Mary Poulton

Efavirenz is associated with severe vitamin D deficiency and increased alkaline phosphatase

Objective(s):To identify factors (including exposure to specific antiretroviral drugs) associated with severe vitamin D deficiency (VDD) in HIV-infected individuals and to explore the effects of severe VDD and antiretroviral drug exposure on serum alkaline phosphatase (ALP) as surrogate marker of bone turnover. Design:Cross-sectional survey of vitamin D status among HIV-infected patients attending for routine clinical care at a large London HIV clinic. Methods:Severe VDD was defined as 25(OH)D levels of less than 10 μg/l (<25 nmol/l). Multivariate logistic regression analysis was used to identify factors associated with severe VDD and upper quartile ALP levels. Results:Vitamin D levels were measured in 1077 patients and found to be suboptimal in 91%. One-third of patients had severe VDD. Black ethnicity, sampling in winter, nadir CD4 cell count less than 200 cells/μl, and exposure to combination antiretroviral therapy were associated with severe VDD. In analyses restricted to patients on combination antiretroviral therapy, current efavirenz use was significantly associated with severe VDD [adjusted odds ratio 2.0 (95% confidence interval 1.5–2.7)]. Current tenofovir [adjusted odds ratio 3.5 (95% confidence interval 2.3–5.2)] and efavirenz use [adjusted odds ratio 1.6 (95% confidence interval 1.02–2.4)], but not severe VDD [odds ratio 1.1 (0.8–1.5)], were associated with increased bone turnover (upper quartile ALP). Conclusion:Efavirenz was associated with severe VDD, a condition associated with multiple adverse health outcomes, and efavirenz and tenofovir with increased ALP. The clinical significance of these findings requires further investigation, given the widespread use of efavirenz and tenofovir in first-line combination antiretroviral therapy.

Total protein, albumin and low-molecular-weight protein excretion in HIV-positive patients

BackgroundChronic kidney disease is common in HIV positive patients and renal tubular dysfunction has been reported in those receiving combination antiretroviral therapy (cART). Tenofovir (TFV) in particular has been linked to severe renal tubular disease as well as proximal tubular dysfunction. Markedly elevated urinary concentrations of retinal-binding protein (RBP) have been reported in patients with severe renal tubular disease, and low-molecular-weight proteins (LMWP) such as RBP may be useful in clinical practice to assess renal tubular function in patients receiving TFV. We analysed 3 LMWP as well as protein and albumin in the urine of a sample of HIV positive patients.MethodsIn a cross-sectional fashion, total protein, albumin, RBP, cystatin C, and neutrophil gelatinase-associated lipocalin (NGAL) were quantified in random urine samples of 317 HIV positive outpatients and expressed as the ratio-to-creatinine (RBPCR, CCR and NGALCR). Exposure to cART was categorised as none, cART without TFV, and cART containing TFV and a non-nucleoside reverse-transcriptase-inhibitor (TFV/NNRTI) or TFV and a protease-inhibitor (TFV/PI).ResultsProteinuria was present in 10.4 % and microalbuminuria in 16.7 % of patients. Albumin accounted for approximately 10 % of total urinary protein. RBPCR was within the reference range in 95 % of patients while NGALCR was elevated in 67 % of patients. No overall differences in urine protein, albumin, and LMWP levels were observed among patients stratified by cART exposure, although a greater proportion of patients exposed to TFV/PI had RBPCR >38.8 μg/mmol (343 μg/g) (p = 0.003). In multivariate analyses, black ethnicity (OR 0.43, 95 % CI 0.24, 0.77) and eGFR <75 mL/min/1.73 m2 (OR 3.54, 95 % CI 1.61, 7.80) were independently associated with upper quartile (UQ) RBPCR. RBPCR correlated well to CCR (r2 = 0.71), but not to NGALCR, PCR or ACR.ConclusionsIn HIV positive patients, proteinuria was predominantly of tubular origin and microalbuminuria was common. RBPCR in patients without overt renal tubular disease was generally within the reference range, including those receiving TFV. RBP therefore appears a promising biomarker for monitoring renal tubular function in patients receiving TFV and for distinguishing patients with normal tubular function or mild tubular dysfunction from those with severe renal tubular disease or Fanconi syndrome.

Improvement in screening for sexually transmitted infections in HIV-positive patients following implementation of a nurse-led clinic.

The objective of this study was to assess changes in the uptake of sexually transmitted infection (STI) screening resulting from implementation of a specific STI clinic for HIV-positive patients. An audit of STI screening in HIV-positive patients was undertaken before and after the establishment of the clinic. Significant increases in the number of patients having a sexual health discussion and annual health screen were seen. High rates of positive results were found in all patient groups. National guidelines recommend regular STI screening for all HIV-positive patients. A specific clinic for HIV-positive patients is feasible and acceptable and may result in an increase in uptake of STI screening.

