Determinants of nonsuppression of HIV viral load among children receiving antiretroviral therapy in the Simiyu region: a cross-sectional study.

BACKGROUND: Despite substantial antiretroviral therapy (ART) coverage among individuals with human immunodeficiency virus (HIV) infection in Tanzania, viral load suppression (VLS) among HIV-positive children receiving ART remains intolerably low. This study was conducted to determine factors affecting the nonsuppression of VL in children with HIV receiving ART in the Simiyu region; thus, an effective, sustainable intervention to address VL nonsuppression can be developed in the future. METHODS: We conducted a cross-sectional study including children with HIV aged 2-14 years who were currently presenting to care and treatment clinics in the Simiyu region. We collected data from the children/caregivers and care and treatment center databases. We used Stata™ to perform data analysis. We used statistics, including means, standard deviations, medians, interquartile ranges (IQRs), frequencies, and percentages, to describe the data. We performed forward stepwise logistic regression, where the significance level for removal was 0.10 and that for entry was 0.05. The median age of the patients at ART initiation was 2.0 years (IQR, 1.0-5.0 years), and the mean age at HIV VL (HVL) nonsuppression was 8.8 ± 2.99 years. Of the 253 patients, 56% were female, and the mean ART duration was 64 ± 33.07 months. In multivariable analysis, independent predictors of HVL nonsuppression were older age at ART initiation (adjusted odds ratio [AOR] = 1.21; 95% confidence interval [CI] 1.012-1.443) and poor medication adherence (AOR, 0.06; 95% CI 0.004-0.867). CONCLUSIONS: This study showed that older age at ART initiation and poor medication adherence play significant roles in HVL nonsuppression. HIV/AIDS programs should have intensive interventions targeting early identification, ART initiation, and adherence intensification.

Prevalence and outcome of HIV infected children admitted in a tertiary hospital in Northern Tanzania.

BACKGROUND: Provider Initiated Testing and Counseling (PITC) among hospitalized children have shown to increase the probability of identifying HIV-infected children and hence be able to link them to HIV care. We aimed at determining the prevalence, clinical characteristics and outcome of HIV-infected children admitted at Bugando Medical Centre (BMC) after active provision of PITC services. METHODS: A cross-sectional study with follow up at three months post enrollment was done. Children with unknown HIV status were tested for HIV infection as per 2012 Tanzanian algorithm. Questionnaires were used to collect demographic, clinical and follow up information. Data was statistically analyzed in STATA v13. RESULTS: A total of 525 children were enrolled in the study. Median [IQR] age was 28 [15-54] months. Males consisted of 60.2% of all the participants. HIV prevalence was 9.3% (49/525). Thirty-three (67.3%) of HIV-infected children were newly diagnosed at enrolment. Thirty-nine (79.6%) of all HIV-infected patients had WHO HIV/AIDS clinical stage four disease, 10 (20.4%) had WHO clinical stage three and none qualified in stage one or two. About 84% (41/49) of HIV infected children had severe immunodeficiency at the time of the study. Factors that were independently associated with HIV infection were, cough (OR 2.40 [1.08-5.31], p = 0.031), oral thrush (OR 20.06[8.29-48.52], p < 0.001), generalized lymphadenopathy (OR 5.61 [1.06-29.56], p = 0.042), severe acute malnutrition (OR 6.78 [2.28-20.12], p = 0.001), severe stunting (OR 9.09[2.80-29.53], p = 0.034) and death of one or both parents (OR 3.62 [1.10-11.87], p = 0.034). The overall mortality (in-hospital and post-hospital) was 38.8% among HIV-infected children compared with 14.0% in HIV-uninfected children. Within three months period after discharge from the hospital, 71.4% (25/35) of discharged HIV-infected children reported to have attended HIV clinic at least once and 60.0% (21/35) were on antiretroviral medications. CONCLUSION: PITC to all admitted children identified significant number of HIV-infected children. Mortality among HIV-infected children is high compared to HIV-uninfected. At the time of follow up about 30% of discharged HIV-infected children did not attend to any HIV care and treatment clinics. Therefore effective efforts are needed to guarantee early diagnosis and linkage to HIV care so as to reduce morbidity and mortality among these children.

Evaluation of Asymptomatic Malaria Antigenaemia and Parasitaemia in Human Immunodeficiency Virus-Infected Children in Benin City, Nigeria.

