Publications

We conducted a longitudinal study of tobacco use among adults initiating antiretroviral therapy (ART) in Mbarara, Uganda where 11 % of men and 3 % of women use tobacco according to the 2011 Demographic and Health Survey. In a prospective cohort, self-reported tobacco use was assessed before starting ART and reassessed every 3-4 months. Plasma cotinine, a nicotine metabolite, was measured in a subset of adults pre-ART to verify self-report. Among 496 subjects, 50 (10 %) reported current tobacco use (20 % of men, 6 % of women). Most (53 %) adults with elevated cotinine levels (>15 ng/mL) reported no tobacco use. By 6 months after ART initiation, 33 % of tobacco users had quit (95 % CI 20-46 %). By 5 years, 64 % quit (95 % CI 47-77 %). Self-reported tobacco use among rural Ugandans starting ART was twice as common as among the local background population and use may be underreported. ART initiation could be an opportunity for tobacco cessation interventions.

PURPOSE OF REVIEW

It is now widely accepted that HIV-infected individuals remain at a higher risk for mortality and age-related morbidities than the general population, but several unresolved issues need to be addressed by the research community in the coming years to further improve the health of HIV-infected individuals in the modern treatment era.

RECENT FINDINGS

Although recent studies have helped to better define the contribution of HIV to life expectancy and morbidity in the modern antiretroviral therapy (ART) era, questions remain about the generalizability of these findings to a future HIV-infected population that is expected to be much older. Furthermore, although a consensus has emerged that the persistent inflammatory state contributes to morbidity and mortality in this setting, the relative contributions of this process, health-related behaviours, comorbidities and medication toxicities remain incompletely understood. Lastly, significant uncertainty remains over the root causes of the persistent inflammatory state, the specific immunologic pathways to target with interventions and the most appropriate biomarkers to use for surrogate outcomes in pilot trials of immune-based interventions.

SUMMARY

Each of these issues will be addressed in this review, highlighting recently published and presented studies that inform the discussion, and recommendations will be made for prioritizing the future research agenda.

Highly potent broadly neutralizing human monoclonal antibodies hold promise for HIV prophylaxis and treatment. We used the SCID-hu Thy/Liv and BLT humanized mouse models to study the efficacy of these antibodies, primarily PG16, against HIV-1 clades A, B, and C. PG16 targets a conserved epitope in the V1/V2 region of gp120 common to 70-80% of HIV-1 isolates from multiple clades and has extremely potent in vitro activity against HIVJR-CSF. PG16 was highly efficacious in SCID-hu mice as a single intraperitoneal administration the day before inoculation of R5-tropic HIV directly into their Thy/Liv implants and demonstrated even greater efficacy if PG16 administration was continued after Thy/Liv implant HIV inoculation. However, PG16 as monotherapy had no activity in humanized mice with established R5-tropic HIV infection. These results provide evidence of tissue penetration of the antibodies, which could aid in their ability to prevent infection if virus crosses the mucosal barrier.