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Summary Background Early infant diagnosis of HIV is crucial for timely initiation of antiretroviral therapy (ART) in infected children who are at high risk of mortality. Early infant diagnosis with dried blood spot testing was provided by the National AIDS Programme in Thailand from 2007. We report ART initiation and vital status in children with HIV after 7 years of rollout in Thailand. Methods Dried blood spot samples were collected from HIV-exposed children in hospitals in Thailand and mailed to the Faculty of Associated Medical Sciences, Chiang Mai University, where HIV DNA was assessed with real-time PCR to establish HIV infection. We linked data from children with an HIV infection to the National AIDS Programme database to ascertain ART and vital status. Findings Between April 5, 2007, and Oct 1, 2014, 16 046 dried blood spot samples were sent from 8859 children in 364 hospitals in Thailand. Median age at first dried blood spot test was 2·1 (IQR 1·8–2·5) months. Of 7174 (81%) children with two or more samples, 223 (3%) were HIV positive (including five unconfirmed). Of 1685 (19%) children with one sample, 70 (4%) were unconfirmed positive. Of 293 (3%) children who were HIV positive, 220 (75%) registered for HIV care and 170 (58%) initiated ART. Median age at ART initiation decreased from 14·2 months (IQR 10·2–25·6) in 2007 to 6·1 months (4·2–9·2) in 2013, and the number of children initiating ART aged younger than 1 year increased from five (33%) of 15 children initiating ART in 2007 to ten (83%) of 12 initiating ART in 2013. 15 (9%) of 170 children who initiated ART died and 16 (32%) of 50 who had no ART record died. Interpretation Early infant diagnosis with dried blood spot testing had high uptake in primary care settings. Further improvement of linkage to HIV care is needed to ensure timely treatment of all children with an HIV infection. Funding None.

OBJECTIVES: To assess the effects of highly active antiretroviral therapy (HAART) on hematological parameters in HIV-1-infected patients with and without thalassemia carriages. METHODS: Prospective study was conducted in HIV-1-infected Thai patients receiving HAART. Their hematological parameters were measured at baseline and during follow-up of 1 year. beta-thalassemia and hemoglobin-E trait were diagnosed using HPLC. PCR-genotyping techniques were used to investigate alpha-thalassemia-1 Southeast Asian type deletion and beta-thalassemia mutation. The changes of hematological parameters were compared according to thalassemia carriage. RESULTS: During follow-up increased levels of CD4 counts hemoglobin mean corpuscular volume (MCV) and mean corpuscular hemoglobin (MCH) were observed in the groups of patients with and without thalassemia. The changes in mean hemoglobin level MCV and MCH in both groups appeared parallel with consistently lower levels in patients with thalassemia. At Months 6 and 12 mean MCV of patients with thalassemia was shifted from microcytic levels (

Objectives To evaluate the effect of haematological alterations resulting from antiretroviral therapy (ART) on the diagnosis of thalassaemia carriers in HIV-1-infected Thai patients. Methods Complete blood cell counts, osmotic fragility (OF) test and haemoglobin (Hb)-A2 values were measured in blood samples of 52 antiretroviral-treated and 14 untreated HIV-1-infected patients. Data were analysed according to thalassaemia type and ART. Results Sixteen patients carried at least one of the investigated thalassaemia types and most of them (87.5%) received ART. Their red cell indices [mean corpuscular Hb (MCH), mean corpuscular Hb concentration (MCHC) and red blood cell distribution width (RDW)], OF test and Hb-A2 values were observed within the critical criteria of each thalassaemia type. Normocytic red cells were observed in α-thalassaemia and Hb-E trait. Among HIV-1-infected patients who are non-thalassaemia carriers, higher values of Hb-A2, MCH, macrocytosis and lower red cell counts were observed in the treated group. Values of RDW, MCHC and OF test for treated and untreated groups were in the normal range. Five treated patients had Hb-A2 values within the critical criteria of β-thalassaemia carriers but β-thalassaemia gene mutations were not observed by polymerase chain reaction analysis. Conclusions ART can alter many haematological figures. Therefore, diagnosis of thalassaemia should be evaluated carefully in combination with those parameters.