BACKGROUND: Malaria and HIV/AIDS are rampant in subSaharan Africa with prevalence of one reinforcing the other and control of one impactful on control of the other. Malaria parasitaemia (MP) prevalence is increased in HIV-infected individuals while certain drugs used in latter cause decline in MP but it is uncertain how they affect malaria antigenaemia (MA). How certain bio-social and disease characteristics affect MA and MP in this cohort is unknown. OBJECTIVES: To determine prevalence of asymptomatic MP and MA and their clinical and social determinants in HIV infected. METHODS: In a prospective cross-sectional study carried out at the University of Benin Teaching Hospital (April to June 2016), 221 HIV-infected children (aged 1-17years) asymptomatic for malaria and 221 apparently healthy HIV-negative controls were studied. MA was assessed using rapid diagnostic test while MP was evaluated using microscopy. Standard method was used to determine parasite count. RESULTS: Prevalence of asymptomatic MP was 24.4% in subjects and 17.6% in controls while MA prevalence in subjects and controls were comparable (20.8% vs 18.1%). Malaria parasitaemia rate (MPr) of 24.4% was higher than malaria antigenaemia rate (MAr) (20.8%). MP and MA rates were independent of socioeconomic status, access to anti-retroviral drugs, their duration of use and clinical disease stage. CONCLUSION: MA occurred frequently enough to warrant its use as malaria case definition surrogate in asymptomatic children with HIV/AIDS receiving trimethoprim-sulfamethoxazole prophylaxis and protease inhibitors.

CONTEXTE: Le paludisme et le VIH / SIDA sont endémiques en Afrique subsaharienne, la prévalence de l'un renforçant l'autre et le contrôle de l'un ayant un impact sur le contrôle de l'autre. La prévalence de la parasitémie du paludisme (MP) est augmentée chez les personnes infectées par le VIH, tandis que certains médicaments utilisés dans ces derniers entraînent une baisse de la MP, mais on ignore comment ils affectent l'antigénémie du paludisme (AM). On ne sait pas comment certaines caractéristiques biosociales et pathologiques affectent l'AMM et la MP dans cette cohorte. OBJECTIFS: Déterminer la prévalence de la MP et de l'AMM et leurs déterminants cliniques-sociaux chez les enfants infectés par le VIH. METHODES: Dans une étude transversale prospective menée à l'hôpital universitaire de l'Université du Bénin (avril et juin 2016), 221 enfants infectés par le VIH (âgés de 1 à 17 ans) asymptomatiques pour le paludisme et 221 témoins séronégatifs apparemment en bonne santé ont été étudiés. La MA a été évaluée à l'aide d'un test de diagnostic rapide tandis que la MP a été évaluée à l'aide de la microscopie à coloration de Giemsa. La méthode standard a été utilisée pour déterminer le nombre de parasites. RESULTATS: La prévalence de la MP asymptomatique était de 24,4% chez les sujets et de 17,6% chez les témoins, tandis que la prévalence de l'AM chez les sujets et les témoins était comparable (20,8% vs 18,1%). Le taux de parasitémie du paludisme (MPr) de 24,4% était plus élevé que le taux d'antigénémie du paludisme (MAr) (20,8%). Les taux de MP et d'AM étaient indépendants du statut socio-économique, de l'accès aux médicaments antirétroviraux, de leur durée d'utilisation et du stade clinique de la maladie. CONCLUSION: l'AMM est survenue suffisamment fréquemment pour justifier son utilisation comme substitut de la définition de cas dans la prise en charge de ces sujets, étant donné l'implication de la parasitémie dans la physiopathologie et la virulence du VIH. MOTS CLÉS: Paludisme, Antigénémie, Parasitémie, Enfants infectés par le VIH, Benin City.

Long-term outcomes of early initiated antiretroviral therapy in sub-Saharan children: a Cameroonian cohort study (ANRS-12140 Pediacam study, 2008-2013, Cameroon).

BACKGROUND: In most studies, the virological response is assessed during the first two years of antiretroviral treatment initiated in HIV-infected infants. However, early initiation of antiretroviral therapy exposes infants to very long-lasting treatment. Moreover, maintaining viral suppression in children is difficult. We aimed to assess the virologic response and mortality in HIV-infected children after five years of early initiated antiretroviral treatment (ART) and identify factors associated with virologic success in Cameroon. METHODS: In the ANRS-12140 Pediacam cohort study, 2008-2013, Cameroon, we included all the 149 children who were still alive after two years of early ART. Virologic response was assessed after 5 years of treatment. The probability of maintaining virologic success between two and five years of ART was estimated using Kaplan-Meier curve. The immune status and mortality were also studied at five years after ART initiation. Factors associated with a viral load < 400 copies/mL in children still alive at five years of ART were studied using logistic regressions. RESULTS: The viral load after five years of early ART was suppressed in 66.8% (60.1-73.5) of the 144 children still alive and in care. Among the children with viral suppression after two years of ART, the probability of maintaining viral suppression after five years of ART was 64.0% (54.0-74.0). The only factor associated with viral suppression after five years of ART was achievement of confirmed virological success within the first two years of ART (OR = 2.7 (1.1-6.8); p = 0.033). CONCLUSIONS: The probability of maintaining viral suppression between two and five years of early initiated ART which was quite low highlights the difficulty of parents to administer drugs daily to their children in sub-Saharan Africa. It also stressed the importance of initial viral suppression for achieving and maintaining virologic success in the long-term. Further studies should focus on identifying strategies that would enhance better retention in care and improved adherence to treatment within the first two years of ART early initiated in Sub-Saharan HIV-infected children.

