HIV infection in childhood is associated with adverse structural and functional vascular changes that are most pronounced in children exposed to PI therapy. Longitudinal studies are required to differentiate the relative impact of HIV disease and ART and to assess the potential for prevention.

HLA class I polymorphism has a major influence on adult HIV disease progression. An important mechanism mediating this effect is the impact on viral replicative capacity (VRC) of the escape mutations selected in response to HLA-restricted CD8+ T-cell responses. Factors that contribute to slow progression in pediatric HIV infection are less well understood. We here investigate the relationship between VRC and disease progression in pediatric infection, and the effect of HLA on VRC and on disease outcome in adult and pediatric infection. Studying a South African cohort of >350 ART-naïve, HIV-infected children and their mothers, we first observed that pediatric disease progression is significantly correlated with VRC. As expected, VRCs in mother-child pairs were strongly correlated (p = 0.004). The impact of the protective HLA alleles, HLA-B*57, HLA-B*58:01 and HLA-B*81:01, resulted in significantly lower VRCs in adults (p<0.0001), but not in children. Similarly, in adults, but not in children, VRCs were significantly higher in subjects expressing the disease-susceptible alleles HLA-B*18:01/45:01/58:02 (p = 0.007). Irrespective of the subject, VRCs were strongly correlated with the number of Gag CD8+ T-cell escape mutants driven by HLA-B*57/58:01/81:01 present in each virus (p = 0.0002). In contrast to the impact of VRC common to progression in adults and children, the HLA effects on disease outcome, that are substantial in adults, are small and statistically insignificant in infected children. These data further highlight the important role that VRC plays both in adult and pediatric progression, and demonstrate that HLA-independent factors, yet to be fully defined, are predominantly responsible for pediatric non-progression.

In this small, preliminary study, semi-structured interviews were conducted with seven adolescents to explore their experiences of transition between paediatric and adult HIV care services. In general, the transition process established between the two health care units was considered by most participants to be beneficial, particularly the introduction of adult service providers early on in the transition preparation period. Four of the participants found the transition 'easy', whereas three had concerns that possibly delayed their transition, including coordination of haemophiliac and HIV care and fear of an adult environment. Individuals who had experienced little input into their care decisions during their paediatric appointments were more positive and ready for transition than those who had been more involved. Confidence and attachment with paediatric staff generally involved those who had been more involved in their care decision making. On transition, some of the participants were not prepared for the predominantly gay male population and were disappointed in not seeing other adolescents. The benefits of transition included the sense of independence, the shift in responsibility to the individual and general satisfaction in being treated as an adult. For those with strong paediatric staff rapport, a sense of loss in these relationships was expressed. Participants were forthcoming in suggesting recommendations for future transitions that are discussed.

Background:Reports of posttreatment control following antiretroviral therapy (ART) have prompted the question of how common immune control of HIV infection is in the absence of ART. In contrast to adult infection, where elite controllers have been very well characterized and constitute approximately 0.5% of infections, very few data exist to address this question in paediatric infection.Methods:We describe 11 ART-naive elite controllers from 10 cohorts of HIV-infected children being followed in South Africa, Brazil, Thailand, and Europe.Results:All but one of the elite controllers (91%) are females. The median age at which control of viraemia was achieved was 6.5 years. Five of these 11 (46%) children lost control of viraemia at a median age of 12.9 years. Children who maintained control of viraemia had significantly higher absolute CD4+ cell counts in the period of elite control than those who lost viraemic control. On the basis of data available from these cohorts, the prevalence of elite controllers in paediatric infection is estimated to be 5–10-fold lower than in adults.Conclusion:Although conclusions are limited by the study design, these data suggest that, whilst paediatric elite control can be achieved, compared with adult elite controllers, this occurs rarely, and takes some years after infection to achieve. Also, loss of immune control arises in a high proportion of children and often relatively rapidly. These findings are consistent with the more potent antiviral immune responses observed in adults and in females.

Adherence to once daily abacavir/lamivudine was good with no evidence of an association between nonadherence and virologic rebound. Acceptability of once daily drugs was best when the whole regimen was dosed once daily.

Levels of circulating naive and memory B cells were measured in human immunodeficiency virus (HIV)-infected children and control subjects to determine whether the irreversible depletion of memory B cells described in HIV-infected adults occurs in children with HIV infection. Depletion of circulating IgD+ memory B cells was seen in HIV-infected children despite control of the HIV load with highly active antiretroviral therapy (HAART) (P =. 04). IgD+ memory B cell percentages did not correlate with CD4+ cell percentages (P =. 027) or disease duration (P =. 026). Naive/transitional and IgD- memory B cell numbers were not affected. Pediatric HIV infection is associated with selective depletion of circulating IgD+ memory B cells despite control of the HIV load with HAART.

HIV-specific Elispot responses were investigated in 57 antiretroviral therapy-naive children, of median age 9.9 years. CD8(+) T-cell responses were detected in 96% children; Nef was the immunodominant protein. Responses broadened over time, but there was no association between magnitude, breadth or specificity of response and viraemia. Gag-specific CD4(+) T-cell responses, detectable in 26% children, correlated inversely with viraemia (R = -0.43, P < 0.001), suggesting that preservation of this cell population may be an important goal of therapeutic/vaccine strategies.

Highly active antiretroviral therapy (HAART) slows the progression of human immunodeficiency virus (HIV) disease and lowers mortality and morbidity in children. Coincident with these advances, an increasing number of side effects are being reported. We describe an adolescent boy with perinatally acquired HIV infection who developed significant bilateral breast enlargement as a result of HAART. He required bilateral mastectomies. Pediatricians need to be aware of less common side effects of HAART.