumption. The irreversibility indices (IRIs) are derived from the Kolmogorov cycle conditions for time reversibility and quantify the degree of nontime reversibility of a process. We have computed STIs and IRIs for the evolutionary process of 2 lineages, Drosophila simulans and Homo sapiens. In the latter case, we use a modified form of the indices that takes into account the CpG decay process. In both cases, we find statistically significant deviations from the ideal case of a process that has reached stationarity and is time reversible.     

HLA-A*2402-restricted HIV-1-specific cytotoxic T lymphocytes and escape mutation after ART with structured treatment interruptions

Although a limited duration of immune activation of structured treatment interruptions (STIs) has been reported, the immune escape mechanism during STIs remains obscure. We therefore investigated the role of three immunodominant cytotoxic T lymphocyte (epitopes) in 12 HLA-A*2402-positive patients participating longitudinally during the clinical study of early antiretroviral treatment (ART) with five series of structured treatment interruptions (STIs). The frequency of HLA-A*2402-restricted CTLs varied widely and a sustained CTL response was rarely noted. However, a Y-to-F substitution at the second position in an immunodominant CTL epitope Nef138-10 (Nef138-2F), which was previously demonstrated as escape mutation, was frequently detected in seven patients primarily and emerged in the remaining five patients thereafter, and the existence of escape mutations was correlated with high pVL levels early in the clinical course. These findings suggest that escape mutation in the immunodominant CTL epitope may be one of the mechanisms to limit HIV-1-specific immune control in STIs.     

Prevalence and Factors Associated with Sexually Transmitted Infections among HIV Positive Women Opting for Intrauterine Contraception

Background

Women living with HIV/AIDS (WLHA) are a high risk group for sexually transmitted infections (STIs). However, the majority of women with STIs are asymptomatic. Data on prevalence of STIs among WLHA in Uganda are limited. The objective of the study was to determine prevalence and factors associated with STIs among WLHA opting for intrauterine contraceptive device (IUD).

Methods

Three hundred fifty one WLHA deemed free of STIs using a syndromic logarithm were enrolled into the study. Endo-cervical swabs were taken before IUD insertion and PCR test for Nisseria gonorrhea (NG), Trichomonas vaginalis (TV) and Chlamydia trachomatis (CT) infections conducted.

Results

Participants’ mean age was 29.4 ± 6.2 years, 83% were under 35years, 50% had secondary education and 73% were married. The majority (69%) had disclosed their HIV sero status to their spouses, 82% used Cotrimoxazole prophylaxis, 70% were on antiretroviral therapy, 90% had CD4 count greater than 350, about 60% reported condoms use and 70% were of parity 2-4. Over 50% of the participants’ spouses were older than 35 years and 72% had attained secondary education. STIs prevalence was 11.1%, (95% CI 7.8-14.4) and individual prevalence for TV, NG, and CT was 5.9%, 5.4% and 0.9% respectively. Factors independently associated with STI were having primary or less education (OR= 2.3, 95% CI: 1.09 - 4.85) having a spouse of primary or less education (OR= 3.3, 95% CI: 1.6 - 6.78) and muslim faith (OR= 0.2, 95% CI: 0.04 - 0.78).

Conclusion

STI prevalence was 11.1%. TV and NG were the commonest STIs in this population. Having primary or less education for both participant and spouse was associated with increased risk while being of muslim faith was associated with reduced risk of STI.     

HIV and STI Prevalence and Determinants among Male Migrant Workers in India

Background

Our objective was to estimate for the first time the prevalence and determinants of human immunodeficiency virus type 1 (HIV-1) and sexually transmitted infections (STIs) among male migrants in India.

Methodology/Principal Findings

We conducted a multi-stage stratified probability sample survey of migrant (defined as not born in Surat city) men aged 18 to 49 years working in the diamond and textile industries in Surat city. Behavioural and biological data were collected. Biological data included laboratory diagnosed herpes simplex virus type 2 (HSV-2), syphilis, chlamydia, gonorrhoea, Trichomonas vaginalis (together defined as ‘any STI’) and HIV-1. Likely recently acquired STIs included chlamydia, gonorrhoea, T.vaginalis and syphilis with rapid plasma reagin ≥1∶8. The response rate was 77% (845/1099). Among 841 participants, HIV-1 prevalence was 1.0%, ‘any STI’ prevalence was 9.5% and 38.9% of these STIs were likely to have been recently acquired. Being a diamond worker, Surat resident for 10+ years and recent antibiotic use were each associated with higher odds of ‘any STI’ (aORs 1.83 (95% CI 1.09–3.09), 1.98 (95% CI 1.22–3.22) and 2.57 (95% CI 1 .17–5.64), respectively) after adjusting for the other two factors and age. The main study limitation was social desirability bias for self-reported sexual behaviour; STIs were diagnosed in some self-reported virgins.

