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IntroductionDue to discontinuation of the Siemens Versant HIV‐1 RNA (bDNA) assay in the UK, our laboratory switched to the Roche Cobas Ampliprep/Taqman HIV‐1 viral load (VL) assay (Roche) in April 2013. This assay has a lower cut‐off of 20 RNA copies/mL (compared with <50 for the Siemens assay). Our laboratory demonstrated previously that a significant proportion (18%) of patients undetectable using bDNA HIV‐1 RNA quantification exhibited low level viraemia (LLV) using the new assay. Local guidelines recommend that patients stable on therapy receive twice‐yearly VLs. We evaluated the impact of the introduction of the new assay on our clinical service.MethodsA retrospective cohort analysis of treated patients with stable undetectable VL by bDNA (<50 copies/mL) followed by ≥ one low‐level (<400 copies/mL) VL with the Roche assay. Demographic data were collected in addition to frequency of VL testing and genotypic resistance assays. Referrals to virtual clinic (VC) were recorded. Patients were identified using laboratory data and information collected from electronic patient records. Results were analyzed with SPSS v18.ResultsOne hundred and ninety patients were included. Demographics: 79.5% male; 60.6% homosexual; mean age of 46 years. Duration on stable treatment was 46.35 (std. dev. 38.15) months. Current treatment regimens were 43.3% PI‐based; 43.3% NNRTI‐based and 13.7% other. Patients were stratified into VL 20–49 copies/mL (n=109); VL 50–199 copies/mL (n=71) and VL 200–399 copies/mL (n=10). In total, there were 471 VLs measured of which 274 were additional as a result of the assay switch. This resulted in six HIV‐1 genotype requests and 16 VC discussions (Table 1). Longer duration on HAART was associated with reduced frequency of VL testing. The relative risk of ongoing detectability according to drug class are: PI 1.62 (95% CI 1.18–2.21); NNRTI 0.507 (95% CI 0.30–0.85) and other 1.09 (95% CI 0.48–2.43).ConclusionsChanges in assay can result in difficulties in interpretation of patient results. The assay switch in our service had significant impact on patient and staff time and cost with an increase in patient recalls; increased frequency of VL measurement, genotypes and discussions in VC. Choice of assay is paramount to running an efficient and cost‐effective clinical service.

BackgroundIEtravirine (ETR) was approved in France in Sept 2008, to be used in combination with a ritonavir‐boosted protease inhibitor (bPI) and others antiretrovirals (ARV) in HIV‐infected pre‐treated patients.ObjectivesTo describe in a real life setting efficacy and tolerability of ETR‐including regimen and factors associated with virologic response.MethodIn the French DatAIDS cohort including 18,647 patients, we selected patients who initiated an ETR‐including regimen between September 2008 and July 2013. Demographic data and clinico‐biological data were collected from the standardized electronic medical record Nadis®. Analyses were done in patients starting ETR and sub‐analyses were performed in pre‐treated patients starting ETR for virologic failure (VF) or maintenance (MT) therapy, with or without bPI.Results2083 patients (ARV‐naïve n=77, VF n=1014, MT n=992) were included: median age 47 years, 73.3% male, median duration of HIV infection 15.7 years, CDC stage C 38.7%, HBV/HCV co‐infection 25.7%. In pre‐treated patients, 75.5% previously received NNRTIs (median duration on EFV and NVP of 480 and 396 days, respectively), 94.3% bPIs, 30.8% raltegravir (RAL) and 19.4% enfuvirtide. The most frequent ARVs associated with ETR were two NRTIs in 37.2% of the cases (21.9% in VF, 52.9% in MT), 1 bPI+RAL in 10.1% (13.5% in VF, 6.6% in MT), RAL in 6.2% (2% in VF, 10.5% in MT). Median duration on ETR was 3.7 and 2.2 years in the VF and MT group, respectively. In the VF group, HIV RNA was <50 c/ml in 71.7% (71.1% without bPI, 72% with bPI) of the patients at M12, 72.8% (71% without bPI, 73.3% with bPI) of the patients at M24. In the MT group, HIV RNA was<50 c/ml in 90.5% of the patients at M12 and 93.1% at M24. ETR was discontinued in 8.8% of the patients (12.8% in VF, 5.4% in MT) for adverse events in 23.9% of cases (21.5% in VF, 29.5% in MT), treatment failure in 15.2% (16.2% in VF, 7.4% in MT) or simplification in 5.4% (4.6% in VF, 7.4% in MT). In the VF group, factors associated with virologic failure in multivariate analysis were a longer duration of HIV infection (OR 2.6; 95% CI 1.7–4.0) and baseline HIV RNA >5 log10 c/ml (OR: 2.0; 95% CI 1.3–3.2) but not the association with a bPI.ConclusionThis large study shows that in ARV‐pre‐treated patients ETR is well tolerated with a high efficacy when combined with other active drugs, even when the regimen does not include a bPI.

