Higher rate of long-term serologic response of four double doses vs. standard doses of hepatitis B vaccination in HIV-infected adults: 4-year follow-up of a randomised controlled trial.

BACKGROUND: We previously reported that four doses or four double doses of hepatitis B vaccination regimens could not significantly increase a response rate compared with standard doses. However, the antibody levels were higher in the four doses and four double doses groups. This study followed those patients for at least 3 years and aimed to evaluate the immunogenicity of the three vaccination regimens. METHODS: HIV-infected adults who had CD4+ cell counts > 200 cells/mm3, undetectable plasma HIV-1 RNA, and negative for all hepatitis B virus markers were randomly assigned to receive one of three recombinant vaccines (Hepavax-Gene® Berna, Korea) regimens: 20 µg IM at months 0, 1, and 6 (standard doses group, n = 44), 20 µg IM at months 0, 1, 2, 6 (four doses group, n = 44), or 40 µg IM at months 0, 1, 2, and 6 (four double doses group, n = 44) between February 2011 and May 4, 2012. Of 132 participants, 126 were evaluated from August 2015 to January 2016; 42 in the standard doses, 43 in the four doses, and 41 in the four double doses groups. RESULTS: At a median duration of 49.7 months (range 46.7-53.7) after completion of the primary vaccination schedule, the percentages of responders with anti-HBs ≥ 10 mIU/mL were 57.1% (95% CI 41.5-72.8%) in the standard doses group; 76.7% (95% CI 63.6-89.9%) in the four doses group (P = 0.067 vs. the standard doses group); and 80.5% (95% CI 67.8-93.2%) in the four double doses group (P = 0.033 vs. the standard doses group). Factors associated with a responder were the vaccination schedule (either four doses or four double doses groups) and a younger age. CONCLUSIONS: Despite the highly effectiveness of the standard hepatitis B vaccination regimen at 6 months after completion, the long-term immunogenicity was lower than the four double doses regimen among HIV-infected adults with CD4+ cell counts > 200 cells/mm3 and undetectable plasma HIV-1 RNA. The standard vaccination regimen may not be the best strategy to provide long-term immune response against hepatitis B virus among HIV-infected individuals. Trial registration NCT1289106, NCT02713620.

Hepatitis B Vaccination Induced TNF-α- and IL-2-Producing T Cell Responses in HIV- Healthy Individuals Higher than in HIV+ Individuals Who Received the Same Vaccination Regimen.

We investigated cytokine production and expression of degranulation marker CD107a after different strategies of hepatitis B virus (HBV) vaccination in human immunodeficiency virus-infected individuals, which were three doses of 20 µg (standard dose group), four doses of 20 µg (four doses group), or four doses of 40 µg (four double doses group), compared to standard dose vaccination in healthy controls. PBMCs collected at different time points were stimulated in vitro with recombinant hepatitis B surface antigen and analyzed by flow cytometry. There was an increase in TNF-α production of total and memory CD4+ T cells at 7 months after vaccination in healthy controls compared to the HIV+ group, which received the same standard vaccination regimen. An increase in the IL-2-producing memory CD4+ T cells in the healthy control group was also observed at 7 months after vaccination. No differences were observed between the healthy controls and both groups of four doses at any time point of study. These results suggest that the standard HBV vaccination schedule might induce better production of TNF-α and IL-2 from CD4+ T cells in healthy individuals. Modification of HBV vaccination schedule by increasing the frequency and/or dosage may improve the CMI response in HIV-infected individuals. This trial is registered with NCT1289106.

Better Antiretroviral Central Nervous System Penetration is Not Associated with Reduced Chronic Pain in People Living with Human Immunodeficiency Virus.