Depression, anxiety and treatment satisfaction in the parents of children on antiretroviral therapy in South Africa.

Parents of children living with HIV are at increased risk of emotional distress, with negative implications for both their health outcomes. There is limited data on depression and anxiety symptoms in the biological parents as caregivers of children on antiretroviral therapy (ART) in South Africa. We investigated the prevalence and correlates associated with depressive and anxiety symptoms in 200 biological caregiving parents of children on ART at a public hospital in KwaZulu-Natal Province, South Africa. Data were obtained from the Patient Health Questionnaire (PHQ-9) for depressive symptoms and the Generalized Anxiety Depression (GAD-7) for anxiety symptoms, along with sociodemographic questionnaire. Most of the parent caregivers assessed were female (n = 190, 95%), younger than 40 years (n = 151, 75.5%), single (n = 173, 86.5%), unemployed (n = 156, 78%) and HIV+ (n = 183, 91.9%). Sixty-five (32.5%) parents screened positive for depression, 37 (18.5%) for anxiety and 31 (n = 31, 15.5%) for both disorders (i.e. depression/anxiety comorbidity). There were significant associations between death of a child to HIV (aOR = 4.66, 95% CI: 1.33-16.28) with depression/anxiety comorbidity as well as with treatment dissatisfaction (aOR = 13.98, CI: 2.09-93.66), but not with other socio-demographic factors. The high prevalence of depression and anxiety amongst the parent caregivers of children living with HIV suggests the need for mental health screening and care among parents of children attending pediatric HIV services, and particularly for those with history of children lost to HIV.

Higher PIK3C2B gene expression of H1N1+ specific B-cells is associated with lower H1N1 immunogenicity after trivalent influenza vaccination in HIV infected children.

Perinatally HIV-infected children (PHIV), despite successful antiretroviral therapy, present suboptimal responses to vaccinations compared to healthy-controls (HC). Here we investigated phenotypic and transcriptional signatures of H1N1-specific B-cells (H1N1-Sp) in PHIV, differentially responding to trivalent-influenza-vaccine (TIV), and HC. Patients were categorized in responders (R) and non-responders (NR) according to hemagglutination-inhibition-assay at baseline and 21 days after TIV. No differences in H1N1-Sp frequencies were found between groups. H1N1-Sp transcriptional analysis revealed a distinct signature between PHIV and HC. NR presented higher PIK3C2B and NOD2 expression compared to R, confirmed by downregulation of PIK3C2B in resting-memory of R after H1N1 in-vitro stimulation. In conclusion this study confirms that qualitative rather than quantitative analyses are needed to characterize immune responses in PHIV. These results further suggest that higher PIK3C2B in H1N1-Sp of NR is associated with lower H1N1 immunogenicity and may be targeted by future modulating strategies to improve TIV responses in PHIV.

Behavioral problems in perinatally HIV-infected young children with early antiretroviral therapy and HIV-exposed uninfected young children: prevalence and associated factors.

Although behavioral problems have been observed in children and adolescents with perinatally-acquired HIV infection (PHIV), behavioral information regarding younger PHIV children are scarce. This study aims to identify behavioral problems in PHIV and HIV-exposed uninfected (HEU) children and to evaluate factors associated with such problems. A prospective study of PHIV and HEU young children was conducted. Behavioral problems were assessed with the Child Behavior Checklist (CBCL) at baseline and 12 months later among children aged 18-60 months old. The Patient Health Questionnaire-9 and the Parenting Styles & Dimensions Questionnaire identified primary caregivers' symptoms of depression and parenting styles, respectively, at both visits. Chi-squared analyses were used to compare the prevalence of behavioral problems between groups. Factors associated with behavioral problems were analyzed by logistic regression. From 2016 to 2017, 121 children (41 PHIV and 80 HEU) were assessed with no significant differences in prevalence of Total, Internalizing, Externalizing, and Syndrome scales problems between PHIV and HEU at both visits (p > 0.5). Primary caregivers' depression and lower education in addition to authoritarian and permissive parenting styles were significantly related to child behavioral problems. Family-centered care for families affected by HIV, including positive parenting promotion, mental health care, and education are warranted.

