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We report a prospective study of mouse brain derived inactivated Japanese encephalitis (JE) vaccine, given in 3-dose EPI program to human immune deficiency virus (HIV)-exposed Thai infants. 18 HIV-infected receiving antiretroviral therapy with median baseline CD4 of 33.1%, and 92 HIV-uninfected children were studied. All but one HIV-infected child seroconverted after the second dose. The geometric mean titers (GMTs) 3 months after the second and third doses in HIV-infected vs HIV-uninfected children were 247 vs 938 (p = 0.022), and 2273 vs 24069 (p = 0.009), respectively. Urticaria or angioedema found in 4% and 6% in HIV-infected and -uninfected children, respectively (p = 1.0). The vaccine was safe and immunogenic but antibody response in HIV-infected children was not as high as in uninfected children.

Summary Background Non-nucleoside reverse transcriptase inhibitor (NNRTI)-based highly active antiretroviral therapy (HAART) has been the most affordable regimen for the HIV-infected in developing countries. There are limited data comparing nevirapine (NVP) to efavirenz (EFV) in HIV-infected children. This study aimed to assess the efficacy and tolerability of NVP-based regimens compared to EFV-based regimens in HIV-infected children in Thailand. Methods The medical records of HIV-infected children who had received NNRTI-based regimens for more than 6 months at the Department of Pediatrics, Siriraj Hospital, Mahidol University, Thailand, were reviewed. Results Of the 139 HIV-infected children studied, 70 were male, and the median age at treatment initiation was 6.08 years (range 0.32–14.56 years); the median duration of follow-up was 36 months (range 6–66 months). The median baseline CD4 cell count was 185cells/mm 3 (range 2–3482cells/mm 3 ) and the median baseline CD4 percentage was 7.20% (range 0.11–36.57%). An NVP-based regimen was initiated in 61 (44%): 38 antiretroviral (ARV)-naive and 23 ARV-experienced. An EFV-based regimen was initiated in 78 (56%): 34 ARV-naive and 44 ARV-experienced. The CD4 cell count and percentage gains were not different between the NVP and EFV groups in both the ARV-naive and the ARV-experienced. However, ARV-naive children who received an EFV regimen had significantly lower baseline CD4 levels than those who received an NVP regimen. ARV-naive children had a better CD4 response than the ARV-experienced. The survival rates of children in the NVP groups were not different from those in the EFV groups for both the ARV-naive and the ARV-experienced. Treatment failure occurred in one ARV-naive NVP case (2.6%), two ARV-naive EFV cases (5.8%), and nine ARV-experienced NVP cases (39%) at 24 months of treatment, and 11 ARV-experienced EFV cases (25%) at 18 months of treatment. Seven (10%) children had adverse effects from treatment with NVP. The main side effects were rash and hepatitis; six had to switch to EFV. Four (5%) children had adverse effects from treatment with EFV; two had to switch to NVP. Conclusions Both NVP- and EFV-based HAART regimens were effective in children in Thailand for at least 3 years. HIV-infected Thai children generally tolerated NNRTI well.

To evaluate the efficacy and safety of short-course therapy with zidovudine plus lamivudine for reduction of perinatal transmission of human immunodeficiency virus type 1 (HIV-1), a single-arm, open-label, prospective, nonrandomized study was conducted. One hundred six treatment-naive pregnant women received zidovudine (300 mg) plus lamivudine (150 mg) twice daily from week 34 of gestation until the onset of labor. During labor, zidovudine and lamivudine were given every 3 h. Neonates received zidovudine syrup for 4 weeks and were bottle fed. The median maternal virus load and CD4 + cell count at weeks 32-34 of gestation were 4.33 log 10 copies/mL and 274 cells/mm 3 , respectively. At delivery, the mothers' mean decrease in virus load was 1.55 log 10 copies/mL and the mean increase in CD4 + cell count was 93 cells/mm 3 , compared with enrollment levels. Three neonates were HIV-1 infected, for a transmission rate of 2.83% (95% confidence interval, 1%-8%). There were no serious adverse events in the mothers. Adverse events noted in neonates were anemia (in 6 neonates), elevated transaminase levels (in 1), and thrombocytopenia (in 3). Short-course therapy with zidovudine plus lamivudine appeared to be safe and effective for prevention of perinatal transmission of HIV-1.

