Increased Risk Of HIV Acquisition Research Articles

Characterising HIV acquisition risk, treatment gaps and populations reached through venue-based outreach and clinical services in Blantyre, Malawi: findings from a district-wide CLOVE Study.

In 2017, Blantyre district had the highest adult HIV prevalence in Malawi (17.7%) and lowest viral suppression (60%). In response, the Ministry of Health expanded prevention and treatment services. We assessed whether outreach to social venues could identify individuals with increased HIV acquisition risk or with unsuppressed HIV not currently reached by clinic-based services. We conducted a cross-sectional bio-behavioral survey in Blantyre, Malawi, from January to March 2022. We visited social venues where people meet new sexual partners and government clinics providing HIV testing or STI screening. Participants aged > 15 years were interviewed, and tested for HIV infection if not on ART. HIV recency tests were performed on those testing positive, and dried blood spots (DBS) was collected to quantify viral load and also to identify acute infection in those with HIV- results. HIV prevalence (18.5% vs 8.3%) and unsuppressed HIV infection (3.9% vs 1.7%) were higher among venue-recruited (n=1802) compared with clinic-recruited participants(n=2313). Among PLHIV at both clinics (n=199) and venues (n=289), 79% were virally suppressed. Few had acute(n=1) or recent infection(n=8). Among women, HIV prevalence was four times higher (38.9% venue vs 8.9% clinic). At clinics, PLHIV reporting visiting venues were less likely to be suppressed (54.6 vs 82.6%). More men at venues than at clinics reported paying for sex (49% vs 30%) or having multiple sex partners in the past 4 weeks (32% vs 16%). Enhanced venue-based prevention and testing for men and women could reduce treatment lapses, HIV treatment outcomes and reduce onward transmission.

A cross-sectional assessment of injection of "salts" and HIV transmission-related behaviours among a cohort of people who inject drugs in Kyrgyzstan.

Despite the increasing availability of new psychoactive substances (hereafter referred to as "salts") in Eastern Europe and Central Asia, there is a dearth of epidemiological data on the relationship between injecting "salts" and HIV risk behaviours. This is particularly relevant in settings where injection drug use accounts for a substantial proportion of the HIV burden, such as in Kyrgyzstan, a former Soviet Republic. This study assessed whether injecting "salts" is associated with sexual and injection-related HIV risk behaviours among people who inject drugs in Kyrgyzstan. The Kyrgyzstan InterSectional Stigma Study is a cohort of people who inject drugs in Kyrgyzstan's capital of Bishkek and the surrounding rural administrative division of Chuy Oblast. We conducted a cross-sectional analysis using survey data collected from cohort participants between July and November 2021, which included information on injection drug use (including "salts") and HIV risk behaviours. To minimize confounding by measured covariates, we used inverse-probability-weighted logistic and Poisson regression models to estimate associations between recent "salt" injection and HIV risk behaviours. Of 181 participants included in the analysis (80.7% men, 19.3% women), the mean age was 40.1 years (standard deviation [SD] = 8.8), and 22% (n = 39) reported that they had injected "salts" in the past 6 months. Among people who injected "salts," 72% (n = 28) were men, and most were ethnically Russian 59% (n = 23), with a mean age of 34.6 (SD = 9.6). Injecting "salts" was significantly associated with a greater number of injections per day (adjusted relative risk [aRR] = 1.59, 95% confidence interval [CI] = 1.30-1.95) but lower odds of using syringe service programmes in the past 6 months (adjusted odds ratio [aOR] = 0.20, 95% CI = 0.12-0.32). Injecting "salts" was also significantly associated with lower odds of condomless sex in the past 6 months (aOR = 0.42, 95% CI = 0.24-0.76) and greater odds of having ever heard of pre-exposure prophylaxis (aOR = 4.80, 95% CI = 2.61-8.83). (PWID) people who inject drugs who inject "salts" are a potentially emergent group with increased HIV acquisition risk in Kyrgyzstan. Targeted outreach bundled with comprehensive harm reduction and pre-exposure prophylaxis services are needed to prevent transmission of HIV and other blood-borne viruses.

The vaginal microbiome and HIV transmission dynamics.

