Impact of Human Immunodeficiency Virus on the Burden and Severity of Influenza Illness in Malawian Adults: A Prospective Cohort and Parallel Case-Control Study

Abstract

Background: The impact of human immunodeficiency virus (HIV) infection on influenza incidence and severity in adults in sub-Saharan Africa is unclear. Seasonal influenza vaccination is recommended for HIV-infected persons in developed settings but is rarely implemented in Africa.

Methods: We conducted a prospective cohort study to compare the incidence of laboratory-confirmed influenza illness between HIV-infected and HIV-uninfected adults in Blantyre, Malawi. In a parallel case-control study, we explored risk factors for severe influenza presentation of severe (hospitalized) lower respiratory tract infection, and mild influenza (influenza-like illness [ILI]).

Results: The cohort study enrolled 608 adults, of whom 360 (59%) were HIV infected. Between April 2013 and March 2015, 24 of 229 ILI episodes (10.5%) in HIV-infected and 5 of 119 (4.2%) in HIV-uninfected adults were positive for influenza by means of polymerase chain reaction (incidence rate, 46.0 vs 14.5 per 1000 person-years; incidence rate ratio, 2.75; 95% confidence interval, 1.02-7.44; P = .03; adjusted for age, sex, household crowding, and food security). In the case-control study, influenza was identified in 56 of 518 patients (10.8%) with hospitalized lower respiratory tract infection, and 88 or 642 (13.7%) with ILI. The HIV prevalence was 69.6% and 29.6%, respectively, among influenza-positive case patients and controls. HIV was a significant risk factor for severe influenza (odds ratio, 4.98; 95% confidence interval, 2.09-11.88; P < .001; population-attributable fraction, 57%; adjusted for season, sanitation facility, and food security).

Conclusions: HIV is an important risk factor for influenza-associated ILI and severe presentation in this high-HIV prevalence African setting. Targeted influenza vaccination of HIV-infected African adults should be reevaluated, and the optimal mechanism for vaccine introduction in overstretched health systems needs to be determined.

Figure 1.

Eligibility criteria for cohort study. Abbreviations: HIV, human immunodeficiency virus; QECH, Queen Elizabeth Central Hospital.

Figure 2.

Eligibility criteria for case-control study. Abbreviations: ILI, influenzalike illness; LRTI, lower respiratory tract infection.

Figure 3.

Recruitment and progress of cohort participants. Flow diagram for recruitment, loss to follow-up, and influenza-like illness events among cohort participants. Reasons for ineligibility included intention to relocate out of Blantyre (n = 10), inability to attend regular study visits (n = 6), inability to give written informed consent (n = 1), evidence of active acute respiratory disease at enrollment (n = 17), and enrollment of another household member in the study (n = 2). Reasons for declining consent included not having time (n = 3), not interested (n = 2), fear of participation (n = 4), and wished to seek spouse’s consent (n = 2). Abbreviations: HIV, human immunodeficiency virus; ILI, influenzalike illness; PCR, polymerase chain reaction; PYFU, person-years follow-up.

Figure 4.

Case-control study recruitment. Abbreviations: ILI, influenza-like illness; LRTI, lower respiratory tract infection.