OBJECTIVE: To determine if better antiretroviral (ARV) central nervous system (CNS) penetration is associated with reduced rates of chronic pain in people living with HIV (PLWH). BACKGROUND: Chronic pain remains prevalent in PLWH despite widespread ARV use. Mechanisms underlying this prevalence remain unknown, though neuroinflammation from persistent CNS HIV infection and maladaptive plastic changes in the CNS have been implicated. Here we hypothesize that better CNS ARV penetration, measured using the CNS Penetration-Effectiveness (CPE) score, would decrease rates of chronic pain. METHODS: We interviewed 254 consecutive adults from an HIV clinic in Chiang Mai, Thailand. We collected data on demographics, HIV history, ARV use, and pain characteristics. Patients were evaluated for depression using a Thai two question Patient Health Questionnaire (PHQ-2). Modified CPE score was calculated using established methods and grouped a priori into "low CPE" (≤7, poor penetration) and "high CPE" (≥8, good penetration). CPE score was compared with chronic pain scores in SPSS using appropriate statistical tests. A relationship between CPE score and a positive depression screen was tested further using multivariable binary logistic models. RESULTS: 245 of 254 subjects were on ARVs. Complete ARV data was available for 235 patients. 137 of these 235 patients (58.3%) had a CPE score ≤7, and 98 (41.7%) had a score ≥8. 49 patients had chronic pain, and 9 had neuropathic pain. Low CPE score was not associated with chronic pain (p=0.64), neuropathic pain (p=0.56), or frequent pain (p=0.80), nor was it associated with the severity of reported "worst pain" or "average pain" in the last 24 hours (p=0.18 and 0.48, respectively). Post-hoc analysis revealed that higher CPE score was a significant independent risk factor for depression measured by a positive PHQ-2 screen [OR (95% CI) = 1.29 (1.04-1.61), p=0.02]. This relationship was mediated primarily by exposure to zidovudine. CONCLUSIONS: CPE score is not associated with chronic pain in PLWH. Post-hoc analysis demonstrated that CPE score, and zidovudine exposure in particular, predicts a positive depression screen. Given the substantial morbidity associated with chronic pain and mood disorders in PLWH, additional studies to determine preventable and treatable factors are imperative.

Comparison of immunogenicity and safety of four doses and four double doses vs. standard doses of hepatitis B vaccination in HIV-infected adults: a randomized, controlled trial.

BACKGROUND: HBV vaccination is recommended in HIV-infected adults with CD4+ cell count >200/mm(3) although the efficacy is only 33.3% -65%. We conducted a randomized, controlled trial to evaluate the efficacy and safety of three regimens of HBV vaccination at Chiang Mai University Hospital, Thailand. METHODS: From February 4, 2011 to May 4, 2012, 132 HIV-infected adults with CD4+ cell counts >200 cells/mm(3), undetectable plasma HIV-1 RNA, and negative for all HBV markers were randomly assigned to receive one of three recombinant vaccine (Hepavax-Gene(®) Berna, Korea) regimens: 20 µg IM at months 0, 1, and 6 (Standard doses group, n=44), 20 µg IM at months 0, 1, 2, 6 (four doses group, n=44), or 40 µg IM at months 0, 1, 2, and 6 (four double doses group, n=44). The primary outcomes were to compare the immunogenicity and safety between the four-doses groups with the Standard doses group. RESULTS: At months 7 and 12, the percentages of responders (anti-HBs ≥ 10 mIU/mL) were 88.6% and 70.4% in the Standard doses group, 93.2% and 86.4% in the four doses group, (P=0.713 and 0.119), and 95.4% and 88.6% in the four double doses group, (P=0.434 and 0.062), respectively. Factors associated with a high titer level (anti-HBs ≥ 100 mIU/mL) were vaccination schedule and younger age. The most common adverse event was pain at the injection site (42.4%); this was significantly more frequent in the four double doses group compared to the Standard doses group. No serious adverse events were observed. CONCLUSIONS: In Northern Thailand, the standard three-doses HBV vaccination in HIV-infected adults with CD4+ cell counts >200 cells/mm(3) and undetectable plasma HIV-1 RNA is highly effective. Although regimens of four injections of either standard or double doses could not significantly increase the response rate, these regimens may induce higher levels of antibody to the virus. TRIAL REGISTRATION INFORMATION: ClinicalTrials.gov; NCT1289106; http://clinicaltrials.gov/ct2/show/NCT01289106.

