Hyppolite K. Tchidjou

Therapeutic DNA Vaccination of Vertically HIV-Infected Children: Report of the First Pediatric Randomised Trial (PEDVAC)

Subjects Twenty vertically HIV-infected children, 6–16 years of age, with stable viral load control and CD4+ values above 400 cells/mm3. Intervention Ten subjects continued their ongoing antiretroviral treatment (ART, Group A) and 10 were immunized with a HIV-DNA vaccine in addition to their previous therapy (ART and vaccine, Group B). The genetic vaccine represented HIV-1 subtypes A, B and C, encoded Env, Rev, Gag and RT and had no additional adjuvant. Immunizations took place at weeks 0, 4 and 12, with a boosting dose at week 36. Monitoring was performed until week 60 and extended to week 96. Results Safety data showed good tolerance of the vaccine. Adherence to ART remained high and persistent during the study and did not differ significantly between controls and vaccinees. Neither group experienced either virological failure or a decline of CD4+ counts from baseline. Higher HIV-specific cellular immune responses were noted transiently to Gag but not to other components of the vaccine. Lymphoproliferative responses to a virion antigen HIV-1 MN were higher in the vaccinees than in the controls (p = 0.047), whereas differences in reactivity to clade-specific Gag p24, RT or Env did not reach significance. Compared to baseline, the percentage of HIV-specific CD8+ lymphocytes releasing perforin in the Group B was higher after the vaccination schedule had been completed (p = 0.031). No increased CD8+ perforin levels were observed in control Group A. Conclusions The present study demonstrates the feasibility, safety and moderate immunogenicity of genetic vaccination in vertically HIV-infected children, paving the way for amplified immunotherapeutic approaches in the pediatric population. Trial registration clinicaltrialsregister.eu _2007-002359-18 IT

Safety and immunogenicity of a monovalent MF59®-adjuvanted A/H1N1 vaccine in HIV-infected children and young adults.

BACKGROUND This Phase IV study evaluated the safety and immunogenicity of a two-dose, MF59®-adjuvanted (Novartis Vaccines, Marburg, Germany), monovalent, A/H1N1 pandemic influenza vaccination schedule in Human Immunodeficiency Virus (HIV) positive children and young adults. METHODS A total of 83 children infected with HIV-1, and 37 non-immunocompromised, age-matched controls were enrolled. All participants received two vaccine doses administered three weeks apart. Antibody responses were assessed by haemagglutination assay at baseline, three weeks after each vaccine dose, and six months after immunization. Vaccines were evaluated according to European influenza vaccine licensure criteria. RESULTS The investigational vaccine was well tolerated. After the first vaccine dose, seroconversion rates were significantly lower in HIV-positive patients (60%) than controls (82%), with GMTs of 419 and 600, respectively. No significant differences in seroconversion rates were observed between the two study groups in response to the second vaccine dose. Persisting antibody titers were similar for both HIV-positive and non-infected controls, six months after immunization. CONCLUSION One dose of MF59-adjuvanted vaccine was sufficient to provide adequate levels of seroprotection against A/H1N1 influenza disease in HIV-positive children. However, a two-dose vaccination schedule may be optimal for this population.

Seasonal Pattern of Hospitalization from Acute Respiratory Infections in Yaoundé, Cameroon

Acute respiratory infections (ARIs) are among the leading causes of childhood morbidity and mortality in Africa. The effects of climatic factors on occurrence of ARIs in the tropics are not clear. During the years 2006-07, we reviewed the clinical registers of the Chantal Biya Foundation (CBF), Yaoundé, Cameroon, paediatric hospital to investigate the association between climatic factors and ARIs in children. Our findings show that rain, high relative humidity and low temperatures are directly associated with an increase in the frequency of hospitalization from ARIs. Given the high frequency of hospitalization from ARIs we suggest that influenza vaccination campaigns should be implemented taking into account the seasonality in Cameroon.

