Sanay Chearskul

Maternal viral load and timing of mother-to-child HIV transmission Bangkok Thailand.

OBJECTIVES To determine the proportion of HIV-1-infected infants infected in utero and intrapartum, the relationship between transmission risk factors and time of transmission, and the population-attributable fractions for maternal viral load. DESIGN Prospective cohort study of 218 formula-fed infants of HIV-1-infected untreated mothers with known infection outcome and a birth HIV-1-positive DNA PCR test result. METHODS Transmission in utero was presumed to have occurred if the birth sample (within 72 h of birth) was HIV-1-positive by PCR; intrapartum transmission was presumed if the birth sample tested negative and a later sample was HIV-1-positive. Two comparisons were carried out for selected risk factors for mother-to-child transmission: infants infected in utero versus all infants with a HIV-1-negative birth PCR test result, and infants infected intrapartum versus uninfected infants. RESULTS Of 49 infected infants with an HIV-1 birth PCR result, 12 (24.5%) [95% confidence interval (CI), 14 -38] were presumed to have been infected in utero and 37 (75.5%) were presumed to have been infected intrapartum. The estimated absolute overall transmission rate was 22.5%; this comprised 5.5% (95% CI, 3-9) in utero transmission and 18% (95% CI, 13-24) intrapartum transmission. Intrapartum transmission accounted for 75.5% of infections. High maternal HIV-1 viral load (> median) was a strong risk factor for both in utero [adjusted odds ratio (AOR) 5.8 (95% CI, 1.4-38.8] and intrapartum transmission (AOR, 4.4; 95% CI, 1.9-11.2). Low birth-weight was associated with in utero transmission, whereas low maternal natural killer cell and CD4(+) T-lymphocyte percentages were associated with intrapartum transmission. The population-attributable fraction for intrapartum transmission associated with viral load > 10 000 copies/ml was 69%. CONCLUSIONS Our results provide further evidence that most perinatal HIV-1 transmission occurs during labor and delivery, and that risk factors may differ according to time of transmission. Interventions to reduce maternal viral load should be effective in reducing both in utero and intrapartum transmission.

Maternal Virus Load and Perinatal Human Immunodeficiency Virus Type 1 Subtype E Transmission, Thailand

To determine the rate and risk factors for human immunodeficiency virus (HIV)-1 subtype E perinatal transmission, with focus on virus load, pregnant HIV-infected women and their formula-fed infants were followed prospectively in Bangkok. Of 281 infants with known outcome, 68 were infected (transmission rate, 24.2%; 95% confidence interval, 19.3%-29.6%). Transmitting mothers had a 4.3-fold higher median plasma HIV RNA level at delivery than did nontransmitters (P<.001). No transmission occurred at <2000 copies/mL. On multivariate analysis, prematurity (adjusted odds ratio [AOR], 4.5), vaginal delivery (AOR, 2.9), low NK cell percentage (AOR, 2.4), and maternal virus load were associated with transmission. As RNA quintiles increased, the AOR for transmission increased linearly from 4.5 to 24.8. Two-thirds of transmission was attributed to virus load>10,000 copies/mL. Although risk is multifactorial, high maternal virus load at delivery strongly predicts transmission. This may have important implications for interventions designed to reduce perinatal transmission.

Primary Infection of Human Herpesvirus 6 in Children with Vertical Infection of Human Immunodeficiency Virus Type 1

The role of human herpesvirus 6 (HHV-6) infection in 227 children born to human immunodeficiency virus (HIV)-seropositive mothers was investigated. Of 41 HIV-uninfected infants, 3 (7%) were positive for HHV-6 DNA in the first month of life, suggesting possible intrauterine infection. The cumulative infection rates of HHV-6 at 6 and 12 months of age were significantly lower in HIV-infected children (11% and 33%, respectively) than in uninfected children (28% and 78%, respectively; P<.001). There was an association between high CD4+ cell numbers (>15%) before HHV-6 infection and high HHV-6 infection rate. Twenty-two infants with HIV classed as Centers for Disease Control and Prevention stages N1 or N2 were studied for an association of HHV-6 infection with progression of HIV disease. Ten of the infants had HHV-6, and 12 did not. In 5 of the infants without HHV-6 (42%), HIV disease had not progressed by 1 year of age; however, HIV disease had progressed in all 10 children with HHV-6 infection. These results suggest an association of HHV-6 infection and progression of HIV disease in the study children with vertical HIV-1 infection (P<.05).

Impact of HIV on families of HIV-infected women who have recently given birth Bangkok Thailand.

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%; p < 0.001), 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%; p < 0.001), largely because of fear of disclosure. The women appeared to have high levels of depression and worry. The womens greatest worries were about their childrens health and the familys 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.

