Bone mineral density, kidney function and participant-reported outcome measures in women who switch from tenofovir disoproxil emtricitabine and a nonnucleoside reverse transcriptase inhibitor to abacavir, lamivudine and dolutegravir.

OBJECTIVES: Tenofovir disoproxil fumarate (TDF) is associated with reduced bone mineral density (BMD). The aim of the study was to evaluate changes in BMD in women who switched from TDF, emtricitabine and a nonnucleoside reverse transcriptase inhibitor (TDF/FTC/NNRTI) to abacavir, lamivudine and dolutegravir (ABC/3TC/DTG). METHODS: We conducted a randomized controlled trial in which women aged ≥ 40 years were randomized 1:2 to continue TDF/FTC/NNRTI or switch to ABC/3TC/DTG. We analysed changes in BMD at the hip and lumbar spine from baseline to week 96 using linear regression, and markers of bone turnover and kidney function using repeated measures mixed effects models with multiple imputation for missing data. We conducted exploratory analyses of weight, mental health, sleep and symptoms attributed to HIV infection and antiretroviral therapy. RESULTS: Ninety-one women [mean (standard deviation) age 50.4 (6.6) years] were randomized. Women who switched to ABC/3TC/DTG maintained viral suppression and experienced improvements in BMD at the lumbar spine (but not the neck of the femur or the total hip), bone resorption markers and proteinuria (total protein, albumin and retinol-binding protein) and modest weight gain without changes in body mass index. Although mean anxiety, depression and sleep scores did not differ between the two study arms, anxiety, depression and sleep disturbance at baseline predicted ABC/3TC/DTG discontinuation for neuropsychiatric side effects [odds ratios (95% confidence intervals) 11.9 (2.0-71.6), 16.0 (2.6-97.9) and 10.0 (1.8-56.0), respectively]. CONCLUSIONS: Switching from TDF/FTC/NNRTI to ABC/3TC/DTG improved the BMD of the lumbar spine and kidney function. These benefits need to be balanced against modest weight gain and the need for antiretroviral therapy substitutions in a proportion of participants.

UK guideline for the use of HIV post-exposure prophylaxis 2021.

We present the updated British Association for Sexual Health and HIV (BASHH) guidelines for post-exposure prophylaxis (PEP) to HIV following sexual exposures, occupational exposures and other nonoccupational exposures in the community. This serves as an update to the 2015 BASHH guideline on PEP following sexual exposures and the 2008 Expert Advisory Group on AIDS guidelines on HIV PEP. We aim to provide evidence-based guidance on best clinical practice in the provision, monitoring and support of PEP for the prevention of HIV acquisition following sexual, occupational and other nonoccupational exposures in the community. The guideline covers when to prescribe PEP, what antiretroviral agents to use and how to manage PEP. This includes (i) evidence of PEP efficacy; (ii) evidence relating to individual-level efficacy of antiretroviral therapy to prevent the sexual transmission of HIV; (iii) data on the detectable (transmissible) prevalence of HIV in specific populations; (iv) risk of HIV transmission following different types of sexual and occupational exposure; (v) baseline risk assessment; (vi) drug regimens and dosing schedules; (vii) monitoring PEP; (viii) baseline and follow-up blood-borne virus testing; (ix) the role of PEP within broader HIV prevention strategies, for example, HIV pre-exposure prophylaxis (PrEP). The guideline also covers special scenarios such as PEP in pregnancy, breastfeeding and chronic hepatitis B virus infection, and when PEP should be considered in people using HIV PrEP. The guidelines are aimed at clinical professionals directly involved in PEP provision and other stakeholders in the field. A proforma to assist PEP consultations is included. A public consultation process was undertaken prior to finalizing the recommendations.

Safety of Tenofovir Alafenamide in People With HIV Who Experienced Proximal Renal Tubulopathy on Tenofovir Disoproxil Fumarate.

BACKGROUND: Proximal renal tubulopathy (PRT) is an infrequent complication of tenofovir disoproxil fumarate (TDF). It remains to be established whether tenofovir alafenamide (TAF) can be safely administered to individuals who experienced PRT on TDF. METHODS: Individuals with a history of TDF-associated PRT and current estimated glomerular filtration rate (eGFR) over 30 mL/min/1.73 m2 initiated TAF and were followed for 96 weeks. The primary outcome of interest was recurrent PRT. Secondary outcomes were changes in kidney biomarkers, bone biomarkers, and bone mineral density (BMD). Data were analyzed using multilevel mixed-effects linear regression models. The trial was registered under EudraCT 2016-003345-29. RESULTS: All 31 participants [median age 55 (inter-quartile range 51, 60) years, 97% men, 87% White ethnicity] remained on TAF at week 96, and none developed glycosuria or recurrent PRT. Participants experienced small declines in eGFR-creatinine [-1.9 (95% confidence interval: -3.5 to -0.3) mL/min/1.73 m2/yr; P = 0.024], but not in eGFR-cystatin C [-0.9 (-2.1 to 0.4) mL/min/1.73 m2/yr; P = 0.16]. Ten (32%) and 5 (16%) participants experienced rapid (>5 mL/min/1.73 m2/yr) decline in eGFR-creatinine and eGFR-cystatin C. No significant change in other kidney biomarkers, bone turnover, or BMD was observed (P > 0.2). CONCLUSIONS: In individuals with a history of PRT on TDF, 96 weeks of TAF was not associated with recurrent PRT or adverse effects on renal tubular function, bone turnover, or BMD. These data suggest that TAF is a treatment option for this vulnerable population.