Among women, having a nonoptimal, highly diverse vaginal microbiome dominated by bacteria other than optimal Lactobacillus species such as L. crispatus or L. jensenii predicts HIV transmission. Reducing HIV acquisition among women requires a better understanding of the mechanisms through which the vaginal microbiome impacts HIV transmission dynamics and how to more effectively treat and intervene. Technological advancements are improving the ability of researchers to fully characterize interacting host-bacteria mechanisms. Consequently, the purpose of this review was to summarize the most innovative research on the vaginal microbiome and its role in HIV transmission in the past year. Studies combining multiomics, experimental, and translational approaches highlight the associations of a nonoptimal microbiome with maladaptive alterations in immune cell functioning, vaginal metabolites, host cell transcription, mucosal immunity, and epithelial barrier integrity. While there are multiple mechanisms proposed to increase HIV acquisition risk, there are virtually zero acceptable and effective treatments to improve the vaginal microbiome and immunity. Women-centered solutions to modify the vaginal microbiome and bacterial metabolites should continue to be explored as a mechanism to reduce HIV acquisition.

Impact of vaginal microbiome communities on HIV antiretroviral-based pre-exposure prophylaxis (PrEP) drug metabolism.

Despite the efficacy of antiretroviral-based pre-exposure prophylactics (PrEP) in men who have sex with men, studies in women have produced widely varying outcomes. Recent evidence demonstrates that vaginal microbial communities are associated with increased HIV acquisition risk and may impact PrEP efficacy. Here, we investigate the mechanisms underlying how vaginal bacteria alter PrEP drug levels and impact HIV infection rates ex vivo. Using cervicovaginal lavages (CVLs) from women with or without bacterial vaginosis (BV), we identified microbial metabolism of PrEP drugs in BV samples through LC-MS/MS analysis of soluble drug levels and metabolite formation in dual T-cell cultures. CVL samples were assessed for microbiome analysis using sequencing of bacterial 16S rRNA genes. We also observed non-Lactobacillus bacteria that are associated with BV may potentially impact PrEP efficacy through increased HIV infection rates in co-cultures containing Lactobacillus or BV bacteria, PrEP drugs, CEM-GFP cells, and HIV-1LAI virus. Finally, we used these data to develop a novel predictive mathematical simulation modeling system to predict these drug interactions for future trials. These studies demonstrate how dysbiotic vaginal microbiota may impact PrEP drugs and provides evidence linking vaginal bacteria to PrEP efficacy in women.

Betamethasone induces potent immunosuppression and reduces HIV infection in a PBMC in vitro model

Genital inflammation is an established risk factor for increased HIV acquisition risk. Certain HIV-exposed seronegative populations, who are naturally resistant to HIV infection, have an immune quiescent phenotype defined by...

Risk for HIV acquisition among sub-Saharan African migrant travelers in Belgium and Portugal

Abstract Migrants often travel back to the origin countries and to other European states after settling in the residence country. Mobility along with structural vulnerabilities may increase HIV acquisition risk. Knowledge on HIV risk exposure when traveling is limited, yet crucial to inform prevention. This study aims to explore risky sexual behaviors and assess HIV prevalence among sub-Saharan African migrants (SAMs) who travel, residing in two European cities. Two cross-sectional biobehavioral surveys were conducted in Lisbon and Antwerp with a venue-based sample of 1508 SAMs. Descriptive and multivariable logistic regression analyses were performed to examine travel patterns and associated sexual risk behaviors. Overall, 68.4% of participants had traveled to other countries after settling in the residence country; 41% had traveled back to Africa and within Europe, 25.2% only to Africa and 33.8% only to Europe. Among travelers who reported sexual encounters abroad (49.2%), condomless sex at last intercourse was high both abroad (62.5%) and in the host country (70.7%). Odds of condomless sex at the last sexual encounter in the host country were five times higher among those who also reported no condom use abroad [OR: 5.32; 95% CI: 2.98-9.25], controlling for gender, age, educational level, relationship status, survey country, partner type and origin, and number of sexual partners over the last year. Condomless sex was higher with a regular partner and with an African partner, both abroad (79.9% and 67.5%, respectively) and in the host country (81.3% and 74.6%, respectively). Among the 75 participants who tested HIV-positive (around 5%), more than half had travelled to other countries; of these, about half reported condomless sex with their last sexual partner abroad. SAMs are a mobile population and are exposed to sexual HIV risk both while traveling and in host countries. Prevention interventions should address the complex interplay between migrants' mobility and HIV risk. Key messages Migrants often travel to their origin home countries and other destinations after having settled in host countries, and this mobility increases exposure to HIV risk. A transnational perspective on HIV prevention and sexual health promotion is needed for effectively reducing migrants’ HIV risk related to their mobility.

