Vaccination against hepatitis B with 4-double doses increases response rates and antibodies titers in HIV-infected adults

BackgroundAntibody responses to standard regimens of hepatitis B (HBV) vaccination are lower in HIV-infected subjects and the best hepatitis B vaccine schedule in this population is not known.ObjectiveTo assess the immunogenicity and to evaluate predictors of serologic response of a modified regimen of a HBV recombinant vaccine in a cohort of HIV-infected subjects.MethodsHIV-infected subjects received 4 doses (40 μg) of a recombinant HBV vaccine at 0, 1, 2 and 6 months. Demographic information as well as CD4 cell count and plasma viral load were assessed at baseline. Protective and strong responses were defined as an anti-HBs titer ≥10 mIU/mL and ≥100 mIU/mL, respectively and were evaluated one month after the third and the fourth doses.Results163 HIV-infected individuals were evaluated 67 (40%) were male and median age was 37 years. Median CD4 cell count was 385 cells/mm³ and 113 (70%) had undetectable HIV-1 viral load. Protective antibody response was observed in 83 and 91% and a strong antibody response was observed in 62 and 80% of the subjects after 3 and 4 doses, respectively.In a multivariate logistic model undetectable HIV-1 viral load and higher CD4 cell counts were independent predictors of a strong antibody response after 4 doses. Patients with undetectable HIV viral load were almost 3 times more likely to have anti-HBs titers above 100 mIU/mL than those with detectable viral load.ConclusionsA 4-double-dose regimen of a recombinant HBV vaccine increased response rates and determined higher antibody titers which may translate in prolonged protection agains HBV. Inclusion of a fourth dose of HBV vaccine for HIV-infected subjects should be considered in the public health setting.     

High rates of serological response to a modified hepatitis B vaccination schedule in HIV-infected adults subjects

We evaluated a modified HBV regimen in a cohort of HIV-infected subjects in Rio de Janeiro, Brazil. HIV-infected subjects with no serologic evidences of previous hepatitis B infection were immunized with 4 doses (40 μg each) of recombinant hepatitis B vaccine given at 0, 1, 2 and 6 months. Blood samples were collected 1 month after the last dose and anti-HBs titers were measured. A protective antibody response was defined as an anti-HBs titer ≥10 mIU/mL. Forty-seven subjects (30 women, 17 men; mean age was 36 years, ranging from 21 to 58 years) were included in the final analysis. Median baseline CD4+ lymphocyte count was 402 cells/mm³ and 33 subjects (70%) had an HIV viral load below 80 copies/mL. A protective antibody response was observed in 42 (89%) subjects. Thirty-seven (78%) and 28 (60%) patients developed anti-HBs titers higher than 100 mIU/mL and 1000 mIU/mL, respectively. 1 out of 5 non-responders (20%) had an HIV viral load below the detection limit, in contrast with 32 (76%) of those with an adequate serologic response (p = 0.02). These findings suggest that 4-double dose alternative schedule may be considered to overcome the lower seroconversion rates observed with the standard regimens in HIV-infected subjects.     

Humoral response to hepatitis B vaccination and its relationship with T CD45RA+ (naïve) and CD45RO+ (memory) subsets in HIV-1-infected subjects

HIV disease leads to defects in cell-mediated immunity, impairing the immune response to new and recall antigens. We studied 55 HIV 1-infected patients who received of recombinant DNA hepatitis B vaccine and 20 controls. The overall hepatitis B virus (HBV) seroconversion rate was 59%. The median CD4+ T cell count among responders was 452 cell/mm(3), higher than non-responders (359 cells/mm(3)). The HIV plasmaviral loads were higher in non-responders. We concluded that total T CD4 cell count, memory T CD4+ cells and lower plasma viral load among HIV-1-infected subjects treated with HAART could be used to predict the immune response to vaccination with hepatitis B vaccine. Thus, considering cost benefits, HVB vaccination should be preferentially provided to HIV-infected patients with T CD4 cells count over 450 cells/mm(3), preferentially whose under HIV replication controlled.     

Comparison of the immunogenicity, efficacy and safety of 10 micrograms and 20 micrograms of a hepatitis B vaccine: a prospective randomized trial.

