Meeting the needs of HIV-infected pregnant women requires understanding their backgrounds and potential barriers to care and safe pregnancy. Foreign-born women are more likely to have language, educational, and economic barriers to care, but may be even more likely to choose to keep a pregnancy. Data from HIV-infected pregnant women and their children in Rhode Island were analyzed to identify trends in demographics, viral control, terminations, miscarriages, timing of diagnosis, and adherence to followup. Between January 2004 and December 2009, 76 HIV-infected women became pregnant, with a total of 95 pregnancies. Seventy-nine percent of the women knew their HIV status prior to becoming pregnant. Fifty-four percent of the women were foreign-born and 38 percent of the 16 women who chose to terminate their pregnancies were foreign-born. While the number of HIV-infected women becoming pregnant has increased only slightly, the proportion that are foreign-born has been rising, from 41 percent between 2004 and 2005 to 57.5 percent between 2006 and 2009. A growing number of women are having multiple pregnancies after their HIV diagnosis, due to the strength of their desire for childbearing and the perception that HIV is a controllable illness that does not preclude the creation of a family.

Background

We have previously demonstrated intrinsic anti-HIV activity in cervicovaginal lavage (CVL) from HIV-infected women with high CD4 counts and not on antiretroviral therapy. However, the impact of HIV disease progression on CVL innate immune responses has not been delineated.

Methods

CVL from 57 HIV-infected women not on antiretroviral therapy were collected by washing the cervicovaginal area with 10 ml of sterile normal saline. We characterized subject HIV disease progression by CD4 count strata: >500 cells/µl, 200–500 cells/µl, or <200 cells/µl of blood. To assess CVL anti-HIV activity, we incubated TZM-bl cells with HIV plus or minus CVL. Antimicrobials, cytokines, chemokines and anti-gp160 HIV IgG antibodies were measured by ELISA and Luminex.

Results

CVL exhibited broad anti-HIV activity against multiple laboratory-adapted and transmitted/founder (T/F) viruses, with anti-HIV activity ranging from 0 to 100% showing wide variation between viral strains. Although there was broad CVL inhibition of most both laboratory-adapted and T/F virus strains, there was practically no inhibition of T/F strain RHPA.c, which was isolated from a woman newly infected via heterosexual intercourse. HIV disease progression, measured by declining CD4 T cell counts, resulted in a selective reduction in intrinsic anti-HIV activity in CVL that paralleled CVL decreases in human beta-defensin 2 and increases in Elafin and secretory leukocyte protease inhibitor. HIV disease progress predicted decreased CVL anti-HIV activity against both laboratory-adapted and T/F strains of HIV. Anti-HIV activity exhibited close associations with CVL levels of fourteen cytokines and chemokines.

Conclusions

Amid a multifaceted immune defense against HIV-1 and other sexually transmitted pathogens, HIV disease progression is associated with selective disturbances in both CVL anti-HIV activity and specific innate immune defenses in the human female reproductive tract (FRT). Overall, these studies indicate that innate immune protection in the FRT is compromised as women progress to AIDS.

Objectives. Compare the Plan B levonorgestrel (LNG) area under the concentration- time curve (AUC12) prior to and with efavirenz (EFV). Design. Prospective, open-label, single-arm, equivalence study. Methods. Healthy HIV-negative subjects underwent 12 hr intensive pharmacokinetic (PK) sampling following single dose LNG alone and after 14 days of EFV. Geometric means, Geometric Mean Ratios, and 90% confidence intervals (CI) are reported for PK Parameters. T-tests were utilized. Clinical parameters and liver function tests (LFTs) were assessed. Results. 24 women enrolled and 21 completed the study. With EFV, LNG AUC12 was reduced 56% (95% CI: 49%, 62%) from 42.9 to 17.8 ng∗hr/mL, and maximum concentration (Cmax⁡) was reduced 41% (95% CI: 33%, 50%) from 8.4 to 4.6 ng/mL. LNG was well tolerated with no grade 3 or 4 treatment-related toxicities. Conclusions. EFV significantly reduced LNG exposures. Higher LNG doses may be required with EFV. These results reinforce the importance of effective contraception in women taking EFV.

