Human Immunodeficiency Virus Shedding Research Articles

Evaluation of Chlamydia trachomatis and HR-HPV infection in women living with HIV: a cross-sectional study

Introduction: Infections caused by Chlamydia trachomatis (CT) and Human Papilloma Virus (HPV) are among the most prevalent sexually transmitted infections (STIs) worldwide. CT infection in women living with the human immunodeficiency virus (HIV) can facilitate HIV transmission by increasing HIV shedding in cervicovaginal secretions. The prevalence of Human papillomavirus (HPV) infection is higher in women living with HIV when compared to HIV-negative women, even when comparing those with the same sociodemographic characteristics. Generally, they have a high viral load and a higher persistence of viral infection, which increases the risk of developing premalignant and malignant lesions in the lower genital tract. Objective: To evaluate the frequency of CT and High-Risk HPV (HR-HPV) infection among women living with HIV and the association with sociodemographic, behavioral and clinical characteristics. Methods: Cross-sectional study carried out with a population of 66 non-pregnant women aged between 18 and 70 years living with HIV and/or acquired immunodeficiency syndrome (AIDS) at the Hospital Universitário Antônio Pedro, Universidade Federal Fluminense (UFF), Niterói (RJ), Brazil, between the period of March 1, 2018 and October 31, 2018. A standardized questionnaire was applied including sociodemographic and behavioral characteristics, and clinical information (use of oral contraceptives, Antiretroviral Therapy (ART), cluster of differentiation 4 (CD4) cell count, and viral load). Endocervical samples were collected for CT (COBAS 4800® system, Roche) and HPV (COBAS® HPV test, Roche) detection. Fisher's Exact Test was used to assess the association between variables. Regression analyses were performed using the logistic model in order to identify the factors associated with the outcomes of interest. Results: A frequency of 1.5% for CT and 21.2% for HR-HPV was found. Age was the single factor that presented statistical significance associated with HR-HPV infection. Conclusion: Our study showed that some women living with HIV promote risky behavior which could facilitate the acquisition of other STIs, such as HPV and CT infection. Some of them, with detected viral load, were not using condoms even with HIV-negative partners. These results may suggest that in addition to treatment and follow-up of women living with HIV, STIs counseling and guidance may play an important role in the control of STIs in this population.

Effects of Urethritis on Human Immunodeficiency Virus (HIV) in Semen: Implications for HIV Prevention and Cure.

Prior to the widespread availability of antiretroviral therapy (ART), men living with human immunodeficiency virus (HIV) with urethritis had increased concentrations of HIV in semen. This study aims to better evaluate HIV shedding in men with urethritis receiving ART, and its implications for the cure of HIV. Men living with HIV with urethritis taking ART ≥12 weeks were enrolled at a sexually transmitted infections clinic in Lilongwe, Malawi. Study follow-up included visits at 1, 2, 4, 8, 12, 24, 36, and 48 weeks after urethritis diagnosis and treatment. Matched blood and semen samples were collected at all visits, and all additional episodes of urethritis were followed with extra visits 1, 2, and 4 weeks after treatment. There were 111 men enrolled in the study between January 2017-March 2019, and 77 (69%) were suppressed in the blood (<400 copies/mL). Among the 77 men, 87 episodes of urethritis were evaluated during follow-up. Of the 87 episodes, 15 episodes (17%) had instances of seminal viral shedding ≥400 copies/mL despite viral suppression in the blood. During nonurethritis follow-up, ≤6% of men at each visit had a viral load ≥400 copies/mL in the semen while maintaining viral suppression in the blood. An HIV cure requires the elimination of HIV from every body compartment, but available ART does not currently accomplish this. Our study highlights the male genital tract as a local source of HIV that can be reversibly activated. A better understanding of this phenomenon is important to advance the HIV cure field.

Impact of Herpes Simplex Virus Type 2 and Human Immunodeficiency Virus Dual Infection on Female Genital Tract Mucosal Immunity and the Vaginal Microbiome.

