Does hormone replacement therapy prevent cognitive decline in postmenopausal women?

NO. Hormone replacement therapy (HRT) does not prevent cognitive decline in postmenopausal women-and in fact, it may slightly increase risk (strength of recommendation, A; systematic review, meta-analysis of randomized controlled trials [RCTs], and individual RCT).

BASHH 2018 UK national audit of HIV partner notification.

HIV partner notification (PN) is a highly effective strategy to identify people living with undiagnosed HIV infection. This national audit of HIV PN is against the 2015 British Association of Sexual Health and HIV (BASHH)/British HIV Association (BHIVA)/Society of Sexual Health Advisers (SHAA)/National AIDS Trust (NAT) HIV PN standards, developed in response to the 2013 BASHH/BHIVA national HIV PN audit. We report significant improvements in the number of contacts tested per index case, likely due, in part, to clearer definitions as well as better ascertainment and reporting. There remains scope for improvement with informing and testing contactable contacts. Recommendations from this audit include further refinement of definitions and development of a national proforma for HIV PN.

Perceived need of, and interest in, HIV pre-exposure prophylaxis amongst men who have sex with men attending three sexual health clinics in London, UK.

HIV pre-exposure prophylaxis (PrEP) has proven efficacy in reducing the risk of HIV infection in men who have sex with men (MSM), but has not yet been commissioned in the UK. The aim of this study was to investigate perceived need and benefit (or experience of) PrEP among HIV-negative MSM attending sexual health clinics. HIV-negative MSM attending three sexual health centres in London, UK were opportunistically invited to complete a questionnaire. Data collected comprised demographic data and sexual and drug use behaviours as well as questions regarding perceptions of risk and need for PrEP. Logistic regression analysis was undertaken to identify variables predicting acceptability of, and intention to use, PrEP. In addition, data were gathered in respondents already taking PrEP. Eight hundred and thirty-nine questionnaires were analysed. The median age of respondents was 35 years (IQR 28-41, range 18-78), 650 (77%) were of white ethnicity and 649 (77%) had a university education. Four hundred and fifty-six (54%) reported at least one episode of condomless anal sex in the preceding three months, 437 (52%) reported recreational drug use in the preceding three months and 311 (37%) had been diagnosed with a sexually transmitted infection within the preceding six months. Four hundred and sixty-three (64%) of 726 strongly agreed with the statement 'I think I would benefit from PrEP'. Multivariate logistic regression analysis demonstrated that having receptive anal intercourse (RAI) without condoms, having an awareness of the risk of unprotected RAI and having belief in the effectiveness of PrEP were independent predictors for someone thinking they would benefit from taking PrEP. Eight percent of respondents (59/724) had already taken or were currently taking PrEP. The results suggest that individuals at risk are likely to perceive themselves as benefiting from PrEP. The majority perceived their risk of acquiring HIV and benefit from PrEP accurately. Overall they appeared to have little concern over the use of PrEP and generally positive attitudes. Further investigation is warranted to understand why those at risk do not perceive benefit from PrEP.

HIV and the menopause: A review.

Effective antiretroviral therapy has resulted in a close to normal life expectancy for people living with HIV. This has led to a shift in the age distribution of women living with HIV in the UK, with one in three attending for HIV care estimated to be aged 45-56 years in 2014. The lack of experience of many HIV physicians in managing menopause, and the perceived complexity of managing menopause in women living with HIV by general practitioners means that many women are unable to access appropriate care and support. This is aggravated by the relative paucity of data on menopause in women living with HIV and conflicting results in this field, for example with regard to age of onset of menopause and symptomatology experienced. Furthermore, women living with HIV have unique considerations such as potential interactions between antiretroviral therapy and menopause hormone therapy (previously called hormone replacement therapy) and other physiological concerns such as a multifactorial propensity towards decreased bone mineral density and potentially increased cardiovascular risk. On the whole, menopause hormone therapy is probably underutilised in this group of women due to perceived concerns around drug-drug interactions, as well as fears shared with women in the general population about menopause hormone therapy. Menopausal women should be given adequate information on symptomatology, lifestyle modification and treatment options including menopause hormone therapy. Furthermore, a holistic approach which considers the increased burden of poor mental health in this population is essential.

