Objectives To evaluate the effect of early versus deferred antiretroviral therapy (ART) on neurodevelopment of infants from Cape Town participating in the CHER (Children with HIV Early Antiretroviral Therapy) trial. Design HIV-infected infants were randomised to early (<3 months) or deferred ART. HIV-uninfected infants (HIV-exposed and HIV-unexposed) provide background data. Methods Neurological examination and Griffiths Mental Development Scales (GMDS) were administered between 10–16 months of age, by testers blind to HIV status and randomised allocation. Mean quotients were compared using paired t-tests. Results 64 infants on early ART and 26 on deferred ART (of potential 77 and 38 respectively on CHER trial) were assessed at median age 11 months (range 10-16). On the GMDS, all scores were lower in the deferred arm and the General Griffiths and Locomotor Scores were significantly lower: mean (standard deviation): 100.1 (13.8) vs 106.3 (10.6) p=0.02; and 88.9 (16.3) vs 97.7 (12.5), p<0.01, respectively. Children with HIV who received early ART performed as well as children without HIV except on the locomotor subscale. Both infected and uninfected mean GMDS scores were within the average range. Conclusions Infants initiated on early ART have significantly better Locomotor and General Scores on the GMDS at median age 11 months compared to infants on deferred ART, despite careful monitoring and ready access to ART in the latter.
The diagnosis and management of childhood tuberculosis (TB) pose substantial challenges in the era of the human immunodeficiency virus (HIV) epidemic. The highest TB incidences and HIV infection prevalences are recorded in sub-Saharan Africa, and, as a consequence, children in this region bear the greatest burden of TB/HIV infection. The tuberculin skin test (TST), which is the standard marker of Mycobacterium tuberculosis infection in immunocompetent children, has poor sensitivity when used in HIV-infected children. Novel T cell assays may offer higher sensitivity and specificity than the TST, but these tests still fail to make the crucial distinction between latent M. tuberculosis infection and active disease and are limited by cost considerations. Symptom-based diagnostic approaches are less helpful in HIV-infected children, because of the difficulty of differentiating TB-related symptoms from those caused by other HIV-associated conditions. Knowing the HIV infection status of all children with suspected TB is helpful because it improves clinical management. HIV-infected children are at increased risk of developing active disease after TB exposure/infection, which justifies the use of isoniazid preventive therapy once active TB has been excluded. The higher mortality and relapse rates noted among HIV-infected children with active TB who are receiving standard TB treatment highlight the need for further research to define optimal treatment regimens. HIV-infected children should also receive appropriate supportive care, including cotrimoxazole prophylaxis, and antiretroviral therapy, if indicated. Despite the difficulties experienced in resource-limited countries, the management of children with TB/HIV infection could be vastly improved by better implementation of readily available interventions.
The disclosure of HIV status to infected children has received relatively little attention to date in sub-Saharan Africa. We conducted 40 semi-structured interviews with healthcare providers working in a large paediatric HIV clinic in Cape Town, South Africa regarding attitudes and experiences around discussing HIV with infected children. Most providers felt that the optimal age for general discussions about an HIV-infected child's health should happen around age 6, but that specific discussions regarding HIV infection should be delayed to a median of 10 years. Though most providers said that primary caregivers were the most appropriate individuals to lead disclosure discussions, there were strong views that caregivers require support from healthcare providers. These findings indicate the complexities involved in the disclosure of HIV status to infected children, and point to the need for interventions to support caregivers and providers in disclosure discussions.
Significant cognitive deficits were documented among HIV+ children at school age, even when started on ART at an early age. Earlier HIV treatment, neuropsychological monitoring, and rehabilitative interventions are all needed. Subsequent testing for 2 more years will help further evaluate how HIV infection and exposure affect the developmental trajectory.
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