Pneumocystis carinii severe pneumonia among human immunodeficiency virus-infected children in Thailand : the effect of a primary prophylaxis strategy

BACKGROUND A knowledge of the epidemiology of Pneumocystis carinii pneumonia (PCP) is important for the development of a strategy for primary PCP prophylaxis and empiric treatment for severe pneumonia in HIV-infected children. However, little is known about the epidemiology of PCP in developing countries. Objective. To measure the relative rate of PCP among hospitalized HIV-infected children with severe pneumonia in Bangkok and evaluate the effect of a strategy of primary PCP prophylaxis in HIV-exposed infants. METHODS All HIV-infected children hospitalized from January, 1996, to December, 1997, for severe pneumonia were investigated for PCP with the use of specimens obtained from bronchoalveolar lavage, endotracheal aspiration or lung tissue necropsy. Characteristics associated with severe pneumonia were described, and the differences between PCP and non-PCP in these severely ill children were analyzed. In June, 1996, a strategy of primary PCP prophylaxis using trimethoprim-sulfamethoxazole in all HIV-exposed infants from 1 to 6 month of age was initiated in our institution. The effect of this strategy was evaluated. RESULTS Of 279 hospitalized HIV-infected children 128 (46%) were diagnosed with pneumonia and 26 (20%) of these had severe pneumonia. P. carinii was identified in 9 (35%) children with severe pneumonia. After June, 1996, the rate of severe pneumonia among all hospitalized children decreased from 16% from January through June, 1996, to 7% from July, 1996, through December, 1997 (P = 0.02). Cases of PCP decreased from 9 in 1996 to zero in 1997. The percentage of HIV-infected children receiving PCP prophylaxis at the time of admission increased from 53% before June, 1996, to 72% in late 1997 (P = 0.04). The overall percentage of patients with severe pneumonia receiving PCP prophylaxis at the time of admission was 34%. Breakthrough PCP occurred in 2 children with poor compliance. Patients with PCP were significantly younger than those without PCP (mean age, 10.6+/-10.6 vs. 29.8+/-28.3 months, P = 0.02). CONCLUSION PCP occurred in one-third of cases of severe pneumonia in HIV-infected children in Bangkok. The data suggest that PCP prophylaxis can prevent both PCP and non-PCP.

Efficacy and tolerability of nevirapine- versus efavirenz-containing regimens in HIV-infected Thai children.

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)-naïve and 23 ARV-experienced. An EFV-based regimen was initiated in 78 (56%): 34 ARV-naïve and 44 ARV-experienced. The CD4 cell count and percentage gains were not different between the NVP and EFV groups in both the ARV-naïve and the ARV-experienced. However, ARV-naïve children who received an EFV regimen had significantly lower baseline CD4 levels than those who received an NVP regimen. ARV-naïve 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-naïve and the ARV-experienced. Treatment failure occurred in one ARV-naïve NVP case (2.6%), two ARV-naïve 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.

Infection with Hepatitis C Virus among HIV-Infected Pregnant Women 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.

V3 sequence diversity of HIV-1 subtype E in infected mothers and their infants

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 (Fischers 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.

A comparative study of the serological response to Japanese encephalitis vaccine in HIV-infected and uninfected Thai children.

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.

Evaluating a new strategy for prophylaxis to prevent pneumocystis carinii pneumonia in Hiv-exposed infants in Thailand

ObjectiveTo evaluate a strategy for prophylaxis against Pneumocystis carinii pneumonia (PCP) for infants in Thailand. MethodsHIV-infected women were offered trimethoprim–sulfamethoxazole for PCP prophylaxis for their children at 1–2 months of age. When the children reached 6 months of age, investigators simulated a decision to continue or stop prophylaxis on the basis of clinical criteria, and compared their decisions with results of polymerase chain reaction (PCR) testing for HIV. We calculated the proportions of children who received and completed prophylaxis, and compared the rates of pneumonia and death from pneumonia with rates from an earlier prospective cohort. ResultsOf 395 eligible infants, 383 (97%) started prophylaxis. By 6 months of age, 10 (2.6%) were lost to follow-up, three (0.8%) were non-adherent, seven (2%) had stopped because of adverse events, four (1%) had died, and 359 (94%) still received prophylaxis. At 6 months of age, 30 (70%) of 43 HIV-infected children and 16 (5%) of 316 uninfected children met the clinical criteria to continue prophylaxis. The incidence of pneumonia at 1 to 6 months of age was 22% (15/68) in the earlier cohort, and 13% (6/46) in the recent cohort [relative risk (RR) 0.6, 95% confidence interval (CI) 0.3–1.4;P = 0.22]; mortality rates were 9% and 4%, respectively (RR 0.5; 95% CI 0.1–2.3;P = 0.47). ConclusionThis PCP prophylaxis strategy appeared to be acceptable and safe, may have reduced morbidity and mortality from pneumonia, and should be considered in developing countries where early laboratory diagnosis of perinatal HIV infection is unavailable.