Concomitant Imbalances of Systemic and Mucosal Immunity Increase HIV Acquisition Risk

We previously reported association of increased cervical RANTES and decreased secretory leukocyte protease inhibitor (SLPI) with higher risk of HIV acquisition in reproductive-age women. We now examine the interaction of concomitantly altered systemic and cervical immunity on such risk. We measured immune biomarkers in 4390 cervical and 2390 paired serum specimens at quarterly visits in 218 HIV seroconverters and 784 seronegative women. We assessed proinflammatory (IL-1β, IL-6, IL-8, MIP-3α, and RANTES), anti-inflammatory (IL-1RA and SLPI), vascular activation (vascular endothelial growth factor and Intercellular Adhesion Molecule-1) and defensin (BD2) cervical biomarkers and systemic (peripheral blood) C reactive protein (CRP), IL-6, IL-7, and sCD14 as indicators of immune dysregulation. Biomarker levels were Box-Cox transformed and odds ratios for HIV acquisition calculated based on top quartile or higher/lower than median levels for all HIV-negative visits. Subsequent HIV acquisition was associated with 5 of 14 individual biomarkers: low systemic CRP [odds ratio (OR) = 1.49, 1.21-1.83] and IL-6 (OR = 1.23, 1.00-1.51), high cervical BD-2 (OR = 1.33, 1.11-1.58) and RANTES (OR = 1.20, 1.01-1.43), and low cervical IL-1RA (OR = 0.65, 0.48-0.86). Low systemic CRP concomitant with altered cervical immunity, especially high BD2, conveyed highest HIV risk (1.63, 1.29-2.05). Additional markers of increased risk emerged when low systemic CRP coincided with: low systemic IL-6 and IL-7 (OR = 1.53, 1.18-1.97); high cervical IL-8 and MIP-3α (OR = 1.40, 1.07-1.83); high cervical IL-1β and IL-6 (OR = 1.43, 1.09-1.86); or low cervical SLPI (OR = 1.36, 1.08-1.71). Changes in both peripheral and mucosal immunity may precede and predispose women to HIV infection. Suppressed systemic immunity (ie, low CRP) alone or in combination with imbalanced cervical innate immunity (high proinflammatory and low anti-inflammatory mediators) indicated increased vulnerability to infection. Understanding these combined effects on HIV susceptibility is essential to preventing new infections.

Diminished HIV Infection of Target CD4+ T Cells in a Toll-Like Receptor 4 Stimulated in vitro Model.

Genital inflammation is associated with increased HIV acquisition risk. Induction of an inflammatory response can occur through the recognition of pathogenic or commensal microbes by Toll-like receptors (TLRs) on various immune cells. We used a in vitro peripheral blood mononuclear cell (PBMC) system to understand the contribution of TLR stimulation in inducing inflammation and the activation of target T cells, and its effect on HIV susceptibility. PBMCs were stimulated with TLR agonists LPS (TLR4), R848 (TLR7/8), and Pam3CSK4 (TLR1/2), and then infected with HIV NL4-3 AD8. Multiplexed ELISA was used to measure 28 cytokines in cell culture supernatants. Flow cytometry was used to measure the activation state (CD38 and HLA-DR), and CCR5 expression on CD4+ and CD8+ T cells. Although TLR agonists induced higher cytokine and chemokine secretion, they did not significantly activate CD4+ and CD8+ T cells and showed decreased CCR5 expression relative to the unstimulated control. Despite several classes of inflammatory cytokines and chemokines being upregulated by TLR agonists, CD4+ T cells were significantly less infectable by HIV after TLR4-stimulation than the unstimulated control. These data demonstrate that the inflammatory effects that occur in the presence TLR agonist stimulations do not necessarily translate to the activation of T cells. Most importantly, the finding that TLR4-stimulation reduces rather than increases susceptibility of CD4+ T cells to HIV infection in this in vitro system strongly suggests that the increased chemokine and possible antiviral factor expression induced by these TLR agonists play a powerful although complex role in determining HIV infection risk.