Conclusions/Significance

HIV and STI prevalence were lower than expected, but prevention interventions remain necessary in Surat since almost 40% of STIs among participants were probably recently acquired and sentinel surveillance HIV prevalence remains high. The participants had a similar HIV prevalence to Surat antenatal clinic attendees, a proxy for the general population. This suggests migrants are not always at higher risk of HIV compared to the general population in their migration destination. Our findings highlight the need to contextualise research findings from a specific setting with other local information to guide HIV/STI prevention interventions.     

Development of a pigtail macaque model of sexually transmitted infection/HIV coinfection using Chlamydia trachomatis, Trichomonas vaginalis, and SHIV(SF162P3)

Background Sexually transmitted infections (STIs) are associated with an increased risk of HIV infection. To model the interaction between STIs and HIV infection, we evaluated the capacity of the pigtail macaque model to sustain triple infection with Trichomonas vaginalis, Chlamydia trachomatis, and SHIV_SF162P3. Methods Seven SHIV_SF162P3‐infected pigtail macaques were inoculated with T. vaginalis only (n = 2), C. trachomatis only (n = 1), both T. vaginalis and C. trachomatis (n = 2), or control media (no STI; n = 2). Infections were confirmed by culture and/or nucleic acid testing. Genital mucosa was visualized by colposcopy. Results Characteristic gynecologic signs were observed for both STIs, but not in control animals. Manifestations were most prominent at days 7–10 post‐infection. STIs persisted between 4 and 6 weeks and were cleared with antibiotics. Conclusions These pilot studies demonstrate the first successful STI‐SHIV triple infection of pigtail macaques, with clinical presentation of genital STI symptoms similar to those observed in humans.     

Deciphering the epidemic synergy of herpes simplex virus type 2 (HSV-2) on human immunodeficiency virus type 1 (HIV-1) infection among women in sub-Saharan Africa

ABSTRACT: BACKGROUND: Herpes Simplex Virus Type 2 (HSV-2) is highly prevalent in regions disproportionately affected by the human immunodeficiency virus (HIV-1) epidemic. The objective of our study was to identify the risk factors of HSV-2 and HIV-1 infections and to examine the association between the two infections. METHODS: The study participants were recruited through a community based cross-sectional study that was conducted from November 2002 to March 2003 in the Moshi urban district of Northern Tanzania. A two-stage sampling design was used in recruiting the study participants. Information on socio-demographics, alcohol use, sexual behaviors, and STIs symptoms were obtained. Blood and urine samples were drawn for testing of HIV-1, HSV-2 and other STIs. RESULTS: The prevalence of HSV-2 infection among all study participants was 43%. The prevalence rate of HSV-2 among the HIV-negative and HIV-positive women was 40% and 65%, respectively. We found 2.72 times odds of having HIV-1 in an HSV-2 positive woman than in an HSV-2 negative woman. Furthermore, HIV-1 and HSV-2 shared common high-risk sexual behavior factors such as early onset of sexual debut, and testing positive for other STIs. CONCLUSIONS: Our findings suggest that HSV-2 may be both a biological and risk-associated cofactor for HIV-1 acquisition. In resource-limited countries, where both infections are prevalent efforts at symptomatic and diagnostic screening and treatment of HSV-2 should be part of HIV-1 prevention programs.     