IntroductionNucleoside reverse transcriptase inhibitors (NRTI)‐sparing regimens have been studied in antiretroviral therapy (ART)‐naïve patients but data with ART‐experienced are scarce. NRTI‐sparing regimens may be an option in patients with toxicities and for simplification reasons.MethodsRetrospective multicentre analysis including ART‐experienced patients starting treatment with darunavir/ritonavir and etravirine (DRV/r 800 mg/100 mg QD or 600 mg/100 mg BID and ETV 400 mg QD or 200 mg BID) with at least six months of follow‐up. Primary endpoint was proportion of patients with VL<50 copies/mL at 48 weeks with an ITT analysis (missing or switch equals failure). Secondary endpoints were safety, CD4 count and lipid changes over 48 weeks.ResultsSeventy‐five patients were included of whom 44 (58.6%) had HIV RNA<50 copies/mL. Baseline characteristics: median age 50 years (IQR 34–65), 72% males, 93% Caucasians, 38.6% hepatitis C, and 45.4% with CDC C stage. Median HIV duration and time on ART were 20 (IQR 7–28) and 14 years (IQR 5–21) respectively. Reasons for switching were virologic failure in 27 (36%), simplification in 25 (33.3%), toxicity in 20 (26.6%) and other 3 (4.1%). Most of them received DRV/r and ETV QD. Thirty‐nine patients had NNRTI resistance mutations [28 K103N (37.3%), 6 Y181I/C (8%), 3 G190A (4%)] and 29 patients had ≥1 primary PI mutations. Main analysis (ITT) showed that 67 (89.3%) had a VL undetectable at 24 weeks (95% CI 83.1–95.5) and 57 (76%) at 48 weeks (95% CI 68.4–83.6). On treatment analysis showed that 94.3% and 89% had a viral load<50 copies at 24 and 48 weeks, respectively. 11 (14.6%) patients discontinued the regimen (three virologic failures, three switching to darunavir/ritonavir monotherapy, two to salvage regimen and three due to toxicity). No significant changes in CD4+ count and lipid changes were observed at 48 weeks.ConclusionsDual therapy with Darunavir/ritonavir and etravirine is an efficacious and safety option in ART‐experienced HIV patients even in patients on virologic failure.

IntroductionSwitch to Stribild (STB) was non‐inferior to continuation of a non‐nucleoside reverse transcriptase inhibitor (NNRTI) with emtricitabine and tenofovir DF (FTC/TDF) at week 48 in virologically suppressed HIV adults [1]. We report the Week 48 efficacy and safety of STB versus nevirapine (NVP) or rilpivirine (RPV) with FTC/TDF in suppressed subjects.Materials and MethodsVirologically suppressed subjects on an NNRTI with FTC/TDF regimens for ≥6 months were randomized (2:1) to switch to STB versus continue their NNRTI regimen. Eligibility criteria included no documented resistance to FTC and TDF, no history of virologic failure and eGFR ≥70 mL/min. The primary endpoint was the proportion of subjects in the modified ITT population who maintained HIV‐1 RNA <50 copies(c)/mL at Week 48 by FDA snapshot algorithm (12% non‐inferiority margin). Subgroup analysis by non‐EFV NNRTI use (NVP [74]; RPV [19]; etravirine [3]) at screening was pre‐specified.ResultsThe mITT population included 433 subjects who were randomized and treated. In the non‐EFV NNRTI subgroup, 59 switched to STB; 37 continued a non‐EFV NNRTI (27 NVP, 10 RPV) with FTC/TDF. At week 48, 97% STB versus 95% non‐EFV NNRTI maintained HIV‐1 RNA <50 c/mL. No emergent resistance was detected in either group. No difference in median increases from baseline in CD4 count at week 48 (cells/µL): 25 STB versus 55 non‐EFV NNRTI (p=0.78). No discontinuation due to adverse events; no cases of proximal renal tubulopathy. As expected, there were no significant changes in the frequency of neuropsychiatric symptoms (i.e. anxiety, insomnia, dizziness, vivid dreams, weird/intense dreams, and nightmares) reported on the HIV Symptom Index at week 48 compared to baseline after switching to STB. There was a greater but non‐progressive decrease from baseline in eGFR in the STB versus non‐EFV NNRTI group; median changes (mL/min) at week 48: −9.1 versus −1.4. Switch to STB was associated with a higher treatment ease (convenience, flexibility, demand, lifestyle, understanding) score (range: −15 to 15) at week 4 (median: 14 vs 11; p=0.047) and week 24 (median: 14 vs 12.5; p=0.038).ConclusionsIn this small group of virologically suppressed subjects, switch to STB vs continuation of NVP or RPV with FTC/TDF was safe, well‐tolerated, and associated with a high rate of virologic suppression at week 48. There was more treatment ease with STB use.

