Phillip Hay

A longitudinal study of bacterial vaginosis during pregnancy

Objective To determine the longitudinal changes in the incidence of bacterial vaginosis in pregnancy.

Loss of CD4+ T Cell Proliferative Ability but Not Loss of Human Immunodeficiency Virus Type 1 Specificity Equates with Progression to Disease

In this study, we compared human immunodeficiency virus (HIV) type 1-specific proliferative responses with HIV-1-induced intracellular cytokine production in a cohort of clinically nonprogressing patients and individuals with progressive HIV-1 infection. We found strong HIV-1-specific proliferative responses in the clinical nonprogressor cohort that correlated with significant numbers of circulating HIV-1-specific CD4(+) T cells. In contrast, HIV-1-specific proliferative responses were absent in most individuals with progressive HIV-1 infection, even though interferon-gamma-producing HIV-1-specific CD4(+) T cells were detectable by flow cytometry. The implication of these data is that the important dysfunction seen in most HIV-positive patients from very early in disease may be an inability of HIV-1-specific CD4(+) memory T cells to proliferate in response to HIV antigens rather than an absolute loss of circulating virus-specific CD4(+) T cells.

British HIV Association guidelines for the management of HIV infection in pregnant women 2012

The overall purpose of these guidelines is to provide guidance on best clinical practice in the treatment and management of human immunodeficiency virus (HIV)-positive pregnant women in the UK. The scope includes guidance on the use of antiretroviral therapy (ART) both to prevent HIV mother-to-child transmission (MTCT) and for the welfare of the mother herself, guidance on mode of delivery and recommendations in specific patient populations where other factors need to be taken into consideration,such as coinfection with other agents. The guidelines are aimed at clinical professionals directly involved with, and responsible for, the care of pregnant women with HIV infection.

Tenofovir-linked hyperparathyroidism is independently associated with the presence of vitamin D deficiency.

Background:To determine patient and treatment characteristics associated with vitamin D deficiency (VDD) in an UK inner city HIV-1-positive adult cohort. Methods:Two hundred twenty-seven HIV-positive patients attending prospectively for routine blood tests in winter had serum 25-hydroxyvitamin D and parathyroid hormone (PTH) concentrations and other routine chemistry measured. Those with and without VDD were defined as having serum 25-hydroxyvitamin D concentrations <50 nmol/L and >75 nmol/L, respectively. Characteristics were compared between patients with and without VDD. The effects of VDD, tenofovir use, and their interaction on chemical measures were investigated. Results:VDD was found in 57% (131 of 227) of patients. Independent associations included nonwhite ethnicity [adjusted odds ratio (95% confidence interval): 7.40 (2.52 to 21.7)], higher random blood glucose [2.38 (1.24 to 4.57) per mmol/L], higher estimated glomerular filtration rate [eGFR: 1.04 (1.01 to 1.06)], and higher PTH [1.19 (1.00 to 1.42)]. PTH was higher in those receiving tenofovir (median 7.2 pmol/L) than other patients (4.3; P < 0.001) overall, but high PTH with tenofovir occurred only in the context of VDD. Tenofovir use was not associated with serum creatinine or eGFR overall but interacted with vitamin D status (P = 0.05 and P = 0.08, respectively), being linked to somewhat higher creatinine and lower eGFR among patients without VDD but higher eGFR in VDD patients. Conclusions:25(OH) VDD is associated with tenofovir-linked hyperparathyroidism and also with higher eGFR.

Prevalence of Mycoplasma genitalium in early pregnancy and relationship between its presence and pregnancy outcome.

Mycoplasma genitalium is associated with cervicitis and pelvic inflammatory disease but little is known about its role in pregnancy. We investigated the prevalence of M. genitalium by polymerase chain reaction assay on urine specimens from 1216 pregnant women (mean age 31years) presenting before 10 weeks of gestation in 32 general practices. The prevalence of M. genitalium was 0.7% (6/915, 95% CI 0.1–1.2). It was more common in women aged <20 years, women of Afro‐Caribbean or black African ethnic origin, women in social classes 3–5 and single women. Only one woman with M. genitalium infection miscarried, and none of those followed up to term had a preterm birth, although the numbers were small. The low prevalence of M. genitalium infection suggests it is unlikely to be an important risk factor in adverse pregnancy outcome in healthy women in the community.

Recurrent bacterial vaginosis

Purpose of review Bacterial vaginosis is a common condition that recurs frequently, adversely affecting womens lives, and is associated with complications including increased risk of sexually transmitted infections, HIV, and adverse pregnancy outcome. Recent findings New molecular techniques have increased our understanding of the numerous bacteria associated with bacterial vaginosis, and a biofilm containing mostly Gardnerella and Atopobium vaginae, which can persist after treatment has been described. Suppressive treatment with metronidazole gel can suppress recurrence. Physiological approaches such as acidification and probiotics have been investigated with variable results. Summary Advances in our understanding of the pathogenesis of bacterial vaginosis allow the opportunity to improve treatments to prevent recurrence, which may require a combination of modalities. We must find ways to help affected women and reduce the complications associated with bacterial vaginosis.