Why is sterility virulence most common in sexually transmitted infections? Examining the role of epidemiology

Sterility virulence, or the reduction in host fecundity due to infection, occurs in many host–pathogen systems. Notably, sterility virulence is more common for sexually transmitted infections (STIs) than for directly transmitted pathogens, while other forms of virulence tend to be limited in STIs. This has led to the suggestion that sterility virulence may have an adaptive explanation. By focusing upon finite population models, we show that the observed patterns of sterility virulence can be explained by consideration of the epidemiological differences between STIs and directly transmitted pathogens. In particular, when pathogen transmission is predominantly density invariant (as for STIs), and mortality is density dependent, sterility virulence can be favored by demographic stochasticity, whereas if pathogen transmission is predominantly density dependent, as is common for most directly transmitted pathogens, sterility virulence is disfavored. We show these conclusions can hold even if there is a weak selective advantage to sterilizing.     

Human immunodeficiency virus-specific CD8(+) T-cell responses do not predict viral growth and clearance rates during structured intermittent antiretroviral therapy

There is a continuing search for better ways to use existing drugs against human immunodeficiency virus (HIV). One idea is to use short therapy interruptions to "autovaccinate" HIV-infected patients. A group of 13 chronically HIV-infected patients enrolled in a trial of such so-called structured treatment interruptions (STIs) were intensively studied with respect to their viral load (VL) and HIV-specific CD8+ T-cell (cytotoxic T-lymphocyte [CTL]) responses. We found that 10 of the 13 patients had plateau VLs after STIs that were lower than their pretreatment VLs. While viral rebound rates became lower over STIs, there were no changes in clearance rates. Although numbers of CTLs did increase over the same time that viral rebounds decreased, there was no correlation between CTL count and either viral rebound rates or clearance rates. Finally, we asked whether absolute numbers of or changes in numbers of CTLs predict plateau VLs after STIs. No measure of CTLs was able to predict plateau VLs. Thus, there was no signature in these data of an important contribution to virological control from HIV-specific CD8+ T lymphocytes.     

Sexual Behavior and Network Characteristics and Their Association with Bacterial Sexually Transmitted Infections among Black Men Who Have Sex with Men in the United States

Background

Black men who have sex with men (MSM) have a high prevalence of bacterial sexually transmitted infections (STIs), and individual risk behavior does not fully explain the higher prevalence when compared with other MSM. Using the social-ecological framework, we evaluated individual, social and sexual network, and structural factors and their association with prevalent STIs among Black MSM.

Methods

The HIV Prevention Trials Network 061 was a multi-site cohort study designed to determine the feasibility and acceptability of a multi-component intervention for Black MSM in six US cities. Baseline assessments included demographics, risk behavior, and social and sexual network questions collected information about the size, nature and connectedness of their sexual network. Logistic regression was used to estimate the odds of having any prevalent sexually transmitted infection (gonorrhea, chlamydia, or syphilis).

Results

A total of 1,553 Black MSM were enrolled in this study. In multivariate analysis, older age (aOR = 0.57; 95% CI 0.49–0.66, p<0.001) was associated with a lower odds of having a prevalent STI. Compared with reporting one male sexual partner, having 2–3 partners (aOR = 1.74; 95% CI 1.08–2.81, p<0.024) or more than 4 partners (aOR = 2.29; 95% CI 1.43–3.66, p<0.001) was associated with prevalent STIs. Having both Black and non-Black sexual partners (aOR = 0.67; 95% CI 0.45–0.99, p = 0.042) was the only sexual network factor associated with prevalent STIs.

Conclusions

Age and the number and racial composition of sexual partners were associated with prevalent STIs among Black MSM, while other sexual network factors were not. Further studies are needed to evaluate the effects of the individual, network, and structural factors on prevalent STIs among Black MSM to inform combination interventions to reduce STIs among these men.     

Association of sexually transmitted infections and human papillomavirus co-infection with abnormal cervical cytology among women in Saudi Arabia

Human papillomavirus (HPV) is a causative agent of cervical and other cancers. Sexually transmitted Infections (STIs) may play a crucial role in HPV persistence, leading to serious complications, including cervical cancer. This study investigated the association of HPV/STI co-infection in cervical samples with cervical dysplasia among women in Saudi Arabia. HPV-positive cervical samples (n = 142) were obtained from previous studies and newly collected samples (n = 209) were obtained from women aged 19–83 years. For HPV detection and genotyping, PCR and Genoflow HPV assay kits were used. STIs were detected using a Genoflow STD array kit. Of 351 samples, 94 (27%) were positive for STIs. Among HPV-positive samples, 36 (25%) were positive for STIs; the most common pathogens were Ureaplasma urealyticum/Ureaplasma parvu (13%) and Mycoplasma hominis (6%). A global significant correlation was detected between HPV and STIs with progression of abnormal cervical cytology (χ² = 176, P < 0.0001). Associations between cervical cytology diagnosis and HPV status, STI types (opportunistic and pathogenic), and the presence of Ureaplasma spp., and Mycoplasma hominis were significant (P < 0.05). Our results suggest that additional study in a larger population is warranted to determine the association between HPV/STI co-infection and cervical neoplasia in Saudi women.     

