Microalbuminuria in Perinatally HIV-Infected Children and Adolescents in the United States.

Background: The kidney is a common target for human immunodeficiency virus (HIV), making renal disease a common noninfectious complication of HIV. Microalbuminuria is an important marker that can detect early renal damage. Timely detection of microalbuminuria is important to initiate renal management and stop the progression of renal dysfunction in people with HIV. Limited data are available about renal abnormalities in people with perinatal HIV infection. The objective of this study was to determine the prevalence of microalbuminuria in a cohort of perinatally HIV-infected children and young adults receiving combination antiretroviral therapy and investigate correlations between microalbuminuria and clinical and laboratory findings. Methods: This was a retrospective study of 71 patients with HIV followed in an urban pediatric HIV clinic in Houston, Texas, between October 2007 and August 2016. Demographic, clinical, and laboratory data were compared between subjects with persistent microalbuminuria (PM) and those without. PM is defined as a microalbumin-to-creatinine ratio ≥30 mg/g on at least 2 occasions separated by at least 1 month. Results: Sixteen of 71 patients (23%) met the definition of PM. In univariate analysis, patients with PM had significantly higher CD8+ T-cell activation and lower CD4+ T-cell nadir. Multivariate analysis demonstrated increased microalbuminuria to be independently associated with older age and CD8+ T-cell activation measured as CD8+HLA-DR+ T-cell percentage. Conclusions: Older age and increased activation of CD8+HLA-DR+ on T cells correlate with presence of microalbuminuria in this cohort of HIV-infected patients.

CD31 Expression on CD4+ Cells: A Simple Method for Quantitation of Recent Thymus Emigrant CD4 Cells.

Measurements of CD4+CD31+ cells gave results consistent with those expected for recent thymus emigrant (RTE) CD4+ cells. The method was markedly simpler than established procedures for measurement of CD4+ RTE cells and is usable in locations with limited facilities and budgets.

Recent Thymus Emigrant CD4+ T Cells Predict HIV Disease Progression in Patients With Perinatally Acquired HIV.

BACKGROUND: Robust immune restoration in human immunodeficiency virus (HIV)-positive patients is dependent on thymic function. However, few studies have investigated thymic function and its correlation with disease progression over time in HIV-positive patients. METHODS: In this longitudinal prospective study, we followed 69 HIV-positive patients who were perinatally infected. Peripheral blood mononuclear cells were stained with monoclonal anti-CD4 and anti-CD31 and recent thymic emigrants (CD4+recently emigrated from the thymus (RTE), CD4+CD31+) quantified by flow cytometry. Statistical analysis used Wilcoxon rank sum test, Kruskal-Wallis, Spearman correlation, and Kaplan-Meier estimates; Cox regression models were performed for the longitudinal analysis. RESULTS: Median age of HIV positive patients enrolled was 13 years (interquartile range [IQR], 8.6). CD4+RTE% decreased with age and was higher in females. Median CD4+RTE% was 53.5%, IQR, 22.9. CD4+RTE% was closely related to CD4+% and absolute counts but independent of viral load and CD8+CD38+%. Antiretroviral compliance as well as higher nadir CD4+% were associated with higher CD4+RTE%. Low CD4+RTE% predicted poor progression of VL and CD4+% over time. CONCLUSIONS: CD4+RTE% predicts disease progression and may reflect history of disease in HIV-positive patients and adolescents. They are easy to measure in the clinical setting and may be helpful markers in guiding treatment decisions.

Incidence and predictors of antiretroviral resistance in perinatally HIV-1 infected children and adolescents.

OBJECTIVES: Individuals with perinatally acquired HIV infection have benefited from antiretroviral therapy. However, they often have complex patterns of major resistance mutations that limit the effectiveness of available antiretroviral medications. Knowledge of incidence rates of major antiretroviral resistance mutations should provide a benchmark enabling comparisons of different HIV care delivery modalities. METHODS: We test the hypothesis that incidence rate of major antiretroviral resistance mutations will decline with improvement in HIV care between 1998 and 2009 to NRTI, NNRTI, PI and triple class resistance in perinatally HIV infected individuals. Logistic regression is used to evaluate predictors of single and triple class resistance. RESULTS: Sixty-six individuals are included from a total population of 97 perinatally HIV infected individuals. The incidence rate of NRTI, NNRTI, PI and triple class resistance decreases with decreasing age in parallel with the introduction of new HIV treatment regimens. The youngest children (born 2000-2007) are free of triple class resistance. Mono-therapy associates with major resistance mutations to NRTI (OR 8.7, CI 1.5-50.9, P 0.02); NNRTI exposure associates with major resistance mutations to NNRTI (OR 24.4, CI 5.7-104.5, P 0.01) and triple class resistance (OR 10.7, CI 1.8-67.1, P 0.01). Cumulative viral load is an important predictor of PI resistance (OR 4.0, CI 1.3-12.3, P 0.02). CONCLUSIONS: There is a progressive decrease in the incidence rate of major resistance mutations to antiretroviral drugs and triple class resistance from the oldest to the youngest birth cohort; where adolescents have the highest risk of harboring resistant viruses. The incidence rate of major antiretroviral resistance mutations provides a benchmark for the comparative measurement of effectiveness of different HIV care delivery modalities.