Intestinal Parasites Infections among HIV Infected Children Under Antiretrovirals Treatment in Yaounde, Cameroon.

BACKGROUND: Intestinal parasitic infections are among the most common communicable diseases worldwide, particularly in developing countries. Human immunodeficiency virus (HIV) causes dysregulation of the immune system through the depletion of CD4+ T lymphocytes which gives rise to opportunistic infections. METHODOLOGY: A cross-sectional study was conducted from January to October 2018. Stool and blood samples were collected from participants aged 1 to 19. Stool samples were analyzed for intestinal parasites. Blood samples were analyzed for HIV and CD4 + T cell counts. RESULTS: Out of 214 children enrolled, 119 (55.6%) were HIV infected and 95 (44.4%) were HIV non-infected. All infected children were on antiretroviral treatment (ART). The prevalence of intestinal parasites was 20.2% in HIV infected and 15.8% in non-infected children. Among the 119 HIV infected children, 33 (27.7%) of them had a CD4+ T cell count less than 500 cells/mm3, and amongst them 5.9% had CD4+ T cell count less than 200 cells/mm3. Among HIV infected children, Cryptosporidium spp. was frequently detected, 7/119 (5.9%), followed by Giardia lamblia 5/119 (4.2%) then Blastocystis hominis 3/119 (2.5%) and Entamoeba coli 3/119 (2.5%). Participants on ART and prophylactic co-trimoxazole for >10 years had little or no parasite infestation. CONCLUSIONS: Although ART treatment in combination with prophylactic co-trimoxazole reduces the risk of parasitic infection, 20.2% of HIV infected children harbored intestinal parasites including Cryptosporidium spp. Stool analysis may be routinely carried out in order to treat detected cases of opportunistic parasites and such improve more on the life quality of HIV infected children.

[Access to the management of HIV infected children: Overview of the healthcare supply in Cameroon in 2014]. / Accès à la prise en charge de l'infection VIH pédiatrique ­ État des lieux de l'offre des soins au Cameroun en 2014.

BACKGROUND: In Cameroon in 2012, the proportion (15%) of children eligible for antiretroviral treatment (ART) was one of the lowest among the 21 Global Fund priority countries. The objective of this study was to carry out a situational analysis of the existing care offer for pediatric HIV in Cameroon. METHODS: A descriptive cross-sectional study was conducted over a 4-month period (April to August 2014) in 12 healthcare facilities in 7 regions of Cameroon selected by systematic sampling. The data were collected in a self-administered questionnaire filled out by the caregiving and administrative personnel included in the study. RESULTS: All in all, 142 persons in charge of pediatric HIV treatment were included in the study, of whom 115 were working at the operational level: 59 (51.2%) health personnel, 44 (38.3%) community agents and 12 (10.4%) department heads; the other 27 exercised responsibilities at the regional (19) and the local (8) levels. An overwhelming majority of the caregivers involved in pediatric VIH treatment were nurses, a factor necessitating the delegation of medical tasks institutionalized in Cameroon. Few standardized nationwide documents take into account these treatment modalities. Inadequate dissemination of the documents at all levels of the healthcare pyramid may justify the non-compliance with the care protocols that has been observed in the training programs dedicated to the subject. CONCLUSION: The updating and large-scale dissemination of standardized nationwide documents taking into account the specificities of HIV-infected children are required to improve implementation at the operational level of the Cameroonian healthcare system of the existing guidelines for pediatric HIV treatment.

Predictors of treatment failure, time to switch and reasons for switching to second line antiretroviral therapy in HIV infected children receiving first line anti-retroviral therapy at a Tertiary Care Hospital in Ethiopia.

BACKGROUND: Treatment failure and delay in switching to second line regimen are major concerns in the treatment of HIV infected children in a resource limited setting. The aim of this study was to determine the prevalence and predictors of first line antiretroviral therapy (ART) regimen failure, reasons and time taken to switch to second line antiretroviral (ARV) medications after treatment failure among HIV-infected children. METHODS: A retrospective cohort study was conducted February 2003 to May 2018 in HIV-clinic at Tikur Anbessa Specialized Hospital (TASH), Ethiopia. All HIV infected children ≤15 years of age and who were taking first line ART for at least 6 months were included. Data abstraction format was used to collect the data from patients' chart and registry. Binary and multivariable logistic regression statistics were used. RESULTS: Out of 318 enrolled HIV-infected children, the prevalence of treatment failure was found to be 22.6% (72/318), among these 37 (51.4%) had only immunologic failure, 6 (8.3%) had only virologic failure and 24 (33.3%) had both clinical and immunological failure. The mean time taken to modify combination antiretroviral therapy (cART) regimen was 12.67 (4.96) weeks after treatment failure was confirmed. WHO Stage 3 and 4 [Adjusted Odds Ratio (AOR), 3.64, 95% CI 1.76-7.56], not having both parents as primary caretakers [AOR, 2.72 95% CI, 1.05-7.06], negative serology of care takers [AOR, 2.69 95% CI, 1.03-7.03], and cART initiation at 11 month or younger were predicting factors of treatment failure. Of the 141 (47.9%) children who had regimen switching or substitution, treatment failure (44.4%) and replacement of stavudine (d4T) (30.8%) were major reasons. Only 6.6% patients had received PMTCT service. CONCLUSION: One fifth of the patients had experienced treatment failure. Advanced WHO stage at baseline, not being taken care of by mother and father, negative sero-status caretakers, and younger age at initiation of cART were the predictors of treatment failure. PMTCT service uptake was very low. There was a significant time gap between detection of treatment failure and initiation of second line cART. Half of the patients encountered regimen switching or substitution of cART due to treatment failure and replacement of stavudine (d4T).

