Publications

INTRODUCTION

Infection with HIV subtype A has been associated with poorer neurocognitive outcomes compared to HIV subtype D in Ugandan children not eligible for antiretroviral therapy (ART). In this study, we sought to determine whether subtype-specific differences are also observed among children receiving ART.

MATERIALS AND METHODS

Children were recruited from a clinical trial in which they were randomized to receive either lopinavir (LPV)- or non-nucleoside reverse transcriptase inhibitor (NNRTI)- based ART (NCT00978068). Age at initiation of ART ranged from six months to six years. HIV subtype was determined by PCR amplification and population sequencing of the pol region derived from peripheral blood mononuclear cell DNA, followed by application of the REGA and Recombinant Identification Programme algorithms. General cognition was assessed using the Kaufman Assessment Battery for Children (Second Edition), attention using the Test of Variables of Attention, and motor skills using the Bruininks-Oseretsky Test of Motor Proficiency (Second Edition). Home environment was assessed using the Home Observation for the Measurement of the Environment (HOME). Age-adjusted test z-scores were entered into a regression model that adjusted for sex, socio-economic status score, HOME score, years of schooling, and ART treatment type.

RESULTS

One hundred and five children were tested; median (interquartile range) age was 7.05 years (6.30 to 8.44), CD4 count was 867.7 cells/mm (416.0 to 1203.5), and duration on ART was 4.03 years (3.55 to 4.23). Seventy-eight children had HIV subtype A and 27 had subtype D; the groups had comparable home and socio-economic status, except that there were more males among children infected with subtype A than D (64.7% vs. 35.3%, p = 0.02). There were no differences between the subtypes in general cognition (estimated mean difference: 0.20; 95% CI: -0.11 to 0.50); p = 0.21), attention (-0.18, 95% CI: -0.60 to 0.24, p = 0.41) and motor skills (1.60, 95% CI: -0.84 to 4.04, p = 0.20).

CONCLUSIONS

Our results imply that ART may diminish the neurocognitive disadvantage seen in treatment-naïve HIV-infected children with subtype A.

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.