IntroductionNo controlled clinical trials had studied the role of maraviroc (MRV) in fully suppressed patients [1].Materials and MethodsMRV‐cohort is an observational, retrospective, multicentric (27 sites) large cohort study of patients starting MRV in clinical practice under different circumstances, with at least 48 weeks of follow‐up. For the present analysis we selected all those patients starting with an HIV‐RNA<50 copies/mL. Demographics, baseline CD4 cell count, past history of antiretroviral treatment (ART), tropism, reasons for MRV use, MRV based therapy and change/end of MRV use were assessed. Paired analysis of lipid, hepatic and kidney profile changes and univariate and multivariate analyses of HIV‐RNA<50 copies/mL at 48 weeks were explored.ResultsWe included 247 out of 667 subjects from the entire cohort. At study entry, their median age was 47 years, 23% were women, 31% MSM, 49% had CDC category C, median CD4+ counts were 468 cells/mm3, 46% were HCV+ and 4.5% AgHBs+. Tropism information was available in 197 (94% R5). Median length of prior ARTV was 10.7 years, with exposure to a median of three drug families. Main reasons for prescribing MRV were: toxicity 38%, inmunodiscordance 23%, simplification 19% and admission in a clinical trial 10.4%. MRV based therapies used were MRV+2NRTIs 9%, MRV+PI 46%, MRV+PI+other 40% and MRV+other 5%. At 48 weeks, 23% of patients had changed or finished MRV therapy due to toxicity 2.4%, virological failure 2%, immunological failure 1.2%, simplification 3,2%, trial requirement 9.7%, medical decision 2.8%, treatment suspension 1.2% and unknown 0.4%. At 48 weeks, no significant changes were observed in lipid, hepatic or kidney profiles, and 85% of patients remained with HIV‐RNA<50 copies/mL. Focusing on viral response univariate and multivariate models did not show any significant baseline variable explaining viral failure.ConclusionsIn clinical practice MRV was used, mostly in R5 positive patients, with adequate efficacy and tolerance, but important number of patients changed due to non‐clinical reasons. In this scenario neither reason for use of MRV nor MRV‐based therapy explained viral failure.

Immune activation has been recognized as an important component of the pathogenesis of HIV infection since the first recognition of cases of AIDS in the early 1980s. Early in the AIDS epidemic, patients with HIV infection were noted to have elevated levels of serum immunoglobulins. CD38 expression on CD4+ T cells was shown to be an independent predictor of survival in 1999. The characterization of HIV‐associated immune activation has become progressively sophisticated over the past several years. A consistent finding has been an association of poor clinical outcomes with markers of monocyte activation (IL‐6 and sCD14) and/or coagulation (D‐dimer). These relationships have been shown to exist even in patients with plasma levels of HIV‐1<50 copies/ml. While it is generally accepted that immune activation is related to HIV infection, there is less clarity regarding the pathways that lead to its expression. Among the forces reported to drive HIV‐associated immune activation are innate and adaptive immune responses to HIV and related co‐infections, homeostatic responses to CD4+ T cell depletion and translocation of microbial products across the intestinal wall. Recent work has identified a potential role for "defective" HIV‐1 transcripts in driving immune activation. Studies examining the connections between the adaptive immune system and the coagulation cascade have led to the identification of PAR‐1 as a potential target for therapeutic intervention. Despite the successes experienced with cART, persistent immune activation in association with HIV infection remains a scientific and clinical problem that is yet to be solved.