Nanoflow-Nanospray Mass Spectrometry Metabolomics Reveals Disruption of the Urinary Metabolite Profiles of HIV-Positive Patients on Combination Antiretroviral Therapy.

BACKGROUND: The use of combination antiretroviral therapy (cART) has substantially improved the outlook for patients with HIV infection. However, lifelong exposure to cART is also associated with adverse metabolic changes and an enhanced risk of renal, hepatic, and cardiovascular dysfunction. This study investigated disruptions of the urinary metabolome of cART-exposed patients, thereby furthering our understanding of some of the side effects of pharmaceutical intervention. METHODS: HIV-positive patients were recruited from an HIV clinic and divided into cART-naive and cART-exposed groups. HIV-negative patients were recruited from a sexual health clinic. All 89 subjects were white males. Targeted biochemistry analyses were performed on plasma samples. Urine samples were collected after an overnight fast and analyzed with a highly sensitive untargeted metabolomic method using nanoflow/nanospray liquid chromatography-time-of-flight mass spectrometry. Data sets were analyzed using projection modeling to detect metabolite markers of cART exposure. RESULTS: Metabolites or parent compounds of all cART drugs were detected in urine extracts of all but one of the cART-exposed patients confirming adherence to the pharmaceutical regimen. Analysis of urine samples from patients on cART revealed significant reductions in selected bile acids, lipid, nucleoside, and androgen metabolites. However, plasma concentrations of free or conjugated testosterone remained unchanged indicating possible disruption of androgen transport or excretion in urine of patients on cART. CONCLUSIONS: Discovery-based metabolomics reveals the potential to identify novel markers of cART intervention and metabolite disruption in HIV-positive patients, which may enable investigation of the efficacy, compliance, and side effects of these pharmaceutical mixtures to be investigated.

Effects of renal tubular dysfunction on bone in tenofovir-exposed HIV-positive patients.

OBJECTIVES: Tenofovir disoproxil fumarate (TDF) may cause renal tubular dysfunction (RTD) and reduce bone mineral density (BMD). We examined the relationship between RTD and BMD in TDF-exposed HIV-positive men. DESIGN AND METHODS: We analysed urinary retinol-binding protein/creatinine ratio (RBPCR) and fractional excretion of phosphate (FEPO4) to quantify RTD in a cross-sectional sample of randomly selected HIV-positive men at a single tertiary outpatient clinic. BMD at the lumbar spine and hip was measured by dual-energy X-ray absorptiometry. Multivariate logistic regression was used to analyse factors associated with RTD, and linear regression to examine the relationship between RTD and BMD. RESULTS: Of 293 men (mean age 48 years, 94% White ethnicity, median TDF exposure 2.1 years), 22.5% had RBPCR-defined RTD and 12.3% had FEPO4-defined RTD. We observed a negative correlation between RBPCR and BMD at the spine (ß -0.2, P = 0.002) and hip (total: ß -0.1, P = 0.02; femoral neck: ß -0.1, P = 0.02), but not between FePO4 and BMD. In multivariable analyses, RTD defined by more than five-fold elevations in RBPCR was associated with significantly lower BMD of the spine. CONCLUSION: In HIV-positive patients receiving TDF-containing antiretroviral therapy, RTD was associated with lower BMD of the spine in HIV-positive men. RBPCR quantification may identify patients at increased risk of TDF-associated BMD loss.

No association between vitamin D deficiency and parathyroid hormone, bone density and bone turnover in a large cohort of HIV-infected men on tenofovir.