Impact of antiretroviral treatment on height evolution of HIV infected children.

BACKGROUND: Antiretroviral treatment (ART) has been shown to have a beneficial effect on the weight evolution but its effect on height remains unclear. We described patterns of height evolution and identified predictors of catch-up growth in HIV-infected children on ART. METHODS: To describe the height evolution from birth to adulthood, we developed a nonlinear mixed effect model using data from perinatally HIV-infected children who initiated ART from 1999 to 2013 in a prospective cohort study in Thailand. The main covariates of interest were: sex, ART regimen (dual nucleoside reverse-transcriptase inhibitor, non-nucleoside reverse transcriptase inhibitor (NNRTI)-, or protease inhibitor (PI)-based), baseline CD4 percentage, HIV-RNA load and CDC HIV Classification stage and occurrence of AIDS-defining events. RESULTS: A total 477 children (43% boys) contributed 18,596 height measurements over a median duration of 6.3 years on ART (interquartile range, 3.0 to 8.3). At ART initiation, median age was 6.2 years (1.8 to 9.6), 16% of children were underweight (weight-for-age z-score < - 2), 49% presented stunting (height-for-age z-score < - 2), and 7% wasting (weight-for-height z-score < - 2). The most frequent regimen at ART initiation was NNRTI-based (79%). A model with 4 components, birth length and 3 exponential functions of age accounting for the 3 growth phases was developed and show that the height-growth velocity was inversely associated with the age at ART initiation, the adult height was significantly lower in those who had experienced at least one AIDS-defining event while, as expected, the model found that adult height in females was lower than in males. Age at ART initiation, type of ART regimen, CDC stage, CD4 percentages, and HIV-RNA load were not associated with the final height. CONCLUSIONS: The younger the children at ART initiation, the greater the effect on height-growth velocity, supporting the World Health Organization's recommendation to start ART as early as possible. However, final adult height was not linked to the age at ART initiation.

Pathways of care for HIV infected children in Beira, Mozambique: pre-post intervention study to assess impact of task shifting.

BACKGROUND: In 2013, Mozambique implemented task-shifting (TS) from clinical officers to maternal and child nurses to improve care for HIV positive children < 5 years old. A retrospective, pre-post intervention study was designed to evaluate effectiveness of a new pathway of care in a sample of Beira District Local Health Facilities (LHFs), the primary, local, community healthcare services. METHODS: The study was conducted by accessing registries of At Risk Children Clinics (ARCCs) and HIV Health Services. Two time periods, pre- and post-intervention, were compared using a set of endpoints. Variables distribution was explored using descriptive statistics. T-student, Mann Whitney and Chi-square tests were used for comparisons. RESULTS: Overall, 588 HIV infected children (F = 51.4%) were recruited, 330 belonging to the post intervention period. The mean time from referral to ARCC until initiation of ART decreased from 2.3 (± 4.4) to 1.1 (± 5.0) months after the intervention implementation (p-value: 0.000). A significant increase of Isoniazid prophylaxis (O.R.: 2.69; 95%CI: 1.7-4.15) and a decrease of both regular nutritional assessment (O.R. = 0.45; 95%CI: 0.31-0.64) and CD4 count at the beginning of ART (O.R. = 0.46; 95%CI: 0.32-0.65) were documented after the intervention. CONCLUSIONS: Despite several limitations and controversial results on nutrition assessment and CD4 count at the initiation of ART reported after the intervention, it could be assumed that TS alone may play a role in the improvement of the global effectiveness of care for HIV infected children only if integrated into a wider range of public health measures.

Candida species from oral cavity of HIV-infected children exhibit reduced virulence factors in the HAART era.