IntroductionPREVALEAT II (PREmature VAscular LEsions and Antiretroviral Therapy II) is an ongoing multicenter, longitudinal cohort study aimed to the evaluation of cardiovascular (CV) risk in advanced HIV‐infected antiretroviral (ARV) naïve patients starting their first antiretroviral therapy (ART).Patients and methodsAll consecutive naïve patients with CD4 cell count<200/mL starting any PI/r‐based or NNRTI‐based + 2 NRTIs regimen from January 2010 to January 2013 in the participant centres were enrolled. At baseline and after 3 (T1), 6 (T2) and 12 (T3) months patients were subjected to epi‐aortic vessels ultrasonography and brachial artery flow mediated dilation (FMD). Viral load, CD4+ cell count, serum lipid values, serum glucose, endothelial activation (ICAM‐1 and VCAM‐1) and inflammatory markers (IL‐6 and hsCRP) values were recorded at the same time. Data about independent risk factors for HIV infection and CV disease are taken at time 0. We enrolled 94 patients: 81% males, 87% caucasians, 40% smokers, 8.2% HCV co‐infected and 3.5% with lipodystrophy; 33% of them were homosexuals, 12% drug addicts; 23% were AIDS at presentation. Statistical data analysis has been conducted by the χ2 nonparametric method.ResultsIn Table 1 it is reported the percentage of patients with pathologic values, moreover, at T3, 60.46% showed undetectable viraemia and 69.77% had CD4 + > 200.ConclusionsOur data evidence at baseline has a relevant deterioration of CV conditions in terms of ultrasonographic data, FMD, inflammation and cytokine markers among advanced naïves. During follow‐up epi‐aortic lesions tend to worsen but not significantly, percentage of pathologic FMD remains stable. Regarding markers of endothelial activation ICAM‐1 significantly worsens during the period of observation; also VCAM‐1 has a trend towards the worsening while not significantly. Conversely, a significant improvement was observed for the markers of inflammation D‐dimers and high sensitivity C‐reactive protein (hsCRP). IL‐6 improved but not significantly. Serum lipid profile shows an increase of HDLc and total cholesterol, but not of LDLc. In conclusion, after a twelve‐month follow‐up period, CV risk of the patients remains high. ARV therapy seems in fact to improve only non‐specific and poor sensitive inflammation biomarkers and HDLc; markers of endothelial activations tend to worsen, intima‐media ultrasonography and FMD do not show relevant modifications. Further data are warranted to better understand the role of the different ARV regimens.

IntroductionHIV patients are at risk of renal dysfunction directly from HIV, indirectly from chronic inflammation as well as from antiretroviral drug toxicity. In particular, tenofovir (TDF) has been associated with proximal renal tubular dysfunction. A joint HIV–renal clinic was set up in 2009 to facilitate a timely review and minimize additional follow‐up appointments. Brighton has a cohort of 2,150 HIV patients, 90% are on ARVs with 910/1,935 (47.0%) on regimens including TDF. This study aims to investigate the utility of this clinic and describe renal disease in this cohort.Materials and MethodsNotes of patients scheduled for assessment at the clinic between 2012 and 2014 were reviewed. Demographics, HIV history, number of visits, reason for referral and outcome information were collected.ResultsSixty‐five patients, median age 51 years (28–88) and median duration of HIV 163 months (20–335), were reviewed. Forty‐two were taking TDF for a mean of 55.8 months (9–122). Forty‐two patients were reviewed once with a median number of visits of 1 (1–4).Of those on TDF with proteinuria, 5 (13.2%) had TDF toxicity diagnosed and were discontinued at once, 27 continued with close monitoring with a further 7 subsequently discontinuing; total discontinued were 12 (32%). Overall, blood pressure control was the commonest intervention, 23/65 (35.4%), with 8/12 (66.7%) in the non‐TDF proteinuria group. Four (6%) patients underwent renal biopsy (2 focal segmental glomerulosclerosis, 1 IgA nephropathy and 1 glomerulonephritis and granuloma). In 4 (6%) creatinine rise was attributed to NSAIDs, creatine or protein supplements usage.ConclusionsTDF toxicity was the commonest reason for referral but only a minority (13.2%) needed to discontinue immediately. Optimizing BP control was the most frequent outcome suggesting this is an underappreciated cause for renal dysfunction amongst HIV physicians, as were other causes such as creatine and protein supplement usage. Running a "one‐stop‐shop" clinic supports continuation of tenofovir in patients with proteinuria, and supports the diagnosis and management of poorly controlled hypertension and streamlines the management of these patients.