Incomplete Reversibility of Estimated Glomerular Filtration Rate Decline Following Tenofovir Disoproxil Fumarate Exposure

Background. Tenofovir disoproxil fumarate (TDF) has been linked to renal impairment, but the extent to which this impairment is reversible is unclear. We aimed to investigate the reversibility of renal decline during TDF therapy. Methods. Cox proportional hazards models assessed factors associated with discontinuing TDF in those with an exposure duration of >6 months. In those who discontinued TDF therapy, linear piecewise regression models estimated glomerular filtration rate (eGFR) slopes before initiation of, during, and after discontinuation of TDF therapy. Factors associated with not achieving eGFR recovery 6 months after discontinuing TDF were assessed using multivariable logistic regression. Results. We observed declines in the eGFR during TDF exposure (mean slopes, −15.7 mL/minute/1.73 m2/year [95% confidence interval {CI}, −20.5 to −10.9] during the first 3 months and −3.1 mL/minute/1.73 m2/year [95% CI, −4.6 to −1.7] thereafter) and evidence of eGFR increases following discontinuation of TDF therapy (mean slopes, 12.5 mL/minute/1.73 m2/year [95% CI, 8.9–16.1] during the first 3 months and 0.8 mL/minute/1.73 m2/year [95% CI, .1–1.5] thereafter). Following TDF discontinuation, 38.6% of patients with a decline in the eGFR did not experience recovery. A higher eGFR at baseline, a lower eGFR after discontinuation of TDF therapy, and more-prolonged exposure to TDF were associated with an increased risk of incomplete recovery 6 months after discontinuation of TDF therapy. Conclusions. This study shows that a decline in the eGFR during TDF therapy was not fully reversible in one third of patients and suggests that prolonged TDF exposure at a low eGFR should be avoided.

Bacterial vaginosis and miscarriage.

Purpose of review This review aims to summarize current knowledge about the relationship between bacterial vaginosis and miscarriage. Recent findings Studies investigating the relationship between bacterial vaginosis and infertility, implantation and early pregnancy loss have produced conflicting results. One study demonstrated a beneficial effect of colonization with hydrogen peroxide producing lactobacilli. A community based study found no association between bacterial vaginosis and first trimester loss, but a positive association with early second trimester loss. In a randomized controlled trial, treatment of bacterial vaginosis with oral clindamycin was associated with a fivefold reduction in the incidence of late miscarriage. Summary The relationship between bacterial vaginosis and infertility and first trimester loss needs further elucidation. Measures to support a healthy lactobacillus flora such as probiotic therapy warrant study. The randomized controlled trials of clindamycin treatment need to be replicated in different settings.

Mycoplasma genitalium in chronic non-gonococcal urethritis

Seventy-eight men with a history of chronic urethritis were referred for investigation. Of 52 men diagnosed as having persistent or recurrent non-gonococcal urethritis (NGU) at the time of referral, 11 (21%) were infected with Mycoplasma genitalium and three with Chlamydia trachomatis. Men who were M. genitalium-positive had not previously received less antibiotic, in terms of treatment duration, than those who were M. genitalium-negative, suggesting a possible resistance to the antibiotics given. In the current investigation, of 11 M. genitalium-positive men with persistent or recurrent NGU who were treated for four to six weeks with erythromycin, 500mg four times daily, nine (82%) responded clinically and microbiologically, but later six relapsed without M. genitalium being detected. The results of observing and investigating a patient for about one year, the only one to have concurrent chlamydial and mycoplasmal infections, is presented, a feature being the intermittent persistence of the mycoplasma.

DETECTION OF TREPONEMAL DNA IN THE CSF OF PATIENTS WITH SYPHILIS AND HIV INFECTION USING THE POLYMERASE CHAIN REACTION

The polymerase chain reaction (PCR) was used to detect Treponema pallidum DNA in the cerebrospinal fluid (CSF) of patients with and without syphilis. The CSF from 10 of 19 patients with positive serological tests for syphilis who were being investigated for late syphilis were treponemal DNA-positive. In contrast, the CSF from only one of 30 patients with no known history of syphilis was DNA-positive. CSF from 28 HIV-positive patients was also tested. Fourteen of these patients had central nervous system (CNS) disease and seven were DNA-positive, whereas none of the 14 without CNS disease were DNA-positive. Five of the seven DNA-positive patients had a history of syphilis. Such a history in an HIV-positive patient who had CNS disease was predictive of finding treponemal DNA in the CSF. The PCR had a sensitivity of 47% and a specificity of 93% for detecting a known history of syphilis and is a potentially useful tool in treponemal diagnosis.