Deborah Williams

Renal tubular disease in the era of combination antiretroviral therapy.

Objectives:To describe the spectrum of renal tubular disease (RTD) in HIV-positive patients and its association with exposure to antiretroviral therapy (ART). Design:Review of 265 consecutive renal biopsies from HIV-positive patients attending eight clinics in the United Kingdom between 2000 and 2012. Methods:We described the clinical characteristics of patients with RTD and compared current/recent exposure (at the time of, or up to 3 months prior to the date of biopsy) to potentially nephrotoxic ART [tenofovir (TDF), atazanavir (ATV), indinavir (IDV) and lopinavir/ritonavir (LPV/r)]. We also analysed the incidence of RTD in the UK CHIC cohort. Kruskall–Wallis, analysis of variance and Fishers exact tests were used to evaluate between-group differences. Results:Of the 60 RTD cases, 54 (90%) were included in the analyses. RTD comprised of three distinct patterns: acute tubular injury (ATI, n = 22), tubulo-interstitial nephritis (TIN, n = 20) and interstitial fibrosis and tubular atrophy (IFTA, n = 12). Compared with TIN and IFTA, ATI cases were less likely to be of black ethnicity (10 vs. 42–55%; P = 0.006), more likely to be on ART (100 vs. 55–68%; P = 0.001), with HIV-RNA below 200 copies/ml (100 vs. 54–58%; P < 0.001), and more likely to have current/recent exposure to TDF (P < 0.001). We did not find evidence for an association between exposure to TDF, ATV/r or LPV/r and either TIN or IFTA. Conclusion:RTD was present in approximately 20% of renal biopsies and comprised three distinct injury patterns with considerable clinical overlap. ATI was associated with TDF exposure, although the overall incidence of biopsy-defined ATI was low.

Penile intraepithelial neoplasia: important lessons from a case series

Summary Seven men presenting to our genitourinary (GU) medicine clinic over a period of 22 months had a histopathological diagnosis of penile intraepithelial neoplasia (PIN). Median duration of symptoms was eight months (range 2–216 months). Macroscopic appearances were different in all cases. All histology was reviewed locally and at a tertiary centre. Six of seven had severe dysplasia (PIN III). Interestingly, only one individual was HIV-positive and one, who was immunocompetent, had multifocal disease. These cases highlight the importance of a full anogenital examination and early biopsy in patients presenting with atypical or persistent penile lesions.

Improved kidney function in patients who switch their protease inhibitor from atazanavir or lopinavir to darunavir

Objective:Atazanavir (ATV) and lopinavir (LPV) have been associated with kidney disease progression in HIV positive patients, with no data reported for darunavir (DRV). We examined kidney function in patients who switched their protease inhibitor from ATV or LPV to DRV. Design:Cohort study. Methods:Data were from the UK CHIC study. We compared pre and post switch estimated glomerular filtration rate (eGFR) slopes (expressed in ml/min per 1.73 m2 per year) in all switchers and those with rapid eGFR decline (>5 ml/min per 1.73 m2 per year) on ATV or LPV. Mixed-effects models were adjusted for age, gender, ethnicity, eGFR at switch and time updated CD4+ cell count, HIV RNA and cumulative tenofovir (tenofovir disoproxil fumarate) exposure. Results:Data from 1430 patients were included. At the time of switching to DRV, median age was 45 years, 79% were men, 76% had an undetectable viral load, and median eGFR was 93 ml/min per 1.73 m2. Adjusted mean (95% confidence interval) pre and post switch eGFR slopes were −0.84 (−1.31, −0.36) and 1.23 (0.80, 1.66) for ATV (P < 0.001), and −0.57 (−1.09, −0.05) and 0.62 (0.28, 0.96) for LPV (P < 0.001). Stable or improved renal function was observed in patients with rapid eGFR decline on ATV or LPV who switched to DRV [−15.27 (−19.35, −11.19) and 3.72 (1.78, 5.66), P < 0.001 for ATV, −11.93 (−14.60, −9.26) and 0.87 (−0.54, 2.27), P < 0.001 for LPV]. Similar results were obtained if participants who discontinued tenofovir disoproxil fumarate at the time of switch were excluded. Conclusions:We report improved kidney function in patients who switched from ATV or LPV to DRV, suggesting that DRV may have a more favourable renal safety profile.

