Vaccination against hepatitis B virus among people who inject drugs - A 20year experience from a Swedish needle exchange program.

BACKGROUND: People who inject drugs (PWID) are at particular risk of hepatitis B virus (HBV) acquisition, but often have poor access or adherence to HBV vaccination. Vaccination against HBV has been offered at a major Swedish needle exchange program (NEP) since 1994. The aim of this study was to evaluate vaccine completion and response rates, and the effect of sequential booster doses to non-responders to the standard vaccination schedule. METHODS: PWID enrolled in the NEP 1994-2013, without serological markers for HBV at baseline (negative for HBsAg/anti-HBc/anti-HBs), were offered a three-dose standard intramuscular vaccination schedule (Engerix®-B, GSK, 20µg/mL, intended to be received at months 0, 1 and 6). Vaccination response was defined as protective levels of anti-HBs (⩾10mIU/mL). Up to three booster doses were then offered for non-responders, each followed by anti-HBs testing. RESULTS: HBV data was available for 2352 identifiable individuals at NEP enrolment, of whom 1516 (64.5%) had no markers for previous HBV exposure or vaccination. Vaccination was initiated for 1142 (75.3%) individuals and 898 (59.2%) completed the standard vaccination schedule. Post-vaccination anti-HBs levels were available from 800 individuals, with 598 (74.8%) responding to the basic vaccination schedule. After up to three booster doses a total of 676 (84.5%) individuals achieved protective anti-HBs levels. Non-response to vaccination was associated with higher age and anti-HCV positivity (p<0.001). Eighteen incident cases of HBV infection were observed among vaccine non-responders, as well as 30 cases among those who had not completed vaccination. CONCLUSION: We demonstrate the feasibility of including HBV vaccination in the services offered by a NEP, with completion of vaccination in a majority of HBV-susceptible PWID. The response to HBV vaccination among PWID was relatively low; however, the addition of up to three booster doses improved the response rate from 74.8 to 84.5%.

Sweden, the first country to achieve the Joint United Nations Programme on HIV/AIDS (UNAIDS)/World Health Organization (WHO) 90-90-90 continuum of HIV care targets.

OBJECTIVES: The Joint United Nations Programme on HIV/AIDS (UNAIDS)/World Health Organization (WHO) 90-90-90 goals propose that 90% of all people living with HIV should know their HIV status, 90% of those diagnosed should receive antiretroviral therapy (ART), and 90% of those should have durable viral suppression. We have estimated the continuum of HIV care for the entire HIV-1-infected population in Sweden. METHODS: The Swedish InfCare HIV Cohort Study collects viral loads, CD4 counts, and viral sequences, along with demographic and clinical data, through an electronic clinical decision support system. Almost 100% of those diagnosed with HIV infection are included in the database, corresponding to 6946 diagnosed subjects living with HIV-1 in Sweden by 31 December 2015. RESULTS: Using HIV surveillance data reported to the Public Health Agency of Sweden, it was estimated that 10% of all HIV-infected subjects in Sweden remain undiagnosed. Among all diagnosed patients, 99.8% were linked to care and 97.1% of those remained in care. On 31 December 2015, 6605 of 6946 patients (95.1%) were on ART. A total of 6395 had been on treatment for at least 6 months and 6053 of those (94.7%) had a viral load < 50 HIV-1 RNA copies/mL. CONCLUSIONS: The 2014 UNAIDS/WHO 90-90-90 goals for HIV care means that > 73% of all patients living with HIV should be virologically suppressed by 2020. Sweden has already achieved this target, with 78% suppression, and is the first country reported to meet all the UNAIDS/WHO 90-90-90 goals.

Minimal transmission of HIV despite persistently high transmission of hepatitis C virus in a Swedish needle exchange program.

The aim of this study was to examine the prevalence and incidence of HIV and hepatitis B and C (HBV and HCV) among injecting drug users in a Swedish needle exchange programme (NEP) and to identify risk factors for blood-borne transmission. A series of serum samples from NEP participants enrolled from 1997 to 2005 were tested for markers of HIV, HBV and HCV (including retrospective testing for HCV RNA in the last anti-HCV-negative sample from each anti-HCV seroconverter). Prevalence and incidence were correlated with self-reported baseline characteristics. Among 831 participants available for follow-up, one was HIV positive at baseline and two seroconverted to anti-HIV during the follow-up of 2433 HIV-negative person-years [incidence 0.08 per 100 person-years at risk (pyr); compared to 0.0 in a previous assessment of the same NEP covering 1990-1993]. The corresponding values for HBV were 3.4/100 pyr (1990-1993: 11.7) and for HCV 38.3/100 pyr (1990-1993: 27.3). HCV seroconversions occurred mostly during the first year after NEP enrolment. Of the 332 cases testing anti-HCV negative at enrolment, 37 were positive for HCV RNA in the same baseline sample (adjusted HCV incidence 31.5/100 pyr). HCV seroconversion during follow-up was significantly associated with mixed injection use of amphetamine and heroin, and a history of incarceration at baseline. In this NEP setting, HIV prevalence and incidence remained low and HBV incidence declined because of vaccination, but transmission of HCV was persistently high. HCV RNA testing in anti-HCV-negative NEP participants led to more accurate identification of timepoints for transmission.