Decreasing HIV transmissions to African American women through interventions for men living with HIV post-incarceration: An agent-based modeling study

BackgroundIncarceration and HIV disproportionately impact African American communities. The mass incarceration of African American men is hypothesized to increase HIV acquisition risk for African American women. Interventions optimizing HIV care engagement and minimizing sexual risk behaviors for men living with HIV post-incarceration may decrease HIV incidence.MethodsUsing an agent-based model, we simulated a sexual and injection drug using network representing the African American population of Philadelphia. We compared intervention strategies for men living with HIV post-incarceration by the number of averted HIV transmissions to women within the community. Three interventions were evaluated: a 90-90-90 scenario scaling up HIV testing, ART provision, and ART adherence; a behavioral intervention decreasing sexual risk behaviors; and a combination intervention involving both.ResultsThe status quo scenario projected 2,836 HIV transmissions to women over twenty years. HIV transmissions to women decreased by 29% with the 90-90-90 intervention, 23% with the behavioral intervention, and 37% with both. The number of men living with HIV receiving the intervention needed in order to prevent a single HIV transmission ranged between 6 and 10.ConclusionInterventions to improve care engagement and decrease sexual risk behaviors post-incarceration for men living with HIV have the potential to decrease HIV incidence within African American heterosexual networks.

Antenatal care presentation and engagement in the context of sex work: exploring barriers to care for sex worker mothers in South Africa

BackgroundLate presentation combined with limited engagement in antenatal care (ANC) increases risk of vertical transmission among mothers living with HIV. Female sex workers (FSW) have more than four times greater burden of HIV than other women of reproductive age in South Africa and the majority of FSW are mothers. For mothers who sell sex and are at increased HIV acquisition risk, timely and routine ANC seeking is especially vital for prevention of vertical transmission. This study represents a mixed-methods study with FSW in Port Elizabeth, South Africa, to characterize factors influencing ANC seeking behaviors in a high HIV prevalence context.MethodsFSW (n = 410) were recruited into a cross-sectional study through respondent-driven sampling between October 2014 and April 2015 and tested for HIV and pregnancy. A sub-sample of pregnant and postpartum women (n = 30) were invited to participate in in-depth interviews (IDIs) to explore their current or most recent pregnancy experiences. IDIs were coded using a modified grounded theory approach and descriptive analyses assessed the frequency of themes explored in the qualitative analysis among the quantitative sample.ResultsIn the quantitative survey, 77% of FSW were mothers (313/410); of these, two-thirds were living with HIV (212/313) and 40% reported being on antiretroviral therapy (ART) (84/212). FSW in the qualitative sub-sample reported unintended pregnancies with clients due to inconsistent contraceptive use; many reported discovering their unintended pregnancies between 4 and 7 months of gestation. FSW attributed delayed ANC seeking and ART initiation in the second or third trimesters to late pregnancy detection. Other factors limiting engagement in ANC included substance and alcohol use and discontent with previous healthcare-related experiences.ConclusionsLate pregnancy discovery, primarily because pregnancies were unplanned, contributed to late ANC presentation and delayed ART initiation, increasing risks of vertical HIV transmission. Given limited ART coverage among participants, addressing the broader sexual and reproductive health and rights needs of mothers who sell sex has important implications for preventing vertical transmission of HIV. Integrating comprehensive family planning services into FSW programming, as well as providing active linkage to ANC services may reduce barriers to accessing timely ANC, decreasing risks of vertical transmission.

Effect of ART scale-up and female migration intensity on risk of HIV acquisition: results from a population-based cohort in KwaZulu-Natal, South Africa

BackgroundDespite increased antiretroviral therapy (ART) coverage, the incidence of HIV infection among women in rural South Africa remains high. While many socio-demographic and behavioral factors have been identified, the effect of female migration intensity on the risk of HIV acquisition before and after ART scale-up has not been evaluated in the country.MethodsWe followed 13,315 female participants aged 15–49 who were HIV-uninfected at baseline and recorded their migration events between 2004 and 2015. Using a Cox proportional hazard model, we estimated the time to HIV acquisition among the women, adjusting for annual migration intensity (high: ≥2 events/year, moderate = 1 event/year, and low = 0 event/year) before and after ART scale-up in 2010.Results1998 (15%) new HIV-infection events were recorded during the observation period. Overall, high migration intensity was associated with an increased HIV acquisition risk among women when compared with low migration intensity (HR = 2.88, 95% CI: 1.56–5.53). Among those with high migration intensity, the risk of HIV acquisition was significantly lower in the post-ART period compared to the pre-ART period, after controlling for key socio-demographic and behavioural covariates (aHR = 0.18, 95% CI 0.04–0.83).ConclusionsWomen who migrated frequently after ART scale-up had a significantly reduced HIV acquisition risk compared to those before its implementation. While this reduction is encouraging, women who migrate frequently remain at high risk of HIV acquisition. In the era of ART, there remains a critical need for public health interventions to reduce the risk of HIV acquisition in this highly vulnerable population.