Pregnancy in HIV-infected teenagers in London.

The aim of the study was to describe pregnancies in HIV‐infected teenagers.

First-trimester markers of aneuploidy in women positive for HIV

Please cite this paper as: Savvidou M, Samuel I, Syngelaki A, Poulton M, Nicolaides K. First‐trimester markers of aneuploidy in women positive for HIV. BJOG 2011;118:844–848.

Utility of therapeutic drug monitoring in the management of HIV-infected pregnant women in receipt of lopinavir

The pharmacokinetics of antiretroviral drugs in pregnancy is poorly understood. We reviewed the use of therapeutic drug monitoring (TDM) in clinical settings to document plasma concentrations of lopinavir during pregnancy and investigated how clinicians acted upon TDM results. A retrospective review was carried out of all HIV-infected pregnant women taking boosted lopinavir-based highly active antiretroviral therapy (HAART) at five National Health Service (NHS) centres in the UK between May 2004 and March 2007. Seventy-three women in receipt of lopinavir were identified, of whom 89% had plasma lopinavir concentrations above the suggested minimum recommended for wild-type HIV. Initial TDM results prompted dosage change in 10% and assessment of adherence and/or pharmacist review in 11%. TDM was repeated in 29%. TDM can play an important role in the clinical management of HIV-positive pregnant women, allowing informed dose modification and an alternative measure of adherence.

Awareness of HIV post-exposure prophylaxis after sexual exposure and emergency hormonal contraception in HIV-positive women.

Women attending a dedicated medical gynaecology and family planning referral clinic for women with HIV were surveyed using a standard questionnaire about their knowledge and attitudes to post-exposure prophylaxis after sexual exposure (PEPSE) and emergency hormonal contraception (EHC). Eighty percent of them had not heard of PEPSE, but once informed about it, 86% said they would inform a partner about it. Less than 10% had any idea of the duration of effectiveness. Seventy-three percent of the women knew about EC and 45% of them had used it previously. Ninety-eight percent of them would use it in the future if necessary. Eighty percent of them knew its period of effectiveness. There is a clear need for information about PEPSE, which needs to be delivered around the time of HIV diagnosis and reinforced later. Some women will need help in discussing it with HIV-negative partners.

Sexual behaviour, condom use and rates of sexually transmitted infections in HIV clinic attendees in South East London

The aim of this study was to examine sexual behaviour, condom use and rates of sexually transmitted infections (STIs) among attendees at a dedicated on-site STI clinic at a South London HIV centre. Data were prospectively collected by using a nurse-completed questionnaire. Ninety-eight percent of women reported one or no sexual partners in the preceding three months, whereas 57% of men who have sex with men (MSM) reported two or more partners. Only 28% of women, 53% of heterosexual men and 29% of MSM always used a condom for vaginal or anal intercourse. Positive STI diagnoses were found in 17.5% of women, 20% of heterosexual men and 49% of MSM. Twenty percent of patients who reported always using a condom and 38% of MSM reporting no sexual activity in the preceding three months had an STI. These results highlight the need for safe sex promotion and STI screening in HIV-infected patients regardless of self-reported sexual activity.

Why are children still being infected with HIV? Experiences in the prevention of mother to child transmission of HIV in South London

Objectives: To evaluate the effectiveness of interventions to prevent mother-to-child transmission of HIV at a large teaching hospital in South East London, and to assess reasons for the small numbers of transmissions that continue to occur. Design: A database of all pregnant women diagnosed as HIV positive between 1993 and 2005 was reviewed, with detailed (retrospective) case-note review of all mother–infant pairs where HIV transmission occurred. Setting: King’s College Hospital, London, UK, a teaching hospital serving an ethnically diverse and socially deprived population. Results: 296 pregnancies to 274 women were recorded. 9 of 296 (3.0%) women were lost to follow-up before the end of the pregnancy. Of 287 pregnancies followed up until after delivery, 6 (2.1%) resulted in HIV infection in the infant. More recently, between 2000 and 2004, this transmission rate was even lower, at 3 in 231 (1.3%). Each of these six women had complications, including late presentation to services and defaulting follow-up appointments, which were likely to increase the risk of HIV transmission. Four of the six transmissions occurred in utero. Conclusion: The overall transmission rate of 2% attests to the efforts of the multidisciplinary care team in managing this population which is often hard to reach. Clearly, good systems are needed to trace those women who default. Further data are needed regarding in utero transmissions.

Care of HIV-positive women aged 50 and over – can we do better?:

A sample of 123 HIV-positive women aged 50 years and over showed high rates of late diagnosis with CD4 count <350 (71%), significant co-morbidities (90%), high rates of premature menopause (6.8%) and early menopause (6.8%) and cervical cytological abnormalities (47%). Specific interventions to improve care in this group should include yearly cervical cytology, early counselling with regard to reproductive options, menopause management and screening for sexually transmitted infections (STIs).