This study aimed to assess, in vitro, the biofilm viability and the phospholipase and protease production of Candida spp. from the saliva of HIV infected children and healthy controls, and to correlate the results with the use of medical data. A total of 79 isolates were analyzed: 48 Candida albicans isolates (33/15) and 20 Candida parapsilosis sensu lato complex isolates (12/8) (from HIV/control patients, respectively), and 8 Candida krusei, 1 Candida tropicalis, 1 Candida dubliniensis and 1 Candida guilliermondii from HIV patients. The XTT (2, 3-bis (2-methoxy-4-nitro-5-sulfophenyl)-2H-tetrazolium-5-Carboxanilide) reduction assay analyzed the biofilm viability. Phospholipase and protease assays were performed using the egg yolk and Bovine Serum Albumin agar plate methods, respectively. All isolates were able to form biofilm with cell viability. Quantitatively, Candida isolates from both groups presented a similar ability to form biofilm (p > 0.05). The biofilm viability activity was higher in C. albicans isolates than in non-albicans Candida isolates (p < 0.05) for both groups. Phospholipase activity was detected in 32 isolates (40.5%) and it was significantly higher in the HIV group (p = 0.006). Protease activity was detected in 66 isolates (84.8%) and most of them were relatively/very strong producers. No statistical association with medical data was found in the HIV group. Although Candida spp. isolates from HIV-positive children presented higher phospholipase production, in vitro they exhibited reduced virulence factors compared to isolates from healthy individuals. This finding may enlighten the role played by immunosuppression in the modulation of Candida virulence attributes.

Assessment of the HBV vaccine response in a group of HIV-infected children in Morocco.

BACKGROUND: Since its development in the early 1980s, Hepatitis B virus (HBV) vaccine has been proven to be highly protective. However, its immunogenicity may be ineffective among HIV-infected children. In Morocco, HBV vaccine was introduced in 1999, and since then all infants, including vertically HIV-infected infants, have been following the vaccination schedule, implemented by the Moroccan ministry of health. An assessment of the immunization of these children is important to optimize efforts aimed at tackling Hepatitis B coinfection, within the country. METHODS: Forty-nine HIV-infected children (HIV group) and 112 HIV uninfected children (control group) were enrolled in this study. Samples were tested by Elisa (Monolisa Anti-HBs, Biorad) to quantify the anti-HBs antibodies. The % of lymphocyte subsets i.e. CD4+ T cells, CD8+ T cells, B cells, and NK, was determined by flow cytometry, using CellQuest Pro software (Becton-Dickinson), and for HIV group, HIV viral load was measured by real time PCR assay (Abbott). All variables were statistically compared in the two groups. RESULTS: The median age was 51 ± 35 months for the HIV group and 50 ± 36 months (p > 0.05) for the control group. Female represented 63% and 41% (p = 0.01), among the HIV group and the control group, respectively. Among HIV-infected children, 71.4% (35/49) were under HAART therapy at the enrollment in the study. Seroprotection titer i.e. anti-HBs ≥10mUI/ml among control group was 76% (85/112), and only 29% (14/49) among the perinatally HIV-infected children (p < 0.0001). Lower % of CD4 + T cells was observed in HIV-infected children with a poor anti-HBs response. CONCLUSION: In this studied group, we have shown that despite the vaccination of HIV-children with HBV vaccine, 71% did not show any seroprotective response. These findings support the need for monitoring HBV vaccine response among HIV-infected children in Morocco, in order to revaccinate non-immunized children.

Effects of Short-Term Probiotic Ingestion on Immune Profiles and Microbial Translocation among HIV-1-Infected Vietnamese Children.

Here, we investigated the effects of the probiotic strain Lactobacillus casei Shirota (LcS) on immune profiles and intestinal microbial translocation among children infected with human immunodeficiency virus (HIV). This prospective study included 60 HIV-infected children-including 31 without antiretroviral therapy (ART) (HIV(+)) and 29 who received ART for a median of 3.5 years (ART(+)) and 20 children without HIV infection (HIV(-)). Participants were recruited in Vietnam. All children were given fermented milk containing LcS (6.5 × 108 cfu) daily for 8 weeks. Before and after LcS ingestion, blood samples were collected for virological, immunological, and bacteriological analyses. After LcS ingestion, peripheral CD4⁺ T-cell and Th2 (CXCR3-CCR6-CD4⁺) counts significantly increased in both HIV-infected groups; Th17 (CXCR3-CCR6⁺CD4⁺) counts increased in all three groups; regulatory T-cell (CD25highCD4⁺) counts decreased in the ART(+) and HIV(-) groups; activated CD8⁺ cells (CD38⁺HLA-DR⁺CD8⁺) decreased from 27.5% to 13.2% (p < 0.001) in HIV(+) children; and plasma HIV load decreased slightly but significantly among HIV(+) children. No group showed a significantly altered frequency of bacterial 16S/23S rRNA gene detection in the plasma. No serious adverse events occurred. These findings suggest that short-term LcS ingestion is a safe supportive approach with immunological and virological benefits in HIV-infected children.