Antimicrobial and inflammatory properties of South African clinical Lactobacillus isolates and vaginal probiotics

Bacterial vaginosis (BV) causes genital inflammation and increased HIV acquisition risk. The standard-of-care for BV, antibiotic therapy, is associated with high recurrence rates. Probiotics may improve treatment outcomes, although substantial heterogeneity in efficacy has been observed during clinical trials. To evaluate the potential to improve existing probiotics, we compared the inflammatory and antimicrobial (adhesion, H2O2, D-lactate and L-lactate production) characteristics of 23 vaginal Lactobacillus isolates from South African women, commercial vaginal probiotics (L. casei rhamnosus, L. acidophilus) and 4 reference strains. All lactobacilli induced inflammatory cytokine production by genital epithelial cells and produced D-lactate. Of six isolates assessed, five suppressed inflammatory responses to Gardnerella vaginalis. Although the L. acidophilus probiotic was the most adherent, many clinical isolates produced greater amounts of H2O2, D-lactate and L-lactate than the probiotics. The most L-lactate and H2O2 were produced by L. jensenii (adjusted p = 0.0091) and L. mucosae (adjusted p = 0.0308) species, respectively. According to the characteristics evaluated, the top 10 isolates included 4 L. jensenii, 2 L. crispatus, 1 L. mucosae, 1 L. vaginalis and the L. acidophilus probiotic. There is potential to develop an improved vaginal probiotic using clinical Lactobacillus isolates. Inflammatory profiles are critical to evaluate as some isolates induced substantial cytokine production.

Effects of Migration on Risky Sexual Behavior and HIV Acquisition in South Africa: A Systematic Review and Meta-analysis, 2000-2017.

While human mobility has been implicated in fueling the HIV epidemic in South Africa, the link between migration and HIV has not been systematically reviewed and quantified. We conducted a systematic review of the role of migration in HIV risk acquisition and sexual behaviour based on 29 studies published between 2000 and 2017. Furthermore, we performed a meta-analysis of the association between migration and HIV risk acquisition in four of the studies that used HIV incidence as an outcome measure. The systematic review results show that HIV acquisition and risky sexual behavior were more prevalent among both male and female migrants compared to their non-migrant counterparts. The meta-analysis results demonstrate that migration was significantly associated with increased HIV acquisition risk (aOR = 1.69, 95% CI 1.33-2.14; I2 = 35.0%). There is an urgent need for effective combination HIV prevention strategies (comprising biomedical, behavioral and structural interventions) that target migrant populations.

Tenofovir and tenofovir-diphosphate concentrations during pregnancy among HIV-uninfected women using oral preexposure prophylaxis.

Pregnancy is a time of increased HIV acquisition risk and pregnancy reduces concentrations of antiretrovirals used for treatment. We assessed whether pregnancy lowers concentrations of tenofovir (TFV) and tenofovir-diphosphate (TFV-DP) among HIV-uninfected women using oral preexposure prophylaxis (PrEP). We analyzed data from an open-label PrEP study, comparing concentrations of TFV in plasma and TFV-DP in dried blood spots (DBS) among 37 pregnant women and 97 nonpregnant women. Analyses controlled for adherence from daily electronic monitoring. The average plasma concentration of TFV among pregnant women was 34.7 ng/ml with 22.2 average recorded doses over the prior month versus 86.5 ng/ml with 23.1 doses among nonpregnant women. After controlling for adherence, TFV concentrations were 58% lower among pregnant women, a statistically significant difference of -50.4 ng/ml (95% CI -68.3 to -32.5). The average TFV-DP concentration was 450.3 fmol/punch among pregnant women and 636.7 fmol/punch among nonpregnant women. This difference was not statistically significant after adjusting for adherence; however, among those with quantifiable TFV-DP, concentrations were 27% lower during pregnancy [-202 fmol/punch (95% CI -384 to -19)]. Among participants with samples before and during pregnancy, there were significant decreases during pregnancy, controlling for adherence: -28.1 ng/ml TFV (95% CI -52.3 to -4.0) and -289.2 fmol/punch TFV-DP (95% CI -439.0 to -139.3). Consistent with studies among HIV-infected women on ART, we found TFV and TFV-DP concentrations were lower during pregnancy. There is no established TFV concentration threshold to achieve HIV prevention. Additional pharmacokinetic studies and studies of PrEP efficacy in pregnancy are needed.