Mechanisms linking herpes simplex virus type 2 (HSV-2) with human immunodeficiency virus (HIV) are not fully defined. We tested the hypothesis that HSV-2 and HIV dual infection is associated with cervicovaginal inflammation and/or vaginal dysbiosis. Genital tract samples were obtained weekly over a 12-week period from 30 women seropositive (+) for HIV and HSV-2 and 15 women each who were seropositive for one or seronegative (-) for both viruses. Immune mediators, antimicrobial activity, and microbial composition and diversity were compared. Significant differences in the concentrations of interferon-γ (P = .002), tumor necrosis factor-α (P = .03), human beta defensin 1 (P = .001), secretory leukocyte protease inhibitor (P = .01), and lysozyme (P = .03) were observed across the 4 groups (Kruskal-Wallis). There were also significant differences in vaginal microbial alpha diversity (Simpson index) (P = .0046). Specifically, when comparing HIV-1+/HSV-2+ to HIV-1-/HSV-2- women, a decrease in Lactobacillus crispatus and increase in diverse anaerobes was observed. The number of genital HSV outbreaks was greater in HIV+ versus HIV- women (39 versus 12) (P = .04), but there were no significant differences when comparing outbreak to non-outbreak visits. Increased microbial diversity and cervicovaginal inflammation in HIV and HSV-2 dually infected women may adversely impact genital health and, in the absence of antiretroviral therapy, facilitate HIV shedding.

Increased Cervical Human Immunodeficiency Virus (HIV) RNA Shedding Among HIV-Infected Women Randomized to Loop Electrosurgical Excision Procedure Compared to Cryotherapy for Cervical Intraepithelial Neoplasia 2/3.

Treatment of human immunodeficiency virus (HIV)-infected women to prevent cervical cancer may stimulate HIV RNA cervical shedding and risk HIV transmission. From 2011 to 2014, 400 HIV-infected women diagnosed with cervical intraepithelial neoplasia 2/3 in Kenya were randomized to loop electrosurgical excision procedure (LEEP) or cryotherapy. Cervical samples were collected at baseline and 3 weekly intervals. Samples were tested for HIV RNA using the Gen-Probe Aptima HIV assay with a minimum detection level of 60 copies/swab and analyzed using generalized estimating equations. Women who received LEEP had significantly higher cervical HIV RNA levels than those who received cryotherapy at weeks 2 (adjusted incident rate ratio [aIRR], 1.07; P = .038) and 3 (aIRR, 1.08; P = .046). Within LEEP, significantly higher cervical shedding was found at weeks 2 (2.03 log10 copies/swab; P < .001) and 3 (2.04 log10 copies/swab; P < .001) compared to baseline (1.80 log10 copies/swab). Cervical HIV RNA was significantly higher following LEEP for up to 3 weeks among women on antiretroviral treatment (ART) (0.18 log10 copies/swab increase; P = .003) and in ART-naive women (1.13 log10 copies/swab increase; P < .001) compared to baseline. Within cryotherapy, cervical shedding increased in ART-naive women (0.72 log10 copies/swab increase; P = 0.004) but did not increase in women on ART. Women randomized to LEEP had a larger increase in post-procedural cervical HIV shedding than cryotherapy. Benefits of cervical cancer prevention outweigh the risk of HIV sexual transmission; our findings underscore the importance of risk-reduction counseling. NCT01298596.

Clinical and Mucosal Immune Correlates of HIV-1 Semen Levels in Antiretroviral-Naive Men.

BackgroundThis study was done to characterize parameters associated with semen human immunodeficiency virus (HIV)-1 ribonucleic acid (RNA) viral load (VL) variability in HIV-infected, therapy-naive men.MethodsPaired blood and semen samples were collected from 30 HIV-infected, therapy-naive men who have sex with men, and 13 participants were observed longitudinally for up to 1 year. Human immunodeficiency virus RNA, bacterial load by 16S RNA, herpesvirus (Epstein-Barr virus and cytomegalovirus [CMV]) shedding, and semen cytokines/chemokines were quantified, and semen T-cell subsets were assessed by multiparameter flow cytometry.ResultsSemen HIV RNA was detected at 93% of visits, with >50% of men shedding high levels of virus (defined as >5000 copies/mL). In the baseline cross-sectional analysis, an increased semen HIV VL correlated with local CMV reactivation, the semen bacterial load, and semen inflammatory cytokines, particularly interleukin (IL)-8. T cells in semen were more activated than blood, and there was an increased frequency of Th17 cells and γδ-T-cells. Subsequent prospective analysis demonstrated striking interindividual variability in HIV and CMV shedding patterns, and only semen IL-8 levels and the blood VL were independently associated with semen HIV levels.ConclusionsSeveral clinical and immune parameters were associated with increased HIV semen levels in antiretroviral therapy-naive men, with induction of local proinflammatory cytokines potentially acting as a common pathway.

