In most HIV-infected patients with prior antiretroviral therapy, the combination of indinavir, zidovudine, and lamivudine reduces levels of HIV RNA to less than 500 copies per milliliter for as long as one year.

Rationale: Before the introduction of combination antiretroviral (ARV) therapy, patients infected with HIV had an increased prevalence of respiratory symptoms and lung function abnormalities. The prevalence and exact phenotype of pulmonary abnormalities in the current era are unknown. In addition, these abnormalities may be underdiagnosed. Objectives: Our objective was to determine the current burden of respiratory symptoms, pulmonary function abnormalities, and associated risk factors in individuals infected with HIV. Methods: Cross-sectional analysis of 167 participants infected with HIV who underwent pulmonary function testing. Measurements and Main Results: Respiratory symptoms were present in 47.3% of participants and associated with intravenous drug use (odds ratio [OR] 3.64; 95% confidence interval [CI], 1.32-10.046; P 5 0.01). Only 15% had previous pulmonary testing. Pulmonary function abnormalities were common with 64.1% of participants having diffusion impairment and 21% having irreversible airway obstruction. Diffusion impairment was independently associated with ever smoking (OR 2.46; 95% CI, 1.16-5.21; P 5 0.02) and Pneumocystis pneumonia prophylaxis (OR 2.94; 95% CI, 1.10-7.86; P 5 0.01), whereas irreversible airway obstruction was independently associated with pack-years smoked (OR 1.03 per pack-year; 95% CI, 1.01-1.05; P , 0.01), intravenous drug use (OR 2.87; 95% CI, 1.15-7.09; P 5 0.02), and the use of ARV therapy (OR 6.22; 95% CI, 1.19-32.43; P 5 0.03). Conclusions: Respiratory symptoms and pulmonary function abnormalities remain common in individuals infected with HIV. Smoking and intravenous drug use are still important risk factors for pulmonary abnormalities, but ARV may be a novel risk factor for irreversible airway obstruction. Obstructive lung disease is likely underdiagnosed in this population.Keywords: HIV; respiratory function tests; smoking; antiretroviral therapy, highly active; AIDS Pulmonary complications have been a major cause of morbidity and mortality in patients with HIV infection (1, 2). With the development of combination antiretroviral (ARV) therapy and improvements in prophylaxis for Pneumocystis pneumonia (PCP) and other opportunistic infections, the incidence of infectious pulmonary complications has decreased drastically in patients with HIV infection (1, 3, 4). Changes in noninfectious pulmonary complications, such as chronic obstructive pulmonary disease (COPD) and asthma, are less clear, and these diseases may actually be increasing. Studies before the introduction of combination ARV demonstrated that persons with HIV infection had a higher prevalence of impaired diffusing capacity for carbon monoxide (DL CO ), increased emphysema, accelerated airway obstruction and small airways disease, and more frequent respiratory symptoms than subjects not infected with HIV (2, 5-8).Limited data exist regarding the extent and types of pulmonary function abnormalities in the current era. In one recent study, veterans with HIV infection had an increased risk of COPD compared wi...

Persistent latent reservoir of replication-competent proviruses in memory CD4 T cells is a major obstacle to curing HIV infection. Pharmacological activation of HIV expression in latently infected cells is being explored as one of the strategies to deplete the latent HIV reservoir. In this study, we characterized the ability of romidepsin (RMD), a histone deacetylase inhibitor approved for the treatment of T-cell lymphomas, to activate the expression of latent HIV. In an in vitro T-cell model of HIV latency, RMD was the most potent inducer of HIV (EC50 = 4.5 nM) compared with vorinostat (VOR; EC50 = 3,950 nM) and other histone deacetylase (HDAC) inhibitors in clinical development including panobinostat (PNB; EC50 = 10 nM). The HIV induction potencies of RMD, VOR, and PNB paralleled their inhibitory activities against multiple human HDAC isoenzymes. In both resting and memory CD4 T cells isolated from HIV-infected patients on suppressive combination antiretroviral therapy (cART), a 4-hour exposure to 40 nM RMD induced a mean 6-fold increase in intracellular HIV RNA levels, whereas a 24-hour treatment with 1 µM VOR resulted in 2- to 3-fold increases. RMD-induced intracellular HIV RNA expression persisted for 48 hours and correlated with sustained inhibition of cell-associated HDAC activity. By comparison, the induction of HIV RNA by VOR and PNB was transient and diminished after 24 hours. RMD also increased levels of extracellular HIV RNA and virions from both memory and resting CD4 T-cell cultures. The activation of HIV expression was observed at RMD concentrations below the drug plasma levels achieved by doses used in patients treated for T-cell lymphomas. In conclusion, RMD induces HIV expression ex vivo at concentrations that can be achieved clinically, indicating that the drug may reactivate latent HIV in patients on suppressive cART.

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Decay of HIV-1 DNA in blood is rapid in the first year after ART initiation (86% decline), slows during years 1-4 (23% decline/year), and subsequently plateaus. HIV-1 DNA decay is not associated with the levels of CD8+ T-cell activation or persistent viremia. The determinants of stable HIV-1 DNA persistence require further elucidation. Clinical Trials Registration. NCT00001137.