The Influence of Cervicovaginal Microbiota on Mucosal Immunity and Prophylaxis in the Battle against HIV.

Young women in sub-Saharan Africa bear a disproportionate burden of the global HIV epidemic. In this review, we examine how cervicovaginal microbiota modulate structural and immune defenses in the female genital tract and influence HIV susceptibility. Highly diverse, anaerobic cervicovaginal microbiota prevalent in sub-Saharan African women increase HIV acquisition risk by over fourfold. These bacteria weaken the barrier properties of the vaginal mucosa and increase local inflammation and HIV target cell recruitment, creating an environment permissive to HIV. These communities also diminish the prophylactic efficacy of topical tenofovir and therefore may modulate both biological susceptibility to HIV and the effectiveness of pre-exposure prophylaxis (PrEP). Cervicovaginal bacteria influence multiple reproductive health outcomes, including HIV acquisition. High-diversity, low Lactobacillus abundance cervicovaginal communities prevalent in many regions with high HIV incidence are associated with increased HIV susceptibility. A better understanding of the host-microbial interactions mediating this risk is important to reduce HIV infections, particularly among women living in sub-Saharan Africa.

A Depot Medroxyprogesterone Acetate Dose That Models Human Use and Its Effect on Vaginal SHIV Acquisition Risk.

Hormonal contraception with depot medroxyprogesterone acetate (DMPA) may increase HIV acquisition risk, but observational human studies are inconclusive, and animal models can help investigate this risk. In this study, we test the impact of a low DMPA dose, designed to resemble human contraceptive use, on Simian-Human Immunodeficiency Virus (SHIV) acquisition risk in pigtail macaques (Macaca nemestrina). Macaques metabolize DMPA faster than humans. We previously identified a per-weight DMPA dose and administration frequency that achieves long-lasting suppression of ovulation in macaques. Eight macaques were given 1.5-mg/kg DMPA monthly, whereas 11 were untreated controls. For comparison, women receive 150 mg (approximately 2 mg/kg) every 3 months. We exposed monkeys to 20 suboptimal SHIV challenges, designed to slowly infect half of controls and allow increased infection in the DMPA group. It took a median 5.5 viral challenges to infect DMPA-treated macaques and 9 challenges for controls (P = 0.27; exact conditional logistic regression). The exact odds ratio was 2.2 (CI: 0.6 to 8.3). Ovulation was suppressed, and the vaginal epithelium was thinned after DMPA treatment in all animals (mean, 30 and 219 mm in DMPA-treated and control macaques, respectively, P = 0.03, t test using the Satterthwaite degrees-of-freedom approximation). SHIV infections in DMPA-treated macaques were 2.2 times those of controls, but this was not statistically significant. The result is remarkably similar to studies of human DMPA use, which have shown HIV risk increases of a similar magnitude and of variable significance. Taken together with previous studies of higher DMPA doses in macaques, the results suggest a dose-dependent effect of DMPA on Simian Immunodeficiency Virus (SIV) or SHIV acquisition.

Genital inflammation, immune activation and risk of sexual HIV acquisition.

Women who have genital inflammation are at increased risk of sexual HIV infection. The purpose of this review is to evaluate the mechanisms for this relationship, causes of genital inflammation, and strategies to manage this condition. We have recently shown in a cohort of South African women that HIV seroconversion was associated with persistently raised genital inflammatory cytokines (including MIP-1α, MIP-1β, and IP-10). Elevated inflammatory cytokine concentrations may facilitate HIV infection by recruiting and activating HIV target cells and disrupting the mucosal epithelial barrier. Bacterial vaginosis and sexually transmitted infections (STIs), which are predominantly asymptomatic in women, cause lower genital tract inflammation and increased HIV acquisition risk. In Africa, where syndromic management of STIs and bacterial vaginosis is standard-of-care, the substantial burden of asymptomatic infections has likely contributed to high-HIV incidence rates. A genital inflammatory profile contributes to the high risk of HIV acquisition in African women. STIs and bacterial vaginosis are poorly managed in Africa and other developing nations and as such remain major drivers of persistent genital inflammation and HIV acquisition among these women.