Detection of human immunodeficiency virus-1 ribonucleic acid in the peritoneal effluent of renal failure patients on highly active antiretroviral therapy.

We evaluated the shedding of human immunodeficiency virus (HIV)-1 particles into continuous ambulatory peritoneal dialysis (CAPD) effluents of HIV-positive patients with end-stage renal disease (ESRD). A total of 58 HIV-positive patients with ESRD on highly active antiretroviral therapy (HAART) who had Tenckhoff catheters inserted between September 2012 and February 2015 were prospectively reviewed and followed for 18 months. Peritoneal dialysis (PD) effluent samples from functioning CAPD catheters and plasma samples were obtained at three points during regular clinic visits on days 45 ± 37, 200 ± 19 and 377 ± 13 after catheter insertion. All specimens were stored at -20°C, and each batch was analysed by Roche quantitative HIV-1 polymerase chain reaction assay to detect HIV-1 particles. Clustered logistic regression was used to test for independent predictors of HIV-1 detection in CAPD effluents. HIV-1 RNA above 20 copies/mL assay limit was detectable in 19% (first batch), 26.3% (second batch) and 20% (third batch) of PD effluent specimens. HIV-1 RNA was detectable in PD fluid, without corresponding detection in the paired plasma in 3.4% (first batch), 5.3% (second batch) and 10% (third batch) of samples. Detection of HIV-1 in plasma sample (odds ratios 3.94; 95% confidence interval 1.14-13.55; P = 0.030), body mass index, serum albumin and HAART regimen were found to be significantly associated with HIV-1 detection in PD effluents. HIV particles are shed in detectable amounts into CAPD effluents even in patients with suppressed plasma viral load, raising concerns of a localized sanctuary site and potential infectivity of HIV-positive CAPD patients on a full complement of HAART.

Penile Immune Activation and Risk of HIV Shedding: A Prospective Cohort Study.

Genital immune activation is suspected to modulate local human immunodeficiency virus (HIV) RNA levels and the risk of sexual HIV transmission. A prospective, observational cohort study of 221 HIV-infected men undergoing male circumcision (MC) was conducted in Rakai, Uganda. Penile lavage samples collected from the coronal sulcus at baseline and 4 weekly visits after MC were assayed for pro-inflammatory cytokines and HIV RNA. The main analysis was limited to 175 men with detectable HIV plasma viral load (VL > 400 copies/mL; n = 808 visits). The primary exposures of interest were individual and total cytokine detection at the previous postoperative visit. Adjusted prevalence risk ratios (adjPRR) of detectable HIV shedding (VL > 40 copies/mL) were estimated by Poisson regression models with generalized estimating equations and robust variance estimators and included adjustment for plasma HIV VL. Among men with a detectable plasma VL, penile HIV shedding was detected at 136 visits (16.8%). Detectable interleukin (IL)-1β (adjPRR = 2.14; 95% confidence interval (CI) = 1.02-4.48), IL-6 (adjPRR = 2.24; 95% CI = 1.28-3.90), IL-8 (adjPRR = 2.42; 95% CI = 1.15-5.08), IL-10 (adjPRR = 2.51; 95% CI = 1.67-3.80), and IL-13 (adjPRR = 1.87; 95% CI = 1.15-3.03) were associated with penile HIV shedding at the subsequent visit. Men with 2-4 (adjPRR = 2.36; 95% CI = 1.08-5.14) and 5-7 (adjPRR = 3.00; 95% CI = 1.28-7.01) detectable cytokines had a greater likelihood of detectable penile HIV shedding at the subsequent visit, compared to men with ≤ 1 detectable cytokine. The total number of detectable cytokines was also associated with a higher penile log10 HIV VL at the subsequent visit among HIV shedders. Pro-inflammatory cytokine production had a dose-dependent and temporal association with penile HIV shedding, suggesting that genital immune activation may increase the risk of sexual HIV transmission by driving local HIV replication.