Four thousand and one hospital staff were screened for hepatitis B virus (HBV) markers in a vaccination programme in Hong Kong. The seropositivity rate for HBsAg, anti-HBs and anti-HBc were significantly higher in the 3160 existing hospital staff than in 841 new recruits. Of the subjects negative for HBV markers, 605 were randomized to receive three doses of either 10 or 20 micrograms of the Merck Institute vaccine (HB-VAX). Compared with the 20 micrograms dose, vaccination with the 10 micrograms dose results in equal immunogenicity and efficacy at the completion of the three injections but induced a slower response rate and lower anti-HBs titres with the first two doses. The commonest side-effect of local soreness was less with the 10 micrograms dose. We conclude that (1) hospital staff working in high endemic areas should be vaccinated on recruitment and (2) the 10 micrograms dose of HB-VAX can replace the recommended 20 micrograms dose for adults, being cheaper and as efficacious.     

Comparison of the immunogenicity, efficacy and safety of 10 micrograms and 20 micrograms of a hepatitis B vaccine: a prospective randomized trial

Four thousand and one hospital staff were screened for hepatitis B virus (HBV) markers in a vaccination programme in Hong Kong. The seropositivity rate for HBsAg, anti-HBs and anti-HBc were significantly higher in the 3160 existing hospital staff than in 841 new recruits. Of the subjects negative for HBV markers, 605 were randomized to receive three doses of either 10 or 20 micrograms of the Merck Institute vaccine (HB-VAX). Compared with the 20 micrograms dose, vaccination with the 10 micrograms dose results in equal immunogenicity and efficacy at the completion of the three injections but induced a slower response rate and lower anti-HBs titres with the first two doses. The commonest side-effect of local soreness was less with the 10 micrograms dose. We conclude that (1) hospital staff working in high endemic areas should be vaccinated on recruitment and (2) the 10 micrograms dose of HB-VAX can replace the recommended 20 micrograms dose for adults, being cheaper and as efficacious.     

Serologic response to hepatitis B vaccine with high dose and increasing number of injections in HIV infected adult patients

Sixty-five HIV-infected patients received high-dose (40mug), short interval HBV vaccine. In non-responders to the initial immunization, 1-3 boosters were administered. Rate of response was 60.0% after primary vaccination, and 89.2% after boosters. However, 12 and 24 months after the last vaccination, only 63% and 32.7% of the responders, respectively, had persistence of protective anti-HBs titers (> or =10 IU/L). The results of logistic regression show that gender, CD4 count, and HIV viral load were significant predictors of vaccination outcome. This study suggests that in HIV-infected patients with relatively high CD4 count, response to high dose of HBV vaccine is suboptimal. Rate of response may be increased by vaccine boosts, but antibody titers are significantly lower in non-responders than in responders to primary vaccination. Since persistence of anti-HBs titers appears significantly related to antibody titers after the immunization procedure, monitoring of anti-HBs, particularly in patients with low level of protective antibody titers after primary vaccination or boosters, seems more than justified.     

Randomized trial of recombinant hepatitis B vaccine in HIV-infected adult patients comparing a standard dose to a double dose

Because HIV and hepatitis B virus share many common risk factors, it is important to try to vaccinate HIV patients against hepatitis B. There are numerous reports describing a variety of dose schedules, limited success and markers associated with impaired response to HBV vaccine in these individuals. All studies have been small in size making it difficult to draw conclusions within and between studies. The purpose of this study was to evaluate a double dose of hepatitis B vaccine under more definitive guidelines: double blinded, randomized, controlled, with numbers for statistical validity. Two hundred and ten HIV infected subjects received a standard dose (20 microg) or a double dose (40 microg) of recombinant hepatitis B vaccine IM 0, 1 and 6 months. Ninety-four receiving standard dose and 98 receiving double dose completed the study. The seroconversion rate (anti-HBs > or = 10 mIU/mL) was 47 and 34% for double dose and standard dose, respectively (p = 0.07). A statistically significant higher seroconversion rate was associated with double dose comparing with standard dose for patients with CD4 cell counts > or = 350 cells/mm3 (64.3% x 39.3%; p = 0.008) but made no difference to seroconversion in those with CD4 <350 (23.8% x 26.3%; p = 0.80). Double dose also improved seroconversion comparing with standard dose for patients with HIV viral load <10,000 copies/mL (58.3% x 37.3%; p = 0.01) but made no difference to seroconversion in those with HIV viral load > or = 10,000 copies/mL (16% x 17%; p = 0.7). Based on the results of this study, the best current strategy for hepatitis B vaccination in HIV patients would be to use a double dose as a primary series when the viral load is likely to be low and CD4> or = 350, when there is likely to be an adequate immune response.     

