Continuous Prophylactic Antiretrovirals/Antiretroviral Therapy Since Birth Reduces Seeding and Persistence of the Viral Reservoir in Children Vertically Infected With Human Immunodeficiency Virus.

BACKGROUND: Early antiretroviral therapy (ART) restricts the size of the human immunodeficiency virus (HIV) reservoir in infants. However, whether antiretroviral (ARV) prophylaxis given to exposed vertically infected children exerts similar effects remains unknown. METHODS: We measured total and integrated HIV DNA, as well as the frequency of CD4 T cells producing multiply spliced RNA (msRNA) after stimulation (inducible reservoir) in vertically infected Thai infants. Eighty-five infants were followed longitudinally for up to 3 years. We compared the size of the reservoir in children who received continuous ARV prophylaxis since birth vs those who never received or discontinued prophylaxis before initiating ART. We used samples from a cross-sectional cohort of 37 Thai children who had initiated ART within 6 months of life to validate our findings. RESULTS: Before ART, levels of HIV DNA and the frequencies of cells producing msRNA were significantly lower in infants who received continuous ARV prophylaxis since birth compared to those in whom ARV prophylaxis was discontinued or never initiated (P < .020 and P < .001, respectively). Upon ART initiation, total and integrated HIV DNA levels decayed significantly in both groups (P < .01 in all cases). Interestingly, the initial differences in the frequencies of infected cells persisted during 3 years on ART. The beneficial effect of prophylaxis on the size of the HIV reservoir was confirmed in the cross-sectional study. Importantly, no differences were observed between children who discontinued prophylactic ARVs before starting ART and those who delayed ART initiation without receiving prior prophylaxis. CONCLUSIONS: Neonatal ARV prophylaxis with direct transition to ART durably limits the size of the HIV reservoir.

Implementation of an active case management network to identify HIV-positive infants and accelerate the initiation of antiretroviral therapy, Thailand 2015 to 2018.

INTRODUCTION: Early initiation of antiretroviral therapy (ART) can reduce HIV-related morbidity and mortality in HIV-positive infants. We implemented an Active Case Management Network to promote early ART initiation Aiming for Cure (ACC) in August 2014. We describe ACC implementation, early infant diagnosis (EID) coverage and ART initiation during August 2014 to July 2018 compared with a national EID survey during October 2007 to September 2011 (pre-ACC). METHODS: Thailand's 2014 HIV Treatment Guidelines recommend that HIV-exposed infants have HIV polymerase chain reaction (PCR) testing at birth, one month and at two to four months. Testing is done at 14 national HIV PCR laboratories. When an HIV-positive infant (HIV PCR+) is identified, PCR laboratory staff send the result to the hospital staff responsible for the infant's care and to the national laboratory case manager (CM). As part of ACC, the national laboratory CM alerts a regional CM who contacts the hospital staff caring for the infant to offer technical support with ART initiation and ART adherence. CMs enter clinical, demographic and laboratory data into the national ACC database. We analysed the ACC data from August 2014 to July 2018 to assess the ACC's impact on EID coverage, ART initiation and time-to-ART initiation. RESULTS: The uptake of EID increased from 64% (pre-ACC) to >95% in 2018 (ACC). The number of HIV-positive infants born declined from 429 cases (pre-ACC) to 267 cases (ACC). Median age at the first-positive PCR declined from 75 days (pre-ACC) to 60 days (ACC); P < 0.001. Among 429 infants diagnosed before ACC was started, 241 (56%) received ART; during ACC, 235 (88%) of 267 HIV-positive infants received ART. The median age at ART initiation declined from 282 days before ACC to 83 days during ACC (P < 0.001) and the median time from blood collection to ART initiation declined from 168 days before ACC to 23 days during ACC (P < 0.001). CONCLUSIONS: An innovative case management network (ACC) has been established in Thailand and results suggest that the network is promoting EID and early ART initiation. The ACC model, using case-managed PCR notification and follow-up, may speed ART initiation in other settings.

CHAMP+ Thailand: Pilot Randomized Control Trial of a Family-Based Psychosocial Intervention for Perinatally HIV-Infected Early Adolescents.