IntroductionThere is limited data available on exposure to anti‐tuberculosis (TB) drugs in this region. Peloquin has described reference ranges [1] however some studies have demonstrated that patients actually achieve concentrations below these ranges [2]. There is limited data about exposure to anti‐TB drugs in the HIV/TB co‐infected population in Sub‐Saharan Africa. Our objective is to describe the concentration of anti‐TB drug levels in a well characterized prospective cohort of adult patients starting treatment for pulmonary TB.MethodsThis study is an ongoing study carried out in the TB/HIV integrated clinic at the Infectious Diseases Institute in Kampala, Uganda. Sputum culture and microscopy was done for all patients. We performed pharmacokinetic blood sampling of anti‐TB drugs for 1 hour, 2 hours and 4 hours post dose at 2 weeks, 8 weeks and 24 weeks after initiation of anti‐TB treatment using ultraviolet high‐performance liquid chromatography (UV‐HPLC). We described the maximum concentration (Cmax) of isoniazid (H), rifampicin (R), ethambutol (E) and pyrazinamide (Z) and compare them with the values observed by Peloquin et al. referenced in other studies.ResultsWe started 113 HIV infected adults on a fixed dose combination of HREZ. The median age of our population was 33 years, of which 52% were male with a median BMI of 19 kg/m2 and a median CD4 cell count of 142 cells/µL. In 90% of the participants, the diagnosis of TB was based on microscopy and or cultures. The boxplot graph shows the median Cmax and IQR of H and R.Levels of H were found to be below the reference ranges (3–6 µg/mL) in 54/77(70.1%), 38/59(64.4%) and 15/24(62.5%) participants at weeks 2, 8 and 24. Rif levels were also found to be below the reference ranges (8–24 µg/mL) in 41/66(62.1%), 26/48(54.2%) and 8/10(8%) participants at weeks 2, 8 and 24, respectively. The mean Cmax of E and Z were within the reference range at week 2 and 8; mean Cmax of 3.2±SD2.1 µg/mL and 4.0±SD3.1 µg/mL for E and 41.6±SD13.1 µg/mL and 42.6±SD16.4 µg/mL for Z.ConclusionWe observed lower concentrations of isoniazid and rifampicin in our study population of HIV/TB co‐infected patients. The implications of these findings are not yet clear. We therefore need to correlate our findings with the response to TB treatment.

IntroductionAntiretroviral drugs in Spain are delivered by law only in hospital pharmacies. Commercial packages meet variable quality standards when dispensed drugs are returned due to treatment changes or adherence problems Nearly 20–25% of the initial regimens will be changed at 48 weeks for different reasons. We evaluated the economic impact on public health system of the inability of using returned drugs due to inefficient packaging.Materials and MethodsWe defined socially efficient packaging as the best adapted one to being delivered in unit dose to outpatients and classified: Class A ‐ Drug packed in unit doses with complete info (name of drug, dosage in mg, lot, and expiring date) in each unit, maintaining complete information of the drug if returned when the external package is opened. Class B ‐ packed in blisters with complete info in the blister, but not in unit doses, without special conservation conditions (should be re‐packed in unit doses in the pharmacy before its dispensation to assure a class A excellence). Class C ‐ packed in plastic containers with complete info written only on a label over the container, would allow repackaging only before its initial delivery, but not when returned. Class D ‐ drug packed in plastic containers with manufacturer's warning that the product cannot be placed outside of the original package due to special conditions of conservation (fridge, humidity) that doesn't allow a unit dose repackaging or reusing an opened container. We analysed a 12‐month period (July 2011–June 2012) in a hospital‐based HIV outpatient pharmacy that serves 2413 treated individuals.ResultsPatients generated 23,574 visits to pharmacy, and received 48,325 drug packages, with 2.529.137 pills delivered. The patients suffered 1051 treatment changes for any reason. A total amount of 122.945€ in treatment were returned to pharmacy in opened packages during the study period. 47.139.91€ would be totally lost, mainly due to being packaged in class C and D boxes, the equivalent of treating 78 patients with rilpivirine/TDF/FTC during 1 month. Class A and B packages in bad condition represented only 1.1% of the cost. However, 75.805€ came from returned packages in good condition that could potentially be reused. Most of the treatment changes were not foreseeable.ConclusionsA significant economic budget is lost through socially inefficient antiretroviral packages. Newer treatments are packaged in C and D categories, therefore maintaining these hidden costs in the near future. Any improvement in the excellence of packaging by the manufacturer, and favouring the choice of drugs supplied through efficient packages (when efficacy, toxicity and convenience are similar) should minimize the treatment expenditures paid by national health budgets.

