Pneumococcal vaccines

Invasive pneumococcal disease (IPD) in HIV-infected persons is a significant cause of morbidity and mortality ¹⁸. Even with improved and increased access to universal ART in South Africa, the relative risk of having IPD among HIV-infected individuals is 35-100 times more than HIV-negative individuals ^{19,18,19,20,21}. Available evidence from Africa suggests that pneumococcal conjugate vaccines (PCV) are effective against the vaccine-type pneumococcal disease when given to HIV-infected adults ^{19, 20}. In South Africa, PCV has been included in the routine childhood immunisation programme since 2009. Early post-vaccine impact data from South Africa showed a 40% reduction in vaccine type IPD over non-vaccine type IPD in HIV-infected adults, indicating that there is some indirect protection to unvaccinated adults²².

However, with such a high burden of disease in the HIV-infected population there is a need to consider additional or complementary strategies to prevent pneumococcal disease in HIV-infected adults. An example would be a combination vaccine strategy of the 13-valent pneumococcal conjugate vaccine (PCV13) and 23-valent pneumococcal polysaccharide vaccine (PPV23). This directly increases protection to serotypes that are in PPV23 but not in PCV13.

Broadly, there are two types of vaccines available for use to prevent pneumococcal disease: the pneumococcal polysaccharide vaccines (PPV) and the pneumococcal conjugate vaccines (PCV). The PPV23 is protective against all-cause pneumonia and pneumococcal disease in HIV-infected adults, although data vary as to whether the protective benefit is irrespective of CD4+ count above a particular threshold or dependent on HIV viral load at time of vaccination ²³. Results from a randomised placebo-controlled trial of PPV in HIV-infected subjects conducted in Uganda found an increase in all-cause pneumonia in the vaccine arm²⁴. As a result, some international guidelines do not recommend vaccination with PPV among HIV-infected adults with CD4+ counts less than 200 cells/μL. The immunological and clinical efficacy of PPV23 for HIV-infected adults, particularly in the absence of ART, remains controversial ¹⁹.

A randomised double-blind placebo-controlled trial of PCV 7 in HIV-infected adults in Malawi showed the vaccine was protective against recurrent IPD ¹⁹. Other studies have confirmed the safety and immunogenicity of PCV 13 in HIV-infected adults ²⁰. The use of PCV in HIV-infection is supported by studies showing prevention of pneumococcal pneumonia in children, and prevention of recurrent IPD in adults ²⁵.

The use of either PCVs or PPVs will be a balance between the resources available to pay for the vaccine and the evidence to support the use of either of the vaccines or even a combination. The evidence suggests that the burden of pneumococcal disease is high in HIV-infected individuals and vaccination against pneumococcal disease is an important strategy to reduce this ²⁶. Globally, different advisory committees on vaccination differ in their recommendations for vaccination against pneumococcus ²⁷. As an example, the United States Advisory Committee on Immunisation Practices (ACIP) and Infectious Diseases Society of America (IDSA) guidelines recommend PCV13 followed by PPV23 in HIV-infected adults; however the evidence supporting this is limited ²⁵. In contrast, the British guideline recommends vaccination with PCV13 only, irrespective of CD4+ count, viral load or ART use ²⁸. Available evidence suggests that the use of PPV23 or PCV13 is safe in HIV-infected individuals on ART or with a CD4+ count greater than 200 cells/μL^8,29.

Vaccination against pneumococcal disease should be recommended for all HIV-infected individuals regardless of CD4+ count, but ideally when HIV viral load is < 1000 copies/mL ²⁹. This guideline supports the prime-boost immunisation approach of first vaccinating with PCV13 followed by PPV23 eight weeks later. Alternatively, PCV13 can be used on its own if available. For those who are to receive PPV23 as the primary vaccine it is suggested that the PPV23 vaccine be given to those who have achieved ART-driven virologic suppression, regardless of the CD4+ count.