Chlamydia trachomatis,Human Immunodeficiency Virus (HIV) Distribution and Sexual Behaviors across Gender and Age Group in an African Setting

ObjectiveThe purpose of this study was to (1) describe the distribution of Chlamydia trachomatis (CT) and Human Immunodeficiency Virus (HIV) cases across gender and age groups in Libreville (Gabon); (2) examine Gabonese Sexually Transmitted Infections (STIs)-related risk behaviour.MethodsThe sampled population was people attending the “Laboratoire National de Santé Plublique”. Between 2007 and 2011, 14 667 and 9 542 people respectively, were tested for CT and HIV infections. 1 854 of them were tested for both infections. We calculated CT and HIV rates across gender and age groups. Also analysed was the groups'' contribution to the general CT and HIV epidemiology.STIs-related risk behaviours were assessed in 224 men and 795 women (between July 2011 and March 2013) who agreed and answered a questionnaire including questions on their marital status, number of sex partners, sexual practices, history of STIs, sex frequency and condom use.ResultsData showed a 24% dropped in the CT infection rate between 2007 and 2010, followed by a 14% increase in 2011. The HIV infection rates for the same period were between 15% and 16%. The risk of a CT-positive subject getting HIV is about 0.71 times the risk of a CT-negative subject.Young adult aged between 18 and 35 years old represented 65.2% of people who had STIs. 80% of women and 66% of men confessed to an inconsistent use of condoms. 11.6% of women and 48% of men declared having multiple sex partners. 61% of questioned women and 67% of men declared knowing their HIV status.ConclusionsIn this Gabonese setting, the population-aged from18 to 35 years is the most affected by STIs. Other matters of concern are the inconsistent use of protection and sex with non-spousal or non-life partners.     

Sexually transmitted infections and prostate cancer risk: A systematic review and meta-analysis

Prostate cancer (PC) is the second most incident cancer and the sixth cause of death by cancer in men worldwide. Despite extensive research efforts, no modifiable risk factors have been consistently identified for PC risk. A number of studies have focused on possible relationships between sexually transmitted infections (STIs) and PC. We performed a meta-analysis to explore the association between infection caused by Neisseria gonorrheae, Treponema pallidum, Chlamydia trachomatis, Trichomonas vaginalis, Ureaplasma urealyticum, Mycoplasma hominis, Herpes Simplex Virus types 1 and 2, Human Herpes Virus 8 and Cytomegalovirus, and PC. We conducted a comprehensive, systematic bibliographic search of medical literature to identify relevant studies. We calculated summary relative risk (SRR) and 95% confidence intervals (CI) for the association between each STI and PC through random effect models. Subgroup, meta-regression and sensitivity analyses were carried out to detect between-study heterogeneity and bias. We included 47 studies published between 1971 and 2011. Men who reported having ever had any STI in lifetime had an increased PC (SRR 1.49, 95% CI 1.19–1.92). We found a significantly increased PC risk in men having had gonorrhoea (SRR 1.20, 95% CI 1.05–1.37). No other single STI was significantly associated with PC. Due to high incidence of both STIs and PC worldwide, prevention of STIs may help preventing a considerable number of PC cases.     

