Effect of calcium and vitamin D supplementation on bone mineral accrual among HIV-infected Thai adolescents with low bone mineral density.

Background: The benefits of calcium and vitamin D supplementation for low bone mass remains controversial. This study assessed the changes in bone mineral density (BMD) during periods without and with calcium and vitamin D supplementation among HIV-infected adolescents with low BMD. Method: Perinatally HIV-infected Thai adolescents aged 12-20 years were enrolled into Phase 1 (pre-supplementation) to evaluate longitudinal change of BMD. We provided education about appropriate dietary intake and exercise. Lumbar spine (L2-L4) BMD and vitamin D status (25-hydroxyvitamin D [25(OH)D]) were assessed at baseline and at 12-24 month intervals. Participants with a BMD Z-score≤-2 were enrolled into Phase 2 (supplementation) that provided calcium 600 mg plus cholecalciferol 200 IU twice daily for 6 months. BMD and 25(OH)D were re-assessed at the end of study. Results: Ninety-four participants were enrolled into the Phase 1. Median age (IQR) was 14.3 (13.0-15.5) years, with 67% at Tanner stage 3-5, 89% with a plasma HIV-1 RNA<50 copies/mL. During Phase 1 and a 22.7-month follow-up, median L2-L4 BMD Z-scores remained unchanged (-1.06 vs -1.08, P=0.08), but 25(OH)D levels increased (24.7 vs 26.7 ng/mL, P=0.01). Twenty-six (28%) adolescents had low BMD and were enrolled into Phase 2, with 24 (92%) completing follow-up. The median L2-L4 BMD Z-scores (-2.59 vs -1.70; P<0.001) and calcium level (9.3 vs 9.5 mg/dL, P=0.04) significantly improved. There was an increase in BMD Z-scores during the 6-months post-supplementation as compared to the 21-month pre-supplementation period (0.65 vs -0.50, P=0.03). Conclusion: HIV-infected adolescents with low BMD had improved bone health after calcium and vitamin D supplementation. A randomised controlled trial is warranted to confirm the benefits of these supplements.

HIV disclosure and its effect on treatment outcomes in perinatal HIV-infected Thai children.

The World Health Organization guideline recommends informing children of their HIV status between the ages of 6-12 years. Primary caregivers of perinatal HIV-infected Thai children ≥6 years were interviewed in order to assess the HIV status disclosure rate. In addition, pill counts of antiretroviral therapy (ART) were performed every three months. CD4 and HIV-RNA were performed every six months. Of the 260 children/adolescents included, the median age of disclosure was 14.8 years. The disclosure rate among those from 6 to 12 years was 21% and for those greater than 12 years of age was 84%. When comparing children aged 6-12 years whose HIV status had been disclosed to them, to children whose HIV had yet to be disclosed, no difference was noted in median ART adherence by pill count, CD4 count, or proportion of HIV-RNA <50 copies/ml (p > 0.05). Factors associated with HIV disclosure were an age of ≥12 years (OR 17.8, 95% CI 8.86-35.79) and a current CD4 ≤ 30% (OR 2.09, 95% CI 1.20-3.62). In conclusion, although the majority of adolescents ≥12 years were aware of their HIV status only one-fifth of children aged 6-12 years were aware. Moreover, the child's/adolescent's disclosure status had no bearing on ART adherence by pill count or immunological and virological outcomes.

Simplifying antiretroviral therapy to lopinavir/ritonavir monotherapy did not improve quality of life and therapy adherence in pretreated HIV-infected children.

We reported quality of life (QOL) and adherence in HIV-infected children after simplifying the antiretroviral regimen by switching to lopinavir/ritonavir monotherapy (mLPV/r). HIV-infected children with HIV-RNA <50 copies/ml while using second-line double boosted protease inhibitors were switched to mLPV/r. Primary caregivers completed PACTG QOL questionnaires at weeks 0, 48, 96, and 144. Adherence by pill count was performed at every visit. Thirty-eight pretreated HIV-infected Thai children were enrolled. The median (IQR) age was 11.5 (10.2-13.2) years and 53% were female. At enrollment, 34 used LPV/r+saquinavir and four used LPV/r+indinavir. The median (IQR) CD4% was 27 (23-30)%. At week 144, QOL scores were similar to baseline for all domains. A transient increase in the symptoms domain score was seen at week 96 (p=0.01), whereas the physical resilience domain score was decreased at weeks 48 and 96 (both p<0.05). Despite the mean number of pills decreasing from 7.9 pills/day before and 3.7 pills/day after mLPV/r (p<0.001), there were no differences over time in adherence rates by pill count and proportion of children with poor adherence (all p>0.05). Our study did not demonstrate improvement of QOL scores and adherence rates by pill count in pretreated HIV-infected children after simplification of the antiretroviral regimen to lopinavir/ritonavir monotherapy.