Undertreatment of pain in HIV+ adults in Thailand.

CONTEXT: Chronic pain remains prevalent in HIV+ adults despite widespread antiretroviral use. Pain continues to be underrecognized and undertreated in this population. In Thailand, similar to the West, HIV care is transitioning toward chronic disease management. Despite the importance of pain management in chronic HIV, the prevalence of pain and adequacy of pain management is unknown in HIV+ adults in Thailand. OBJECTIVES: This cross-sectional study aimed to determine the prevalence of chronic pain, the burden of inadequate analgesia, and risk factors for chronic pain in HIV+ adults in Thailand. METHODS: A total of 254 HIV+ adults were recruited from an outpatient clinic in Thailand. Interviewers obtained information on demographics, clinical data, and pain characteristics. The burden of inadequate analgesia was assessed using the Brief Pain Inventory. Risk factors were identified with logistic regression analysis. RESULTS: Frequent pain was reported by 27% of participants; 22% reported chronic pain. Pain was significantly associated with education less than primary school, a positive depression screen, and the number of years on combined antiretroviral therapy. Eighty-six percent of patients with frequent pain were inadequately treated. Of 34 patients with moderate or severe pain, none received adequate analgesia. Inadequate analgesia was a significant risk factor for poorer quality of life. CONCLUSION: Despite widespread antiretroviral use, pain remains common and undertreated in HIV+ adults in Thailand. Undertreated pain negatively impacts quality of life. It is imperative that policy makers and HIV caregivers address this treatment gap to advance the care of people living with HIV in Thailand.

Immune response to 2009 H1N1 vaccine in HIV-infected adults in Northern Thailand.

BACKGROUND: In late 2009, the Thai Ministry of Public Health provided two million doses of the monovalent pandemic influenza H1N1 2009 vaccine (Panenza®, Sanofi Pasteur), which was the only vaccine formulation available in Thailand, to persons at risk of more severe manifestations of the disease including HIV infection. Several studies have shown poorer immune responses to the 2009 H1N1 vaccines in HIV-infected individuals. There are limited data in this population in resource-limited countries. RESULTS: At day 28 post-vaccination, seroconversion was found in 32.0% (95%CI 24.5 - 40.2) of the HIV-infected group and 35.0% (95%CI 15.4- 59.2) of the healthy controls (p = 0.79). Seroprotection rate was observed in 33.3% (95%CI 25.8-41.6) and 35.0% (95%CI 15.4-59.2) of the HIV-infected group and the control group, respectively (p = 0.88). Among HIV-infected participants, the strongest factor associated with vaccine response was age 42 y or younger (p = 0.05). METHODS: We evaluated the immunogenicity of a single, 15µg/0.5ml dose of a monovalent, non-adjuvanted 2009 H1N1 vaccine in 150 HIV-infected Thai adults and 20 healthy controls. Immunogenicity was measured by hemagglutination inhibition assay (HI) at baseline and 28 d after vaccination. Seroconversion was defined as 1) pre-vaccination HI titer < 1:10 and post-vaccination HI titer ≥ 1:40, or 2) pre-vaccination HI titer ≥ 1:10 and a minimum of 4-fold rise in post-vaccination HI titer. Seroprotection was defined as a post-vaccination HI titer of ≥ 1:40. CONCLUSIONS: A low seroconversion rate to the 2009 H1N1 vaccine in both study groups, corresponding with data from trials in the region, may suggest that the vaccine used in our study is not very immunogenic. Further studies on different vaccines, dosing, adjuvants, or schedule strategies may be needed to achieve effective immunization in HIV-infected population.