Within Asia, HIV prevalence is highest in Thailand, including thousands of children and adolescents. Care for children born with HIV [perinatal transmission of HIV (PHIV)] will need to focus on adolescents for the foreseeable future. Thai PHIV adolescents experience significant mental health and psychosocial challenges, including treatment adherence. Yet, few, if any, comprehensive interventions for them exist. CHAMP+, an evidence-based intervention adapted for Thailand, was evaluated with a pilot randomized control trial at four HIV clinics. Eighty-eight dyads of 9- to 14-year-old PHIV young adolescents/caregivers were randomized to CHAMP+ or standard of care (SOC). Eleven cartoon-based sessions were delivered over 6 months. Participants completed baseline, 6-month (postintervention), and 9-month surveys, measuring youth outcomes (e.g., mental health and adherence), contextual factors (e.g., demographics and caregiver factors), and self- and social-regulation factors (e.g., HIV knowledge and youth-caregiver communication). Multi-level modeling to account for clustering within individuals was used to assess longitudinal changes within and between groups. All families randomized to CHAMP+ completed the intervention. Although the study was not statistically powered to detect differences in treatment effects, the CHAMP+ group significantly improved at 6 months in youth mental health and adherence, HIV knowledge, youth-caregiver communication, internalized stigma, and HIV-related social support, with most improvements sustained at 9 months and significantly better improvements than the SOC group on a number of outcomes. High levels of baseline viral suppression highlight the importance of reaching these young PHIV adolescents at a period of lower risk before adherence and other challenges emerge. Designed to be delivered with limited cost/resources, CHAMP+ Thailand holds scale-up potential.

Strategies to improve the uptake of effective contraception in perinatally HIV-infected adolescents.

OBJECTIVE: To assess strategies to improve safe-sex practices in sexually active female adolescents living with HIV, through linking reproductive health (RH) care with HIV care. METHODS: A single arm, 48-week prospective study was conducted with 77 sexually active adolescents in five sites in Thailand. Guided RH education was carried out through video, brochures and individual counselling. Participants were offered free effective contraception (EC), in addition to a barrier method (dual contraception) versus barrier method only. Changes in EC use were assessed with McNemar's test; predicting factors with logistic regression. RESULTS: Median age was 19 years; 95% were perinatally infected; 30% had been pregnant. All but one showed RH-knowledge improvement after RH education. Individual counselling was most often rated the 'most helpful' educational method. At the screening visit 21% were using dual contraception; 53% a male condom only; 8% EC method only; and 18% were not using any contraceptive method. Dual-contraception use improved with time, reaching 74% at week 48. EC-use at the baseline visit was associated with having ever used EC prior to study entry (P<0.0001), and the study site (P<0.0001). Having ever used EC was associated with a history of pregnancy (P=0.0085) and forced sex (P=0.0386). CONCLUSION: Offering continuous RH care, linked with HIV care, resulted in increased use of dual contraception. Healthcare providers played a significant role in the process. RH education should address the main predictors for EC use by adolescents, including past, personal experience.

Carbohydrate, lipid, bone and inflammatory markers in HIV-positive adolescents on antiretroviral therapy and hormonal contraception.

BACKGROUND: Little is known about the cumulative effect of HIV antiretroviral therapy (ART) and hormonal contraception (HC) on metabolism and inflammation in HIV-positive women. METHODS: We conducted a cross-sectional assessment of markers for carbohydrate, lipid, bone metabolism, inflammation and coagulation in HIV-positive adolescents on ART and HC (n=37) versus on ART only (n=51) in Thailand. The Wilcoxon rank-sum test was used to assess differences between groups. RESULTS: The median age was 19.5 years. Most adolescents (95%) were perinatally infected. All were on ART for a median of 9 years. HC used was progestin only (n=21); combined oral contraceptive (COC) tablets (n=6) for the whole study period or alternating between progestin only and COC (n=10). Prevalence of any metabolic abnormalities was 99%. Four biomarkers were significantly higher with HC vs no HC: insulin (10.3 vs 6.2 µU/mL, P=0.002), insulin resistance (1.89 vs 1.19 mass units, P=0.005), 25-OH vitamin D (33.2 vs 20.2 ng/mL, P<0.0001) and C-terminal telopeptide (690 vs 530 ng/L, P=0.011). Triglycerides and D-dimer were significantly lower with HC (103 vs 139 mg/dL, P=0.014 and 140 vs 155 ng/mL, P=0.003, respectively). There was no relationship between the type of HC or ART and the above differences. CONCLUSION: Perinatally infected HIV-positive adolescents on ART in this pilot study had a high prevalence of metabolic abnormalities. Bone turnover markers and insulin resistance were significantly higher with HC. Research on the cumulative effect of HIV, ART and HC on metabolism and inflammation in adolescents with HIV is important in order to devise strategies for preventing and mitigating long-term comorbidities.