Objective. To identify correlates of incident bacterial vaginosis (BV) diagnosed with Nugent scoring among high-risk women. Study Design. We conducted both cohort and case-crossover analyses, stratified by HIV infection status, based on 871 HIV-infected and 439 HIV-uninfected participants in the HIV Epidemiology Research Study, conducted in 4 US sites in 1993–2000. Results. BV incidence was 21% and 19% among HIV-infected and -uninfected women, respectively. Fewer correlates of BV were found with case-crossover than with cohort design. Reporting frequent coitus (regardless of consistency of condom use) was correlated with BV in cohort analyses but not in case-crossover analyses. The sole correlate of BV in both types of analyses was the detection of spermatozoa on Gram stain, which is a marker of semen exposure. Conclusion. The inconsistent association between condom use and BV in prior studies could be from reporting bias. We found evidence of a relationship between semen exposure and incident BV.

Objective. To evaluate associations between common vaginal infections and human papillomavirus (HPV). Study Design. Data from up to 15 visits on 756 HIV-infected women and 380 high-risk HIV-uninfected women enrolled in the HIV Epidemiology Research Study (HERS) were evaluated for associations of bacterial vaginosis, trichomoniasis, and vaginal Candida colonization with prevalent HPV, incident HPV, and clearance of HPV in multivariate analysis. Results. Bacterial vaginosis (BV) was associated with increased odds for prevalent (aOR = 1.14, 95% CI: 1.04, 1.26) and incident (aOR = 1.24, 95% CI: 1.04, 1.47) HPV and with delayed clearance of infection (aHR = 0.84, 95% CI: 0.72, 0.97). Whereas BV at the preceding or current visit was associated with incident HPV, in an alternate model for the outcome of incident BV, HPV at the current, but not preceding, visit was associated with incident BV. Conclusion. These findings underscore the importance of prevention and successful treatment of bacterial vaginosis.

Background

Human papillomaviruses (HPVs) remain a serious world health problem due to their association with anogenital/oral cancers and warts. While over 100 HPV types have been identified, a subset is associated with malignancy. HPV16 and 18 are the most prevalent oncogenic types, while HPV6 and 11 are most commonly responsible for anogenital warts. While other quantitative PCR (qPCR) assays detect oncogenic HPV, there is no single tube assay distinguishing the most frequent oncogenic types and the most common types found in warts.

Results

A Sybr Green-based qPCR assay was developed utilizing degenerate primers to the highly conserved HPV E1 theoretically detecting any HPV type. A single tube multiplex qPCR assay was also developed using type-specific primer pairs and TaqMan probes that allowed for detection and quantitation of HPV6,11,16,18. Each HPV type was detected over a range from 2 × 101 to 2 × 106copies/reaction providing a reliable method of quantitating type-specific HPV in 140 anogenital/cutaneous/oral benign and malignant specimens. 35 oncogenic and low risk alpha genus HPV types were detected. Concordance was detected in previously typed specimens. Comparisons to the gold standard detected an overall sensitivity of 89% (95% CI: 77% - 96%) and specificity of 90% (95%CI: 52% - 98%).

Conclusion

There was good agreement between the ability of the qPCR assays described here to identify HPV types in malignancies previously typed using standard methods. These novel qPCR assays will allow rapid detection and quantitation of HPVs to assess their role in viral pathogenesis.

Background

We investigated the impact of antimicrobials in cervicovaginal lavage (CVL) from HIV(+) and HIV(−) women on target cell infection with HIV. Since female reproductive tract (FRT) secretions contain a spectrum of antimicrobials, we hypothesized that CVL from healthy HIV(+) and (−) women inhibit HIV infection.

Methodology/Principal Findings

CVL from 32 HIV(+) healthy women with high CD4 counts and 15 healthy HIV(−) women were collected by gently washing the cervicovaginal area with 10 ml of sterile normal saline. Following centrifugation, anti-HIV activity in CVL was determined by incubating CVL with HIV prior to addition to TZM-bl cells. Antimicrobials and anti-gp160 HIV IgG antibodies were measured by ELISA. When CXCR4 and CCR5 tropic HIV-1 were incubated with CVL from HIV(+) women prior to addition to TZM-bl cells, anti-HIV activity in CVL ranged from none to 100% inhibition depending on the viral strains used. CVL from HIV(−) controls showed comparable anti-HIV activity. Analysis of CH077.c (clone of an R5-tropic, mucosally-transmitted founder virus) viral inhibition by CVL was comparable to laboratory strains. Measurement of CVL for antimicrobials HBD2, trappin-2/elafin, SLPI and MIP3α indicated that each was present in CVL from HIV(+) and HIV(−) women. HBD2 and MIP3α correlated with anti-HIV activity as did anti-gp160 HIV IgG antibodies in CVL from HIV(+) women.