CYP3A induction and inhibition by different antiretroviral regimens reflected by changes in plasma 4beta-hydroxycholesterol levels.

OBJECTIVE AND METHODS: A member of the major human cytochrome P450 superfamily of hemoproteins, CYP3A4/5, converts cholesterol into 4beta-hydroxycholesterol. We studied plasma 4beta-hydroxycholesterol levels prior to and 4 weeks after initiating antiretroviral therapy that included efavirenz, ritonavir-boosted atazanavir or ritonavir-boosted lopinavir with the aim of exploring the usefulness of plasma 4beta-hydroxycholesterol levels as an endogenous biomarker of CYP3A activity. Efavirenz is an inducer of CYP3A, whereas the ritonavir-boosted regimens are net inhibitors of CYP3A. RESULTS: In patients treated with efavirenz, the median plasma 4beta-hydroxycholesterol level increased by 46 ng/mL (p = 0.004; n = 11). In contrast, patients given ritonavir-boosted atazanavir showed a median decrease in plasma 4beta-hydroxycholesterol of -9.4 ng/mL (p = 0.0003; n = 22), and those given ritonavir-boosted lopinavir showed a median change from baseline of -5.8 ng/mL (p = 0.38; n = 19). There were significant between-group differences in the effects of antiretroviral treatment on plasma 4beta-hydroxycholesterol levels (p < 0.0001). CONCLUSION: Changes in plasma 4beta-hydroxycholesterol following the initiation of efavirenz- or atazanavir/ritonavir-based antiretroviral therapy reflected the respective net increase and decrease of CYP3A activity of these regimens. The plasma 4beta-hydroxycholesterol level did not indicate a net CYP3A inhibition in the lopinavir/ritonavir arm, possibly because of concomitant enzyme induction.

Diagnosis of primary HIV-1 infection and duration of follow-up after HIV exposure. Karolinska Institute Primary HIV Infection Study Group.

OBJECTIVE: To determine the sensitivity of 33 currently available and seven earlier tests for the detection of HIV or HIV antibody in primary HIV-1 infection, to estimate the duration of the 'window period' and the influence of early initiated antiretroviral treatment (ART). DESIGN: A prospective cohort study of 38 patients with primary HIV-1 infection. ART was initiated at a median time of 13 (range 0-23) days after the onset of symptoms in 10 patients. MAIN OUTCOME MEASURES: The time from infection to onset of symptoms and from onset of symptoms to the appearance of HIV antibody as measured by 36 different tests, and the start and duration of viraemia, as detected by four different tests. RESULTS: The illness appeared 13-15 days after infection in 12 of 15 determinable cases, and seroconversion was detected within 1-2 weeks after the onset of illness by 27 of 30 currently available tests for HIV antibody, in contrast to the 2-7 weeks or more needed by the old tests. HIV RNA appeared during the week preceding the onset of illness and was detected in all subsequent samples, except when ART had been initiated, which also induced a delay of the antibody response. CONCLUSION: Many tests for HIV or HIV antibody can now be employed for an early confirmation of primary HIV infection (PHI). Currently available screening tests proved much more sensitive than older tests, and seroconversion was usually detected within one month after infection. Consequently, in Sweden we now recommend only 3 months of follow-up after most cases of HIV exposure.

Neurological complications in herpes zoster.

This paper discusses the complications associated with herpes zoster, with emphasis on its neurological manifestations. These complications, which are particularly prevalent in elderly and immunodeficient patients, include focal muscle paralysis, contralateral hemiplegia, myelitis, cranial nerve palsies and meningoencephalitis. A causative relationship with herpes zoster in many of these syndromes is probably more common than previously suspected due to difficulties in diagnosis and lack of awareness among clinicians. Zoster sine herpete-- reactivation of varicella zoster virus without rash--is associated with a spectrum of neurological disease and, for obvious reasons, is particularly difficult to diagnose. The polymerase chain reaction could be a valuable tool in overcoming these diagnostic problems, especially in patients without characteristic eruptions, allowing the early initiation of effective antiviral therapy.