Strategies for successful designing of immunocontraceptive vaccines and recent updates in vaccine development against sexually transmitted infections - A review

BackgroundThe world population is continuously growing. It has been estimated that half of the world’s population is from the Asian continent, mainly from China and India. Overpopulation may lead to many societal problems as well as to changes in the habitat. Birth control measures are thus needed to control this growth. However, for the last 50–60 years, there have not been any improvements in the field of contraception. Nevertheless, the immunocontraceptive vaccine is an emerging field, and it might be the only replacement for the existing mode of contraception for the next millennium. Sexually transmitted infections (STIs) are frequent, and their transmission rate increases yearly. As antibiotics are the prevailing treatment for this kind of infections, resistance in humans has increased; therefore, having effective antibiotic treatments for STIs is now a concern. Vaccines against STIs are now needed. It is thought that the improvements in the fields of proteomics, immunomics, metabolomics, and other omics will help in the successful development of vaccines.ObjectiveTo collect and review the literature about recent advancements in immunocontraception and vaccines against sexually transmitted diseases/infections.MethodsReliable scientific databases, such as PubMed Central, PubMed, Scopus, Science Direct, and Goggle Scholar, were consulted. Publications bearing important information on targeted antigens/immunogens for contraceptive vaccine design and advancements in vaccine development for STIs were gathered and tabulated, and details were analyzed as per the theme of each study.ResultsImportant antigens that have a specific role in fertility have been studied extensively for their contraceptive nature. Additionally, the advancements in the screening for the best antigens, according to their antigenic nature and how they elicit immune responses for an extended period were also studied. Herd immunity for STIs and advancements in the development of vaccines for syphilis, gonorrhea, and herpes simplex virus were also studied and tabulated in this review. An extensive knowledge on STIs vaccines was gained.ConclusionThis extensive review is aimed to provide insights for active researchers in vaccinology, immunology, and reproductive biology. Advancements in the development of vaccines for different STIs can be gathered as a wholesome report.     

Prevalence of HIV,STIs, and Risk Behaviors in a Cross-Sectional Community- and Clinic-Based Sample of Men Who Have Sex with Men (MSM) in Lima,Peru

Background

Further research is necessary to understand the factors contributing to the high prevalence of HIV/STIs among men who have sex with men (MSM) in Peru. We compared HIV/STI prevalence and risk factors between two non-probability samples of MSM, one passively enrolled from an STI clinic and the other actively enrolled from community venues surrounding the clinic in Lima, Peru.

Methods

A total of 560 self-identified MSM were enrolled between May-December, 2007. 438 subjects enrolled from a municipal STI clinic and 122 subjects enrolled during community outreach visits. All participants underwent screening for HIV, syphilis, HSV-2, gonorrhoea, and chlamydia and completed a survey assessing their history of HIV/STIs, prior HIV testing, and sexual behavior.

Results

HIV prevalence was significantly higher among MSM enrolled from the clinic, with previously undiagnosed HIV identified in 9.1% compared with 2.6% of community participants. 15.4 % of all MSM screened were infected with ≥1 curable STI, 7.4% with early syphilis (RPR≥1∶16) and 5.5% with urethral gonorrhoea and/or chlamydia. No significant differences between populations were reported in prevalence of STIs, number of male sex partners, history of unprotected anal intercourse, or alcohol and/or drug use prior to sex. Exchange of sex for money or goods was reported by 33.5% of MSM enrolled from the clinic and 21.2% of MSM from the community (p = 0.01).

Conclusions

Our data demonstrate that the prevalence of HIV and STIs, including syphilis, gonorrhoea, and chlamydia are extremely high among MSM enrolled from both clinic and community venues in urban Peru. New strategies are needed to address differences in HIV/STI epidemiology between clinic- and community-enrolled samples of MSM.     

The Epidemic of HIV,Syphilis, Chlamydia and Gonorrhea and the Correlates of Sexual Transmitted Infections among Men Who Have Sex with Men in Jiangsu,China, 2009

Background

In China, the HIV/AIDS epidemic is expanding among men who have sex with men (MSM). As independent risk factors of HIV infection, the epidemics of Chlamydia (CT) and Gonorrhea (NG) in MSM were not well studied, particular for the risk factors of these infectious. The objectives of current reported study were to understand the dynamics of HIV and other sexual transmitted infections (STIs) among MSM in Jiangsu, China, and to measure factors that correlated with STIs.

Methods

In order to gain more participants, a multisite cross-sectional study design was used in our study, by using convenience-sampling to recruit MSM in two Changzhou and Yangzhou, Jiangsu, China, between the July and October of 2009.