Predictors of survival among HIV-positive children on ART in Swaziland.

The objective of the study was to determine predictors of survival among HIV-positive children (<15 years) in Swaziland. A retrospective cohort analysis of medical records for 4 167 children living with HIV who were initiated on antiretroviral therapy (ART) between 2004 and 2008, and followed up until 2014 was conducted in clinical settings at 36 health facilities. The Kaplan Meier Estimator, signed-ranks test, and the Cox proportional hazards regression model were applied to determine survival probabilities, significant difference among stratified survival functions and adjusted hazard ratios respectively. The results reveal that the median survival time for children was 78 months (95% CI: 77-79). Children who were initiated early on ART had higher survival probability over time (HR: 0.35 [95% CI: 0.21-0.57], p < 0.001) compared to those whose ART initiation was delayed. Children within the age group of <1 years had higher hazard (HR = 1.55 [95% CI: 1.16-2.08], p < 0.001) of death than children within the age group of 1-14 years. Children who were nourished had 88% lower hazard of death (HR: 0.12 [95% CI: 0.07-0.19], p < 0.001) than severely malnourished children. The study demonstrates that ART paediatric services are effective in increasing survival among HIV infected children and early initiated children have high survival probability. Active tuberculosis (TB), malnutrition, and delayed ART initiation remain predictors of poor survival among children living with HIV.

Malaria infection and anaemia in HIV-infected children in Mutengene, Southwest Cameroon: a cross sectional study.

BACKGROUND: Malaria is one of the leading causes of morbidity and mortality in children and HIV infection as well as other factors may worsen the situation. This study was aimed at determining the factors influencing malaria parasite prevalence and density as well as anaemia in HIV-infected children in Mutengene, Cameroon from November, 2012 to April, 2013. METHODS: A semi-structured questionnaire was used to record information on socio-demographic factors and use of preventive measures by caregivers of HIV-infected children aged 1-15 years and of both sexes. Venous blood was collected; blood films were prepared and Giemsa-stained for parasite detection and speciation. Haemoglobin concentration was measured and the anaemic status determined. Data was analysed using Epi Info 7 software. RESULTS: A total of 234 children were studied. The overall malaria parasite prevalence was 24.8 % (58) and was significantly higher (31.9 %, P = 0 .004) in females, those who did not implement any preventive measure at all (66.7 %, P = 0.03) and children who used antiretroviral therapy (ART) (28.6 %, P = 0.02) when compared with their respective counterparts. Geometric mean parasite density (GMPD) was significantly higher (3098.4, P = 0.02) in children who presented with fever, had CD4 T cells ≥500 cells/µL (491.3, P = 0.003) and those with moderate anaemia (1658.8, P = 0.03) than their respective counterparts. Although there was no significant difference, GMPD was however higher in males (549.0); those not on ART (635.0) and highest in children <5 years old (633.0) than their respective counterparts. The overall prevalence of anaemia was 49.6 % (116). The value was significantly highest (58.3 %, P = 0.01) in the 11-15 years age group; those with CD4 T cell level 200-499 (72.7 %, P = 0.001) and children with fever (85.7 %, P = 0.01). CONCLUSION: Implementation of proper and integrated malaria preventive measures as well as frequent monitoring of anaemia on prescription of ART could likely improve the health conditions of HIV-infected children thus avoiding malaria-related morbidity and mortality.

HIV-exposed children account for more than half of 24-month mortality in Botswana.

BACKGROUND: The contribution of HIV-exposure to childhood mortality in a setting with widespread antiretroviral treatment (ART) availability has not been determined. METHODS: From January 2012 to March 2013, mothers were enrolled within 48 h of delivery at 5 government postpartum wards in Botswana. Participants were followed by phone 1-3 monthly for 24 months. Risk factors for 24-month survival were assessed by Cox proportional hazards modeling. RESULTS: Three thousand mothers (1499 HIV-infected) and their 3033 children (1515 HIV-exposed) were enrolled. During pregnancy 58 % received three-drug ART, 23 % received zidovudine alone, 11 % received no antiretrovirals (8 % unknown); 2.1 % of children were HIV-infected by 24 months. Vital status at 24 months was known for 3018 (99.5 %) children; 106 (3.5 %) died including 12 (38 %) HIV-infected, 70 (4.7 %) HIV-exposed uninfected, and 24 (1.6 %) HIV-unexposed. Risk factors for mortality were child HIV-infection (aHR 22.6, 95 % CI 10.7, 47.5 %), child HIV-exposure (aHR 2.7, 95 % CI 1.7, 4.5) and maternal death (aHR 8.9, 95 % CI 2.1, 37.1). Replacement feeding predicted mortality when modeled separately from HIV-exposure (aHR 2.3, 95 % CI 1.5, 3.6), but colinearity with HIV-exposure status precluded investigation of its independent effect. Applied at the population level (26 % maternal HIV prevalence), an estimated 52 % of child mortality occurs among HIV-exposed or HIV-infected children. CONCLUSIONS: In a programmatic setting with high maternal HIV prevalence and widespread maternal and child ART availability, HIV-exposed and HIV-infected children still account for most deaths at 24 months. Lack of breastfeeding was a likely contributor to excess mortality among HIV-exposed children.

