The purpose of the study. To characterize the immune response to the pneumococcal vaccine in HIV positive individuals and to dissect the most appropriate timing and frequency of vaccination.

All potential study candidates will be asked to fill out a questionnaire concerning their medical history and medications. This survey will determine eligibility. If eligible, as part of the experimental protocol the HIV positive participants will agree to be randomized to immediate vs. delayed pneumococcal immunization and 3 blood draws around the time of immunization. The HIV negative control population will agree to immunization with pneumococcal polysaccharide vaccine (PPV), not standard of care for this population, and 3 blood draws around the time of immunization. The investigators will study the effect of pneumococcal vaccination in HIV positive adults. At the present time it is recommended that all HIV positive individuals receive the pneumococcal vaccine at the time of diagnosis with those with cluster of differentiation (CD4) count <200 to be vaccinated either immediately or alternatively, treated with highly active antiretroviral therapy (HAART) for 6 months followed by PPV. All patients are recommended to be re-vaccinated at 5 years. This is the standard of care. It is however unclear how the HIV positive patients respond to PPV. In the 1st part of the study, Part I, newly diagnosed HIV positive individuals will be recruited. As standard of care, these individuals will receive the pneumococcal vaccine regardless of their participation in this study. Those that agree to participate in the study will be grouped according to their CD4 count: >500, 200-500 or <200. Those with a CD4 count <200 will be randomly assigned to receive the vaccine immediately or to receive HAART for 6 months prior to vaccination, this is in accordance with the present recommendations, either immediate vaccination or giving HAART for 6 months prior to vaccination is considered acceptable.. Thus ALL HIV positive individuals will receive the vaccine as presently recommended. The HIV positive volunteers agree to (experimental part of the protocol):

1. Be randomized to either immediate vaccination vs. 6 months after start of HAART if the CD4 count is <200
2. Donate blood specimens at 3 different times: day 0, day of vaccination: 2 mL, at day 7, 40 mL and at day 28-42 a one time sample of 2 mL.
3. Have their blood samples subjected to antibody analysis (concentration and functional activity) and antibody gene usage analysis There will be 4 HIV positive groups in this part of the study: CD4>500, CD4 200-500, CD4 < 200 immediate vaccination and CD4 <200, delayed vaccination.

There will be 19 individuals per group. The HIV negative controls in Part I of the study (n=19) who agree to participate will also be vaccinated with the pneumococcal vaccine. This is NOT a vaccine recommended for healthy adults but is NOT contra-indicated.

Thus as part of the experimental procedure for these individuals they will:

1. Receive the FDA approved pneumococcal vaccine
2. Blood samples will be obtained at day 0: 2 mL, day 7 40 mL and day 28-42, one time sample of 2 mL.
3. Blood samples will be analyzed for antibody concentration, functional activity and gene family usage.

In summary, we will study a total of 5 groups in Part I:

Group 1: HIV positive CD4>500 Group 2: HIV positive CD4 200-500 Group 3: HIV positive CD4 < 200 immediate vaccination Group 4: HIV positive CD4<200 delayed (6 months) vaccination Group 5: HIV negative In part II of the study the investigators will evaluate the effect of a second pneumococcal vaccination, which is presently recommended, in HIV positive individuals, to be received 5 years after the first vaccination. Again, only those HIV positive individuals who are due for their second pneumovax will be asked to participate. They will be grouped according to their CD4 counts as CD4 >500 or CD4 200-500. Thus ALL HIV positive individuals will receive the vaccine as recommended.

The HIV positive volunteers solely agree to;

1. Donate blood specimens at 3 different occasions: day 0, day of vaccination: 2 mL, at day 7, 40 mL and at day 28-42 a one time sample of 2 mL.
2. Have their blood samples subjected to antibody analysis (concentration and functional activity) and antibody gene usage analysis There will be 2 HIV positive groups: CD4>500 and CD4 count 200-500. There will be 19 individuals per group.

The HIV negative controls in Part II of the study who agree to participate will be recruited from the population of individuals previously vaccinated with pneumovax. They will also be vaccinated for the second time with the pneumococcal vaccine, 5 years after the first vaccination. This is NOT a vaccine recommended for healthy adults but is NOT contra-indicated. Thus as part of the experimental procedure for these individuals they will:

1. Receive the FDA approved pneumococcal vaccine
2. Blood samples will be obtained at day 0: 2 mL, day 7 40 mL and day 28-42 one time sample of 2 mL.
3. Blood samples will be analyzed for antibody concentration, functional activity and gene family usage.

In summary, we will study 3 groups in Part II of the study Group 6: HIV positive CD4>500, 2nd PPV Group 7: HIV positive CD4 200-500, 2nd PPV Group 8: HIV negative, 2nd PPV.

Inclusion Criteria:

• HIV negative:
• never immunized with PPV23
• HIV positive:
• need for PPV23 per standard of care

Exclusion Criteria:

• steroid use
• other immunosuppressive agents;
• pregnancy
• incapable of completing consent form