Real-world persistence with antiretroviral therapy for HIV in the United Kingdom: A multicentre retrospective cohort study

Summary Objectives Persistence with an antiretroviral therapy (ART) regimen for HIV can be defined as the length of time a patient remains on therapy before stopping or switching. We aimed to describe ART persistence in treatment naïve patients starting therapy in the United Kingdom, and to describe differential persistence by treatment regimen. Methods We performed a retrospective cohort study at eight UK centres of ART-naïve adults commencing ART between 2012 and 2015. Aggregate data were extracted from local treatment databases. Time to discontinuation was compared for different third agents and NRTI backbones using incidence rates. Results 1949 patients contributed data to the analysis. Rate of third agent change was 28 per 100 person-years of follow up [95% CI 26–31] and NRTI backbone change of 15 per 100 person-years of follow up [95% CI 14–17]). Rilpivirine, as co-formulated rilpivirine/tenofovir/emtricitabine had a significantly lower discontinuation rate than all other third agents and, excluding single tablet regimens, co-formulated tenofovir/emtricitabine had a significantly lower discontinuation rate than co-formulated abacavir/lamivudine. The reasons for discontinuation were not well recorded. Conclusions Treatment discontinuation is not an uncommon event. Rilpivirine had a significantly lower discontinuation rate than other third agents and tenofovir/emtricitabine a lower rate than co-formulated abacavir/lamivudine.

Acute hepatitis C in HIV-uninfected men who have sex with men who do not report injecting drug use:

Dear Editor, There has been an epidemic of acute hepatitis C in HIV-infected men who have sex with men since 2000 associated with injecting drug use (IDU) and high-risk sexual activity including group sex, fisting, condomless anal sex and HIV pre-exposure prophylaxis (PrEP) use. Curiously, there are few reports in HIV-uninfected MSM who do not report IDU, and no international guideline suggests routine testing in HIVuninfected MSM. BASHH (British Association of Sexual Health and HIV) recommends testing in highrisk MSM. Locally, we have been screening all MSM and IDUs per year for hepatitis C since 2005. We looked at cases of acute hepatitis C diagnosed in our integrated sexual health and HIV service per calendar year from 2012 to 2016 and looked at HIV status, injecting drug use and sexual behaviour. We performed 8775 hepatitis C tests in HIV-negative MSM in the five-year study period (2012: 1741, 2013: 1811, 2014: 1890, 2015: 1873, 2016: 1460). No MSM tested hepatitis C positive on initial testing. There were nine HIV-negative MSM who initially tested negative for hepatitis C and subsequently tested positive in the study period (2012: 3/1741, 2013: 3/1811, 2014: 1/1890, 2015: 2/1873, 2016: 0/1460). There were five of nine HIV-negative MSM diagnosed with acute hepatitis C who gave a history of IDU and four of nine HIV who did not report IDU, but all had a recent history of condomless anal sex at chem-sex parties; two of four had engaged in fisting and none were using PrEP at the time of hepatitis C diagnosis. There appears to be a very small amount of hepatitis C transmission in HIV-negative MSM who do not report IDU, and these were associated with high-risk sexual behaviour: condomless anal sex at parties involving sexualised recreational drugs and fisting. It is unclear why so few HIV-negative MSM have acquired acute hepatitis C within an epidemic of hepatitis C in HIV-infected MSM: one explanation is that these groups represent distinct sexual networks and HIVnegative MSM are infrequently coming into sexual contact with other MSM with infectious hepatitis C unless they are engaging in these particular risk factors (condomless anal sex at chem-sex parties and fisting). We suggest that HIV-uninfected MSM who do not inject drugs but who give a history of condomless anal sex in association with sexualised recreational drug use and fisting should be routinely (on a yearly basis) tested for hepatitis C.