Prevalence of protective level of hepatitis B antibody 3 years after revaccination in HIV-infected children on antiretroviral therapy

After responding to highly active antiretroviral therapy (HAART), HIV-infected children had a good response to hepatitis B immunization. However, there are limited data on the durability of antibody to hepatitis B surface antigen (anti-HBs) in these children. The primary objective of this study is to determine the prevalence of protective anti-HBs level 3 years after a 3-dose HBV revaccination among HIV-infected children with immune recovery (CD4 cell ≥15%) while on HAART. The secondary objective is to assess immunologic memory among children who had waning of anti-HBs. An anti-HBs level of ≥10 mIU/mL was defined as a protective antibody level. Sixty-nine HIV-infected children who had history of a 3-dose HBV revaccination while receiving HAART were enrolled. The mean (SD) of CD4 cell and duration of HAART at time of revaccination was 27.2% (6.7) and 5.9 years (0.4), respectively. The proportion of children with protective anti-HBs level 3 years after the revaccination was 71.0% [95% CI, 58.8-81.3]. The geometric mean titer was 114(SD 5) IU/mL. By multivariate logistic analysis, the predictors for protective anti-HBs level 3 years after revaccination were CD4 cell count ≥500 cells/mm³ at the time of vaccination (p = 0.04) and anti-HBs level ≥ 100 IU/mL at 1 month after completion of the 3-dose vaccination (p < 0.001). Anamnestic response after one booster dose was demonstrated among 14 of 17 children who had waning protective anti-HBs level (82.4% [95% CI, 62.2-102.6]). Our findings support the recommendation of giving a 3-dose HBV vaccination to HIV-infected children with immune recovery while receiving HAART.     

Assessing the immunological response to hepatitis B vaccination in HIV-infected patients in clinical practice

Hepatitis B vaccination is recommended in HIV-infected patients. Achieving seroprotection rates (anti-HBs ≥ 10I U/L) comparable to the general population remains a challenge. The aim of this study was to analyze the proportion of responders among patients infected with HIV receiving primary HBV vaccination and identify factors associated with seroprotection rates. We analyzed the response to vaccination (antiHBs titers) in 474 HIV-infected patients receiving ≥ 1 doses of vaccine between 1994 and 2009. Factors associated with response to vaccination were analyzed using a logistic regression model. Considering the first vaccine courses administered, a response rate of 60.3% (286/474) was obtained. Eighty-seven patients began a second course, responding in 58.6% of cases. Regardless of the number of doses, schedules, and whether or not they completed the course, the response rates were 71.1% (337/474). After adjustment for year of reception of the first dose, responders were less likely to have a higher baseline HIV 1-RNA viral load (OR: 0.78 95% CI: 0.68-0.91) and more likely to have a CD4 count ≥ 350 cells/μL (OR: 1.64, 95% CI: 1.03-3.62). Patients receiving less than three doses of vaccine (OR: 0.31 95% CI 0.15-0.61) or three doses of the rapidly accelerated schedule (OR: 0.35 95% CI 0.15-0.81) had a lower probability of response in comparison with those receiving three doses of an accelerated schedule. In patients diagnosed with HIV, HBV vaccination before evolution to greater immunosuppression (CD4 < 350 cells/μL) or delaying vaccination until the CD4 count is higher could provide better seroprotection rates. The rapidly accelerated vaccination schedule should be used with caution, due to its lower effectiveness. If seroprotection is not achieved after the first course, revaccination seems to be effective in increasing the proportion of responders.     

