Endothelial Activation, Innate Immune Activation, and Inflammation Are Associated With Postbronchodilator Airflow Limitation and Obstruction Among Adolescents Living With HIV.

BACKGROUND: Chronic inflammation, innate immune activation, T-cell imbalance and endothelial activation have been linked with lung diseases. We sought to determine whether markers of these pathophysiologic pathways were associated with spirometry and chest computed tomography (CT) abnormalities among adolescents living with HIV (ALWH). SETTING: Coptic Hope Center for Infectious Diseases in Nairobi, Kenya. METHODS: We performed a cross-sectional study of ALWH (10-19 years old). Participants underwent chest CT, spirometry, and venipuncture for serum biomarkers. We also collected demographic, anthropometric, T-cell subset, antiretroviral therapy, and exposure data. We compared characteristics and biomarkers by airflow obstruction [postbronchodilator FEV1/FVC z-score (zFEV1/FVC) < -1.64]. We used multivariable linear regression to determine associations of log10-transformed biomarkers and chest CT abnormalities with lower postbronchodilator zFEV1/FVC (airflow limitation). We performed exploratory principal components analysis on biomarkers, and determined associations of factors with postbronchodilator zFEV1/FVC and chest CT abnormalities. RESULTS: Of 47 participants with acceptable quality spirometry, 21 (45%) were female, median age was 13 years and 96% had perinatally-acquired HIV. Median CD4 was 672 cells/µL. Overall, 28% had airflow obstruction and 78% had a chest CT abnormality; airflow obstruction was associated with mosaic attenuation (P = 0.001). Higher endothelial activation (sVCAM-1, sICAM-1), inflammation and innate immune activation (serum amyloid-A, sTREM-1, sCD163), and T-cell imbalance (lower CD4/CD8) markers were associated with airflow limitation. Factors comprising endothelial and innate immune activation were associated with airflow limitation. CONCLUSIONS: Endothelial activation, innate immune activation, T-cell imbalance, and chronic inflammation are associated with airflow limitation and obstruction, providing insights into chronic lung disease pathophysiology among ALWH.

Cervical squamous intraepithelial lesions among HIV-positive women on antiretroviral therapy in Kenya.

BACKGROUND: The prevalence of cervical squamous intraepithelial lesions (SIL) among HIV-infected women on antiretroviral therapy in sub-Saharan Africa has not been well described. METHODS: HIV-infected women enrolled in an HIV treatment clinic in Nairobi, Kenya were offered free cervical screening with Papanicolaou (Pap) smear testing if they were 30 to 39 years of age and on antiretroviral therapy. Women with SIL were compared to those without SIL with univariate analyses and logistic regression. RESULTS: Of 595 eligible women, 267 accepted Pap testing and had available cytology results, of whom 258 (97%) were on a non-nucleoside reverse transcriptase inhibitor (NNRTI) based regimen. Median duration of antiretroviral therapy was 13 months [interquartile range (IQR), 8-19]. Abnormal cytology was found in 123 women (46%) with 70 women (26%) having low grade squamous intraepithelial lesions (LSIL), 22 (8%) high grade squamous intraepithelial lesions (HSIL), 30(11%) atypical squamous cells of unknown significance (ASCUS) and 1 (0.4%) atypical glandular cells (AGC). Women with SIL had lower median CD4 cell count (239 vs 287 cells/mm3; P=0.02), lower income (<70 USD per month: 57% vs 38%; P=0.01), and less regular condom use (24% vs 40%; P=0.02) compared to those with no SIL. Duration and type of antiretroviral regimen were not significantly associated with SIL. CONCLUSION: SIL is prevalent among women on antiretroviral therapy and is associated with immunosuppression, low income, and less frequent condom use. Cervical cancer screening and counseling on condom use should be routinely offered to HIV-infected women in antiretroviral treatment clinics in Africa.

Younger age at HAART initiation is associated with more rapid growth reconstitution.

OBJECTIVES: Patterns of growth following highly active antiretroviral therapy (HAART) administration among children are not well defined. The objective of this study was to determine rates and predictors of growth reconstitution among children on HAART. METHODS: A study was conducted among HIV-1-infected children initiating HAART at an HIV treatment clinic in Kenya. Kaplan-Meier survival curves and Cox proportional hazards regression models compared catch-up growth (Z-score ≥ 0) at 12 months post-HAART. Multivariate linear mixed-effects models determined rates and predictors of growth following HAART. RESULTS: One hundred and seventy-three HIV-1-infected children initiated HAART with a median age of 4.7 years [interquartile range (IQR) 2.4, 7.0]. At baseline, children below 3 years had lower weight-for-age (WAZ) and weight-for-height (WHZ) Z-scores than children 3-5 and 6-10 years (WAZ: P = 0.03; WHZ: P = 0.006). Adjusting for baseline growth, children below 3 years were two to three-fold more likely to attain population age-norms (Z-score = 0) than 6-10 years (WAZ: P = 0.055; WHZ: P = 0.005) at 12 months post-HAART. After adjustment, children below 3 years had higher increases in WAZ and WHZ following HAART than 6-10 years (WAZ: P = 0.006; WHZ: P = 0.005). Children at WHO stage at least 3 at baseline experienced more rapid WHZ reconstitution (P = 0.002). Food supplementation while on HAART was associated with increased monthly gains in weight indices (WAZ: P = 0.001; WHZ: P = 0.005), and multivitamins were associated with greater increases in height (P < 0.01). CONCLUSION: Following HAART initiation, younger children had more rapid catch-up to the population-average weight of their peers than older children, demonstrating growth benefit of earlier HAART. In addition to HAART, food supplementation and multivitamins may also accelerate growth reconstitution.