To elucidate genetic characteristics of HIV-1 subtype E involved in vertical transmission, V3 regions of HIV-1 subtype E isolated from 17 infected mothers (M1-M17) and their infants (I1-I17) at 1 month after birth were sequenced after cloned into pCRII vectors. At least three clones of each sample were collected. All mothers were asymptomatic and had been infected through a heterosexual route. Nine infants (I9-I17) showed mild symptomatic and immunosuppression within the first year of life. The interpatient nucleotide distance of mothers and infants in this group (0.065+/-0.008) were of greater diversity than those of a nonimmunosuppression group (0.039+/-0.006) by a significant amount (Fischer's exact test, p = .003). The substitution with asparagine (N) at threonine (T) at position 13 and aspartic acid (D) at position 29 of the V3 sequence were significantly associated with nonimmunosuppression in the first year of life (F-test, p = 0.003). Either a single or multiple viral variants could transmit from mothers to their infants.At least 1.5 million children worldwide are infected with HIV-1. Most HIV-infected children obtained the virus from their mother either in utero, at delivery, or postpartum through breast-feeding. Since the V3 loop of HIV is an important determinant for viral neutralization and cellular tropism, mutations in the V3 region could possibly affect mother-to-child transmission. Serum specimens from 17 HIV-1-seropositive mother-child pairs being treated at the pediatric clinic of Siriraj Hospital, Bangkok, in 1994 and 1995, were studied to better understand the genetic characteristics of HIV-1 subtype E involved in vertical transmission. The V3 regions of HIV-1 subtype E isolated from the subjects at 1 month after birth were sequenced after being cloned into pCRII vectors, with at least 3 clones of each sample collected. All mothers were asymptomatic and had been infected through a heterosexual route. 9 infants were mildly symptomatic and had evidence of immunosuppression during their first year of life. The nucleotide sequences of asymptomatic infants were significantly closer to maternal sequences than those of the AIDS cases. The data suggest that 1 or 2 genotypes from the mother were selected, transmitted to the infant, and then became diverse. The substitution with asparagine at threonine at position 13 and aspartic acid at position 29 of the V3 sequence were significantly associated with nonimmunosuppression during the first year of life.

The objective of this study was to assess changes in the family situation of HIV-infected women who have recently given birth. As part of a prospective perinatal HIV transmission study, interviews were conducted with a subset of HIV-infected women at 18 to 24 months postpartum, and answers were compared with baseline information obtained during pregnancy. Standardized scales were used to assess levels of psychosocial functioning. A convenience sample of 129 HIV-infected women enrolled during pregnancy was interviewed at 18 to 24 months postpartum. At delivery, the women were young (median age, 22 years), primiparous (57%), and asymptomatic (93%). When baseline and follow-up data were compared, more women were living alone (1% versus 6%; p = 0.03), fewer women were living with their partners (98% versus 73%; p0.001), and 30% of families had reduced incomes. At follow-up, 10% of partners had died, and more partners than wives had become ill or died (21% versus 4%; p = 0.02). Most children (78%) were living with their mothers, but only 57% of the HIV-infected women were the primary caretakers. Fewer women had disclosed their HIV status to others (e.g., family, friends) than to their partners (34% versus 84%; p0.001), largely because of fear of disclosure. The women appeared to have high levels of depression and worry. The women's greatest worries were about their children's health and the family's future. Within 2 years after childbirth, substantial change within the families of HIV-infected women was evident. These were manifest by partner illness or death, family separation, reduced family income, shifting responsibilities for child care, and signs of depression and isolation. Providing family support is a major challenge in Thailand as the perinatal HIV epidemic progresses.As part of a larger prospective perinatal HIV transmission study in Bangkok, Thailand (1992-94), interviews were conducted with a subset of 129 HIV-infected women 18-24 months after delivery and the results were compared with data obtained from these women during pregnancy. The median age of women at delivery was 22 years; 57% were primiparous and 93% were asymptomatic at delivery. 25 infants (19.4%) had confirmed HIV infection and 2 had died by the time of the follow-up interview. By follow up, 21% of male partners had died or developed HIV-related functional impairments. The proportion of women living alone rose from 1% at baseline to 6% at follow up, while the proportion living with their partner declined from 98% to 73%. 30% of families had reduced incomes at follow-up compared with baseline. Although 78% of infants were living with their mothers, they were the primary caretakers in only 57% of families. Only 34% of HIV-infected mothers had disclosed their HIV status to friends or family other than their partner. 43% of women scored above the cut-off on the depression scale. Mothers worried extensively about their child's health and their family's future. However, only 37% believed they could find someone to talk to about their feelings related to HIV. 58% were interested in joining a support group for women with HIV. These findings of family disruption, reduced family income, shifting responsibilities for child care, depression, and isolation indicate an urgent need for increased social support for HIV-infected mothers in Thailand.