Since the free therapy program was started by the Thai government, the number of patients infected by HIV-1 with access to antiretroviral drugs has increased. The selection of effective interpretation algorithms for antiretroviral drug resistance has become even more important for clinical management. In this retrospective study, the level of agreement was evaluated in 721 antiretroviral-therapy failing HIV-1 subjects. Regarding genetic diversity, about 89% was recognized as non-B variants (CRF01_AE). The level of complete concordant interpretation score in all seven algorithms was recognized in non-nucleoside reverse transcriptase inhibitors (NNRTIs) and protease inhibitors (PIs) (67%), but not in nucleoside reverse transcriptase inhibitors (NRTIs) (52%). Over 10% of the major discordance score with TRUGENE was revealed in didanosine (Agence Nationale de Recherches sur le SIDA[ANRS]; Detroit Medical Centre [DMC]), abacavir (ANRS; Centre Hospitalier de Luxembourg [CHL]), and also with delavirdine, indinavir and amprenavir (Grupo de Aconselhamento Virologico [GAV]). A good to excellent agreement range of kappa scores was detected for most antiretroviral drugs. However, poor agreement with the TRUGENE system (k

OBJECTIVE The objective of this study was to analyze human immunodeficiency virus (HIV) dynamics across the blood-retinal barrier and to determine whether the high levels of HIV in the eye are associated with any ocular disorders in HIV-infected patients. DESIGN This study included a prospective case series of 40 HIV-positive patients with uveitis. INTERVENTION Clinical and laboratory examinations included plasma and intraocular HIV-1 RNA loads as well as the clinical manifestations of uveitis. RESULTS Intraocular HIV-1 RNA was detected in 32% (13/40) of HIV-positive patients with uveitis. Intraocular HIV-1 RNA loads were associated with high HIV-1 RNA plasma loads (P < 0.001) and not being on HAART therapy (P = 0.005). In addition, detectable intraocular HIV-1 RNA levels were higher in patients with the absence of retinal lesions (P = 0.008). In three patients, the HIV load in the eye largely exceeded that of plasma. These three patients had all bilateral anterior uveitis and/or vitritis without retinal lesions and exhibited no evidence of other intraocular infectious agents causing uveitis than HIV itself. CONCLUSION The eye can form a sanctuary where HIV might replicate and cause an inflammatory reaction.

The exaggerated immune response to the subclinical opportunistic microorganisms or their antigens can be found in HIV-1 infected patients after receiving antiretroviral (ARV) therapy. We report a case of unmasking tuberculosis-associated immune reconstitution inflammatory syndrome (TB-IRIS) in the HIV-1 infected patient who had no previous history of mycobacterial infection. She had tuberculosis of intestines, peritoneum and mesenteric glands within 2 months of ARV. However, her sputum acid-fast bacilli stain, sputum, blood and cervical lymph node aspiration cultures for mycobacterium were negative. Her CD4 cell count increased of from 46 cells/microL at baseline before receiving ARV to 155 cells/microL at month 6 of ARV. In addition, her plasma pro-inflammatory (IFN-gamma and TNF-alpha) and anti-inflammatory (IL-10) cytokine measurement was supported the occurrence of immune restoration reaction. Therefore, the changing in these cytokine profiles may be an important marker of developing unmasking TB-IRIS.

We report a human immunodeficiency virus-1 (HIV-1)-infected couple, where the woman in the 11th week of gestation, carried a Hb E trait. She and her spouse were referred to the hemoglobinopathy counselors. Her spouse's blood was subsequently tested and showed an increased Hb A(2) value. However, his red cell indices and osmotic fragility test were different from those found in beta-thalassemia (beta-thal) carriers. The beta-thal genes were investigated further and no mutations were observed. Therefore, it is unlikely that he is a beta-thal carrier and the increased Hb A(2) value is a result of receiving antiretroviral drugs. As antenatal thalassemia screening becomes more widespread, measuring the Hb A(2) values should be taken in all HIV-1-infected couples before the initiation of antiretroviral drugs to rule out misdiagnosis of beta-thal. However, if these tests are not available, the results of the red cell indices and osmotic fragility test should be considered as they may provide great value for beta-thal investigations.

Purpose: To determine the seroprevalence of various infectious agents in Thai patients with uveitis. Methods: Prospective study of 101 consecutive patients with uveitis, 100 HIV-infected retinitis patients, and 100 nonuveitis controls. Results: Antibodies against T. gondii were detected in 31/101 non-HIV patients, mostly with posterior uveitis and focal retinitis, and were significantly higher than in other groups examined. Antibodies for T. pallidum and Leptospira were observed more frequently in patients with HIV-infected retinitis. Active tuberculosis in non-HIV patients was not found. Conclusions: Seroprevalence of T. gondii antibodies in patients with non-HIV posterior uveitis was higher than in nonuveitis controls and HIV patients with retinitis.

Mother-to-child transmission (MTCT) of HIV-1 provides a model for studying the role of passively acquired antibodies in preventing HIV infection. We determined the titers of neutralizing antibodies (NAbs) against six primary isolates of clades B and CRF01_AE in sera from 45 transmitting and 45 nontransmitting mothers matched for the main independent factors associated with MTCT in Thailand. A lower risk of MTCT, particularly for intrapartum transmission, was associated only with higher NAb titers against the CRF01_AE strain, MBA. The envelope glycoprotein of this strain showed an unusually long V2 domain of 63 amino acids, encoding six potential N-linked glycosylation sites. We provided experimental data indicating that the extended V2 domain contributed to the higher level of resistance to neutralization by mothers' sera in this strain. Taken together the data suggest that some primary isolates with specific properties may be useful indicators for identifying protective antibodies.