IntroductionTelaprevir (TVR) plus peg interferon (PEG‐IFN) and ribavirin (RBV) substantially increase treatment efficacy for genotype 1 chronic hepatitis C virus (HCV) infection but data about its safety in HIV patients with cirrhosis are lacking. Our purpose was to evaluate estimated Glomerular Filtration Rates (eGFR) variations during combination therapy in a difficult‐to‐treat HIV/HCV population with advanced fibrosis/cirrhosis through three different scores commonly used in clinical practice: CKD‐EPI (Chronic Kidney Disease Epidemiology Collaboration), Modification of Diet in Renal Disease (MDRD) scores (that consider gender, ethnicity, age, serum creatinine level [SCL]) and MDRD 6 variable (that considers the previous parameters plus blood urea nitrogen and serum albumin). Second objective was to identify any association between creatinin clearance and haemoglobin (Hb) variation during combination therapy.Materials and MethodsWe conducted an observational retrospective study including 18 HIV/HCV patients attending our clinic who started combination therapy for HCV, including in the analysis the first 16 weeks of therapy. Treatment included TVR 1125 mg BID (twice a day) for 12 weeks, PEG‐IFN α‐2a 180 mcg QW and RBV daily dose according to body weight (800 mg in individuals <60 kg; 1000 mg in individuals 60–75 kg; 1200 mg in individuals >75 kg). Advanced fibrosis was defined as Metavir score=F3 or Ishak 3–4 and cirrhosis was defined as Metavir score F4 or Ishak 5–6 assessed by liver biopsy or transient elastography respectively. P per trend were assessed to evaluate any change of SCL and eGFR (according to different formulas). Multilevel linear regression analysis was performed to estimate factors associated with reduction of Hb.ResultsBaseline characteristics and HCV virological responses were collected. Figure 1 shows median SCL and eGFR trends across follow‐up period: SCR p‐per‐trend was 0.28, for CKD‐EPI was 0.50, for MDRD was 0.48, for MDRD‐6 variables was 0.27. Hb trend was also assessed and a significant decrease of Hb across follow‐up (p per trend <0.001) was noted. Multilevel regression analysis found an association between SCL and Hb change, after adjustment for age, sex, basal BMI, tenofovir exposure and proteinuria (assessed at baseline) as shown in Table 1.ConclusionsIn our experience, combination therapy with TPV in cirrhotic HIV‐HCV patients did not significantly affect renal function. As expected, Hb levels decreased during treatment and it is likely related to RBV exposure. In multivariable analysis, reduction of Hb appeared to be related to SCL higher levels, thus suggesting even a mild decrease of renal function.