HIV-indicator-condition-driven HIV testing: clinically effective but still rarely implemented.

In the UK, outcomes for people living with HIV are excellent. However, a quarter of those living with HIV do not know their status, and almost half are diagnosed late. Strategies to broaden HIV testing are needed. HIV indicator conditions are those thought to be associated with HIV infection because they share risk factors (eg viral hepatitis) or because they arise as a result of early or late immunodeficiency (eg bacterial pneumonia, Kaposi's sarcoma). They comprise all AIDS-defining conditions, but also many non-AIDS-defining conditions spanning the spectrum of medicine. Patients presenting with indicator conditions should routinely be offered an HIV test. This approach is likely to be clinically effective, because knowledge of HIV status is essential in the management of many conditions. It is cost effective if the prevalence of HIV infection is greater than 0.1%. The strategy removes the need for risk assessment, and is acceptable to patients and healthcare practitioners. If broadly implemented, it is likely to be effective at a public health level, and will help to reduce both undiagnosed HIV and late diagnoses of HIV. Here we review the emerging evidence base that supports the value of routine HIV testing in indicator conditions.

Pharmacokinetic and pharmacodynamic drug interactions between antiretrovirals and oral contraceptives.

More than 50 % of women living with HIV in low- and middle-income countries are of reproductive age, but there are limitations to the administration of oral contraception for HIV-infected women receiving antiretroviral therapy due to drug-drug interactions caused by metabolism via the cytochrome P450 isoenzymes and glucuronidation. However, with the development of newer antiretrovirals that use alternative metabolic pathways, options for contraception in HIV-positive women are increasing. This paper aims to review the literature on the pharmacokinetics and pharmacodynamics of oral hormonal contraceptives when given with antiretroviral agents, including those currently used in developed countries, older ones that might still be used in salvage regimens, or those used in resource-limited settings, as well as newer drugs. Nucleos(t)ide reverse transcriptase inhibitors (NRTIs), the usual backbone to most combined antiretroviral treatments (cARTs) are characterised by a low potential for drug-drug interactions with oral contraceptives. On the other hand non-NRTIs (NNRTIs) and protease inhibitors (PIs) may interact with oral contraceptives. Of the NNRTIs, efavirenz and nevirapine have been demonstrated to cause drug-drug interactions; however, etravirine and rilpivirine appear safe to use without dose adjustment. PIs boosted with ritonavir are not recommended to be used with oral contraceptives, with the exception of boosted atazanavir which should be used with doses of at least 35 µg of estrogen. Maraviroc, an entry inhibitor, is safe for co-administration with oral contraceptives, as are the integrase inhibitors (INIs) raltegravir and dolutegravir. However, the INI elvitegravir, which is given in combination with cobicistat, requires a dose of estrogen of at least 30 µg. Despite the growing evidence in this field, data are still lacking in terms of large cohort studies, randomised trials and correlations to real clinical outcomes, such as pregnancy rates, in women on antiretrovirals and hormonal contraception.

Trichomonas vaginalis: an audit of clinical practice and the demography of infected patients at three London genitourinary medicine clinics.

This audit aimed to review clinical standards for Trichomonas vaginalis against British Association of Sexual Health and HIV (BASHH) guidelines. Case notes for patients who had a positive microscopy or culture result were reviewed retrospectively. There was a 0.23% positivity rate for T. vaginalis (n = 84 cases); 96% were female with an average age of 33 years, with proportionally more patients seen in the African/Caribbean population, despite the number of cases being comparable between white (n = 36) and African/Caribbean (n = 34) groups. Seventy percent of patients had both microscopy- and culture-positive results for T. vaginalis. Contact tracing occurred in 87% of patients; 56% of these patients confirmed at least one contact had been treated in the last month. Overall, our data demonstrated a lower positivity rate than expected. Wet microscopy and liquid medium cultures were both important in identifying the infection, but more needs to be done to ensure partner notification has been documented and contacts have been treated.