High virologic response rate after second-line boosted protease inhibitor-based antiretroviral therapy regimens in children from a resource limited setting.

BACKGROUND: Limited data exist for the efficacy of second-line antiretroviral therapy among children in resource limited settings. We assessed the virologic response to protease inhibitor-based ART after failing first-line non-nucleoside reverse transcriptase inhibitor (NNRTI)-based regimens. METHODS: A retrospective chart review was conducted at 8 Thai sites of children who switched to PI -based regimens due to failure of NNRTI -based regimens. Primary endpoints were HIV RNA < 400 copies/ml and CD4 change over 48 weeks. RESULTS: Data from 241 children with median baseline values before starting PI-based regimens of 9.1 years for age, 10% for CD4%, and 4.8 log10 copies/ml for HIV RNA were included; 104 (41%) received a single ritonavir-boosted PI (sbPI) with 2 NRTIs and 137 (59%) received double-boosted PI (dbPI) with/without NRTIs based on physician discretion. SbPI children had higher baseline CD4 (17% vs. 6%, p < 0.001), lower HIV RNA (4.5 vs. 4.9 log10 copies/ml, p < 0.001), and less frequent high grade multi-NRTI resistance (12.4% vs 60.5%, p < 0.001) than the dbPI children. At week 48, 81% had HIV RNA < 400 copies/ml (sbPI 83.1% vs. dbPI 79.8%, p = 0.61) with a median CD4 rise of 9% (+7%vs. + 10%, p < 0.005). However, only 63% had HIV RNA < 50 copies/ml, with better viral suppression seen in sbPI (76.6% vs. 51.4%, p 0.002). CONCLUSION: Second-line PI therapy was effective for children failing first line NNRTI in a resource-limited setting. DbPI were used in patients with extensive drug resistance due to limited treatment options. Better access to antiretroviral drugs is needed.

Neonatal dengue infection: report of dengue fever in a 1-day-old infant.

A male infant was admitted because of fever. He was born at 37-weeks' gestation. His mother had experienced acute febrile illness with headache and myalgia. Her illness persisted with onset of active labor pain on day 5, which prompted cesarean section; postoperatively, the hematocrit decreased, requiring transfusion. The infant was well until fever developed at 16 hours after birth. There were petichiae on his face and trunk and the liver was enlarged. Fever subsided on day 5 without evidence of plasma leakage or severe hemorrhage. He made an uneventful recovery after 8 days of illness. Leukopenia and thrombocytopenia were present in the mother and infant. Both were diagnosed as dengue fever. Dengue type 1 was recovered from the infant by polymerase chain reaction. The dengue enzyme-linked immunoassay showed secondary infection in the mother and primary infection in the infant. In dengue-endemic areas, clinicians should be alert to dengue fever/dengue hemorrhagic fever in pregnant women presenting with acute febrile illness, and be prepared for proper management.

Ventilator-associated pneumonia in a newborn intensive care unit.

A prospective observational study was conducted in a neonatal intensive care unit to identify factors associated with the development of ventilator-associated pneumonia (VAP) in 170 infants aged less than 30 days who required mechanical ventilation for longer than 48 hours. VAP occurred in 85 infants (50 cases per 100 mechanically-ventilated infants) or 70.3 cases per 1,000 ventilator days. Stepwise logistic regression analysis identified 3 factors independently associated with VAP: umbilical catheterization [adjusted odds ratio (AOR)=2.5; 95% confidence interval (CI)=1.3 to 4.7; p=0.007]; respiratory distress syndrome (AOR=2.0; 95% CI=1.0 to 3.9; p=0.03); and insertion of orogastric tube (AOR=3.0; 95% CI=1.3 to 7.2; p=0.01). Infants with VAP had longer duration on ventilator (14.2 days vs 5.9 days; p<0.001) and longer hospital stay (28.2 days vs 13.8 days; p<0.001). Organisms were isolated in 42 specimens (49.4%) from endotracheal aspirate culture and in 17 specimens (20.0%) from hemoculture; Pseudomonas aeruginosa, Klebsiella pneumoniae and Acinetobacter spp were predominant. Polymicrobial infection was found in 11 specimens (12.9%) from endotracheal aspirate culture. Leukocytosis and blood gas values could not predict the presence of VAP. The mortality of infants with VAP (29.4%) did not differ significantly from that of infants without VAP (30.6%) (p=0.87). Certain clinical interventions might potentially affect the incidence of VAP and outcome associated with VAP.