HIV persists in lung macrophages of people on suppressive ART

HIV could be detected in lung alveolar macrophages of antiretroviral-naive people as well as people taking partially or completely suppressive antiretroviral therapy. HIV frequency in macrophages did not correlate with plasma viral load. [1]

HIV persistence in cellular and tissue reservoirs despite suppression in plasma with combination antiretroviral therapy is a well-appreciated phenomenon.

Because HIV-infected alveolar macrophages can be detected in bronchoalveolar lavage samples from antiretroviral-naive people with HIV, researchers in Malawi, the UK, and the US conducted a three-way comparison study, postulating that lung macrophages could be an HIV reservoir.

The researchers recruited HIV positive and negative people at the Queen Elizabeth Central Hospital in Blantyre, Malawi. The study involved 5 HIV negative adults, 12 HIV positive antiretroviral-naive adults, and 37 adults taking combination antiretroviral therapy.

Twenty-seven treated people were taking a first-line regimen of nevirapine, stavudine, and lamivudine, and 10 were taking first-line efavirenz, tenofovir, and lamivudine.

The researchers collected bronchoalveolar lavage and blood samples from all participants. They used flow cytometry, immunophenotyping, and fluorescence in situ hybridization (FISH) to identify HIV-infected alveolar macrophages in lavage samples. The investigators divided study participants into HIV negative (2 men and 3 women), antiretroviral-naive (3 men and 9 women), antiretroviral experienced for under 4 years (6 men and 16 women), and antiretroviral experienced for 4 years of more (6 men and 9 women).

Ages in those four groups averaged 29.6, 28.5, 31.5, and 37.0, and CD4 counts averaged 657, 336, 459, and 428. The group with fewer than 4 years experience had taken antiretrovirals for an average 1.4 years (range 0.3 to 3.9), and the group with 4 or more years experience had been treated for an average 6.1 years (range 4.0 to 8.9).

All antiretroviral-naive people had a detectable viral load. Among people with treatment experience, 6 (27%) with fewer than 4 years experience, and 4 (27%) with 4 or more years experience had a detectable viral load. Viral loads averaged 216,852 copies in the naive group, 14,939 copies in the group with under 4 years of treatment, and 4812 copies in the group with 4 or more years of therapy.

HIV-infected alveolar macrophages could be detected in everyone with HIV infection at the following frequencies:

HIV-infected macrophage frequency did not correlate with HIV RNA in plasma (r = 0.005, p = 0.67).

The researchers concluded that “HIV persists in alveolar macrophages during potent ART,” a finding “implying that the lung may be an important reservoir of HIV.” They suggested that “understanding the formation and maintenance of this viral reservoir could provide important clues for the development of strategies to clear HIV from latently infected host cells.”

Comment

It is unclear from this report why the results were not presented separately for people who had undetectable viral load on ART. This information would have the most important significance.

Average results when both treatment groups included people with ongoing replication appear to miss the main area of interest, namely the degree to which optimal ART may impact on this site.

Similar findings in breast milk suggests that macrophages may be another long lived and difficult to eradicate reservoir, in addition to latently infected memory CD4+ T cells.

Mwandumba HC, Jambo KC, Banda DH, et al. Persistence of HIV in alveolar macrophages during antiretroviral therapy. ICAAC 2014. September 5-9, 2014. Washington, DC. Abstract H-1636.