Increased Epstein–Barr virus in breast milk occurs with subclinical mastitis and HIV shedding

Epstein-Barr virus (EBV) in breast milk and subclinical mastitis (SCM) are both associated with human immunodeficiency virus (HIV) shedding and possibly with postnatal HIV transmission. The objective of this nested case-control study was to investigate the interplay between SCM and EBV replication in breast milk of HIV-infected mothers.The relationships between EBV deoxyribonucleic acid (DNA) shedding, HIV-1 ribonucleic acid (RNA) level, and SCM were explored in breast milk samples of Zambian mothers participating in the ANRS 12174 trial. Mammary gland inflammation was defined as a breast milk sodium to potassium ratio (Na/K) greater than 0.6 and further subclassified as either "possible SCM" (Na/K ratio 0.6-1.0) or SCM (Na/K ratio ≥ 1.0). Breast milk interleukin 8 (IL-8) was measured as a surrogate marker of mammary gland inflammation.EBV DNA was detected in breast milk samples from 42 out of 83 (51%) participants and was associated with HIV-1 shedding in breast milk (P = 0.006). EBV DNA levels were higher in samples with SCM and "possible SCM" compared to non-SCM breast milk samples (P = 0.06; P = 0.007). An EBV DNA level of >200 copies/mL was independently associated with SCM and "possible SCM" (OR: 2.62; 95%: 1.13-6.10). In patients with SCM, higher EBV replication in the mammary gland was associated with a lower induction of IL-8 (P = 0.013). Resistance to DNase treatment suggests that EBV DNA in lactoserum is encapsidated.SCM and decreased IL-8 responses are associated with an increased EBV shedding in breast milk which may in turn facilitate HIV replication in the mammary gland.

Mycoplasma genitalium infection is associated with microscopic signs of cervical inflammation in liquid cytology specimens.

Cervicitis is a common clinical finding often attributed to sexually transmitted infections (STIs), but no etiologic agent is identified in the majority of cases. In this study, we comparatively assessed inflammation among the common infectious etiologies of cervicitis and assessed the potential value of liquid cytology specimens for predicting STIs. Among 473 Louisiana women at low risk for acquiring STIs, the prevalences of Mycoplasma genitalium, Chlamydia trachomatis, Neisseria gonorrhoeae, and Trichomonas vaginalis in liquid-based cytology specimens were 1.5, 2.1, 0.6, and 4.4%, respectively. N. gonorrhoeae and human papillomavirus 18 (HPV18) infections were significantly more common among subjects infected with M. genitalium. Using direct microscopy, we observed significant increases in leukocyte infiltrates among subjects with monoinfections with M. genitalium or C. trachomatis compared to women with no detectable STIs. Inflammation was highest among subjects with M. genitalium. Using a threshold of ≥ 2 leukocytes per epithelial cell per high-powered field, the positive predictive values for M. genitalium, C. trachomatis, N. gonorrhoeae, and T. vaginalis were 100, 70, 67, and 20%, respectively. Several novel M. genitalium genotypes were identified, all of which were predicted to be susceptible to macrolide antibiotics, suggesting that different strains may circulate among low-risk women and that macrolide resistance is substantially lower than in high-risk populations. This study highlights the capacity of M. genitalium to elicit cervical inflammation and, considering the strong epidemiologic associations between M. genitalium and human immunodeficiency virus (HIV), provides a potential mechanism for acquisition and shedding of HIV via chronic leukocyte recruitment to the cervical mucosa.

Quotidian changes of genital tract cytokines in human immunodeficiency virus-1-infected women during the menstrual cycle.

The role of hormonal changes throughout the menstrual cycle on genital tract inflammation during chronic human immunodeficiency virus (HIV) infection is not well defined, but it has implications for HIV prevention. We assessed daily levels of 26 vaginal cytokines and chemokines from 15 women infected with HIV-1. Taking into account coexisting sexually transmitted infections, behavioral factors, and menstruation, this study illustrates cyclic patterns of granulocyte macrophage colony-stimulating factor, interferon-α2, interleukin (IL)-6, IL-10, macrophage inflammatory protein (MIP)-1α, MIP-1β, and tumor necrosis factor (TNF)-α. Progesterone was associated with levels of granulocyte colony-stimulating factor, IL-1α, and monocyte chemoattractant protein-1. Interferon-α2, IL-6, MIP-1α, MIP-1β, and TNF-α levels predicted HIV shedding, but these associations were heavily influenced by the menstrual cycle.