BACKGROUND: In resource-limited settings, most perinatally HIV-1-infected infants do not receive timely antiretroviral therapy because early HIV-1 diagnosis is not available or affordable. OBJECTIVE: To assess the performance of a low-cost in-house real-time polymerase chain reaction (PCR) assay to detect HIV-1 DNA in infant dried blood spots (DBS). METHODS: One thousand three hundred nineteen DBS collected throughout Thailand from non-breast-fed infants born to HIV-1-infected mothers were shipped at room temperature to a central laboratory.In-house real-time DNA PCR results were compared with Roche Amplicor HIV-1 DNA test (Version 1.5) results. In addition, we verified the Roche test performance on DBS sampled from 1218 other infants using as reference HIV serology result at 18 months of age. RESULTS: Real-time DNA PCR and Roche DNA PCR results were 100% concordant. Compared with HIV serology results, the Roche test sensitivity was 98.6% (95% confidence interval: 92.6% to 100.0%) and its specificity at 4 months of age was 99.7% (95% confidence interval: 99.2% to 99.9%). CONCLUSIONS: In-house real-time PCR performed as well as the Roche test in detecting HIV-1 DNA on DBS in Thailand. Combined use of DBS and real-time PCR assays is a reliable and affordable tool to expand access to early HIV-1 diagnosis in remote and resource-limited settings, enabling timely treatment for HIV-1-infected infants.

We analyzed the characteristics of the envelope genes of human immunodeficiency virus type 1 in 17 mother-infant pairs infected with variants of the CRF01_AE clade. A total of 353 sequences covering almost the entire glycoprotein (gp) 120 region were available for analysis. We found that, even if the virus population in the mother was complex, only viruses of a restricted subset were transmitted to her infant, independently of whether transmission occurred in utero or during the intrapartum period. We did not find that shorter gp120 regions or fewer potential N-glycosylation sites (PNGS) were characteristic of viruses transmitted from mother to infant. However, our data suggest that a limited number of PNGS that seem to be conserved in all variants in infants but are not uniformly present in variants in mothers may confer an advantage for transmission of the virus, thereby highlighting the potentially important role of the "glycan shield." This finding was particularly significant for the PNGS at positions N301 and N384.

Introduction : Early infant diagnosis (EID) has been a component of Thailand’s prevention of mother-to-child HIV transmission (PMTCT) programme since 2007. This study assessed the uptake, EID coverage, proportion of HIV-exposed infants receiving a definitive HIV diagnosis, mother-to-child transmission (MTCT) rates and linkage to HIV care and treatment. Methods : Infant polymerase chain reaction (PCR) testing data from the National AIDS Program database were analyzed. EID coverage was calculated as the percentage of number of HIV-exposed infants receiving ≥1 HIV PCR test divided by the number of HIV-exposed infants estimated from HIV prevalence and live-birth registry data. Definitive HIV diagnosis was defined as having two concordant PCR results. MTCT rates were calculated based on infants tested with PCR and applied as a best-case scenario, and a sensitivity analysis was used to adjust these rates in average and worst scenarios. We defined linkage to HIV care as infants with at least one PCR-positive test who were registered with Thailand’s National AIDS Program. Chi-squared tests for linear trend were used to analyze changes in programme coverage. Results : For 2008 to 2011, the average EID coverage rate increased from 54 to 76% ( p

A randomized double blind placebo controlled trial to determine the efficacy and safety of combined-herbs (SH) given with zidovudine (ZDV) and zalcitabine (ddC) for the treatment of HIV infection in Thai adults was conducted in 3 hospitals in northern Thailand during 2002 to 2003. The eligible subjects were HIV-infected Thai adults who had never received anti-retrovirals, had a Karnofski Performance Score (KPS) ofor = 70, and had no opportunistic infections. The subjects were randomized to receive either a combination of ZDV 200 mg three times per day, ddC 0.75 mg three times per day, and SH 2.5 g three times per day or a combination of ZDV 200 mg three times per day, ddC 0.75 mg three times per day, and placebo 2.5 g three times per day for 24 weeks. The main outcome measures were HIV-RNA, CD4 cells, and blood chemistry profiles prior to the treatment and then every 4 weeks for 24 weeks. The baseline characteristics of 60 evaluable subjects, 40 in the SH group and 20 in the placebo group, were not significantly different. HIV RNA at week 4 and thereafter was significantly decreased from the baseline value in both groups (p0.001). However, the decline in HIV RNA in the SH group was significantly more than that in the placebo group. The CD4 cells in the SH group at week 12 and thereafter were significantly increased from the baseline value. Serious adverse events in the two groups were not observed. It is concluded that an addition of SH herbs to two nucleoside reverse transcriptase inhibitors has greater antiviral activity than antiretrovirals only. The SH herbs may be an alternative for the third anti-retroviral agent in the triple drug regimen for the treatment of HIV infected patients in countries with limited resources.