HIV is associated with thrombophilia and high D-dimer in children and adolescents.

Background and objective:Atherosclerosis and other cardiovascular diseases associated with thrombosis appear more relevant and anticipated in HIV-infected patients after combination antiretroviral therapy (cART) has reduced AIDS-related diseases and has improved survival. The association between viral replication and coagulation abnormalities in a cohort of HIV-infected children and adolescents was investigated here. Methods:Protein S, protein C anticoagulant and antithrombin activity, together with fibrinogen, D-dimer, high-sensitive C-reactive protein and homocysteine were assayed in a cross-sectional study among a cohort of HIV-infected children and adolescents. Results in patients with high viral load (HVL, HIV-RNA > 1000 copies/ml) were compared with those in patients with a lower replication (LVL), adjusting for other demographic, clinical and therapeutic covariates. Results:Eighty-eight patients (mean age 13.5 years, CD4 30%, 72% with LVL) were enrolled. A prevalence of protein S and protein C deficiency of 51 and 8% was, respectively, found. HVL group compared to LVL showed a significant reduction of protein S, protein C and antithrombin activities, and an increase of D-dimer levels. The independent association of HVL with decreased protein S activity (−11.2%, P = 0.04) and increased D-dimer levels (+0.13 μg/ml, P = 0.004) was confirmed in the multivariate model. Conclusions:HIV-infected children and adolescents present high prevalence of thrombophilic abnormalities. The multivariate model confirmed that high viral replication is independently associated with decrease of protein S and increase of D-dimer, suggesting the advantage of suppressive therapy on coagulation homeostasis and the opportunity of an active control of cardiovascular risk factors starting at a younger age.

The PEDVAC trial: preliminary data from the first therapeutic DNA vaccination in HIV-infected children.

The PEDVAC study is the first trial designed to analyze safety and immunogenicity of a therapeutic vaccination with a multiclade multigene HIV DNA vaccine (HIVIS) in infected children. Twenty HIV-1 vertically infected children (6-16 years of age), on stable antiretroviral treatment for at least 6 months with HIV-1 RNA<50 copies/ml and stable CD4 counts (> 400 cells/mm³ or 25%) over 12 months of follow-up, were recruited into the study. Enrolled patients have been randomized into two arms: a control group of 10 children who continued previous antiretroviral treatment (HAART) (arm A) and a group of 10 children immunized intramuscularly with the HIVIS DNA vaccine in addition to previous HAART (arm B). Immunizations took place at week 0, 4, 12 and the boosting dose is planned at week 36. The 10 children in the vaccine group have received the first 3 priming doses of the HIVIS vaccine. Safety data showed good tolerance to the vaccination schedule. Mild cutaneous self-limeted reactions consisted of local irritation, usually itching or erythema +/- swelling at the injection site, were reported. No severe systemic adverse events have been observed. No vaccinated children had a decrease of CD4 T-cell counts from baseline. None experienced virological failure. Analysis of cellular immune responses was scheduled at week 0, 4, 12, 16, 20, 40, 60, 72 and 96 by standard lymphoproliferation assay, intracellular cytokine staining and cell-ELISA, a miniaturized assay to measure antigen-induced IFNγ secretion. Evaluation of these results is in progress and will provide key information on the status and changes of antigen specific immunity during HIV DNA immunization.

HIV-Infected or -Exposed Children Exhibit Lower Immunogenicity to Hepatitis B Vaccine in Yaoundé, Cameroon: An Appeal for Revised Policies in Tropical Settings?

Background Since 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. Methodology Prospective, 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. Results Children 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. Conclusions Anti-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.