Distinct Cytokine Patterns in Semen Influence Local HIV Shedding and HIV Target Cell Activation

Semen is the main vector for human immunodeficiency virus (HIV) transmission from men to women. We investigated the influence of cytokines in semen on local HIV burden and activated T cells. Blood and semen were collected from 42 HIV-negative and 38 HIV-positive men. Concentrations of 20 cytokines were measured by Luminex, and frequencies of activated T cells were measured by flow cytometry. Semen contained higher concentrations of proinflammatory (monocyte chemotactic protein-1, interleukin [IL]-8, IL-6, Fractalkine, macrophage inflammatory protein (MIP)-1β, granulocyte macrophage colony-stimulating factor) and adaptive cytokines (IL-7 and IL-15) and higher frequencies of activated T cells compared to blood. Plasma IL-2, eotaxin, MIP-1β, and IL-15 and semen eotaxin and granulocyte colony-stimulating factor (G-CSF) concentrations were associated with T-cell activation. Cytokines in semen were highly coregulated in HIV-negative men; however, this network was disrupted during HIV infection. Several cytokines in semen correlated with HIV shedding (G-CSF, tumor necrosis factor-alpha [TNF-α], interferon-gamma [IFN-γ], IL-10). Higher levels of inflammation and T-cell activation were observed in semen compared with blood. Seminal G-CSF, which influences neutrophil survival, T-cell function, and dendritic cell activation, was associated with T-cell activation and HIV shedding and may be an important target for reducing HIV shedding or risk.

Shedding of HIV and Human Herpesviruses in the Semen of Effectively Treated HIV-1–Infected Men Who Have Sex With Men

Current antiretroviral therapy (ART) suppresses human immunodeficiency virus (HIV) in blood to undetectable levels in most infected individuals; however, some men shed HIV in semen despite suppressed levels in blood. This study included 114 chronically HIV type 1-infected men who have sex with men, who were receiving ART with blood plasma HIV <500 copies/mL. Asymptomatic participants were screened for bacterial sexually transmitted infections (STIs) and nonspecific genital inflammation. Levels of HIV and 7 human herpesviruses were measured by real-time polymerase chain reaction in seminal plasma. Predictors of HIV seminal shedding were determined for the entire cohort, and on the subset of 100 subjects with blood plasma HIV <50 copies/mL. Eleven subjects (9.6%) had detectable levels of seminal HIV (median, 2.1 log10 copies/mL), and 72 (63.2%) had at least 1 herpesvirus detected in their seminal plasma. Detectable levels of seminal HIV were present more often in persons with plasma HIV between 50 and 500 copies/mL compared to those <50 copies/mL (P values adjusted for false discovery rate [FDR] = 0.08). There was a trend for high-level cytomegalovirus (CMV; >4 log10 DNA copies/mL; FDR-adjusted P = .08), and presence of Epstein-Barr virus (FDR-adjusted P = .06) in semen to be associated with detectable seminal HIV levels. In a subanalysis of 100 subjects with blood plasma HIV <50 copies/mL, high levels of CMV in semen was the only significant predictor for seminal HIV shedding. Low-level HIV replication in blood and high-level seminal CMV shedding, but not presence of asymptomatic STIs, is associated with seminal shedding of HIV in men receiving ART, conferring a potential risk for HIV transmission.

Cyclic Changes in HIV Shedding From the Female Genital Tract During the Menstrual Cycle

Factors increasing genital human immunodeficiency virus (HIV) shedding may increase female-to-male HIV transmission risk. We examined HIV shedding in 67 women with HIV type 1 and herpes simplex virus type 2 coinfection, during 2 menstrual cycles. Shedding occurred in 60%, 48%, and 54% of samples during the follicular, periovulatory, and luteal phases, respectively (P = .01). Shedding declined after menses until ovulation, with a slope -0.054 log10 copies/swab/day (P < .001), corresponding to a change of approximately 0.74 log10 copies between peak and nadir levels. Shedding increased during the luteal phase only among women with CD4 counts of <350 cells/µL. In reproductive-aged women, shedding frequency and magnitude are greatest immediately following menses and lowest at ovulation.

