Hyperlactataemia in HIV-infected patients: the role of NRTI-treatment

BACKGROUND: Long-term treatment with nucleoside reverse transcriptase inhibitors (NRTIs) can induce mitochondrial dysfunction, most severely represented by lactic acidosis. Diagnostic tests for mitochondrial dysfunction are lacking, although persistently elevated serum lactate might be a surrogate marker. OBJECTIVES: To determine the occurrence of hyperlactataemia in HIV-infected patients on NRTI-treatment and to evaluate the possible risk factors. METHODS: Cross-sectional analysis of lactic-acid levels in asymptomatic HIV-infected patients. Hyperlactactaemia was considered mild if between 2.0-5 mmol/l, serious if >5 mmol/l and lactic acidosis was defined as lactic acid levels >5 mmol/l with bicarbonate <20 mmol/l. Possible risk factors, such as current and preceding NRTI-treatment as well as treatment with non-nucleoside reverse transcriptase inhibitors or protease inhibitors and concurrent liver disease, were analysed. RESULTS: Two hundred and twenty three asymptomatic HIV-infected patients were studied, including 174 patients (78%) on NRTI treatment, 12 patients (5%) treated without NRTIs and 37 patients (17%) not treated. Mild hyperlactataemia was found in 42 patients (19%), from whom 38/42 (90%) were NRTI-treated and the remaining patients (4/42, 10%) received no treatment (chi2, P <0.05). The significant risk factors for hyperlactataemia in the univariate analysis were NRTI-treatment as a group (P=0.03) and elevated ALT (P=0.008). In multivariate analysis NRTI use (P=0.05) and ALT level (P=0.03) remained a significant determinant of hyperlactataemia. Among the different individual NRTIs, a stavudine-containing (P=0.004) and a zalcitabine-containing (P=0.07) regimen were most notably associated with the development of hyperlactataemia, whereas for the combinations of NRTIs, such association was only found for stavudine/lamivudine (P=0.05). CONCLUSIONS: A correlation between hyperlactataemia and NRTI treatment was found, but the value of routine lactate measurement for individual treatment monitoring remains uncertai

Prophylaxis and follow-up after possible exposure to HIV, hepatitis B virus, and hepatitis C virus outside hospital: evaluation of policy 2000-3

Problem Prophylactic treatment and follow-up after exposure to HIV, hepatitis B, and hepatitis C outside hospital needs to be improved. Background and setting Until January 2000, people in Amsterdam Could report exposure outside hospital to either a hospital or the municipal health service. If they reported to the municipal health service, they were then referred to hospitals for HIV prophylaxis, whereas the municipal health service handled treatment and follow-up related to hepatitis B and hepatitis C and traced sources. For cases reported to a hospital, hospital staff often did not trace HIV sources or follow up patients for hepatitis B and hepatitis C. Key measures for improvement Providing adequate treatment for HIV, hepatitis B and hepatitis C after exposure for all reported exposures outside hospital. Strategies for change On 1 January 2000, a new protocol was introduced in which three Amsterdam hospitals and the municipal health service collaborated in the treatment and follow-up of exposures outside hospital. Both municipal health service and hospitals can decide whether HIV prophylaxis is necessary and prescribe accordingly. All people exposed in the community who report to hospitals are subsequently referred to the municipal health service for further treatment and follow-up. Effects of change The protocol is effective in that most people comply with treatment and follow-up. When indicated, HIV prophylaxis is started soon after exposure. In nearly two thirds of cases the municipal health service traced and tested tire source. Lessons learnt Provision of treatment and follow-up in one place enables treatment, tracing and testing sources, and follow-tip, including counselling and registration of all reported exposures in Amsterdam, which allows for swift identification of emerging epidemiological trends. Since May 2004 all Amsterdam hospitals have participated in the protoco

Protective effect of hepatitis B virus-active antiretroviral therapy against primary hepatitis B virus infection

Current guidelines advise to vaccinate every hepatitis B virus (HBV)-susceptible HIV patient against HBV until sufficient antibody titers have been reached. However, in this era of combination antiretroviral therapy (cART), acute HBV infection rarely occurs in patients who lack this immune protection. We analyzed whether HBV-active cART (lamivudine, emtricitabine, tenofovir) might work as a preexposure prophylaxis (PrEP) to explain this effect. From our HIV cohort at the Onze Lieve Vrouwe Gasthuis hospital (N=2942), patients were selected retrospectively for negative HBV serology (HBsAg, anti-HBs and anti-HBc-negative) at cohort entry. Men who have sex with men (MSM) with a second HBV serology available were included for analysis. The incidence of anti-HBc conversion was determined and correlated with the use of HBV-active drugs. Kaplan-Meier curves and log-rank tests were used to compare HBV-free survival for MSM. In total, 33 HBV infections occurred in 381 eligible MSM over a median follow-up of 2470 days (interquartile range 1146-3871.5). The incident rate per 100 patient-years of follow-up was 1.10 overall, but differed strongly dependent on the use of HBV-active drugs: 2.85/100 patient-years of follow-up in the absence of HBV-active drugs, 1.36 when only lamivudine was used, and 0.14 in the presence of tenofovir. Furthermore, HBV-free survival rate was significantly higher when HBV-active cART was used, in particular when this HBV-active cART contained tenofovir (log-rank P <0.001). Our findings demonstrate that HBV-active cART protects against the occurrence of de-novo HBV infection, most strongly when tenofovir is use

High treatment uptake in human immunodeficiency virus/ hepatitis C virus-coinfected patients after unrestricted access to direct-acting antivirals in the Netherlands

Background The Netherlands has provided unrestricted access to direct-acting antivirals (DAAs) since November 2015. We analyzed the nationwide hepatitis C virus (HCV) treatment uptake among patients coinfected with human immunodeficiency virus (HIV) and HCV. Methods Data were obtained from the ATHENA HIV observational cohort in which >98% of HIV-infected patients ever registered since 1998 are included. Patients were included if they ever had 1 positive HCV RNA result, did not have spontaneous clearance, and were known to still be in care. Treatment uptake and outcome were assessed. When patients were treated more than once, data were included from only the most recent treatment episode. Data were updated until February 2017. In addition, each treatment center was queried in April 2017 for a data update on DAA treatment and achieved sustained virological response. Results Of 23574 HIV-infected patients ever linked to care, 1471 HCV-coinfected patients (69% men who have sex with men, 15% persons who [formerly] injected drugs, and 15% with another HIV transmission route) fulfilled the inclusion criteria. Of these, 87% (1284 of 1471) had ever initiated HCV treatment between 2000 and 2017, 76% (1124 of 1471) had their HCV infection cured; DAA treatment results were pending in 6% (92 of 1471). Among men who have sex with men, 83% (844 of 1022) had their HCV infection cured, and DAA treatment results were pending in 6% (66 of 1022). Overall, 187 patients had never initiated treatment, DAAs had failed in 14, and a pegylated interferon-alfa–based regimen had failed in 54. Conclusions Fifteen months after unrestricted DAA availability the majority of HIV/HCV-coinfected patients in the Netherlands have their HCV infection cured (76%) or are awaiting DAA treatment results (6%). This rapid treatment scale-up may contribute to future HCV elimination among these patients