Publications

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.

OBJECTIVE

To determine whether earlier initiation of antiretroviral therapy (ART) is associated with better economic outcomes.

DESIGN

Prospective cohort study of HIV-positive patients on ART in rural Uganda.

METHODS

Patients initiating ART at a regional referral clinic in Uganda were enrolled in the Uganda AIDS Rural Treatment Outcomes study starting in 2005. Data on labor force participation and asset ownership were collected on a yearly basis, and CD4 cell counts were collected at pre-ART baseline. We fitted multivariable regression models to assess whether economic outcomes at baseline and in the 6 years following ART initiation varied by baseline CD4 cell count.

RESULTS

Five hundred and five individuals, followed up to 6 years, formed the estimation sample. Participants initiating ART at CD4 cell count at least 200 cells/μl were 13 percentage points more likely to be working at baseline (P < 0.01, 95% confidence interval 0.06-0.21) than those initiating below this threshold. Those in the latter group achieved similar labor force participation rates within 1 year of initiating ART (P < 0.01 on the time indicators). Both groups had similar asset scores at baseline and demonstrated similar increases in asset scores over the 6 years of follow-up.

CONCLUSION

ART helps participants initiating therapy at CD4 cell count below 200 cells/μl rejoin the labor force, though the findings for participants initiating with higher CD4 cell counts suggests that pretreatment declines in labor supply may be prevented altogether with earlier therapy. Baseline similarities in asset scores for those with early and advanced disease suggest that mechanisms other than morbidity may help drive the relationship between HIV infection and economic outcomes.