In humans, the interaction of the natural killer group 2 member D (NKG2D)-activating receptor on natural killer (NK) and CD8(+) T cells with its major histocompatibility complex class I-related chain (MIC) and UL16 binding protein (ULBP) ligands (NKG2DLs) promotes recognition and elimination of stressed cells, such as tumor or infected cells. Here, we investigated the capacity of HIV-1 to modulate NKG2DL expression and escape NGK2D-mediated immunosurveillance. In CD4(+) T lymphocytes, both cell surface expression and release of MICA, MICB, and ULBP2 were up-regulated >2-fold by HIV-1 infection. In HIV-infected CD4(+) T lymphocytes or Jurkat T-cell lines, increased shedding of soluble NKG2DLs (sNKG2DLs) was impaired by a matrix metalloproteinase inhibitor (MMPI). Moreover, naive HIV(+) patients displayed increased plasma sMICA and sULBP2 levels and reduced NKG2D expression on NK and CD8(+) T cells compared to patients receiving highly active antiretroviral therapy (HAART) or healthy donors. In individual patients, HAART uptake resulted in the drop of sNKG2DL and recovery of NKG2D expression. Finally, sNKG2DLs in patients' plasma down-regulated NKG2D on NK and CD8(+) T cells and impaired NKG2D-mediated cytotoxicity of NK cells. Thus, NKG2D detuning by sNKG2DLs may promote HIV-1 immune evasion and compromise host resistance to opportunistic infections, but HAART and MMPI have the potential to avoid such immune dysfunction.

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BackgroundSince 2005, anti-hepatitis B virus (anti-HBV) vaccine is part of the Expanded Program on Immunization (EPI) for infants born in Cameroon, with 99% anti-HBV coverage. In a context of generalized HIV epidemiology, we assessed paediatric anti-HBV vaccine response according to HIV status, feeding option and age in a tropical context.MethodologyProspective, observational and cross-sectional study conducted among 82 children (27 [IQR: 9–47] months, min-max: 6–59), after complete anti-HBV vaccination (Zilbrix Hepta: 10μg AgHBs) at the Essos Health Centre in Yaounde, Cameroon, classified as group-A: HIV unexposed (28), group-B: HIV-exposed/uninfected (29), group-C: HIV-infected (25). Quantitative anti-HBs ELISA was interpreted as “no”, “low-” or “protective-response” with <1, 1–10, or ≥10 IU/L respectively; with p-value<0.05 considered significant.ResultsChildren were all HBV-unexposed (AcHBc-negative) and uninfected (HBsAg-negative). Response to anti-HBV vaccine was 80.49% (66/82), with only 45.12% (37/82) developed a protective-response (≥10IU/L). According to HIV status, 60.71% (17/28) developed a protective-response in group-A, vs. 51.72% (15/29) and 20% (5/25) in group-B and group-C respectively, Odds Ratio (OR): 2.627 [CI95% 0.933–7.500], p = 0.041. According to feeding option during first six months of life, 47.67% (21/45) developed a protective-response on exclusive breastfeeding vs. 43.24% (16/37) on mixed or formula feeding, OR: 1.148 [CI95% 0.437–3.026], p = 0.757. According to age, protective-response decreased significantly as children grow older: 58.33% (28/48) <24 months vs. 26.47% (9/34) ≥24 months, OR: 3.889 [CI95% 1.362–11.356], p = 0.004; and specifically 67.65% (23/34) ≤6 months vs. 0%, (0/5) 33–41 months, p = 0.008.ConclusionsAnti-HBV vaccine provides low rate of protection (<50%) among children in general, and particularly if HIV-exposed, infected and/or older children. Implementing policies for early vaccination, specific immunization algorithm for HIV-exposed/infected children, and monitoring vaccine response would ensure effective protection in tropical settings, pending extensive/confirmatory investigations.

BackgroundKidney disease is an important complication in HIV infected people, and this may be related to infection or antiretroviral therapy (ART). Our aim is to assess renal function in HIV infected paediatric patients, who may be particularly affected and are likely to take ART for longer than adults, and investigate the long term role of Tenofovir Disoproxil Fumarate (TDF) alone or co-administered with Ritonavir-boosted Protease Inhibitors (PI).MethodsSerum creatinine, phosphate and potassium levels, with estimated Glomerular Filtration Rate (eGFR), had been prospectively evaluated for 2 years in a cohort of HIV infected children and adolescents (age 9-18) on ART, and data analyzed according to the exposure to TDF or simultaneous TDF and PI.ResultsForty-nine patients were studied (57% female, mean age 14). Sixty-three percent were treated with ART containing TDF (Group A), and 37% without TDF (Group B); 47% with concomitant use of TDF and PI (Group C) and 53% without this combination (Group D). The groups didn't differ for age, gender or ethnicity. The median creatinine increased in the entire cohort and in all the groups analyzed; eGFR decreased from 143.6 mL/min/1.73 m2 at baseline to 128.9 after 2 years (p = 0.006) in the entire cohort. Three patients presented a mild eGFR reduction, all were on TDF+PI. Phosphatemia decreased significantly in the entire cohort (p = 0.0003) and in TDF+PI group (p = 0.0128) after 2 years. Five patients (10%) developed hypophosphatemia (Division of Acquired Immune Deficiency AE grade 1 or 2), and four of them were on TDF+PI.ConclusionsRenal function decrease and hypophosphatemia occur over time in HIV infected children and adolescents on ART. The association with co-administration of TDF and PI appears weak, and further studies are warranted.