Luciferase inhibition by a novel naphthoquinone.

The novel naphthoquinone 12,13-dihydro-N-methyl-6,11,13-trioxo-5H-benzo[4,5]cyclohepta[1,2-b]naphthalen-5,12-imine (hereafter called TU100) was created as a potential chemotherapeutic agent. Previous work showed it is an irreversible inhibitor of type I and II topoisomerases that alkylates specific enzyme thiols. While analyzing the effect of TU100 on cancer cells, we discovered it is a potent inhibitor of luciferase derived from both Photinus pyralis (fireflies) and Renilla reniformis (sea pansy). Pre-incubation experiments showed that TU100 does not irreversibly inactivate luciferase, indicating its mechanism is different from that observed with topoisomerases. Firefly luciferase generates light using ATP and luciferin as substrates (bioluminescence). An examination of TU100 inhibition at varying substrate concentrations revealed the drug is uncompetitive with respect to ATP and competitive with respect to luciferin. The TU100 binding constant (K(I)) is 2.5±0.7 µM as determined by Dixon plot analysis. These data suggest TU100 specifically binds the luciferase-ATP complex and prevents its interaction with luciferin. Given the novel structure of TU100, unique mechanism of action, and ability to target luciferase from different species, these results identify TU100 as an important new reagent for investigating and regulating bioluminescent enzymes.

Disordered follicle development in ovaries of prenatally androgenized ewes.

Exposure to excess androgens in utero induces irreversible changes in gonadotrophin secretion and results in disrupted reproductive endocrine and ovarian function in adulthood, in a manner reminiscent of the common clinical endocrinopathy of polycystic ovary syndrome (PCOS). We have recently identified an abnormality in early follicle development in PCOS which we suggested might be an androgenic effect. We propose that altered ovarian function in androgenized ewes is due to prenatal androgens not only causing an abnormality of gonadotrophin secretion, but also exerting a direct effect on the early stages of folliculogenesis. Therefore, in this study, we explored the possible differences between small preantral follicles in the ovarian cortex of androgenized female lambs with those of normal lambs. At 8 months of age, small ovarian cortical biopsies (approximately 5 mm3) were obtained at laparotomy from nine female lambs that had been exposed to androgens in utero from embryonic days 30 to 90 of a 147-day pregnancy, and 11 control female lambs. Further, ovarian tissue was obtained at 20 months of age from ten androgenized and nine control animals. Tissue was either fixed immediately for histology or cultured for up to 15 days prior to fixing. The number of follicles in haematoxylin and eosin-stained sections was counted and recorded along with the stage of development. Before culture, the total follicle density (follicles/mm3 tissue) was not statistically significantly different between the two types of ovary at either 8 or 20 months of age. Furthermore, there were no statistically significant differences in the density of follicles at each stage of development. However, there was a lower percentage of primordial follicles, but a higher percentage of primary follicles, in biopsies taken at 8 months from androgenized lambs when compared with controls. At 20 months, the proportions of follicles at the primordial and primary stages were not significantly different between the two groups, but this was mainly attributable to an increase in the proportion of growing follicles in biopsies from control animals. Culture of ovarian cortex from 8-month-old lambs resulted in a progressive increase in the proportion of growing follicles when compared with tissue fixed on the day of surgery. However, there was no difference between androgenized and control tissue in the percentage of growing follicles. The increase in the proportion of growing follicles in the cortex of androgenized animals is reminiscent of similar observations in human polycystic ovaries and suggests that excess exposure to androgen in early life plays a part in the accelerated progression of follicle development from the primordial to the primary stage in polycystic ovaries.