Do women with HIV/AIDS on anti-retroviral therapy have a lower incidence of symptoms associated with menstrual dysfunction?

BACKGROUND: Symptoms associated with menstruation and endometriosis are common amongst women of reproductive ages and the pathogenesis of these illnesses is postulated to be associated with aberrations in endometrial regeneration, immune response and in endometrial stem cell function. Highly active antiretroviral therapy (HAART) has been shown to enhance events seen in biological aging of tissues, with HIV/AIDS patients enduring the premature appearance of illnesses associated with stem-cell aging. Considering the intricate relationship between dysregulation of stem cell function, in both HAART therapy and in menstrual disorders/endometriosis, we sought to examine the prevalence of menstrual related symptoms (MRS) associated with endometriosis in women on HIV/AIDS therapy. METHODS: A menstrual related symptoms (MRS) questionnaire adapted from the British Society of Gynaecological Endoscopists (BSGE) pelvic pain questionnaire, which has been used in both clinical and research setting, was completed by 100 women living with HIV (WLWH) attending a specialist HIV clinic and by 100 women without a diagnosis of HIV attending the Sexual Health clinic (WWH). HIV related demographic details, including results from recent blood tests, were also recorded prospectively from the WLWH. RESULTS: WLWH were slightly older (37.7 vs. 34.8 years, P = 0.01); with higher BMI (28.9 vs. 24.8, P < 0.001); and were likely to be parous (85% vs. 54% P < 0.001) and non-Caucasian (79% vs 18%) compared with WWH. Most women in both groups had regular periods (77.9% vs. 74.7%), and WLWH were more likely to have a shorter duration of bleeding compared with WWH (81.4% vs 69.3% P = 0.05). However, WLWH were more likely to suffer with pre-menstrual tension compared with WWH (60.8% vs 50.6% P = 0.01). CONCLUSION: Our data suggests that WLWH, despite being older and of higher BMI, have a shorter duration of menstrual bleeding, and we hypothesise that this may possibly be due to the (beneficial) side effects of some HAART components. Further research is needed to explore the effect of HAART on MRS to determine if these therapies could be used in the future as a fertility retaining treatment for MRSs/endometriosis.

Isolated pharyngeal Neisseria gonorrhoeae in heterosexual male contacts.

Pharyngeal infection with Neisseria gonorrhoeae (NG) in heterosexual men is thought to be of low prevalence and the value of routinely testing this group of patients is uncertain. We present two cases of NG, isolated only in the pharynx, in asymptomatic heterosexual male contacts. The presence of pharyngeal NG was found irrespective of direct oropharyngeal sexual exposure.

Contraceptive provision in genitourinary medicine clinics in the UK.

The objective of this study was to assess current and future contraceptive provision in genitourinary (GU) medicine clinics in the United Kingdom. Questionnaires were sent to 18 British Co-Operative Clinical Group regional representatives for distribution to clinical leads. Of 185 clinics, 124 (67%) responded. All clinics provided condoms, 116 (94%) the 'morning after' pill and 31 (25%) would fit an intrauterine contraceptive device (IUCD) for emergency contraception. Twenty-three (18.5%) regarded their clinic as already providing a comprehensive service and most of these could provide a wide range of contraceptive methods. Of all clinics, which included eight (34%) clinics already providing a comprehensive service, 69 (56%) anticipated developing their contraceptive provision within the next five years. In conclusion, contraceptive provision varies between clinics. A reduction in unwanted pregnancies and sexually transmitted infections (STIs) would most likely be achieved if clinics expanded their provision of contraceptive services.

Intracellular and plasma pharmacokinetics of efavirenz in HIV-infected individuals.

OBJECTIVES: The site of action of efavirenz is inside HIV-infected cells. Measurement of intracellular (IC) concentrations of efavirenz may therefore provide further understanding of therapeutic failure, especially where virological rebound occurs despite adequate plasma levels, and a lack of detectable viral resistance. Here, we determined IC and plasma pharmacokinetics of efavirenz and their relationship with plasma protein binding and P-glycoprotein (P-gp, an active drug efflux transporter) expression. PATIENTS AND METHODS: Venous blood samples from 10 HIV-infected patients receiving efavirenz (600 mg once a day plus two nucleoside reverse transcriptase inhibitors) were collected over the 24 h dosing interval. Plasma and peripheral blood mononuclear cells (PBMCs) were isolated. Plasma protein bound and unbound efavirenz were separated using ultrafiltration. IC (or cell-associated), total plasma and unbound plasma efavirenz levels were quantified using HPLC-UV. P-gp expression was measured by flow cytometry. Area under the concentration-time curves (AUC0-24) were then calculated using non-compartmental analyses and the IC accumulation expressed as a ratio of IC to plasma AUC0-24. RESULTS: The median (range) % unbound and IC accumulation ratio was 0.6% (0.4-1.5%) and 1.3 (0.7-3.3), respectively. There was a linear relationship between IC and total AUC0-24 (r2= 0.59, P = 0.01) but not unbound AUC0-24 (r2= 0.13, P = 0.75). An inverse correlation between IC AUC0-24 and % unbound was observed (r2= 41, P = 0.05). There was no relationship between IC AUC0-24 and P-gp expression on the cell surface (r2< 0.01, P = 0.98). CONCLUSIONS: There was a direct relationship between % bound efavirenz in plasma and IC accumulation implying that the IC accumulation of efavirenz is related to binding to IC proteins or other cellular constituents. Studies investigating the unbound concentration of antiretrovirals inside the cell are now required.

Intracellular and plasma pharmacokinetics of nevirapine in human immunodeficiency virus-infected individuals.

BACKGROUND AND OBJECTIVE: Plasma concentrations of nevirapine have been linked to human immunodeficiency virus (HIV) treatment outcome. However, because the site of action of nevirapine is within HIV-infected cells, intracellular concentrations may better relate to antiviral exposure. Investigation of factors that alter the intracellular pharmacokinetics of nevirapine may also aid in our understanding of therapeutic failure. Our objective was to determine intracellular (or cell-associated) nevirapine concentrations over the full dosing interval and to relate protein binding and P-glycoprotein (P-gp) expression to intracellular exposure. METHODS: Plasma and peripheral blood mononuclear cells were isolated from blood samples taken from 10 HIV-infected patients at 0, 2, 4, 8, and 12 hours after dosing. Intracellular and plasma (total and unbound) concentrations were determined by liquid chromatography-tandem mass spectrometry, and the ratios of intracellular to total plasma exposure (area under the concentration-time curves) were calculated. P-gp expression was measured by flow cytometry. RESULTS: The median intracellular accumulation ratio was 0.005 (range, 0.001-0.054) and remained unchanged over the dosing interval. There was an association between higher plasma concentrations and lower cellular concentrations of nevirapine (total r(2) = 0.62, P = .007). There was no relationship between percent unbound nevirapine and intracellular nevirapine. There was a correlation between higher plasma nevirapine exposure and higher P-gp expression (r(2) = 0.77, P = .03), whereas intracellular nevirapine exposure decreased with higher P-gp expression (r(2) = 0.62, P = .01). CONCLUSIONS: The intracellular accumulation of nevirapine was low, did not change over the dosing interval, and was not related to protein binding. In this small study, cells with higher P-gp expression had lower cellular concentrations of nevirapine. Further studies are required to explore the influx and efflux transporter profile of this drug.