IntroductionTenofovir is a commonly used component of antiretroviral therapy (ART) to reduce vertical transmission of HIV. Although systematic review of tenofovir use in pregnancy concluded it to be low risk for foetal abnormalities [1], data is limited on its impact on renal function in pregnant women. A recent South African study [2] concluded that renal dysfunction in HIV‐infected pregnant women is significantly less common than in other HIV‐infected adults, however there is currently no UK data. We aimed to investigate the effect of tenofovir on renal function in HIV‐1 positive pregnant women in a UK clinic.MethodsWe retrospectively analyzed data on renal function in pregnancy from a cohort of women attending a busy inner city London antenatal clinic. All women were screened for renal function throughout pregnancy via serum creatinine and estimated glomerular filtration rate (eGFR) calculated using modification of diet in renal disease (MDRD) and corrected for ethnicity.ResultsNinety‐seven HIV‐1 positive women were registered at Homerton Hospital antenatal service of a total of 105 pregnancies between January 2010 and September 2013. Tenofovir was prescribed in 71/105 pregnancies (67.6%). Of the 71 pregnancies, 41 were prescribed tenofovir pre‐conception (57.7%). Of the pregnant women who started tenofovir in pregnancy, 21/31 (67.7%) were initiated before week 24 of pregnancy, in line with British HIV association (BHIVA) guidelines [3]. There was no deterioration in median serum creatinine or decline in eGFR in women prescribed tenofovir during pregnancy. At six weeks after delivery, in the 42 women who continued tenofovir therapy and had eGFR measured, one woman had eGFR=60, all others eGFR >90 (Table 1).ConclusionsConsistent with current guidelines and experience, this study shows tenofovir did not cause decline in renal function in pregnancy in our cohort of HIV‐1 positive women, whether started during pre‐conception or during pregnancy. More evidence should be prospectively collected looking at effects of tenofovir on other measures of tubular renal function in pregnancy such as proteinuria and protein‐creatinine ratio.

IntroductionIn South Africa where replacement feeding may not be affordable, feasible or sustainable, HIV‐infected women are recommended to exclusively breastfeed their infants during the first six months of life. The question arises whether HIV disease progression and its metabolic impact on the mother will affect the nutrient composition of breast milk. The aim was to determine the possible association between HIV disease progression, as measured by the immunological markers, and the nutrient composition of breast milk.MethodsThe nutrient composition of breast milk of 100 HIV‐infected and 50 non‐infected volunteered (control group) lodging/day visiting mothers at Paediatric/Neonatal wards of National, Pelonomi and Universitas hospitals, Bloemfontein, were measured. The HIV‐infected group was subdivided into HIV‐naïve and HIV‐ARV treatment group. Breast milk and blood samples were obtained. Macronutrients namely lactose, proteins, fat, total solids and the energy content of the breast milk and micronutrient namely calcium and phosphate were measured. Blood and immunological parameters comprised of CD4/CD8+T cell counts, viral loads and full blood counts.ResultsProtein levels amongst the HIV‐infected group showed a significant elevation (p<0.0001) compared to the control group. The calcium levels of the HIV‐infected group were significantly lower (p=0.0081) than the control group. No statistically significant differences were recorded of the measured nutrients between mothers receiving treatment and the HIV‐naïve group. All the HIV patients were anaemic with haemoglobin, haematocrit and RDW below the normal range. The Spearman Correlation Coefficient was used to determine if HIV disease progression have an influence on the nutrient composition. For the HIV‐naïve group, a significant correlation was found between the viral load and percentage total solids in breast milk. A correlation between the CD4+T cell count, the percentage total solids and energy content of the breast milk was determined in the HIV‐ARV treatment group. No strong positive correlation could be established between the immunological markers, HIV disease progression and the nutrient composition in the breast milk.ConclusionsHIV mothers can breastfeed their babies even at a more advanced stage of HIV disease progression, but emphasis has been placed on exclusive breastfeeding.