Conclusions/Significance

These findings indicate that CVL from healthy HIV(+) and HIV(−) women contain innate and adaptive defense mechanisms that inhibit HIV infection. Our data suggest that innate endogenous antimicrobials and HIV-specific IgG in the FRT can act in concert to contribute toward the anti-HIV activity of the CVL and may play a role in inhibition of HIV transmission to women.

Background. Fastidious bacteria have been associated with bacterial vaginosis (BV) using PCR methods. We assessed the prevalence of these bacteria in HIV-1 infected women and their relationship with vaginal pH and shedding of HIV-1 RNA. Methods. 64 cervicovaginal lavage (CVL) samples were collected from 51 women. Vaginal microbiota were characterized using 8 bacterium-specific quantitative PCR assays. Results. Women with the fastidious bacteria Bacterial Vaginosis Associated Bacterium (BVAB) 1, 2, and 3 showed a trend to increased HIV-1 shedding (OR 2.59–3.07, P = .14–.17). Absence of Lactobacillus crispatus (P < .005) and presence of BVAB2 (P < .001) were associated with elevated vaginal pH. BVAB1, 2, and 3 were highly specific indicators of BV in HIV-infected women, with specificities of 89%–93%. Conclusions. Fastidious bacteria (BVAB 1, 2, and 3) remain specific indicators of BV in HIV-infected women, and BVAB2 may contribute to the elevated vaginal pH that is a hallmark of this syndrome.

Background

The mechanism of human immunodeficiency virus (HIV) transmission via heterosexual intercourse is unknown. We sought to determine whether the presence of inflammatory cells in the vagina is associated with the presence of genital tract HIV type 1 (HIV-1) RNA.

Methods

Analysis of a longitudinal prospective cohort was performed. Women with HIV-1 infection were assessed with use of paired plasma and cervicovaginal lavage specimens. Viral load measurements were performed using nucleic acid sequence—based amplification. White blood cells found in the genital tract (GT WBCs) were quantified using a hemacytometer. Common lower genital tract infections assessed for association with viral shedding (i.e., genital tract viral load [GTVL]) included bacterial vaginosis, candidiasis, and trichomoniasis. Generalized estimating equations were used to estimate the prevalence and odds of detectable GTVL by GT WBC. The association was examined both in the presence and in the absence of lower genital tract infections.

Results

A total of 97 women and 642 visits were included in the analysis. Median duration of follow-up was 30.4 months. Thirty women (31%) had detectable GTVL at any visit. The median CD4 cell count at baseline was 525 cells/μL. Most women were antiretroviral therapy naive at baseline. After adjustment for plasma viral load, the odds of detectable GTVL increased as GT WBC increased, with an odds ratio of 1.36 (95% confidence interval, 1.1–1.7) per 1000-cell increase in GT WBC among women without lower genital tract infections. After adjustment for plasma viral load and lower genital tract infections by incorporating them in a regression model, GT WBC remained significantly associated with GTVL, with an adjusted odds ratio of 1.22 (95% confidence interval, 1.08–1.37).

Conclusions

The presence of GT WBC is associated with an increased risk of detectable GTVL.

Summary

Objectives:

The number of HIV-infected refugees entering the USA is increasing. There is little data describing the HIV-infected refugee population and the challenges encountered when caring for them. We performed a retrospective case–control analysis of HIV-infected refugees in order to characterize their co-morbidities, baseline HIV characteristics, and longitudinal care compared to HIV-infected non-refugees.

Methods:

A retrospective chart review was performed of HIV-infected refugees and non-refugees who were matched for gender, age, and time of establishment of initial HIV care.

Results:

The refugee population studied was largely from West Africa. Refugees were more likely than non-refugees to have heterosexual risk for HIV infection, latent tuberculosis infection, and active hepatitis B. Refugees were less likely than non-refugees to have a history of substance use, start antiretrovirals, and be enrolled in a clinical study. The baseline CD4 counts and HIV plasma viral loads were similar between the two groups.

