Risk factors for kidney disease among HIV-1 positive persons in the methadone program.

BACKGROUND: Kidney injury is a serious comorbidity among HIV-infected patients. Intravenous drug use is listed as one of the risk factors for impaired renal function; however, this group is rarely assessed for specific renal-related risks. METHODS: Patients attending methadone program from 1994 to 2015 were included in the study. Data collected included demographic data, laboratory tests, antiretroviral treatment history, methadone dosing and drug abstinence. Patients' drug abstinence was checked monthly on personnel demand. We have evaluated two study outcomes: (1) having at least one or (2) three eGFR < 60 ml/min (MDRD formula). RESULTS: In total, 267 persons, with 2593 person-years of follow-up were included into analyses. At the time of analyses, 251 (94%) were on antiretroviral therapy (ARV). Fifty-two (19.5%) patients had 1eGFR and 20 (7.5%) 3eGFR < 60. In univariate analysis, factors significantly increasing the odds of impaired renal function were: female gender, detectable HIV RNA on ART, age at registration per 5 years older, atazanavir use and time on antiretroviral treatment per 1 year longer. In the multivariate model, only female gender (OR 4.7; p = 0.002), time on cART (OR 1.11; p = 0.01) and baseline eGFR (OR 0.71; p = 0.001) were statistically significant. CONCLUSIONS: We have demonstrated a high rate of kidney function impairment among HIV-1 positive patients in the methadone program. All risk factors for decreased eGFR in this subpopulation of patients were similar to those described for general HIV population with very high prevalence in women. These findings imply the need for more frequent kidney function monitoring in this subgroup of patients.

Suspected unexpected and other adverse reactions to antiretroviral drugs used as post-exposure prophylaxis of HIV infection - five-year experience from clinical practice.

INTRODUCTION: With increased use of antiretroviral drugs (ARVs) in HIV uninfected persons, proper reporting on suspected unexpected serious adverse reactions (SUSARs) and continued insight into adverse drug reactions (ADRs) are needed for adequate information on safety of ARVs in such populations. MATERIAL AND METHODS: Medical documentation of persons receiving ARVs after non-occupational HIV exposure (non-occupational post-exposure prophylaxis - nPEP) during 5 successive years (2009-2013) was evaluated by two HIV physicians. Adverse drug reactions s and SUSARs were defined according to international standards. In statistical analyses Cox proportional hazard models were used to identify independent predictors of developing a first ADR. RESULTS: In total 375 persons received nPEP with the following indications: needle stick (43%), unprotected sexual intercourse (17%), rape (10%) and first aid (10%). In 84 (22%) cases the source patient was HIV positive or an active injecting drug user. In total 170 ADRs were reported. One hundred thirty-nine persons had only 1 ADR. The most frequent first ADRs were gastrointestinal disorders (22%), followed by general symptoms (9%), hypersensitivity reactions (1.6%) and CNS symptoms (1.3%). The remaining events represented less than 1% of all patients. Eight (2.1%) patients developed a SUSAR. In multivariate analyses only age at first visit to the clinic was an independent predictor of developing an ADR (HR = 1.17, 95% CI: 1.03-1.34; p = 0.02). CONCLUSIONS: In our observations ADRs in reaction to nPEP were frequent yet usually mild events, mostly occurring in the first 2 weeks and rarely causing discontinuation. The only significant factor increasing the risk of ADR was age. SUSARs were rare, transient and clinically insignificant.

The suspected unexpected and serious adverse events of antiretroviral drugs used as HIV prophylaxis in HIV uninfected persons.

INTRODUCTION: With increased usage of antiretroviral drugs (ARVs) in HIV uninfected persons proper reporting on suspected unexpected serious adverse reactions (SUSARs) and continued insight into serious adverse events (SAEs) is needed for adequate information on ARVs safety in such populations. METHODS: We have evaluated medical documentation of persons receiving ARVs after non-occupationally HIV exposure (nPEP) during five concomitant years (2009-2013). SAEs and SUSARs were evaluated by two HIV physicians and defined according to international standards. In statistical methods, Kaplan Meier survival analysis was used to estimate the probability of SAE and Cox proportional hazard models to identify independent predictors of developing SAE. Only the first SAE was included in these analyses. RESULTS: In total, 375 persons received nPEP. The most common reason was needle stick (43%), followed by unprotected sexual intercourse (17%), rape (10%) and first aid (10%). In 84 (22%) cases, the source patient was either known to be HIV positive or within a high risk group (active injecting drug user). In total, 170 SAEs were reported, 139 persons had only one SAE and majority developed it within first two weeks. The most frequent first SAEs were gastrointestinal disorders (22%), followed by general symptoms (9%), hypersensitivity reactions (1.6%) and CNS symptoms (1.3%). The remaining events were laboratory abnormalities of liver and kidney function, haematological disorders, other and unknown, each contributing to less than 1% of all patients. 8 (2.1%) patients have developed a SUSAR (bradycardia, vivid dreams, lymphadenopathy of the neck, increased platelet count, swelling and pain of large joints, swelling of lower limbs, peripheral oedema and loss of concentration). 22 (5.9%) persons discontinued nPEP due to adverse event and 19 (5.1%) required a paid sick leave from work. In multivariate analyzes, only age was independent predictor of developing SAE (HR 1.17; [95% CI 1.03-1.34]; p=0.02). CONCLUSIONS: In our observation, SAEs in reaction to nPEP were frequent yet usually mild events, mostly occurring in first two weeks and rarely causing discontinuation. The only significant factor increasing the risk of SAE was age. SUSARs were rare and moderately significant. More insight into this important area is required in order to ascertain proper pharmacovigilance of ARVs usage in HIV uninfected persons.