Patients With HIV at Higher Risk for COVID Breakthrough Infections

Patients with HIV who were fully vaccinated against COVID-19 were more likely to develop a breakthrough infection, according to a study of the Corona-Infectious-Virus Epidemiology Team (CIVET)-II cohort.

Among nearly 114,000 fully vaccinated patients, those with HIV had a 28% higher risk of breakthrough infection compared with those without HIV (adjusted hazard ratio [aHR] 1.28, 95% CI 1.19-1.37), with rates of 55 versus 43 cases per 1,000 person-years, reported Keri Althoff, PhD, MPH, of the Johns Hopkins Bloomberg School of Public Health in Baltimore, and colleagues.

Although the cumulative incidence of breakthrough infections was low at 9 months post-vaccination (3.8%), suggesting a strong protective effect, it was greater for those with HIV than for those without it (4.4% vs 3.5%, P<0.001), regardless of vaccine type, the authors wrote in JAMA Network Open.

"These findings should alert all people with HIV to their greater risk of COVID-19 breakthrough, and can inform official recommendations about COVID-19 vaccination for people with HIV," Althoff told MedPage Today.

Overall, risk of breakthrough infections was greatest with the Johnson & Johnson vaccine (5.7%), followed by the Pfizer-BioNTech (4.4%) and Moderna vaccines (2.8%).

Certain factors were associated with this greater risk, such as younger age (≤44) and not receiving an additional vaccine dose. Moreover, having a history of COVID-19 was linked to a nearly twofold increased risk (aHR 1.96, 95% CI 1.65-2.33).

Breakthrough infections can provide evidence on the utility of the vaccines, Althoff's group noted. However, prior reports have not consistently shown a greater risk of breakthrough infections among HIV patients.

"Currently, the CDC includes people with untreated or advanced (i.e., CD4 <200 cells/mm³) HIV in their definition of people 'moderately or severely immunocompromised' and recommends an additional vaccine dose in their primary series, in addition to boosters," Althoff said. "Our findings suggest those with HIV who do not meet these criteria may also benefit from an additional vaccine dose in the primary series."

"Policymakers who establish the guidelines should consider the benefits and risks of an additional dose of vaccine in the primary series not only for those with severe or untreated HIV, but also include those with moderate immune suppression or even all persons with HIV," said co-author Sally Coburn, PhD, MPH, also of the Johns Hopkins Bloomberg School of Public Health, in a press release.

For this study, Althoff and colleagues examined data on 113,994 adults (33,029 with HIV and 80,965 without HIV) who were fully vaccinated against COVID-19 with approved vaccines -- two doses of mRNA vaccines or one dose of the Johnson & Johnson vaccine -- before June 30, 2021. The group used the CIVET II cohort, which includes four prospective electronic health record-based cohorts from integrated health systems and academic health centers.

Follow-up occurred through December 2021. The authors adjusted for demographics, primary vaccine series type, timing of third dose, and an interaction between history of COVID-19 and 3-month calendar periods (January-March, April-June, July-September, and October-December).

Nearly all patients were men, 70% were ages 55 and up, 41% were Black, and 38% were white. Most received mRNA vaccines (93%). One-quarter of HIV patients had a history of AIDS prior to vaccination, but most (91%) reached viral suppression once fully vaccinated.

Althoff and colleagues found a lower risk of breakthrough infections among older patients (ages 55 and up), suggesting that this may be due to behavioral modifications, "including adoption of masking and social distancing."

Notably, a high CD4 count (500 vs <200 cells/mm³ ) was linked to fewer breakthrough infections among HIV patients (aHR 0.66, 95% CI 0.50-0.88). No relationship was seen for HIV viral suppression.

The authors acknowledged that their findings may not be generalizable to all HIV patients or those without regular healthcare access. Furthermore, comorbidities were not accounted for and could affect the risk of breakthrough infections. The study occurred during circulation of the Alpha, Delta, and Omicron variants, they noted.

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