Conclusions:

Clinicians caring for West African HIV-infected refugees should be knowledgeable about likely co-morbidities and the impact of cultural differences on HIV care. Further studies are needed to develop culturally competent HIV treatment, education, and prevention programs for refugees who are beginning a new life in the USA.

Current diagnostic assays for HIV-1 do not always test for the presence of HIV-2 in the United States. We present the case of a patient from Cape Verde, who was admitted to our hospital with rapidly deteriorating neurological function and multiple white matter lesions on MRI likely secondary to progressive multifocal leukoencephalopathy (PML). Initially, the patient had a positive EIA for HIV, but a negative HIV-1 Western Blot and no viral load detected on a branched-DNA assay. A repeat viral load by reverse transcriptase methodology (RT-DNA) detected 121,000 copies and an HIV-2 Western Blot was positive. The case highlights an extremely rare presentation of HIV-2 with severe neurological disease. We discuss the different tests available for the diagnosis and monitoring of HIV-2 in the United States.

Genital tract infections and cytokine perturbations are associated with increased HIV acquisition and transmission. We measured the relationship between bacterial vaginosis (BV) and concentrations of Interleukin-8 (IL-8), Interleukin-1β (IL-1β), and Interleukin-6 (IL-6) in cervicovaginal lavage (CVL) specimens collected longitudinally from 16 HIV-infected and 8 HIV-uninfected high-risk women. CVL samples were analyzed when women presented with BV, and at their next visit, after successful treatment, when BV was cleared. A subset of participants had cytokine levels evaluated at three consecutive clinic visits: before developing BV, at the time of BV diagnosis, and after clearing BV. Significantly higher IL-8, but not IL-1β or IL-6 levels were present when women had active BV compared to when BV was absent. Trends in cytokine levels were similar for HIV-infected and HIV-uninfected women. BV in these women was associated with significantly higher concentrations of genital tract IL-8 which decreased 2.4 fold when BV was cleared.

Specific morphotypic profiles of normal and abnormal vaginal flora, including bacterial vaginosis (BV), were characterized. A prospective study of 350 women yielded concurrent Gram-stain data and clinical assessment (n = 3455 visits). Microbiological profiles were constructed by Gram stain. Eight profile definitions were based on dichotomizing the levels of Lactobacillus, Gardnerella, and curved, Gram-negative bacillus (Mobiluncus) morphotypes. Of these, two were rare, and the other six demonstrated a graded association with the clinical components of BV. The proposed profiles from the Gram stain reflect the morphotypic categories describing vaginal flora that may enable clearer elucidation of gynecologic and obstetric outcomes in various populations.

Background: Bacterial vaginosis is a common gynecologic infection that has been associated with a variety of gynecologic and obstetric complications, including pelvic inflammatory disease, postabortal infection and premature delivery. Recent studies suggest that bacterial vaginosis may increase a woman’s risk for human immunodeficiency virus (HIV). We undertook this study to assess whether the prevalence and characteristics of bacterial vaginosis differed according to HIV status in high-risk US women.

Methods: Prevalence of bacterial vaginosis was assessed by Gram’s stain and clinical criteria for 854 HIV-infected and 434 HIV-uninfected women enrolled in the HIV Epidemiology Research (HER) Study.Multiple logistic regression techniques were used to determine whether HIV infection independently predicted bacterial vaginosis.

Results: Almost half (46%) the women had bacterial vaginosis by Gram’s stain. The prevalence of bacterial vaginosis was 47% in the HIV-positive women compared with 44% in the HIV-negativewomen; this difference was not statistically significant (p = 0.36). After adjustment for other covariates, HIV-positive women were more likely than HIV-negative women to have bacterial vaginosis (odds ratio (OR) 1.31; 95% confidence interval (CI) 1.01-1.70) by Gram's stain but not by clinical criteria (OR 1.16; CI 0.87-1.55). Among HIV-positive women, use of antiretroviral drugs was associated with a lower prevalence of bacterial vaginosis (adjusted OR 0.54; Cl 0.38 -0.77).

Conclusions: In this cross-sectional analysis of high-risk US women, HIV infection was positively correlated with bacterial vaginosis diagnosed by Gram’s stain.