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

OBJECTIVE: 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. METHODS: 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. RESULTS: 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). CONCLUSION: Our findings demonstrate that HBV-active cART protects against the occurrence of de-novo HBV infection, most strongly when tenofovir is used.

Comparison of two HIV postexposure prophylaxis regimens among men who have sex with men in Amsterdam: adverse effects do not influence compliance.

OBJECTIVES: To compare 2 regimens for HIV postexposure prophylaxis (PEP) as to safety, adherence, outcome, and follow-up in men who have sex with men (MSM) in Amsterdam. METHODS: Since 2000, all MSM starting HIV PEP in Amsterdam have been followed in 1 location. The regimen was comprised of zidovudine or lamivudine and nelfinavir (regimen 1) until 2005, when nelfinavir was replaced by atazanavir (regimen 2). All patient data, including data on PEP side effects and testing for alanine aminotransferase (ALT), were systematically recorded and compared between the 2 regimens from 2000 to 2007. RESULTS: HIV PEP was prescribed 309 times to MSM. Of the 261 who were followed up, 237 (91%) completed their 28-day course. Although fewer patients had diarrhea on regimen 2 than on regimen 1 (P = 0.00), the proportion completing either course was the same: 98 of 110 (89%) and 139 of 151 (92%), respectively (P = 0.42). Only 1 patient with severely elevated ALT was advised to stop PEP, he also had serious illness. MSM at least 30 years of age and MSM who had sex with a partner known to be HIV-positive completed their course significantly more often than those under 30 and those who had sex with a partner of unknown HIV status (P < 0.005). Of MSM who completed PEP, 5 seroconverted for HIV despite good adherence to PEP. None of their viruses were resistant to the PEP regimen used. CONCLUSIONS: No difference in adherence was found between the 2 regimens, even though fewer adverse effects were reported on regimen 2. ALT need not be routinely tested to monitor adverse effects. The 5 seroconversions were not likely caused by PEP failure, but rather by ongoing HIV exposures.

Osteoarticular infections in HIV-infected patients: 23 cases among 1,515 HIV-infected patients.

BACKGROUND: The reported incidence of osteoarticular infections in HIV-infected patients has varied in the literature. PATIENTS AND METHODS We determined the incidence and characteristics of osteoarticular infections reported in a database of 1,515 HIV-infected patients between 1983 and 2003. RESULTS: 23 HIV-infected patients were identified with an osteoarticular infection, 11 of whom had a spondylodiscitis. 16 were intravenous drug abusers; this was identified as a risk factor for developing an osteoarticular infection. The most common agent was Staphylococcus aureus. 6 patients required surgical intervention and in a worst-case scenario more than one-fifth had recurrence of their infection. CONCLUSION: Development of an osteoarticular infection is a rare complication in this group of HIV-infected patients, but a remarkably high number of infections of the spine were seen.

Trends in HIV postexposure prophylaxis prescription and compliance after sexual exposure in Amsterdam, 2000-2004.

OBJECTIVE: The objective of this study was to evaluate trends in HIV postexposure prophylaxis (PEP) requests after sexual exposure, compliance, and outcome of follow-up HIV tests. STUDY DESIGN: The authors conducted a retrospective analysis of all HIV PEP requests after sexual exposure between January 1, 2000, and December 31, 2004, in Amsterdam. RESULTS: In 5 years, there was a very modest increase in PEP requests, of which most (75%) came from men who have sex with men (MSM). Although 70% reported side effects, 85% completed their PEP course. Sexual assault victims less often completed their course (odds ratio [OR] = 0.1; 95% confidence interval [CI] = 0.05-0.4, P = 0.001). People who used HIV PEP more often complied with follow-up tests than people who did not use PEP (OR = 3.5; 95% CI = 1.6-7.9, P = 0.002). One HIV seroconversion was found caused by a later exposure than that for which PEP was given. CONCLUSIONS: Despite a widely available PEP program in Amsterdam, the number of PEP requests remained low. Most people completed their PEP course; compliance with follow-up HIV testing was high.

The risk of needle stick accidents during surgical procedures: HIV-1 viral load in blood and bone marrow.

Health-care workers are at risk to acquire HIV through occupational exposure to blood of HIV-infected patients. The mean risk after a percutaneous exposure is approximately 0.3%. A large inoculum and a source patient with a high plasma viral load increases the transmission risk. To ensure the safety of the operating team, we try to reduce HIV viral load in plasma prior to high-risk interventions (cardiothoracic and orthopaedic surgery). However, in 15.7% of the exposures occurring in the operating room, the possible source material is bone marrow. To make more accurate exposure risk assessments, we measured HIV-1 RNA in both plasma and bone marrow of five HIV-infected patients undergoing surgery. We found that the plasma viral load was not different from the viral load in bone marrow.

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 the source. LESSONS LEARNT: Provision of treatment and follow-up in one place enables treatment, tracing and testing sources, and follow-up, 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 protocol.

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 uncertain.

Post-exposure prophylaxis.

The mean risk of acquiring HIV after an occupational exposure, injecting drug use or sexual exposure varies from < 0.1 to 3%. A high plasma HIV-RNA of the source increases the risk of each of the exposures. Other factors, such as the volume of the inoculum involved to which the individual was exposed, other sexually transmitted diseases and ruptures of mucous membranes are associated with a higher risk of HIV transmission. Based on the calculated risk, post-exposure prophylaxis (PEP) should be recommended. In the Netherlands, prescription of PEP in the occupational setting is a standard procedure and has proved to be feasible. This was associated with a high percentage (62%) of mild and reversible toxicity and a small percentage (2%) of serious adverse events related to antiretroviral drugs, i.e. nephrolithiasis (due to indinavir) and toxic hepatitis (due to nevirapine). In The Netherlands so far no HIV-seroconversions have been recorded after an occupational accident.