Impact of HIV Infection and Anti-Retroviral Therapy on the Immune Profile of and Microbial Translocation in HIV-Infected Children in Vietnam.

CD4⁺ T-lymphocyte destruction, microbial translocation, and systemic immune activation are the main mechanisms of the pathogenesis of human immunodeficiency virus type 1 (HIV) infection. To investigate the impact of HIV infection and antiretroviral therapy (ART) on the immune profile of and microbial translocation in HIV-infected children, 60 HIV vertically infected children (31 without ART: HIV(+) and 29 with ART: ART(+)) and 20 HIV-uninfected children (HIV(-)) aged 2-12 years were recruited in Vietnam, and their blood samples were immunologically and bacteriologically analyzed. Among the HIV(+) children, the total CD4⁺-cell and their subset (type 1 helper T-cell (Th1)/Th2/Th17) counts were inversely correlated with age (all p < 0.05), whereas regulatory T-cell (Treg) counts and CD4/CD8 ratios had become lower, and the CD38⁺HLA (human leukocyte antigen)-DR⁺CD8⁺- (activated CD8⁺) cell percentage and plasma soluble CD14 (sCD14, a monocyte activation marker) levels had become higher than those of HIV(-) children by the age of 2 years; the CD4/CD8 ratio was inversely correlated with the plasma HIV RNA load and CD8⁺-cell activation status. Among the ART(+) children, the total CD4⁺-cell and Th2/Th17/Treg-subset counts and the CD4/CD8 ratio gradually increased, with estimated ART periods of normalization being 4.8-8.3 years, whereas Th1 counts and the CD8⁺-cell activation status normalized within 1 year of ART initiation. sCD14 levels remained high even after ART initiation. The detection frequency of bacterial 16S/23S ribosomal DNA/RNA in blood did not differ between HIV-infected and -uninfected children. Thus, in children, HIV infection caused a rapid decrease in Treg counts and the early activation of CD8⁺ cells and monocytes, and ART induced rapid Th1 recovery and early CD8⁺-cell activation normalization but had little effect on monocyte activation. The CD4/CD8 ratio could therefore be an additional marker for ART monitoring.

Treatment Failure in HIV-Infected Children on Second-line Protease Inhibitor-Based Antiretroviral Therapy.

BACKGROUND: Human immunodeficiency virus (HIV)-infected children failing second-line antiretroviral therapy (ART) have no access to third-line antiretroviral drugs in many resource-limited settings. It is important to identify risk factors for second-line regimen failure. METHODS: HIV-infected children initiating protease inhibitor (PI)-containing second-line ART within the Program for HIV Prevention and Treatment observational cohort study in Thailand between 2002 and 2010 were included. Treatment failure was defined as confirmed HIV type 1 RNA load >400 copies/mL after at least 6 months on second-line regimen or death. Adherence was assessed by drug plasma levels and patient self-report. Cox proportional hazards regression analyses were used to identify risk factors for failure. RESULTS: A total of 111 children started a PI-based second-line regimen, including 59 girls (53%). Median first-line ART duration was 1.9 years (interquartile range [IQR], 1.4-3.3 years), and median age at second-line initiation was 10.7 years (IQR, 6.3-13.4 years). Fifty-four children (49%) experienced virologic failure, and 2 (2%) died. The risk of treatment failure 24 months after second-line initiation was 41%. In multivariate analyses, failure was independently associated with exposure to first-line ART for >2 years (adjusted hazard ratio [aHR], 1.8; P = .03), age >13 years (aHR, 2.9; P < .001), body mass index-for-age z score < -2 standard deviations at second-line initiation (aHR, 2.8; P = .03), and undetectable drug levels within 6 months following second-line initiation (aHR, 4.5; P < .001). CONCLUSIONS: Children with longer exposure to first-line ART, entry to adolescence, underweight, and/or undetectable drug levels were at higher risk of failing second-line ART and thus should be closely monitored.