Efficacy of granulocyte-macrophage colony-stimulating factor (GM-CSF) as a vaccine adjuvant for hepatitis B virus in patients with HIV infection

Recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF) is a cytokine with a potential vaccine adjuvant activity. It is also known that human immunodeficiency virus (HIV) infected patients often show poor immunologic responses to immunization. We examined whether the use of GM-CSF could augment the immunologic response to recombinant vaccine against the hepatitis B virus (HBV) in 80 HIV infected patients (18-35 years old). They received a double dose (40 microg) of recombinant HBV vaccine IM at 0, 1 and 6 months and were randomized to receive either concurrent 20 microg of GM-CSF (n=40) or placebo IM (n=40) with the first vaccine dose. A significant increase in the seroconversion rate was observed after the second vaccine dose in the GM-CSF group (62% GM-CSF versus 30% control group P<0.0074). The average anti-HBs titers measured on days 28, 60 and 210 were 40.3; 366.5 and 644.8 milli-international units per milliliter (mIU/ml), respectively, in the GM-CSF group, and 62.4; 166.4 and 375.0 mIU/ml, respectively, in the control group, with significant differences at 60 and 210 days (P<0.01). There were no significant differences between CD4/CD8 cells, viral load, risk factors, age, sex and the serological responses to the HBV vaccine. This study suggests that GM-CSF increases the immunogenicity of recombinant HBV vaccine in HIV infected individuals.     

慢性乙型肝炎患者血清表面抗原与抗体同时阳性结果分析

目的:探讨乙型肝炎患者HBsAg和抗HBs共存模式及与HBV DNA的关系。方法:采用增强化学发光法检测血清乙肝标志物,并采用荧光定量PCR法检测HBV DNA。结果:5717例慢性乙肝患者检测出HBsAg和抗HBs双阳性248例,占4.34%,其中多数与HBV DNA同时出现。结论:HBsAg和抗HBs同时阳性并不少见,慢性乙肝患者出现抗HBs,不完全代表病毒复制终止,需结合HBV DNA定量综合分析。     

Study Protocol - Accurate assessment of kidney function in Indigenous Australians: aims and methods of the eGFR Study

Background

Coinfection with hepatitis B virus (HBV) or hepatitis C virus (HCV) in HIV-infected patients receiving a commonly used nevirapine-based antiretroviral therapy is a major concern for African clinicians owing to its high prevalence, the infrequent testing and treatment of viral hepatitis, and the impact of liver disease on the tolerability and effectiveness of anti-HIV treatment. We compared the hepatotoxicity and the immunological, virological and clinical effectiveness of a nevirapine-based antiretroviral therapy between patients infected with HIV only and patients coinfected with hepatitis B or C virus in Cameroon.

Methods

A retrospective cohort study was conducted among HIV-1-infected patients. Plasma HBV DNA and HCV RNA were tested in positive or indeterminate samples for HBsAg or HCV antibodies, respectively. All patients received nevirapine and lamivudine plus stavudine or zidovudine.

Results

Of 169 HIV-1-infected patients with a median baseline CD4 count of 135 cells/mm³ (interquartile range [IQR] 67-218), 21% were coinfected with HBV or HCV. In coinfected patients, the median viral load was 2.47 × 10⁷ IU/mL for HBV (IQR 3680-1.59 × 10⁸) and 928 000 IU/mL for HCV (IQR 178 400-2.06 × 10⁶). Multivariate analyses showed that the risk of hepatotoxicity was 2-fold higher in coinfected patients (p < 0.01). The response to antiretroviral therapy was however comparable between monoinfected and coinfected patients in terms of CD4 cell count increase (p = 0.8), HIV-1 viral load below 400 copies/mL (p = 0.9), death (p = 0.3) and death or new AIDS-defining event (p = 0.1). Nevirapine was replaced by a protease inhibitor in 4 patients owing to hepatotoxicity.

Conclusion

This study suggests that the nevirapine-based antiretroviral therapy could be used safely as first-line treatment in patients with low CD4 cell count in Africa despite frequent coinfections with HBV or HCV and infrequent testing of these infections. Although testing for HBV and HCV should be systematically performed before initiating antiretroviral therapy, transaminases elevations at baseline or during treatment should be a decisive argument for testing when hepatitis status is unknown.     

