Publications

Despite a poor toxicity profile, zidovudine supersedes abacavir (ABC) as an alternative first-line agent in most international treatment guidelines because of concerns about HLA-B*57:01-related ABC-hypersensitivity. We detected one case of HLA-B*57:01 carriage among 513 HIV-infected individuals in Uganda, which, in combination with previous reports, supports the safety of ABC in the region.

BACKGROUND

The World Health Organization defines HIV virologic failure as 2 consecutive viral loads >1000 copies/mL, measured 3-6 months apart, with interval adherence support. We sought to empirically evaluate these guidelines using data from an observational cohort.

SETTING

The Uganda AIDS Rural Treatment Outcomes study observed adults with HIV in southwestern Uganda from the time of antiretroviral therapy (ART) initiation and monitored adherence with electronic pill bottles.

METHODS

We included participants on ART with a detectable HIV RNA viral load and who remained on the same regimen until the subsequent measurement. We fit logistic regression models with viral resuppression as the outcome of interest and both initial viral load level and average adherence as predictors of interest.

RESULTS

We analyzed 139 events. Median ART duration was 0.92 years, and 100% were on a nonnucleoside reverse-transcriptase inhibitor-based regimen. Viral resuppression occurred in 88% of those with initial HIV RNA <1000 copies/mL and 42% if HIV RNA was >1000 copies/mL (P <0.001). Adherence after detectable viremia predicted viral resuppression for those with HIV RNA <1000 copies/mL (P = 0.011) but was not associated with resuppression for those with HIV RNA >1000 copies/mL (P = 0.894; interaction term P = 0.077).

CONCLUSIONS

Among patients on ART with detectable HIV RNA >1000 copies/mL who remain on the same regimen, only 42% resuppressed at next measurement, and there was no association between interval adherence and viral resuppression. These data support consideration of resistance testing to help guide management of virologic failure in resource-limited settings.

BACKGROUND

A low proportion of CD28CD8 T cells that express CD57 is associated with increased mortality in HIV infection. The effect of increasing body mass index (BMI) changes in the proportion of CD57CD28CD8 T cells among HIV-infected individuals on antiretroviral therapy is unknown.

SETTING

In a US cohort of HIV-infected women, we evaluated associations of BMI and waist circumference with 3 distinct CD8 T cell phenotypes: % CD28CD57CD8 T cells, % CD57 of CD28CD8 T cells, and % CD28 of all CD8 T cells.

METHODS

Multivariable linear regression analysis was used to estimate beta coefficients for each of 3 T-cell phenotypes. Covariates included HIV parameters (current and nadir CD4, current viral load), demographics (age, race, income, and study site), and lifestyle (tobacco and alcohol use) factors.

RESULTS

Of 225 participants, the median age was 46 years and 50% were obese (BMI >30 m/kg). Greater BMI and waist circumference were both associated with higher % CD28CD57CD8 T cells and % CD57 of all CD28CD8 T cells in multivariable analysis, including adjustment for HIV viral load (all P < 0.05). The association between greater BMI and the overall proportion of CD28 CD8 cells in fully adjusted models (0.078, 95% confidence interval: -0.053 to 0.209) was not significant.

CONCLUSIONS

In this analysis, greater BMI and waist circumference are associated with greater expression of CD57 on CD28CD8 T cells and a greater proportion of CD57CD28 CD8 T cells. These findings may indicate that increasing BMI is immunologically protective in HIV-infected women. Future research is needed to understand the prognostic importance of these associations on clinical outcomes.