Mechanisms of HIV-1 in utero mother-to-child transmission (MTCT) protection provided by AZT are not completely understood. The placental cytokine network is involved in the control of HIV-1 in utero transmission but the effect of AZT on this network is unknown. To evaluate the effects of AZT on placental cytokine expression, the chorionic villi from HIV-1 uninfected women term placentae were cultured with 0, 100, and 2000ng/ml AZT. Tissue fragments were harvested at days 1, 4, and 7 to determine the level of cytokine mRNA by real-time RT-PCR. The viability and morphology of the placental histocultures were monitored by the expression of beta-human chorionic gonadotropin (beta-hCG) gene, lipopolysaccharide (LPS) activation, and microscopic examination. AZT at 2000ng/ml significantly down-regulated TNF-alpha mRNA expression at day 1 and day 4, but had no effect on beta-hCG, stromal cell-derived factor 1 (SDF-1), and IL-10 gene expression. AZT did not induce any deleterious impact on placental tissue structure. Furthermore, activation of chorionic villi by LPS for 24h up-regulated IL-10 and TNF-alpha mRNA expression. Down-regulation of TNF-alpha mRNA could represent a mechanism through which AZT can decrease the risk of HIV-1 MTCT, in addition to its direct effect on HIV-1 replication. Fil: Pornprasert, Sakorn. Institut Pasteur de Paris; Francia. Mahidol University; Tailandia. Chiang Mai University; Tailandia Fil: Faye, Albert. Institut National de la Santé et de la Recherche Médicale; Francia. Institut Pasteur de Paris; Francia Fil: Mary, Jean Yves. Institut National de la Santé et de la Recherche Médicale; Francia. Université Paris Diderot - Paris 7; Francia Fil: Dolcini, Guillermina Laura. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Institut Pasteur de Paris; Francia Fil: Leechanachai, Pranee. Chiang Mai University; Tailandia Fil: Chaouat, Gérard. Institut National de la Santé et de la Recherche Médicale; Francia Fil: Ngo, Nicole. Chiang Mai University; Tailandia Fil: Barré Sinoussi, Françoise. Institut Pasteur de Paris; Francia Fil: Menu, Elizabeth. Institut National de la Santé et de la Recherche Médicale; Francia. Institut Pasteur de Paris; Francia

A single intrapartum dose of nevirapine for the prevention of mother-to-child transmission of human immunodeficiency virus (HIV) leads to the selection of resistance mutations. Whether there are clinically significant consequences in mothers who are subsequently treated with a nevirapine-containing regimen is unknown.We randomly assigned 1844 women in Thailand who received zidovudine during the third trimester of pregnancy to receive intrapartum nevirapine or placebo. In the postpartum period, 269 of the women with a CD4 count below 250 cells per cubic millimeter began a nevirapine-containing antiretroviral regimen. Plasma samples were obtained 10 days post partum and analyzed for resistance mutations. Plasma HIV type 1 (HIV-1) RNA was measured before the initiation of therapy and three and six months thereafter.After six months of therapy, the HIV-1 RNA level was less than 50 copies per milliliter in 49 percent of the women who had received intrapartum nevirapine, as compared with 68 percent of the women who had not received intrapartum nevirapine (P=0.03). Resistance mutations to nonnucleoside reverse-transcriptase inhibitors were detectable in blood samples obtained 10 days post partum from 32 percent of the women who had received intrapartum nevirapine; the most frequent mutations were K103N, G190A, and Y181C. Among the women who had received intrapartum nevirapine, viral suppression was achieved at six months in 38 percent of those with resistance mutations and 52 percent of those without resistance mutations (P=0.08). An HIV-1 RNA level at or above the median of 4.53 log10 copies per milliliter before therapy and intrapartum exposure to nevirapine were independently associated with virologic failure. After six months of therapy, there was no significant difference between groups in the CD4 count (P=0.65).Women who received intrapartum nevirapine were less likely to have virologic suppression after six months of postpartum treatment with a nevirapine-containing regimen. Our data suggest the need for strategies to maximize the benefits of both antiretroviral prophylaxis against mother-to-child transmission of HIV and antiretroviral therapy for mothers.