Low vaccine coverage among children born to HIV infected women in Niamey, Niger

Background: The effect of mother’s HIV-status on child vaccination is an important public health issue in countries with high HIV prevalence. We conducted a study in a primary healthcare center located in Niamey, the capital of Niger, which offers free of charge services to HIV positive and/or underprivileged mothers, with the aim of assessing: 1) vaccination coverage for children 0–36 months old, born to HIV-infected mothers, and 2) the impact of maternal HIV status on child vaccination. Methods: Mothers of children less than 36 months old attending the center were interviewed, to collect information on vaccines administered to their child, and family’s socio-demographic characteristics. Results: Overall, 502 children were investigated. Children of HIV-seropositive mothers were less likely to receive follow up vaccinations for Diphtheria-Tetanus-Pertussis (DTP) than those of HIV-seronegative mothers, with a prevalence ratio (PR) of 2.03 (95%CI: 1.58–2.61). Children born to HIV-seropositive mothers were less likely to miss vaccination for MMR than those born to HIV negative mothers, with a RR of 0.46 (95%CI: 0.30–0.72). Conclusions: Vaccine coverage among children born to HIV infected mothers was rather low. It is important to favor access to vaccination programs in this population.

Immunization status of internationally adopted children in Rome, Italy

AIMS International adoption medicine is a relatively new specialty in pediatrics that has emerged to address the specific health care needs of internationally adopted children in high-income countries. This study ascertains the seroprotection rate for vaccine-preventable diseases, especially against pneumococcal diseases. PATIENTS AND METHODS We evaluated 67 internationally adopted children that reached the International Adoption Unit of Bambino Gesù Childrens Hospital, Rome-Italy. We collected demographic information, data from preadoption immunization records, results of laboratory testing for immunity to vaccine-preventable diseases (tetanus, pneumococcus, hepatitis B, hemophilus influenzae type b (Hib), measles), as well as results of screening for HIV, hepatitis C, quantiferon, immunological and nutritional status. RESULTS For children that had received ≥3 vaccine doses of tetanus, overall protection was 94% of 31 vaccinated children; with 1-2 vaccine doses for hepatitis B and Hib respectively, protection was 45% of 29 vaccinated children and 63% of 8 vaccinated children, respectively. For children with one or more doses of measles vaccine, protection was 63% of 32 vaccinated children. Regarding pneumococcus vaccine (documented for eight children), 88% of children with one or more doses of vaccine had developed protective immunity. CONCLUSIONS International adoptees without a valid vaccine record need to undergo a complete schedule in accordance with their age and should receive all the vaccines in the adoptive countrys schedule.

Paediatric HIV Infection in Western Africa: The Long Way to the Standard of Care

In sub-Saharan Africa, newborns and children continue to suffer from insufficient access to early diagnosis and antiretroviral (ARV) treatments. A survey had been conducted in Burkina Faso, Ghana and Ivory Coast, from January 2010 to February 2011 to identify the major challenges regarding HIV prophylaxis and treatment of children in western Africa. The results of this survey highlight that only a small proportion of HIV-exposed newborns receive ARV prophylaxis. However, this problem is often not perceived at the national level. The problem could be faced by improving the communication process between the peripheral health services and the national procurement system. Moreover, supporting the development of local pharmaceutical industries could facilitate the availability of child-sized drugs, contextualized to the socio-cultural needs of such area, adequate not only in terms of efficacy, safety and tolerability, but also in terms of palatability, storage, distribution and cost.

Raising awareness of non-Hodgkin lymphoma in HIV-infected adolescents: report of 2 cases in the HAART era.

Human immunodeficiency virus (HIV) chronically infected patients are at increased risk of developing non-Hodgkin lymphoma compared with the general population. Highly active antiretroviral therapy has had a dramatic effect on the natural history of HIV infection, reducing the incidence of acquired immunodeficiency syndrome-related non-Hodgkin lymphoma and improving overall survival. However, problems related to adherence to treatment, frequently experienced during adolescence, may increase the risk of acquired immunodeficiency syndrome-related cancers. Optimizing highly active antiretroviral therapy and monitoring noncompliant patients with persisting HIV replication should be considered by physicians who take care of these patients. We herein report 2 cases of relapsed/progressive Burkitt lymphoma in HIV vertically infected adolescents.