HORMONAL CONTRACEPTION AND THE RISK OF HIV ACQUISITION

AbstractIntroduction:More than 100 million women worldwide use hormonal contraceptive, including using DMPA ororal contraceptive. There is particular concern about a putative link between hormonalcontraception and HIV infection. The aim of this review article was to evaluate the associationbetween hormonal contraception use and risk of HIV infectionMethods:We were retrieved through a systematic search of electronic databases such as PubMed, ScienceDirect, Elsevier, BMJ, JAMA by utilizing keywords HIV prevention, hormonal contraception,women's` health, risk factors and human immunodeficiency virus (HIV). This search conducted forrelevant literature published between 1989 and 2013.Finding:An estimated 40 million people live with human immunodeficiency virus (HIV) globally. Most HIVinfected human are of reproductive age 15–49 years. Approximately 45% of women usinghormonal contraceptions. Long term used of Progestin-only Injectable such as DMPA and NETEN,may cause thinning of cervico-vaginal mucosa, it may lead to abrasions that facilitate access ofHIV to CD4+ target cells in submucosal tissue and increased simian immunodeficiency virusacquisition. Although the clinical significance of this thinning remains uncertain.Conclusions:The data do not support an association between use of oral contraceptives and increased risk ofHIV acquisition. Nonetheless, family planning services are an important venue for HIV preventionactivitiesKeywords:Hormonal Contraception, HIV, Risk Factors, Women Health

Transient global T cell activation after vaccination of rhesus macaques with a DNA-poxvirus vaccine regimen for HIV

Persistent T cell activation following immunization with HIV vaccines may increase HIV acquisition risk. We investigated the magnitude and kinetics of T cell activation following vaccination of rhesus macaques with a candidate HIV vaccine consisting of a recombinant DNA and MVA vaccination regimen. We show that global CD4+ and CD8+ T cell activation, as measured by the expression of Ki67 and Bcl-2, peaked one week after boosting with MVA, but then waned rapidly to pre-vaccination levels. Furthermore, increased frequencies of CD4+ CCR5+ T cells, which represent potential HIV target cells, were short-lived and decreased to baseline levels within two months. Activated CD4+ T cells were predominantly of a central memory phenotype, and activated CD8+ T cells were distributed between central and effector memory phenotypes. Thus, only transient changes in T cell activation occurred following poxvirus vaccination, indicating a lack of persistent immune activation.

Injectable Contraceptive Use Correlates with Increased HIV Target Cells at the Cervix in Young South African Women

Background: The use of progestin-only injectable contraception (IC) has been epidemiologically associated with increased risk of HIV acquisition but it remains unclear whether this relationship is causal and if so the mechanisms by which progestin-only contraceptives increase risk. Methods: Demographic and behavioral data along with blood and female genital tract (FGT) samples were obtained from a cohort of 18-23 year old HIV uninfected women in Durban South Africa. Cervical cytobrush cells were analyzed by flow cytometry and plasma progesterone measured by chemiluminescence. Cytokines in cervico-vaginal lavage (CVL) were measured by luminex. Results: Women using IC disproportionately accounted for new HIV infections during the study (RR 2.55 [1.90-3.42] p=0.0018). While 31.5% of women in the cohort used IC 72.7% of women who became HIV positive used IC (8 of 11); 9.09% of infected women did not use contraception. This difference was not accounted for by behavioral or demographic differences. The use of IC was significantly associated with a higher frequency of CD4+CCR5+ T cells of CD45+ cells in the cervix relative to those not on hormonal contraception (1.18% [0.33 4.53] vs. 0.29% [0.13 0.48] respectively; p=0.036). Women with high endogenous progesterone (>0.3ng/mL luteal phase) in the absence of IC use had significantly increased frequency of CD4+CCR5+ T cells in the cervix relative to those with low progesterone (follicular phase; 1.16% [0.51 3.76] of CD45+ cells vs 0.29% [0.13 0.48] respectively; p=0.042). High endogenous progesterone was also associated with a higher frequency of cervical CD4+CCR5+HLADR+CD38+ T cells (p=0.034). There was no observed difference based on IC use in soluble cytokine or chemokine levels in CVL. Conclusions: The increased frequency of HIV target cells at the site of exposure in the context of IC and high endogenous progesterone provides a potential biological mechanism for the increased HIV acquisition risk for women using injectable progestin-only contraceptives.