A comparison of responsiveness to hepatitis B vaccination in patients on hemodialysis and peritoneal dialysis

The doses of hepatitis B vaccine given to peritoneal dialysis (PD) patients are currently based on responsiveness data from hemodialysis (HD) patients. To determine whether the doses are also appropriate from PD patients, we did a head-to-head comparison of short-term and 2-year responses to hepatitis B vaccination of HD patients and PD patients. We evaluated serum titers of the antibody to hepatitis B surface antigen (anti-HBs) after the patients had completed a course of four consecutive intramuscular vaccinations (40 microg of Engerix-B administered into the deltoid muscle at 0, 1, 2, and 6 months) in 69 dialysis patients (47 HD and 22 PD patients) who were both hepatitis B surface antigen (HBsAg) and anti-HBs negative. No patients had received a hepatitis B vaccination prior to the study. There was no significant difference in response to hepatitis B vaccination between the HD and PD groups (78.7% versus 77.3%, p=0.33). The seroconversion rate defined as anti-HBs > or = 10IU/L was influenced only by age (p=0.011). There was also no significant difference in responsiveness between the HD and PD groups (60% versus 50%, p=0.41) at a 2-year follow-up. We conclude that doses of HBV vaccine being used for HD patients are also appropriate for PD patients and a booster dose of vaccine is required to maintain seroprotection for those who lost protecting anti-HBs.     

母亲乙型肝炎病毒感染状态对婴儿接种乙型肝炎疫苗后免疫应答的影响

161例婴儿接种乙型肝炎(简称乙肝)疫苗后免疫应答良好。接种20μg疫苗的婴儿抗-HBs阳转率为100%,几何平均滴度为1:448.9;接种10μg疫苗的婴儿抗-HBs阳转率为97.3%,滴度为1:217.8。母亲的HBV感染状态与婴儿对乙型肝炎疫苗的免疫应答有密切关系。母亲单独抗-HBs阳性的婴儿,接种乙型肝炎疫苗后的抗-HBs应答最佳(阳转率为100.0%,几何平均滴度1:670.4),依次为母亲HBV感染标记全阴性的婴儿(100.0%,1:376.4)。母亲抗-HBs和抗-HBc共阳性的婴儿(100.0%,1:218.2);而母亲为HBsAg阳性或单独抗-HBc阳性的婴儿的抗-HBs应答较差(75.0%,1:40.3;或100.0%,1:28.5)。本次研究提示机体的遗传特征以及母体HBV传染性强弱对婴儿接种乙型肝炎疫苗后的免疫应答起决定作用。     

Immunogenicity of a recombinant hepatitis B vaccine (Euvax-B) in haemodialysis patients and staff

Hepatitis B vaccine is the most effective strategy for preventing the transmission of hepatitis B virus (HBV) in haemodialysis centers. Nevertheless, lower vaccine responses have been reported in haemodialysis patients as compared with healthy subjects. This study examines the response to Euvax-B in Brazilian haemodialysis patients and staff. A total of 102 eligible patients (n = 42) and staff members (n = 60) consented to be studied. Patients were immunized intramuscularly with four doses of 40 g of Euvax-B vaccine at 0, 1, 2 and 6 months. In staff members, the vaccine was administered in three doses of 20 g at 0, 1, and 6 months. Post-vaccine samples were taken from all subjects 1 month after each dose. The vaccine response was determined by measuring antibody to the hepatitis B surface antigen (anti-HBs) levels using ELISA. Subjects with anti-HBs titres equal to or higher than 10 UI/L were considered immune protected. Of the haemodialysis patients who received four doses of hepatitis B vaccine, 89.5% responded to Euvax-B vaccine. The geometric mean of anti-HBs titres was 322.8 IU/L (95% CI: 317.7–328). Among staff members, 93.3% reached anti-HBs protective titres after the third vaccine dose. The geometric mean of anti-HBs titres was 2209 IU/L (CI: 2198–2219). Age, male gender and body mass index were not associated with vaccine response in either group. This study showed a good immunogenicity response to Euvax-B in haemodialysis patients and staff.     

