Immune responses in patients with HIV infection after vaccination with recombinant Hepatitis B virus vaccine.

BACKGROUND: Patients with HIV infection are at risk of co-infection with HBV, as the routes of transmission are shared and thus immunization with HBV vaccine could be protective in them. The aim of the present study was to assess the efficacy of recombinant vaccine in treatment-naive HIV positive patients and healthy controls, and to dissect out differences if any, in different limbs of immune response. METHODS: Forty HIV positive patients and 20 HIV negative controls, negative for HBsAg, HBsAbs and HBcAbs were vaccinated with three doses of 40 microg and 20 microg of vaccine respectively. Patients were divided into high CD4 and low CD4 group based on CD4+ lymphocytes of 200 and < 200/mm3 respectively. Group II consisted of healthy controls. Detection of phenotypic markers was done by flowcytometry. Cytokine estimation was done by sandwich ELISA. HBsAbs were estimated in serum by ELISA. RESULTS: After vaccination, CD4+, CD8+ and CD3+ cells increased significantly in all the groups. There was no increase in NK cell activity in patients with high CD4+ lymphocytes and only a marginal increase in patients with low CD4+ lymphocytes (170 to 293/mm3) whereas a marked increase was observed in controls (252 to 490/mm3). After vaccination, although an increase in memory cells was observed in HIV positive patients, yet HBsAb levels were significantly lower than controls (P < 0.05) indicating a functional defect of memory cells in HIV/AIDS patients. Basal IFN-gamma levels were also significantly lower in HIV/AIDS patients (P < 0.01). Although the levels increased after vaccination, the peak level remained lower than in controls. HBsAb titers were much lower in HIV positive patients compared to controls. (High CD4+ group: 8834 mIU/ml, low CD4+ group: 462 mIU/ml Vs. CONTROLS: 16,906 mIU/ml). IL-4 and IL-10 were low in patients. CONCLUSION: Despite a double dose in patients, IL-4 and IL-10, which regulate antibody response, were also lower in patients, and this together with low CD4+ counts and lack of T help, accounted for low HBsAb levels. Vaccination in patients with CD4+ lymphocytes < 50/mm3 was ineffective. Thus early immunization is advocated in all HIV positive patients at a stage when they are still capable of mounting an adequate immune response.

Poor responses to recombinant HBV vaccination in patients with HIV infection.

The study was conducted with an aim to assess the efficacy of recombinant HBV vaccination in untreated HBV seronegative HIV/AIDS subjects as compared to normal controls. The second objective was to identify differences in CD4 and CD8 T cell numbers/kinetics/functions and levels of TH2 cytokines (IL4 and IL10) in different groups during the three-dose vaccination regimen. 40 HIV/AIDS patients were subdivided into groups 1A where patients had a high CD4 (> 200/mm3) count and IB where patients had a low CD4 (< 200/mm3) count. Twenty normal healthy control subjects were also recruited in the study (group II). Patients received 40 micro and controls received 20 micro of recombinant HBV vaccine in each dose. All subjects received 3 doses of the vaccine. Detection of CD4 and CD8 cells was done by flowcytometry. TH2 type of cytokines IL4 and IL10 were estimated in the culture supernatant of PHA stimulated leukocyte rich plasma by sandwich ELISA. Anti-HBs levels were estimated in the serum by ELISA. Anti-HBs response was severely compromised in patients as compared to controls. Groups II, 1A and 1B showed titers of 16906 +/- 21303, 8834 +/- 14136 and 462 +/- 814 m/U/m/ respectively. Both CD4 and CD8 cells increased significantly after vaccination in all the groups irrespective of the disease status. On the other hand, IL4/IL10 responses to PHA stimulation in the HIV-positive groups were much lower than in controls (P< 0.1). Despite a double dose of vaccine in patients, the antibody response was significantly lower which correlated with a lower CD4 count. Cytokines IL4 and IL10 which regulate antibody response, were also lower in-patients and this together with a low CD4 count possibly accounted for the low anti-HBs levels. All patients with high CD4 lymphocyte count were responders while only 47% of patients with low CD4 lymphocyte count responded to immunization. Patients with a CD4 count of less than 50 failed to respond. Thus early immunization is advocated in all HIV patients at a stage when they are still capable of mounting an adequate immune response.