Objective. The purpose of this study was to describe the epidemiology of coinfection with hepatitis C virus (HCV) and HIV among a cohort of pregnant Thai women.Methods. Samples from 1771 pregnant women enrolled in three vertical transmission of HIV studies in Bangkok, Thailand, were tested for HCV.Results. Among HIV-infected pregnant women, HCV seroprevelance was 3.8% and the active HCV infection rate was 3.0%. Among HIV-uninfected pregnant women, 0.3% were HCV-infected. Intravenous drug use by the woman was the factor most strongly associated with HCV seropositivity. Among 48 infants tested for HCV who were born to HIV/HCV coinfected women, two infants were HCV infected for an HCV transmission rate of 4.2% (95% 0.51–14.25%).Conclusions. HCV seroprevalence and perinatal transmission rates were low among this Thai cohort of HIV-infected pregnant women.

The objective of this study was to evaluate a practical method to assess adherence to antiretroviral therapy by observing virological and immunological responses. We conducted a 12-month longitudinal cohort study of 162 HIV-infected Thai children. Adherence was assessed using 5 methods (self reporting calendar, records of missed doses, pill counts, physician assessment, and an interview questionnaire). CD4 count, percentage and viral load were performed at baseline and at 12 months. Mean adherence rates at 2, 6, and 12 months were 98, 100, and 99% by the calendar method; 98, 100, and 100% by recording missed doses; 96, 96, and 92% by pill count; and 90, 94, and 97% by physician assessment. Poor agreement (kappaor = 0.1) was found among the methods. There was a statistically significant difference (p = 0.05) in virological response between participants withor = 95% adherence (0.8 log10) and those with95% adherence (0.2 log10) when pill counts were used to assess adherence. In conclusion, despite poor agreement among these tools, a pill count appeared to be the only practical, validated method to differentiate the virological outcome between those who were fully and partially adhere to the treatment regimen.

The appropriate timing of antiretroviral (ARV) therapy initiation in children with human immunodeficiency virus (HIV) infection has been uncertain. There was evidence of poorer outcome in adults who initiated treatment at lower baseline CD4 cell count. However, early initiation may not be possible in resource-limited setting and would increased risk of long term side effects and non-adherence.To elucidate the outcome of HIV-infected children who ARV treatment was initiated at different disease stages.Data from medical records of HIV-infected children who had been followed at Infectious Disease Division, Department of Pediatric Siriraj Hospital were retrospectively reviewed. Clinical response and outcome data were analyzed.From September 1996 to March 2004, there were 200 patients with a median age at treatment initiation of 38 (2-175) months. The median duration of follow up period was 26 (1-91) months. The median baseline CD4 cell count was 545 (2-5016) cells/mm3. The median baseline CD4 percentage was 14.25 (0.11-60). Monotherapy or dual nucleoside reverse transcriptase inhibitor (NRTI) regimens were initiated in 134 (67%), and HAARTwas initiated in 66 (33%) patients. The survival rate in patients who initiated with HAART tended to be better than those initiated with dual NRTI regimens but salvaged appropriately (p=0.2377). The survival rate in those initiated treatment at baseline CD4or = 15% was better than those initiated at baseline CD415% (p=0.0471).Initiation of ARV treatment at CD4 more than 15% resulted in a better survival rate than at CD4 below 15%. Initiation with HAART regimen tended to improve survival and resulted in higher CD4 gain especially in cases with baseline CD415%.