INTRODUCTION: Combination antiretroviral therapy (cART) may affect vitamin D [25(OH)D], parathyroid hormone (PTH), bone mineral density (BMD) and bone turnover (BT). Reduced BMD and secondary hyperparathyroidism have been reported with tenofovir (TDF). We investigated the associations between TDF and bone markers, especially in 25(OH)D-deficient patients. MATERIALS AND METHODS: In a single-centre longitudinal study investigating BMD in HIV-positive men, serum 25(OH)D, calcium, phosphate, PTH and alkaline phosphatase (ALP) were measured. Lumbar spine, non-dominant total hip and non-dominant femoral neck BMD (g/cm(2)) were measured using dual-energy X-ray absorptiometry. BT was assessed by serum type 1 procollagen (P1NP) and carboxy-terminal collagen cross-links (CTX). Mann-Whitney U tests compared serum markers and BT, and t-tests compared BMD according to TDF in all and 25(OH)D-deficient patients. RESULTS: A total of 422 men were recruited: mean age 47 (SD 9.8) years, 94% white ethnicity, 93% MSM, diagnosed HIV positive for median 9.6 (IQR 5.0,15.5) years, median CD4 547 (IQR 411,696) cells/µL, HIV RNA <40 copies/mL in 87% (96% of those on cART). 25(OH)D (nmol/L) was normal (>75), insufficient (50-75), deficient (25-50) and severely deficient (<25) in 14%, 29%, 50% and 7%, respectively. Of 381 men on cART, 77% were currently on TDF. TDF was not associated with median calcium (p=0.69) or phosphate (p=0.52), but patients had higher (but normal) median ALP [81 (IQR 69,103) vs. 73 (IQR 60,89) IU/L, p=0.005) compared to non-TDF cART. There was no difference in the association between vitamin D and PTH according to whether someone currently was (r=0.11, p=0.06, Figure 1) or was not using TDF (r=0.12, p=0.29, Figure 1). TDF was also not associated with PTH, BMD or BT in either all patients on cART (Table 1a) or in patients with 25(OH)D deficiency (Table 1b). CONCLUSIONS: In this largely TDF-experienced cohort of HIV-positive men, there was no association between TDF and 25(OH)D deficiency, hyperparathyroidism, reduced BMD or increased BT, although patients on TDF had higher but normal ALP. We found no evidence to support additional monitoring of bone markers in patients on TDF regardless of 25(OH)D status.

Effects of vitamin D deficiency and combination antiretroviral therapy on bone in HIV-positive patients.

OBJECTIVES: In the era of combination antiretroviral therapy (cART), vitamin D deficiency, low bone mineral density (BMD) and fractures have emerged as subjects of concern in HIV-positive patients. Testing for vitamin D deficiency has been widely adopted in clinical practice even though the benefits of vitamin D supplementation in this population remain uncertain. The objective of this review was to evaluate the evidence for such a strategy. DESIGN: Systematic review of the literature on vitamin D deficiency in HIV infection, the effects of cART on vitamin D status, and the effects of vitamin D deficiency and cART on parathyroid hormone (PTH), bone turnover, BMD and the incidence of fractures in HIV-positive patients. METHODS: PubMed was used to identify relevant articles up to September 2011. RESULTS: Vitamin D deficiency, secondary hyperparathyroidism and low BMD are common in HIV-positive patients. Efavirenz is associated with a reduction in 25-hydroxy vitamin D levels, tenofovir with secondary hyperparathyroidism, and cART with increased bone turnover and low BMD. The clinical significance of low BMD, however, remains unclear, especially in younger patients. Although the incidence of fractures may be increased in HIV-positive patients, the contribution of low BMD and vitamin D deficiency to these fractures is uncertain. Limited data on vitamin D supplementation in HIV-positive patients have shown transient, beneficial effects on PTH, but no effects on BMD. CONCLUSION: The benefits of vitamin D supplementation in this population need to be demonstrated before widespread 'test and treat' policies can be recommended as part of routine clinical practice.

A laboratory-based evaluation of the BioStar Optical ImmunoAssay point-of-care test for diagnosing Neisseria gonorrhoeae infection.

The development of gonococcal point-of-care tests (POCTs) has been challenging due to the relatively monomorphic nature of the Neisseria genus. The BioStar Optical ImmunoAssay (OIA) POCT for diagnosing Neisseria gonorrhoeae infection detects a specific epitope on the L7/L12 ribosomal protein, which reduces cross-reactivity with other neisseriae, and produces a highly specific test. A laboratory-based evaluation of this POCT was performed to determine its analytical sensitivity and specificity. A panel of N. gonorrhoeae (n=158) and non-gonococcal Neisseria (n=62) isolates were examined. The OIA GC POCT positively reacted with 99.4% of N. gonorrhoeae isolates and produced no reaction with 88.7% of non-gonococcal Neisseria isolates. It cross-reacted with six strains of N. meningitidis and one non-speciated Neisseria sp., but failed to produce a positive result with one isolate of N. gonorrhoeae. The OIA GC POCT required a bacterial suspension of ~6.4×10(5) c.f.u. N. gonorrhoeae ml(-1) and ~6.2×10(6) c.f.u. N. meningitidis ml(-1) to produce a reactive result. The OIA POCT detected the majority of N. gonorrhoeae (99.4%) isolates examined.