A cross-sectional study of the magnitude, barriers, and outcomes of HIV status disclosure among women participating in a perinatal HIV transmission study, "the Nevirapine Repeat Pregnancy study".

BACKGROUND: HIV status disclosure is a difficult emotional task for HIV-infected persons and may create the opportunity for both social support and rejection. In this study, we evaluated the proportions, patterns, barriers and outcomes of HIV- 1 status disclosure among a group of women in Uganda. METHODS: An exit interview was conducted one year post-partum for 85 HIV-infected women who participated in a study of HIV-1 transmission rates among NVP-experienced compared with NVP-naïve women in "The Nevirapine Repeat Pregnancy (NVP-RP) Study" at the Makerere University-Johns Hopkins University Research Collaboration, Kampala-Uganda, between June 2004 and June 2006. RESULTS: Of the 85 women interviewed, 99 % had disclosed their HIV status to at least one other person. Disclosure proportions ranged between 1 % to employer(s) and 69 % to a relative other than a parent. Only 38 % of the women had disclosed to their sex partners. Women with an HIV-infected baby were more likely than those with an uninfected baby to disclose to their sex partner, OR 4.9 (95 % CI, 2.0 -11.2), and women were less likely to disclose to a partner if they had previously disclosed to another relative than if they had not, OR 0.19 (95 % CI, 0.14-0.52). The most common reasons for non-disclosure included fear of separation from the partner and subsequent loss of financial support 34 %, and not living with the partner (not having opportunities to disclose) 26 %. While most women (67 %) reported getting social support following disclosure, 22 % reported negative outcomes (neglect, separation from their partners, and loss of financial support). Following disclosure of HIV status, 9 % of women reported that their partner (s) decided to have an HIV test. CONCLUSION: Results from this study show high overall HIV disclosure proportions and how this disclosure of HIV status can foster social support. However, proportions of disclosure specifically to male sex partners were low, which suggests the need for interventions aimed at increasing male involvement in perinatal care, along with supportive counseling.

Findings from integrated behavioral and biologic survey among males who inject drugs (MWID) - Vietnam, 2009-2010: evidence of the need for an integrated response to HIV, hepatitis B virus, and hepatitis C virus.

INTRODUCTION: Given the overlapping modes of transmission of HIV, hepatitis B virus (HBV), and hepatitis C virus (HCV), understanding the burden and relationship of these infections is critical for an effective response. Representative data on these infections among males who inject drugs (MWID), the key high-risk population for HIV in Vietnam, are currently lacking. METHODS: Data and stored specimens from Vietnam's 2009-2010 Integrated Biologic and Behavioral Survey, a cross-sectional study among high-risk populations, were used for this analysis. Plasma samples were tested for HIV, HBV, and HCV using commercial assays. A questionnaire was administered to provide demographic, behavior, and service-uptake information. Provincial-level analyses were conducted to profile MWID enrollees and to provide estimates on the prevalence of HIV, HBV, and HCV infection. RESULTS: Among 3010 MWID sampled across 10 provinces, the median (range) HIV prevalence was 28.1% (1.0%-55.5%). Median prevalence for current HBV infection (HBsAg+) was 14.1% (11.7%-28.0%), for previous exposure to HBV (total anti-HBc+) was 71.4% (49.9%-83.1%), and for current or past HCV infection (HCV Ag/Ab+) was 53.8% (10.9%-80.8%). In adjusted analysis, HBsAg+ (aOR: 2.09, 1.01-4.34) and HCV Ag/Ab+ (aOR: 19.58, 13.07-29.33) status were significantly associated with HIV infection; the association with total anti-HBc+ approached significance (aOR: 1.29, 0.99-1.68). CONCLUSION: The prevalence and association between HIV, HBV, and HCV are high among MWID in Vietnam. These findings indicate the need for integrated policies and practice that for the surveillance, prevention, screening, and treatment of both HIV and viral hepatitis among MWID in Vietnam.

Enhancing the benefits of antiretroviral therapy in Vietnam: towards ending AIDS.

Vietnam has a concentrated HIV epidemic, with the highest HIV prevalence being observed among people who inject drugs (PWID). Based on its experience scaling-up robust HIV interventions, Vietnam aims to further strengthen its response by harnessing the preventive benefits of antiretroviral therapy (ART). Mathematical modelling suggests that prioritizing key populations for earlier access to ART, combined with other prevention interventions, may have significant impact on the epidemic, cost-effectively reducing new HIV infections and deaths. Pilot studies are being conducted to assess feasibility and acceptability of expansion of HIV testing and counselling (HTC) and early ART among key populations and to demonstrate innovative service delivery models to address challenges in uptake of services across the care cascade. Earlier access of key populations to combination prevention interventions, combined with sustained political commitment and supportive environment for key populations, are essential for maximum impact of ART on the HIV epidemic in Vietnam.

Strengthening global health security capacity--Vietnam demonstration project, 2013.