Long-term lopinavir/ritonavir monotherapy in HIV-infected children.

BACKGROUND: Long-term data are limited on lopinavir/ritonavir monotherapy (mLPV/r) as a treatment simplification strategy in virologically suppressed children. METHODS: Children with confirmed plasma HIV viral load (VL) <50 copies/mL while receiving double protease inhibitors (dPI) were switched to mLPV/r therapy. Virologic failure (VF) was defined as 2 consecutive VL ≥ 500 or 3 consecutive VL ≥ 50 copies/mL. dPI was resumed within 4 weeks in children with VF. Primary endpoint was the proportion of children with VL < 50 copies/mL while still receiving mLPV/r at week 144. RESULTS: Forty children were enrolled; 90% were receiving LPV/r + saquinavir and 10% LPV/r + indinavir before simplifying to mLPV/r. Median age was 11.7 years; 50% were female. Median CD4% was 27%. Four (10%) had VL > 50 copies/mL at entry. At week 144, the proportion of children still receiving mLPV/r who had VL < 50 copies/mL was 22 of 40 (55%). The proportion of all children with VL < 50 copies/mL at week 144 was 33 of 40 (82.5%). Among 16 children who had VF and resumed dPI, 11 (69%) achieved VL < 50 copies/mL at week 144. No children with VF had major LPV/r mutations. Having detectable VL at entry and adherence by pill count <95% for >3 times at any visits during the study period significantly predicted VF on mLPV/r (both P = 0.025). The proportion of children with elevated total cholesterol (>200 mg/dL) decreased from 65% at baseline to 40% at week 144 (P = 0.007). CONCLUSIONS: About half of children maintained virologic suppression on mLPV/r for almost 3 years. VF was common but the majority achieved suppression after resuming dPI and none had major LPV/r mutations. mLPV/r should only be considered for simplified maintenance therapy if frequent VL monitoring to detect VF is available.

Prevalence and risk factors of low bone mineral density among perinatally HIV-infected Thai adolescents receiving antiretroviral therapy.

BACKGROUND: Low bone mineral density (BMD) has been reported among 10%-54% of HIV-infected adolescents in developed countries. We studied the prevalence and predictors of low BMD among HIV-infected Thai adolescents receiving antiretroviral therapy. METHODS: A cross-sectional study of lumbar spine (L2-L4) BMD as measured by dual-energy X-ray absorptiometry in Thai HIV-infected adolescents aged 12-20 years was performed. The BMD Z score was analyzed using age-matched healthy Thai children as a reference. Serum 25-hydroxyvitamin D was performed. Osteopenia was defined as BMD Z score ≤ -2. RESULTS: From October 2010 to February 2011, 101 adolescents, 50% male, with a median age of 14.3 (range: 13.0-15.7) years were enrolled. The median [interquartile range (IQR)] current CD4 T-cell count was 646 (506-796) cells per cubic millimeter and 90% had plasma HIV-1 RNA <50 copies per milliliter. The mean BMD among HIV-infected adolescents and controls were 0.855 and 0.980 g/cm (P < 0.001). The median (IQR) L2-L4 spine BMD Z score was -1.0 (-1.9 to -0.1), of which 24% had BMD Z score ≤ -2.0. The median (IQR) of 25-hydroxyvitamin D level was 24.8 (20.0-31.4) ng/mL, of which 25% had vitamin D level < 20 ng/mL. In multivariate analysis, the height for age Z score < -1.5 (adjusted odds ratio: 6.2; 95% confidence interval: 2.2 to 17.7) and history of World Health Organization clinical stage 4 before antiretroviral therapy (adjusted odds ratio: 3.7; 95% confidence interval: 1.3 to 10.7) were significantly associated with osteopenia. CONCLUSION: One fourth of HIV-infected Thai adolescents have osteopenia. Children with history of advanced-staging or having low height for age are at risk of osteopenia. Preventive measures to prevent osteopenia should be incorporated in routine care for these adolescents.