High dose aerosol pentamidine for secondary Pneumocystis carinii pneumonia prophylaxis in AIDS patients.

In a prospective trial of aerosolized pentamidine as secondary prophylaxis for Pneumocystis carinii pneumonia (PCP) 18 patients received 400 mg once weekly for a mean period of 15.5 months. Pentamidine aerosol was administered with an MA2 jet nebulizer. No PCP relapses were observed and no serious side effects occurred.

Herpes simplex virus--the most frequently isolated pathogen in the lungs of patients with severe respiratory distress.

308 consecutive patients with severe or complicated respiratory tract infections underwent fiber-optic bronchoscopy in the search for a microbiological etiology. Protected brush specimens were used for bacterial cultures and bronchoalveolar lavage (BAL) for virus isolation and cytological examination. Herpes simplex virus (HSV) was the most commonly found pathogen and was isolated in 37 patients. 20 (54%) of them also had serological and/or cytological signs of HSV infection. 132 patients required assisted ventilation (AV) and in this group 34 (92%) of the 37 HSV positive patients were found. Isolation of HSV was significantly (p less than 0.001) associated with AV compared to patients not requiring AV. Of all patients treated with AV 26% had positive HSV isolation in conjunction with suspected acute lower respiratory infection. Coinfection with HSV and bacteria occurred in only 8 (22%) patients. HSV was more common in patients with burns (47%) compared to other patient groups such as patients with AIDS (3%) or other immunodeficiencies (9%).

Ultrastructural development of Kaposi's sarcoma in relation to the dermal microvasculature.

Ultrastructural subtypes of endothelial cells in Kaposi's sarcoma were compared with lymphatics and the normal dermal microcirculation in different stages of lesional development. In the earliest patch stage, lymphatic channels, recognised by their dissecting growth pattern and a lack of a basal lamina and pericytes, were prominent. Venous endothelium was recognised by virtue of its multilaminated basal lamina and often showed markedly irregular luminal and abluminal cytoplasmic projections. As the histological stage progressed toward spindle cells, venous endothelium showed a tetrad of changes: dissolution of the basal lamina; fragmentation and disappearance of the pericyte sheath, decreased and often rudimentary intercellular junctions and markedly reduced numbers of Weibel-Palade bodies. These were also features of spindle cells, which were rarely seen to emerge from narrow vascular channels of indeterminate type. Spindle cells showed sparse intercellular junctions and minimal basal lamina but no Weibel-Palade bodies. These progressive venous alterations thus resulted in a mixed intermediate subtype of endothelium with the morphological traits resembling lymphatics as well as venous blood vessels. The mixed subtype included endothelial tubes surrounded by a complete basal lamina but lacking pericytes, and much more commonly, tubes with pericytes but a scanty basal lamina. Both forms had remarkably few or no Weibel-Palade bodies. In the spindle cell stage, normal vessels were largely replaced by the mixed subtype and an indeterminate type of frequently disrupted endothelial tube which lacked a basal lamina as well as a pericytic investment. Dissecting lymphatic channels could not be confidently distinguished from the latter vessels.(ABSTRACT TRUNCATED AT 250 WORDS)

Short course of aerosol pentamidine as treatment of Pneumocystis carinii pneumonia in AIDS.

Since July 1987, 20 HIV-positive patients with Pneumocystis carinii pneumonia (PCP) admitted to the Department of Infectious Diseases, Malmö General Hospital, Sweden have been treated with 10 consecutive days of aerosol pentamidine as sole antimicrobial therapy in a prospective open non-controlled trial. 16 patients (80%) responded to 10 days of 400 mg aerosol pentamidine daily. One patient responded after a prolonged treatment, one patient received simultaneous trimethoprim-sulfamethoxazole due to lack of improvement during aerosol therapy. Two patients died 26 and 41 days after initiation of treatment. No systemic side effects occurred. In conclusion, we found that 10 days of aerosol pentamidine may be a safe and effective treatment of PCP. Controlled studies are needed.

Herpes simplex virus hepatitis in a renal transplant recipient: successful treatment with acyclovir.

Herpes simplex virus (HSV) hepatitis in adults is a rare and severe disease usually occurring in immunocompromised patients or pregnant women. We report on a case of primary HSV type I hepatitis in a 48-year-old male renal transplant recipient with successful outcome after acyclovir treatment.