Persistently high perinatal transmission of HIV: assessment of risk factors.

BACKGROUND: Despite dramatic decreases in rates of perinatal mother-to-child-transmission (PMTCT) of HIV in the United States, rates in some groups remain above the national average. Our objective was to examine factors contributing to a high rate of PMTCT of HIV. METHODS: We conducted a retrospective chart review of HIV-exposed infants and their mothers referred to the University of Texas-Houston Pediatric HIV Clinic from January 2000 to June 2007. RESULTS: Of 367 newborns studied, 22 (6%) acquired HIV infection perinatally. Associated risk factors included inadequate prenatal care, failure to receive antiretroviral therapy during pregnancy, detectable viral load and intravenous drug abuse. CONCLUSIONS: The composite rate of PMTCT in this high risk cohort was at least 3-fold higher than expected from the current standard of care. Reduction of rates of PMTCT in our population will require ensuring access to appropriate prenatal care, including delivery of antiretroviral therapy and addressing issues of illicit drug use.

Use of nucleoside reverse transcriptase inhibitor-only regimens in HIV-infected children and adolescents.

OBJECTIVE: In adults, nucleoside reverse transcriptase inhibitor-only antiretroviral regimens (NOARs) with ≥3 nucleoside reverse transcriptase inhibitors are less potent than highly active antiretroviral therapy (HAART). Published pediatric experience with NOARs is limited; thus, we wished to better define the virological, immunological and toxicological effects of NOARs in children and adolescents. METHODS: We analyzed data from NOAR-treated participants in LEGACY, a multicenter observational cohort study of HIV-infected children and adolescents. NOAR-treated case-participants were matched to participants without prior NOAR who initiated HAART during the same year for comparison. RESULTS: Of 575 participants with data from time of HIV diagnosis through 2006, 67 (12%) received NOARs for at least 24 weeks; most (46%) received the fixed dose combination of zidovudine/lamivudine/abacavir. NOAR use peaked in 2001 to 2002. NOAR-treated participants were significantly older and more treatment experienced than HAART-treated participants. Virologic outcomes, including the percentage of participants with a plasma HIV RNA viral load <400 copies/mL at week 24 (47% versus 34%) and the mean 24-week change in log10 plasma HIV RNA viral load from baseline (-0.63 versus -1.02), were similar between NOAR- and HAART-treated participants, but virologic rebound was more likely in NOAR-treated participants (77% versus 54%, P = 0.02). Increase in CD4 percentage points from baseline to 24 weeks was negligible in NOAR-treated participants compared with HAART-treated participants (0.95% versus 10.1%, P < 0.001). Anemia and leukopenia were more commonly reported with NOARs than HAART. DISCUSSION: Week 24 virologic outcomes were similar between NOAR- and HAART-treated participants, but NOAR durability was poorer and their use was associated with less immunologic reconstitution. NOARs should play a limited role in pediatric and adolescent antiretroviral therapy.

Prevalence and risk factors associated with resistance-associated mutations to etravirine in a cohort of perinatally HIV-infected children.

BACKGROUND: Etravirine is a second-generation non-nucleoside reverse transcriptase inhibitor (NNRTI) with reduced cross-resistance to first-generation NNRTIs. Because many perinatally HIV-infected patients have been treated with first-generation NNRTIs, they may have acquired resistance-associated mutations to etravirine (RAMe). METHODS: We determined for the interval 1998-2009 the prevalence and factors associated with the presence of RAMe. RESULTS: Twenty-three of 66 (34.8%) children had RAMe; the most common were 181C (19.6%), 190A (7.5%), 98G (6%), 106I (4.5%), 179D (4.5%), 100I (3%), 181I (1.5%), 138A (1.5%) and 179T (1.5%). Eleven children with RAMe (17%) had a mutation score between 2.5 and 3.5 and 1 (1.5%) a score ≥4, indicating an intermediate and reduced response to etravirine. For each 1% increase in CD4% there is a 7% decrease in the odds of RAMe (OR 0.93; 95% CI 0.88-0.97; P < 0.01). History of nevirapine use (OR 8.95; 95% CI 2.31-34.73; P < 0.01) and Hispanic ethnicity (OR 4.76; 95% CI 1.03-21.87; P = 0.04) are significantly associated with risk of RAMe. CONCLUSIONS: RAMe are present and common among antiretroviral-experienced perinatally HIV-infected children without previous exposure to etravirine. This could limit the efficacy of etravirine-based regimens. In addition, our results underscore the importance of taking previous history of nevirapine into account for combined antiretroviral therapy regimens that contain etravirine.