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HAART associated with decreased pulmonary HIV burden
HAART may help decrease patients’ susceptibility to other infections.
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Highly active antiretroviral therapy was associated with significant decreases in pulmonary HIV burden and a return to normal alveolar cellular constituents in the lung.
Results from the first longitudinal study on the effect of HAART specifically in the lung may confirm that different responses to therapy occur in different tissue compartments. By returning the alveolar environment to normal, pulmonary immune functions can be improved and susceptibility to retroviruses and other opportunistic infections can be decreased. Study results appeared in The Journal of Infectious Diseases.
“We initially hypothesized the lung might be a protected site for HIV, but we found that it appears to respond well to HAART,” Homer L. Twigg, III, MD, associate professor of medicine and chief of the division of pulmonary, allergy, critical care and occupational medicine at Indiana University Medical Center, told Infectious Disease News. “As in other tissue compartments, HAART resulted in a dramatic decrease in the HIV viral load in the lung. However there seems to be greater immunologic reconstitution in the lung compared to other compartments such as the gastrointestinal tract.”
Physicians should be aware that improvement in pulmonary immunity associated with HAART may paradoxically present as symptoms of other infections.
“If patients have increased lung symptoms including fevers and coughs three to four weeks after starting HAART, it is possible that the newly restored immune cells are reacting to pre-existing infections. Ultimately, that is good,” Twigg said.
Patient selected
Protease inhibitor and nonnucleoside reverse transcriptase inhibitor (NNRTI)-naive patients with HIV (n=40) were selected to undergo bronchoscopy with bronchoalveolar lavage before and after HAART initiation. The longitudinal study was a multicenter perspective study by the AIDS Clinical Trials Group Protocol 723.
All patients were older than 18 years and had been free of respiratory tract infections for the past 30 days. Seventy-five percent of patients were men; 69% were smokers. Median age was 38 years. Median plasma HIV load at baseline was 75,000 copies/mL and median cluster designation (CD) 4 count at baseline was 203 cells/mcL.
Bronchoalveolar lavage fluid and samples were taken at baseline, four weeks and 24 weeks after therapy initiation. Bronchoscopy data for week 24 data were conducted at a median 168 days after HAART initiation.
Measurements of HIV RNA in acellular lavage and HIV RNA and DNA in bronchoalveolar lavage cells were compared with similar measurements in blood. Comparisons were made to determine the effect of HAART on pulmonary HIV and to determine vascular and pulmonary compartment response.
Viral burden in lungs
Twenty-nine patients completed the study. At week 24, 50% of patients’ plasma viral loads were below the lower limit of quantitation. Eighty-two percent reached the combined end point of a 1-log10 decrease in plasma viral load or undetectable levels.
HAART induced a rapid decrease in detectable HIV in acellular bronchoalveolar lavage fluid. Decreased HIV burden was also demonstrated by a decrease in HIV RNA and DNA loads in bronchoalveolar lavage cells.
HAART also was associated with a significant decrease in the percentage and the absolute number of CD8 alveolar lymphocytes. At 24 weeks, a correlation between residual bronchoalveolar lavage cell DNA and absolute number of CD4 lymphocytes in the alveolar space also was detected. – Kirsten H. Ellis
For more information:
- Twigg III HL, Weiden M, Valentine F, et al. Effect of highly active antiretroviral therapy on viral burden in the lungs of HIV-infected subjects. J Infect Dis. 2008;197;109-116.