Cervical Human Papillomavirus Infection and Shedding of Human Immunodeficiency Virus in Cervicovaginal Fluids

We evaluated the association between human papillomavirus cervical infection and HIV shedding in cervicovaginal lavage fluid (CVL), studying 89 HIV-infected women recruited at the Department of Infectious Diseases of Brescia (Italy). HIV shedding in CVL was found in a similar proportion of women with (30%; 21/70) and without (31.6%; 6/19) cervical human papillomavirus infection. A statistically significant correlation was found between HIV viral load in serum and CVL among the 27 women with detectable HIV in CVL (r = 0.4; P = 0.04). However, women on highly active antiretroviral therapy were more likely to have detectable HIV-RNA in CVL despite negative viremia (80% vs. 8%; P < 0.005).

British HIV Association guidelines for the management ofHIVinfection in pregnant women 2012

British HIV Association guidelines for the management of<scp>HIV</scp>infection in pregnant women 2012

Correlates of human immunodeficiency virus cervicovaginal shedding among postmenopausal and fertile-aged women

The aims of this study were to compare the intensity of human immunodeficiency virus (HIV)-RNA genital shedding among postmenopausal (PM) and fertile-aged (F) women and to investigate the association between viral shedding and gynecological features, HIV plasma viral loads, and other markers of HIV disease progression. We interviewed 146 HIV-infected women (73 PM/73 F) in search of gynecological complaints and signs and symptoms of HIV disease and obtained additional information concerning HIV infection by medical chart review. Cervicovaginal lavages (CVLs) were collected for assessment of HIV shedding. Laboratory analyses included CD4 cell counts, HIV-RNA quantitation in plasma and CVL, and screening for concurrent genital infections. HIV-RNA genital shedding was detected in 16.4% of PM and 21.9% of F women (P = 0.400), and the intensity of HIV shedding did not differ between both groups (means-PM: 1.4log/mL; F: 1.4log/mL; P = 0.587). Three women (2 PM/1 F) exhibited viral shedding in the absence of detectable viremia. HIV plasma viral loads correlated with HIV shedding in both groups. In multivariable analysis, HIV plasma viral loads were independently associated with HIV shedding in both groups. Moreover, the intensity of shedding was independently associated with vaginal pH, tumor necrosis factor α concentrations in CVL, and HIV plasma viral loads. Despite significant changes that occur in the vaginal mucosa of PM women, HIV cervicovaginal shedding was not significantly influenced by this state in our cohort. In contrast, increased vaginal pH and genital inflammation, evidenced by increased tumor necrosis factor α concentrations in CVL and HIV plasma viral loads, were independently associated with the intensity of HIV shedding in PM and F women.

Immune Activation in the Female Genital Tract During HIV Infection Predicts Mucosal CD4 Depletion and HIV Shedding

Plasma viral load predicts genital tract human immunodeficiency virus (HIV) shedding in HIV-infected women. We investigated whether local mucosal T-cell activation (HLA-DR, CD38, CCR5, and Ki67) contributed to HIV shedding in the genital tracts of HIV-infected women. We showed that cervical cytobrush-derived T cells expressed higher frequencies of T-cell activation markers (CD38+ and HLA-DR+) than blood-derived T cells. Expression was significantly higher in HIV-infected women than in uninfected women. We found that the frequency of activated proliferating cervical T cells (Ki67+; Ki67+CCR5+) broadly predicted HIV shedding in the genital tract in HIV-infected women, independently of plasma viral loads. Furthermore, activated cervical T cells (HLA-DR+CD38+ and HLA-DR+CCR5+) and local HIV shedding were independently associated with CD4 depletion in the genital tract. These data suggest that the presence of high frequencies of activated T cells in the female genital mucosa during HIV infection facilitates both local HIV shedding and CD4 T-cell depletion.