天津市20岁以上成人乙型病毒性肝炎控制效果分析

目的 评价天津市20岁以上人群乙型病毒性肝炎(简称乙肝)的控制效果,为乙肝的防治提供科学依据.方法 对2005和2010年天津市20岁以上成人急性乙肝报告的发病率,以及1992和2010年天津市疾病预防控制中心乙肝血清学抽样监测结果进行评价.结果 天津市2010年共监测20岁以上成人3198人,乙肝病毒表面抗原、表面抗原抗体和核心抗原抗体阳性率分别为3.28％、40.68％和13.13％;各年龄组间表面抗原阳性率以50 ～ 59岁组最高(4.56％),20 ～29岁组表面抗原抗体阳性率(48.23％)高于其他年龄组;同1992年监测结果相比,表面抗原阳性率下降39.82％(x2=8.16,P=0.004),表面抗原抗体阳性率上升25.44％ (x2=17.79,P＜0.001).天津市2010年20岁以上人群急性乙肝报告发病率为3.06/10万,较2005年的7.26/10万下降57.85％( x2=160.66,P＜0.001).结论 发病率和血清学监测结果均证实天津市20岁以上人群乙肝控制效果明显.     

An open-label,single-arm study evaluating the immunogenicity and safety of the hepatitis B vaccine HepB-CpG (HEPLISAV-B®) in adults receiving hemodialysis

BackgroundHemodialysis patients are at increased risk of hepatitis B virus (HBV) infection and are poorly responsive to HBV vaccines. Current vaccine recommendations for hemodialysis patients utilize more than twice the amount of hepatitis B surface antigen (HBsAg) used for healthy adults and achieve lower immune responses.MethodsAn open-label, single-arm, multicenter trial was conducted among adults 18 years of age and older who were initiating or undergoing hemodialysis who had not previously received hepatitis B vaccine. Participants received four doses of HepB-CpG (HEPLISAV-B®) (20 mcg rHBsAg + 3000 mcg CpG 1018, a Toll-like receptor 9 agonist) administered at 0, 4, 8, and 16 weeks. Participants are being followed for 68 weeks. This paper reports the final immunogenicity analysis of the primary endpoint at study week 20 and an interim safety analysis.ResultsWe enrolled 119 participants receiving hemodialysis who were followed for a median of 47.4 weeks. Of the 119 participants, 75 were in the per-protocol population. At week 20, the seroprotection rate (% with antibodies to hepatitis B surface antigen [anti-HBs] ≥ 10 mIU/mL) was 89.3% and the percentage of participants with anti-HBs ≥ 100 mIU/mL was 81.3%. The anti-HBs geometric mean concentration was 1061.8 mIU/mL. HepB-CpG was well tolerated with no observed safety concerns.ConclusionIn patients receiving hemodialysis, HepB-CpG given as four doses was well tolerated and induced very high anti-HBs concentrations and seroprotection in a very high proportion of recipients.     

长沙地区无偿献血人群隐匿性乙型肝炎病毒感染情况分析

目的 了解长沙地区无偿献血人群隐匿性乙型肝炎病毒感染(occult hepatitis B virus infection,OBI)流行情况,探讨HBV基因型分布特征和S区氨基酸突变的情况。方法 对长沙地区检测结果为HBsAg-/HBV DNA+的无偿献血血液样本进行HBV血清标志物检测,对其中的OBI样本进行HBV病毒载量检测和S区基因扩增,分析血清学标志物抗HBs与病毒载量检出与否的关系,并对扩增产物进行HBV基因分型和突变位点分析。结果 2019年1月—2020年1月长沙地区173 893份无偿献血标本共确认58例OBI样本,OBI流行率为0.033%;共发现7种血清学模式,抗HBc单独阳性最多,占38.98%,所有样本中抗HBc阳性率为89.83%;16例样本能检测出病毒载量,其中14例样本浓度小于100 IU/ml;抗HBs阳性组和阴性组间的病毒载量检出率无统计学差异;75.0%(12/16)样本扩增出S区序列,基因型均为B型,均发生突变,其中11例的HBsAg抗原决定簇及周边主要亲水区域(major hydrophilic region, MHR)发生氨基酸突变。结论 长沙地区无偿献血者中的OBI感染率在全国属于偏低水平;HBV基因型主要是B型,MHR区的氨基酸突变可能是造成OBI的原因,突变有本地特点。     

Vaccination coverage against hepatitis A and B viruses, Streptococcus pneumoniae, seasonal flu,and A(H1N1)2009 pandemic influenza in HIV-infected patients

Background

Several vaccines are recommended in HIV-infected patients due to an increased risk of vaccine-preventable infections, severe forms of the disease, or shared transmission routes. Few data are available regarding vaccination coverage and its determinants in this population.