IntroductionEvidence from HIV‐negative cohorts suggests a link between osteoporosis and cardiovascular disease. We evaluated the presence and distribution of abdominal aortic calcifications (AAC) and its correlation with bone mineral density (BMD) and vertebral fractures (VF) in a cohort of HIV‐positive patients.Materials and MethodsIn this cross‐sectional study, 280 asymptomatic HIV‐positive patients from the SPID ("San Paolo" Infectious Diseases) cohort were submitted to lateral spine X‐ray and DXA. AAC was identified using the AAC‐8 score, which estimates the total length of calcification of the anterior and posterior aortic walls in front of vertebrae L1–L4. Low BMD was defined by T‐score or Z‐score <−1 at lumbar spine or femoral neck. VF were identified by morph‐metric analysis of X‐ray and were defined by the "spine deformity index" (SDI) ≥1 according to semiquantitative method by Genant. Associations between AAC, BMD and SDI were evaluated by univariate and multivariate logistic regression models. The relationship between the grade of AAC and SDI was evaluated by Spearman's correlation.ResultsAAC≥1 was present in 65 patients (23.2%); of these 15 patients showed moderate/severe calcifications (AAC>2). Low BMD was found in 163 patients (58.2%) and VF (SDI≥1) in 47/274 patients (17.1%). By univariate analysis, factors associated with AAC>=1 were: age (for additional 10 years older HR 3.81 [IC95% 2.64–5.51], p<0.0001) lower CD4 nadir (for additional 50 CD4 HR 0.89 [IC95% 0.82–0.97], p=0.01) AIDS‐diagnosis (HR 2.13 [IC95 % 1.11–4.08], p=0.02) and being on HAART (HR 2.75 [IC95% 1.28–5.90], p=0.009). In multivariate analysis, only age (OR 2.62, IC95% 1.72–3.99, p<0.0001) resulted significantly associated with AAC≥1. Patients with AAC≥1 had twofold increase in the risk of low BMD (HR 2.45 [IC95% 1.32–4.45], p=0.004) and VF (SDI>=1: HR 2.17 [IC95% 1.1–4.2], p=0.02) compared to patients without AAC. The grade of AAC was directly correlated with the grade of SDI (rho=0.16; p=0.008): AAC>2 determines a sixfold increase in the risk of VF (HR 6.44 [IC95% 2.21–18.79], p=0.0006). AAC≥1 predict VF independently from BMD, vitamin D status and bone turnover marker (Table 1).ConclusionsIn our HIV population, AAC resulted a strong predictor of both low BMD and VF, irrespective of factors involved in bone formation. The grade of AAC was directly correlated with the grade of VF.

IntroductionDisruption in bone homeostasis with increased osteoclastic resorption may lead to osteoporosis. HIV tat has been found to increase differentiation of precursor cells into osteoclast (OC) [1]. Presence of soluble HIV proteins in virally suppressed HIV patients on ART may drive a bone resorption phenotype. We investigated the role of soluble HIV proteins (tat, gp120 Mn and Bal, rev and p55‐gag) on osteoclastogenesis and OC resorptive capacity.MethodsMouse monocyte RAW 264.7 cells were cultured in vitro and induced to differentiate into OCs with 50 ng/mL RANKL and 25 ng/mL mCSF. Medium was supplemented with 100 ng/mL of recombinant HIV tat, gp120 (Mn and Bal), rev, nef and p55‐gag, respectively, with zolendronate as negative control. Differentiated OCs were stained for TRAP and counted. OC resorption function was examined by culturing differentiated OCs (in the presence of respective HIV proteins) on dentin‐coated plates and examining the following (i) sealing zone formation, (ii) volume of resorption pits and (iii) area of resorption pits per field using confocal microscopy. Expression of OC specific genes including NFATc1 and cathepsin K was investigated by qPCR. Reactive oxygen species (ROS) production is essential in RANKL‐induced OC differentiation [2,3]; effect of these proteins on ROS production was assessed using the fluorescent H2DCFH‐DA. Mean fluorescence intensity was then measured by flow cytometry. TNFα production by OC precursors when incubated with tat and rev was measured by ELISA.ResultsTat and rev treatment was associated with increased OC formation by 70 and 26%, respectively (p<0.01), relative to control, while zolendronate significantly inhibited OC formation by 75%. Gp120 Mn and Bal, nef and p55‐gag treatment had no effect on OC differentiation. Interestingly, neither tat nor rev treatment caused significant increases in sealing zone formation but increased dentin resorption pit area by 28 and 19%, respectively, and resorption pit volume by 11 and 6%, respectively. Tat protein treatment was associated with upregulation of NFATc1 and cathepsin K mRNA expression by 20 and 15%, respectively. Incubation with tat and rev led to a dose‐dependent increase in intracellular ROS production in the monocytes and OC precursors and significant upregulation in TNFα cytokine production by the OC precursors.ConclusionsIn addition to their effect of OC differentiation, we demonstrated the effects of tat and rev on OC resorption. HIV tat and rev are both biologically active in driving a pro‐osteoclastic phenotype.