15 Nov, 16 | by EBM
By Dr. Geoffrey Modest
There are 2 potentially very serious bacterial infections, both with functional vaccines available but not previously recommended, that seem to be more common in HIV infected patients: HIB (haemophilus influenzae type B) and meningococcus. The Advisory Committee on Immunization Practices, ACIP, just came out with recommendations to immunize HIV-positive patients against meningococcus.
- For the HIB infection: I had been immunizing all HIV patients with HIB vaccine until a few years ago, based on a case-control study about 20 years ago showing a higher prevalence of invasive HIB infections in HIV positive patients. Though the data on efficacy were lacking, it seemed to me that the potential benefit far outweighed the very low risk of this tried-and-true vaccine. The current feeling, from my reading, is that while HIV may be a risk factor for invasive HIB infections, the incidence of HIB infections overall has plummeted due to the aggressive HIB immunizations of children, dramatically decreasing the HIB reservoir and shifting the serotype of prevalent H flu infections dramatically away from typable to nontypables. So, it does seems unnecessary to immunize. But, it still may still be reasonable to vaccinate those patients who come from and return to countries without universal pediatric HIB immunization.
- Meningococcal vaccine: I also began immunizing my HIV patients with meningococcal conjugate vaccine several years ago, after the outbreak of meningococcal disease in HIV-positive people in New York, though I stopped a couple years ago because of strong and persistent statements by the CDC not to do so. The new recommendations, however, are that all HIV-infected persons be immunized pretty aggressively (see https://www.cdc.gov/mmwr/volumes/65/wr/mm6543a3.htm?s_cid=mm6543a3_x ).
- Those < 2 years old should get MenACWY-CRM (Menveo) at 2, 4, 6, and 12-15 months, or get MenACWY-D (Menactra) at ages 9-23 months and then 12 weeks later (with the caveats that this last one be given: only if >4 weeks after finishing the pneumococcal conjugate vaccine and either before or concomitantly with DTaP — see below)
- Those > 2 years old and not previously vaccinated should get a 2-dose primary series of the conjugate vaccine (either of the above), 8-12 weeks apart
- Those who had most recent vaccine dose < age 7 years should get a booster 3 years later, then every 5 years thereafter
- Those who had most recent vaccine dose > age 7 years should get a booster 5 years later, and every 5 years throughout life.
- The immunogenicity study (comparing a single vs a series of 2 vaccines in patients with CD4 percent>15%) noted serious adverse events in 2.2-6.5% six weeks post-vaccination, the number of adverse events being inversely related to CD4 percent, and only one of the serious adverse events (ocular pain) felt to be related to MenACWY-D. A study in kids aged 2-10 found 5% had a serious adverse event, but none felt to be attributable to the vaccine
- Overall, from a lifetime perspective, vaccination was calculated to lead to the prevention of approx 122 cases of meningococcal disease and 23 deaths, and 385 quality-adjusted life years (QALY) could be saved, with mean cost of $732,000 per QALY if the primary series of vaccines and lifelong boosters every 5 years were given.
- The risk of meningococcal infection in HIV patients, from data from the US, UK, and South Africa, is 5-13x that of non-HIV infected, with prevalence of 3.6-6.6 per 100,000, and with a case-fatality rate that is a bit mixed: those with HIV in South Africa had about twice the meningococcal case fatality rate (20% vs 11%), though this was not found in New York or the UK.
- The risk of meningococcal disease is higher in those with high viral loads or low CD4 counts, though the immunogenicity of the vaccine is about 50% lower in those with lower CD4 counts (i.e., better to wait until the CD4 increases in those with uncontrolled infections, though unclear exactly what the cut-point here is from the studies. The one study the MMWR quoted used the CD4 cutpoint of 200 from a New York study, finding a 5.3-fold increased risk with CD4<200). Similar risk in men and women.
- The majority of meningococcal infections in HIV-infected people are of serogroups A,C,W, and Y. One issue is that the largest database, the passive National Notifiable Diseases Surveillance System, does not include HIV status. The Active Bacterial Core surveillance (ABCs), a smaller database from 10 sites and representing 14% of the US population, does include HIV status. Based on these somewhat limited data, there were 62 cases of meningococcal disease in HIV-infected patients from 1995-2015, 13% were serogroup B and 10% were of unknown serotypes; 92% of cases were in people aged 20-59 years old
- They do note that the only licensed vaccine for those >55 years old is the meningococcal polysaccharide vaccine; they still recommend the MenACWY conjugate vaccine, based on limited data.
- The recommendations for infants 2-23 months are complex: they recommend the MenACWY-CRM and not the MenACWY-D because of potential immune interference with the PCV conjugate vaccine with the latter, as well as potential interference of DTaP with MenACWY-D if the MenACWY-D was given 30 days after the DTaP, but not if the 2 are given simultaneously or if the MenACWY-D is given first
- Ndata on efficacy or adverse events if meningococcal vaccine given during pregnancy or lactation
- So, the bottom line for me: I do plan to restart giving HIB vaccine to HIV-infected patients who are going back and forth to countries without routine HIB vaccination for kids (not CDC recommended, but makes sense to me). in addition, i will adopt the meningococcal conjugate vaccine according to the ACIP schedule above, including the booster immunization every 5 years, though i will wait until the CD4 increases to a level of >15% or until it plateaus at its highest CD4 percent (using the CD4 percent, as in the studies they quoted: there was no mention of the absolute CD4 count). I will also wait until the viral load is suppressed, since the limited data found a better response if the viral load was lower, in one of the studies if <400. The CDC does not mention anything about meningococcal serogroup B vaccination, but i would consider using the meningococcal B vaccine if there were a local outbreak of serogroup B infections (though my literature search revealed nothing on the immunogenicity or efficacy of that vaccine in HIV-positive patients).