Results

In this comprehensive survey involving MSM in two cities of Jiangsu province of China, the prevalence of STIs of CT (6.54%), NG (3.63%), syphilis (20.34%) and HIV (11.62%) were measured. Overall, the STIs prevalence (CT, NG or syphilis) for the participants in our study was 26.39%, meanwhile, 3.4% (14 out of the 413) participants had at least two kinds of STIs. Meeting casual partners at parks, public restrooms or other public areas, having had anal sex with men in the past six months, having had STI symptoms in the past year were positively correlated with STIs positive, with adjusted ORs of 4.61(95%CI 1.03–20.75), 1.91(95%CI 1.14–3.21) and 2.36(95%CI 1.07,5.24).

Conclusion

Our study findings reiterate the fact that Chinese MSM are highly susceptible to acquiring syphilis, CT, NG and HIV, and there is an urgent need for intervention targeted towards this population. Behavioral measures should constitute an important part of the targeted intervention. Furthermore, the already implemented preventive and diagnostic services for HIV should be expanded to include syphilis CT and NG, too.     

Lactobacillus-dominated cervicovaginal microbiota associated with reduced HIV/STI prevalence and genital HIV viral load in African women

Cervicovaginal microbiota not dominated by lactobacilli may facilitate transmission of HIV and other sexually transmitted infections (STIs), as well as miscarriages, preterm births and sepsis in pregnant women. However, little is known about the exact nature of the microbiological changes that cause these adverse outcomes. In this study, cervical samples of 174 Rwandan female sex workers were analyzed cross-sectionally using a phylogenetic microarray. Furthermore, HIV-1 RNA concentrations were measured in cervicovaginal lavages of 58 HIV-positive women among them. We identified six microbiome clusters, representing a gradient from low semi-quantitative abundance and diversity dominated by Lactobacillus crispatus (cluster R-I, with R denoting ‘Rwanda'') and L. iners (R-II) to intermediate (R-V) and high abundance and diversity (R-III, R-IV and R-VI) dominated by a mixture of anaerobes, including Gardnerella, Atopobium and Prevotella species. Women in cluster R-I were less likely to have HIV (P=0.03), herpes simplex virus type 2 (HSV-2; P<0.01), and high-risk human papillomavirus (HPV; P<0.01) and had no bacterial STIs (P=0.15). Statistically significant trends in prevalence of viral STIs were found from low prevalence in cluster R-I, to higher prevalence in clusters R-II and R-V, and highest prevalence in clusters R-III/R-IV/R-VI. Furthermore, only 10% of HIV-positive women in clusters R-I/R-II, compared with 40% in cluster R-V, and 42% in clusters R-III/R-IV/R-VI had detectable cervicovaginal HIV-1 RNA (P_trend=0.03). We conclude that L. crispatus-dominated, and to a lesser extent L. iners-dominated, cervicovaginal microbiota are associated with a lower prevalence of HIV/STIs and a lower likelihood of genital HIV-1 RNA shedding.     

Territorial aggression and hormones during the non-breeding season in a tropical bird

The hormonal control of territorial aggression in male and female vertebrates outside the breeding season is still unresolved. Most vertebrates have regressed gonads when not breeding and do not secrete high levels of sex steroids. However, recent studies implicate estrogens in the regulation of non-breeding territoriality in some bird species. One possible source of steroids during the non-breeding season could be the adrenal glands that are known to produce sex steroid precursors such as dehydroepiandrosterone (DHEA). We studied tropical, year-round territorial spotted antbirds (Hylophylax n. naevioides) and asked (1). whether both males and females are aggressive in the non-breeding season and (2). whether DHEA is detectable in the plasma at that time. We conducted simulated territorial intrusions (STIs) with live decoys to male and female free-living spotted antbirds in central Panama. Non-breeding males and females displayed robust aggressive responses to STIs, and responded more intensely to decoys of their own sex. In both sexes, plasma DHEA concentrations were detectable and higher than levels of testosterone (T) and 17beta-estradiol (E(2)). In males, plasma DHEA concentrations were positively correlated with STI duration. Next, we conducted STIs in captive non-breeding birds. Captive males and females displayed robust aggressive behavior. Plasma DHEA concentrations were detectable in both sexes, whereas T was non-detectable (E(2) was not measured). Plasma DHEA concentrations of males were positively correlated with aggressive vocalizations and appeared to increase with longer STI durations. We conclude that male and female spotted antbirds can produce DHEA during the non-breeding season and DHEA may serve as a precursor of sex steroids for the regulation of year-round territorial behavior in both sexes.