Low-dose combined oral contraceptive and cervicovaginal shedding of human immunodeficiency virus

Background The role of low-dose oral contraceptives on HIV cervicovaginal shedding among HIV-positive women is controversial. Study Design We evaluated the effect of low-dose oral contraceptives on HIV cervicovaginal shedding in a cohort of 285 HIV-seropositive women followed for a median of 20 months. A sensitive, competitive polymerase chain reaction (cPCR) and a reverse transcription PCR (cRT-PCR) were applied for the quantification of HIV-associated and cell-free RNA and proviral DNA in cervicovaginal cells, as well as HIV-RNA in plasma. Results In multivariable logistic generalized estimating equations, plasma viral load >100 copies/mL (OR=1.81, 95% CI=1.3–2.53) and bacterial vaginosis (OR=1.49, 95% CI=1.1–2.02) were associated with an increased risk of HIV-1 DNA shedding, whereas current use of oral contraceptive was associated with a reduced risk (OR=0.55, 95% CI=0.33–0.92). Oral contraceptives were also associated with a reduction of risk (OR=0.38, 95% CI=0.21–0.69) of cell-associated but not cell-free HIV-1 RNA. Conclusions In HIV-positive women with low levels of HIV viremia, low-dose oral contraceptives were associated with a modest but significant reduction of HIV-1 DNA and cell-associated HIV-1 RNA genital shedding.

Elevated Cervical White Blood Cell Infiltrate Is Associated with Genital HIV Detection in a Longitudinal Cohort of Antiretroviral Therapy–Adherent Women

Identification of factors associated with the presence of human immunodeficiency virus (HIV) in female genital secretions is critical for intervention strategies targeting transmission and eliminating replication of genital virus. We sought to monitor the prevalence of genital HIV shedding in antiretroviral therapy-adherent women over time and to assess changes in the genital microenvironment. Levels of cell-free HIV (HIV RNA) and HIV-infected cells (HIV DNA) were monitored in peripheral blood samples and cervical and vaginal fluid samples at monthly intervals in 11 women for 1 year. Genital tract infections and fluctuations in cervical and vaginal white blood cell counts were also evaluated at each study visit. Plasma HIV was undetectable at the majority of study visits; when detected, it was only at low levels. Throughout the study, genital HIV RNA and DNA were detected in each person. Combined genital HIV (RNA and DNA) was detected at 49.2% of study visits and was associated with an elevated concentration of cervical white blood cell infiltrate (odds ratio, 2.52 [95% confidence interval, 1.01-6.22]; P = .04). Infiltrate was not associated with a clinical disorder or patient-reported symptoms. Despite antiretroviral therapy adherence and clinically suppressed plasma viremia, HIV was intermittently detected in genital secretions and was associated with subclinical inflammation and cells trafficking to the cervical mucosa.

Determinants of HIV Type 1 Shedding from Genital Ulcers among Men in South Africa

Our study evaluated correlates of human immunodeficiency virus (HIV)-1 lesional shedding among men with genital ulcer disease (GUD). Participants were recruited at primary health care clinics as part of a randomized trial of episodic acyclovir among men with GUD. This analysis was done among HIV-positive men identified at baseline. Participants were serologically screened for HIV infection, syphilis, and herpes simplex virus type 2 infection and for urethritis and ulcer etiology by polymerase chain reaction. Plasma and genital ulcer HIV-1 loads and CD4 cell counts were quantified. We evaluated variables associated with the presence and quantity of HIV-1 in ulcers. Among 387 HIV-positive men, the median plasma HIV-1 load and CD4 cell count were 87,200 copies/mL and 282 cells/mm(3). Overall, 173 (45.6%) had detectable HIV-1 RNA in ulcers. Men with Trichomonas vaginalis infection had higher ulcer viral loads on average than did those who were not infected (mean difference, 0.62; 95% confidence interval [CI], 0.07-1.2; P=.027). After multivariable analysis, higher plasma HIV-1 load (odds ratio [OR], 2.5; 95% CI, 1.7-3.5; P< .001), larger lesions (OR, 2.5; 95% CI, 1.5-4.1; P < .001), purulent ulcers (OR, 2.2; 95% CI, 1.1-4.2; P <.02), multiple ulcers (>5; OR, 3.6; 95% CI, 1.6-8.4; P=.002), and herpes seropositivity (OR, 3.4; 95% CI, 1.7-7.0; P < .001) remained associated with increased odds of HIV-1 lesional shedding. Ulcers associated with herpes simplex virus type 2 infection were less likely to shed (OR, 0.6; 95% CI, 0.3-1.0; P =.05), compared with ulcers with unknown etiology. HIV-positive men should be screened and treated for GUD to minimize HIV shedding and transmission to uninfected sexual partners.