HIV-1 and bacterial pneumonia in the era of antiretroviral therapy

Abstract

Community-acquired pneumonia affects approximately 4 million people in the United States, with 40,000 deaths per year. The incidence is increased about 35-fold in HIV-infected individuals, and this rate has decreased since the antiretroviral era has begun. Bacterial pneumonia has decreased from 5 to 20 cases per 100 person-years to less than 1 to 5 cases per 100 person-years in the era of antiretroviral therapy. HIV-1 infection impairs the function of neutrophils in the lung and infects CD4⁺ cells and alveolar macrophages. Opportunistic infections dramatically increase local HIV replication in the lung cells, especially alveolar macrophages and CD4⁺ cells. This enhanced replication increases viral mutations and provides opportunities for viral escape from latent reservoirs. Mortality is increased with more comorbidities in this highly susceptible population. Immunization with vaccines is recommended, especially pneumococcal vaccines, although the vaccine itself may stimulate viral replication. Recent studies show that the lower respiratory tract is a microbial reservoir in HIV-infected individuals rather than being a sterile environment, as originally thought. This may provide new opportunities for preventing opportunistic infections in HIV-infected subjects. Bacterial pneumonia presents an ongoing challenge in these high-risk individuals, particularly in studying the functions of the innate and acquired immune response.

Figure 1.

Representative CT scan showing a right upper lobe infiltrate corresponding to a bacterial pneumonia in an HIV-infected patient.

Figure 2.

Quantitative PCR with molecular beacons of nasal brushing, endobronchial brushing, and bronchoalveolar lavage (BAL). Universal primers for bacterial 16S rDNA. The location of brushing is shown on the x axis. The brushes were placed in lysozyme solution and incubated at 65°C for 30 minutes followed by the addition of sodium dodecyl sulfate and proteinase K. The BAL was kept on ice and spun at low speed, followed by separation of fluid from the cell pellet. Aliquots of BAL fluid (200 μl) were then incubated in sodium dodecyl sulfate and proteinase K for 12 hours at 65°C. DNA was extracted from 100,000 BAL cells. In all samples, 2.5% of a 200 μl extract were used in the quantitative PCR reactions.

Figure 3.

Bacterial rDNA sequence analysis and amount from lung cells and BAL fluid of three patients with HIV from the longitudinal cohort. All had normal BAL cell differentials and chest radiographs.