Methods

A cross-sectional study was performed in HIV-infected patients included in a hospital-based cohort in 2011. Vaccination coverage against hepatitis A virus (HAV), hepatitis B virus (HBV), seasonal and A(H1N1)2009 pandemic influenza, and invasive pneumococcal diseases (IPD) were recorded. Factors associated with vaccination were assessed by multivariate logistic regression.

Results

2467 patients were included (median age: 47 years; male gender 71.5%; men having sex with men (MSM): 43.9%; CDC stage C: 24.3%; HBV and/or hepatitis C virus co-infection: 14.4%). Median duration of HIV infection was 10 years and 93.1% of patients received combination antiretroviral therapy. At baseline, the median CD4 count was 527 cells/mm³ and HIV viral load was <50 copies/mL in 83.3% of cases. Vaccination coverage for HBV, HAV, seasonal influenza, A(H1N1)2009 pandemic influenza, and IPD were 61.9%, 47.4%, 30.9, 48.3%, and 64.6%, respectively. Factors independently associated with vaccination were a younger (HBV) or an older age (influenza), male gender (HBV, HAV), MSM (HBV), CD4 count >200/mm³ and HIV-RNA <50 copies/mL (IPD, influenza), longer duration of HIV infection (IPD, influenza), and follow-up by an experienced physician (HBV, IPD).

Conclusions

Vaccination coverage remained insufficient for all vaccine-preventable infections investigated in this study. Determinants for vaccination were largely not evidence-based, and efforts should be focused on improving physicians’ knowledge about guidelines.     

Immune response to the hepatitis B vaccine among HIV-infected adults in Uganda

BackgroundCo-infection with hepatitis B virus (HBV) and human immunodeficiency virus (HIV) is common in sub-Saharan Africa (SSA) and can rapidly progress to cirrhosis and hepatocellular carcinoma. Recent data demonstrate ongoing HBV transmission among HIV-infected adults in SSA, suggesting that complications of HIV/HBV co-infection could be prevented with HBV vaccination. Because HBV vaccine efficacy is poorly understood among HIV-infected persons in SSA, we sought to characterize the humoral response to the HBV vaccine in HIV-seropositive Ugandan adults.MethodsWe enrolled HIV-infected adults in Kampala, Uganda without serologic evidence of prior HBV infection. Three HBV vaccine doses were administered at 0, 1 and 6 months. Anti-HBs levels were measured 4 weeks after the third vaccine dose. “Response” to vaccination was defined as anti-HBs levels ≥ 10 IU/L and “high response” as ≥ 100 IU/L. Regression analysis was used to determine predictors of response.ResultsOf 251 HIV-positive adults screened, 132 (53%) had no prior HBV infection or immunity and were enrolled. Most participants were women [89 (67%)]; median (IQR) age was 32 years (27–41), and 68 (52%) had received antiretroviral therapy (ART) for > 3 months. Median (IQR) CD4 count was 426 (261–583), and 64 (94%) of the 68 receiving ART had undetectable plasma HIV RNA. Overall, 117 (92%) participants seroconverted to the vaccine (anti-HBs ≥ 10 IU/L), with 109 (86%) participants having high-level response (anti-HBs ≥ 100 IU/L). In multivariate analysis, only baseline CD4 > 200 cells/mm3 was associated with response [OR = 6.97 (1.34–34.71), p = 0.02] and high-level response [OR = 4.25 (1.15–15.69)], p = 0.03].ConclusionHBV vaccination was effective in eliciting a protective humoral response, particularly among those with higher CD4 counts. Half of the screened patients did not have immunity to HBV infection, suggesting a large at-risk population for HBV infection among HIV-positive adults in Uganda. Our findings support including HBV vaccination as part of routine care among HIV-positive adults.