Publications

OBJECTIVES

HIV-infected controllers have provided novel insights into mechanisms of viral control. We investigated the degree to which HIV DNA and RNA are present in gut-associated lymphoid tissue (GALT) of controllers.

DESIGN

Cross-sectional cohort study.

METHODS

Colorectal biopsy pieces were obtained from five untreated noncontrollers, five ART-suppressed patients, and nine untreated controllers.

RESULTS

Rectal HIV DNA was lower in controllers (median 496 copies/10(6) CD4 T cells) than in untreated noncontrollers (117483 copies/10(6) CD4+ T cells, P = 0.001) and ART-suppressed patients (6116 copies/10(6) CD4 T cells, P = 0.004). Similarly, rectal HIV RNA was lower in controllers (19 copies/10(6) CD4 T cells) than in noncontrollers (15210 copies/10(6) CD4+ T cells, P = 0.001) and ART-suppressed patients (1625 copies/10(6) CD4+ T cells, P = 0.0599). Rectal HIV RNA/DNA ratios were not statistically different between the three groups.

CONCLUSION

Despite being able to maintain very low plasma HIV RNA levels in the absence of antiretroviral therapy (ART), HIV-infected controllers have readily measurable levels of HIV DNA and RNA in GALT. As expected, controllers had lower rectal HIV DNA and RNA compared with untreated noncontrollers and ART-suppressed individuals. Compared with the mechanisms of 'natural' viral control of controllers, long-term ART does not reduce the total HIV reservoir to the level of controllers.

OBJECTIVE

To assess whether CD8 T-cell activation predicts risk of AIDS and non-AIDS morbidity during suppressive antiretroviral treatment (ART).

DESIGN

Post-hoc analyses of ART-naive participants in prospective ART studies. Participants with HIV-RNA levels 200 copies/ml or less and CD8 T-cell activation data (%CD38HLA-DR) at year-1 of ART were selected to determine years 2-5 incidence of AIDS and non-AIDS events.

METHODS

We censored data at time of ART interruption or virologic failure. Inverse probability of censoring-weighted logistic regression was used to correct for informative censoring.

RESULTS

We included 1025 participants; 82% were men, median age 38 years, pre-ART CD4 cell count 255 cells/μl, and year-1-activated CD8 T cells 24%. Of these, 752 had 5 years of follow-up; 379 remained on ART and had no confirmed plasma HIV-RNA more than 200 copies/ml. The overall probability of an AIDS or non-AIDS event in years 2-5 was estimated at 13% [95% confidence interval (CI) 10-15%] had everyone remained on suppressive ART. Higher year-1-activated CD8 T-cell percentage increased the probability of subsequent events [odds ratio 1.22 per 10% higher (95% CI 1.04-1.44)]; this effect was not significant after adjusting for age. Among those age 50 years at least (n=108 at year 1), the probability of an event in years 2-5 was 37% and the effect of CD8 T-cell activation was more apparent (odds ratio=1.42, P=0.02 unadjusted and adjusted for age).

CONCLUSION

CD8 T-cell activation is prognostic of clinical events during suppressive ART, although this association is confounded by age. The consequences of HIV-associated immune activation may be more important in patients 50 years and older.

A real-time wireless electronic adherence monitor (EAM) and weekly self-report of missed doses via interactive voice response (IVR) and short message service (SMS) queries were used to measure antiretroviral therapy adherence in 49 adults and 46 children in rural Uganda. Median adherence was 89.5% among adults and 92.8% among children by EAM, and 99-100% for both adults and children by IVR/SMS self-report. Loss of viral suppression was significantly associated with adherence by EAM (odds ratio 0.58 for each 10% increase), but not IVR/SMS. Wireless EAM creates an exciting opportunity to monitor and potentially intervene with adherence challenges as they are happening.

We compared the plasma viromes of HIV-infected subjects with low versus high CD4(+) T cell counts from the United States and Uganda by using deep sequencing and detected HIV, hepatitis C virus, hepatitis B virus, GB virus C, anellovirus, and human endogenous retrovirus (HERV) reads. An increase in the proportion of reads for anelloviruses, a family of highly prevalent and genetically diverse human viruses, was seen in subjects with AIDS from both countries. The proportion of endogenous human retrovirus reads was increased in AIDS subjects from Uganda but not the United States. Progression to AIDS is therefore associated with changes in the plasma concentration of commensal viruses.