To evaluate the feasibility, duration of efficacy, and outcome of therapy with dual nucleoside reverse transcriptase inhibitors (NTRI) initiated in HIV-infected infants with mild to moderate disease.During 1998-2000, a multi-center prospective open-labeled operational study was conducted. Antiretroviral naôve HIV-infected infants were enrolled in seven hospitals to receive either zidovudine (AZT) plus lamivudine (3TC) or AZT plus didanosine (ddI). Infants who were in CDC stage "C3" were excluded from the study.Of the 88 infants, the mean age of treatment initiation was 6.8 months, and the mean initial CD4 was 1538 cells/mm3 (21.4%). The z-scores for weight and height increased after 4-8 months of treatment, and by the 24th month, were +0.89 and +0.69 higher than at enrollment. The CD4% peak increased at 8 months of treatment, by a mean increment of 4.19%, but decreased to the level of 1.08% above baseline by the 24th month of treatment. Three (3.4%) infants died, 11 (12%) had disease progression, 7 (8%) was prematurely discontinued from the study protocol due to poor compliance, and 37 (42%) were lost to follow-up. At the end of 24 months, all remaining 30 children were in stable condition with a chance of clinical and immunological stability of 34% and 68% by intention-to-treat and on-treatment analysis, respectively.Clinical and immunological benefit from dual NRTI was limited. Treatment of HIV-infected infant with mild to moderate disease in a resource-limited setting may have limited feasibility due to the high drop-out rate.

Although most of Thai children older than 2 years are immune against Haemophilus influenzae type b (Hib) without prior vaccination, it may not be the case in HIV-infected children. Of 44 HIV-infected children tested before vaccination at the mean age of 36 months (range 24-84 months), 32 (73%) were susceptible (anti-PRP0.15 microg/ml). At 6 months after a single dose of tetanus-conjugated Hib vaccination, 67% developed anti-PRP/=0.15 microg/ml, however, only 33% developed titer of/=1 microg/ml. Four of seven (57%) with anti-PRP 0.15-0.99 microg/ml at baseline were boosted to the titer of/=1 microg/ml after vaccination. Seroconversion rate and geometric mean titer (GMT) level in response to the vaccination did not correlate with HIV stage, but did correlate with viral load level of 100,000 copies/ml. HIV-infected children older than 2 years would benefit from Hib vaccination, although, one dose catch-up schedule is not sufficient in a third of these children. A second dose is needed in these children especially those with viral load of level of100,000 copies/ml.

Objective. To describe survival and signs of human immunodeficiency virus (HIV) infection in perinatally infected children in Thailand.Methods. At 2 large Bangkok hospitals, 295 infants born to HIV-infected mothers were enrolled at birth from November 1992 through September 1994 and followed up with clinical and laboratory evaluations every 1 to 3 months for 18 months. Infected children remained in follow-up thereafter. For the infected children, we used data collected through October 2000 to estimate survival times and compare characteristics among those whose disease progressed at rapid (died within 1 year), intermediate (died at 1–5 years), and slow (survived at least 5 years) rates.Results. None of the 213 uninfected children died during the follow-up period. Of the 68 infected children, 31 (46%) died; median survival was 60 months (95% confidence interval: 31–89 months). The most common cause of death was pneumonia (52% of deaths). Thirty-two children (47%) started antiretroviral therapy. Six children died in their first year before developing specific signs of HIV infection; all others developed signs of HIV infection between 1 and 42 months old (median: 4 months). Severe clinical (Centers for Disease Control and Prevention Class C) conditions were diagnosed in 23 children at a median age of 12 months, 15 (65%) of whom died a median of 3 months later. Compared with children whose disease progressed slowly, those whose disease progressed rapidly gained less weight by 4 months old (median 1.7 vs 2.6 kg), and their mothers had higher viral loads (median 5.1 vs 4.5 log10 copies/mL) and lower CD4+ counts (median 350 vs 470 cells/μL) at delivery.Conclusions. Among HIV-infected Thai children, survival times are longer than among children in many African countries, but shorter than among children in the United States and Europe. Signs of HIV develop early in most children. Growth failure and advanced maternal disease can predict rapid HIV disease progression and may be useful markers for treatment decisions.