Over the past decade, Vietnam has successfully responded to global health security (GHS) challenges, including domestic elimination of severe acute respiratory syndrome (SARS) and rapid public health responses to human infections with influenza A(H5N1) virus. However, new threats such as Middle East respiratory syndrome coronavirus (MERS-CoV) and influenza A(H7N9) present continued challenges, reinforcing the need to improve the global capacity to prevent, detect, and respond to public health threats. In June 2012, Vietnam, along with many other nations, obtained a 2-year extension for meeting core surveillance and response requirements of the 2005 International Health Regulations (IHR). During March-September 2013, CDC and the Vietnamese Ministry of Health (MoH) collaborated on a GHS demonstration project to improve public health emergency detection and response capacity. The project aimed to demonstrate, in a short period, that enhancements to Vietnam's health system in surveillance and early detection of and response to diseases and outbreaks could contribute to meeting the IHR core capacities, consistent with the Asia Pacific Strategy for Emerging Diseases. Work focused on enhancements to three interrelated priority areas and included achievements in 1) establishing an emergency operations center (EOC) at the General Department of Preventive Medicine with training of personnel for public health emergency management; 2) improving the nationwide laboratory system, including enhanced testing capability for several priority pathogens (i.e., those in Vietnam most likely to contribute to public health emergencies of international concern); and 3) creating an emergency response information systems platform, including a demonstration of real-time reporting capability. Lessons learned included awareness that integrated functions within the health system for GHS require careful planning, stakeholder buy-in, and intradepartmental and interdepartmental coordination and communication.

Utility of Cryptococcal Antigen Screening and Evolution of Asymptomatic Cryptococcal Antigenemia among HIV-Infected Women Starting Antiretroviral Therapy in Thailand.

Cryptococcal meningitis (CM) remains a significant HIV-associated opportunistic infection in Southeast Asia and Africa, with a high burden of disease and a high mortality rate despite the availability of antiretroviral therapy (ART). We retrospectively examined the utility of cryptococcal antigen screening to identify risk for CM among 211 Thai women initiating ART. Antigenemia prevalence was 11% (n = 9) among 84 women with a CD4 count <100 cells/mm(3). Screening identified all women who later developed CM. Cryptococcal antigen titers decreased over time with ART. Our study confirmed findings from previous studies in Thailand and South Africa and provided novel observational data regarding the course of cryptococcal antigenemia in patients initiating ART and the poor efficacy of low-dose fluconazole prophylaxis in preventing CM among patients with antigenemia.

An evaluation of hepatitis B virus diagnostic methods and responses to antiretroviral therapy among HIV-infected women in Thailand.

Coinfection with HIV and hepatitis B virus (HBV) is common in resource-limited settings but is frequently not diagnosed. The authors retrospectively tested specimens for HBV in HIV-infected Thai women who had participated in an antiretroviral therapy (ART) clinical study. A substantial proportion (27 of 211; 13%) of HIV-infected women were HBV coinfected. Among HIV/HBV-coinfected women, the authors observed similar rates of antiretroviral-associated liver toxicity (despite nevirapine [NVP] use) and CD4 count reconstitution as observed in HIV-monoinfected women. Hepatitis B surface antigen (HBsAg) screening detected the majority (81%) of HBV coinfections, including all 5 HBV-coinfected women who did not suppress HBV despite 48 weeks of lamivudine (3TC)-containing ART and could be used to tailor ART for patients diagnosed with HBV coinfection in accordance with World Health Organization guidelines. Although HBsAg screening did not diagnose 5 occult HBV coinfections, these women achieved HBV suppression on 3TC-containing ART, suggesting that not detecting occult HBV coinfection would have limited clinical impact.

Prevalence of cryptococcal antigenemia and cost-effectiveness of a cryptococcal antigen screening program--Vietnam.

BACKGROUND: An estimated 120,000 HIV-associated cryptococcal meningitis (CM) cases occur each year in South and Southeast Asia; early treatment may improve outcomes. The World Health Organization (WHO) recently recommended screening HIV-infected adults with CD4<100 cells/mm(3) for serum cryptococcal antigen (CrAg), a marker of early cryptococcal infection, in areas of high CrAg prevalence. We evaluated CrAg prevalence and cost-effectiveness of this screening strategy in HIV-infected adults in northern and southern Vietnam. METHODS: Serum samples were collected and stored during 2009-2012 in Hanoi and Ho Chi Minh City, Vietnam, from HIV-infected, ART-naïve patients presenting to care in 12 clinics. All specimens from patients with CD4<100 cells/mm(3) were tested using the CrAg lateral flow assay. We obtained cost estimates from laboratory staff, clinicians and hospital administrators in Vietnam, and evaluated cost-effectiveness using WHO guidelines. RESULTS: Sera from 226 patients [104 (46%) from North Vietnam and 122 (54%) from the South] with CD4<100 cells/mm(3) were available for CrAg testing. Median CD4 count was 40 (range 0-99) cells/mm(3). Nine (4%; 95% CI 2-7%) specimens were CrAg-positive. CrAg prevalence was higher in South Vietnam (6%; 95% CI 3-11%) than in North Vietnam (2%; 95% CI 0-6%) (p = 0.18). Cost per life-year gained under a screening scenario was $190, $137, and $119 at CrAg prevalences of 2%, 4% and 6%, respectively. CONCLUSION: CrAg prevalence was higher in southern compared with northern Vietnam; however, CrAg screening would be considered cost-effective by WHO criteria in both regions. Public health officials in Vietnam should consider adding cryptococcal screening to existing national guidelines for HIV/AIDS care.

Development of a diagnosis disclosure model for perinatally HIV-infected children in Thailand.

While disclosure of HIV status to perinatally HIV-infected children has become an increasingly important clinical issue, specific disclosure guidelines are lacking. We developed a pediatric HIV diagnosis disclosure model to support caretakers. All HIV-infected children greater than 7-years-old at two participating hospitals in Bangkok, Thailand, and their caretakers, were offered disclosure according to the 4-step protocol: (1) screening; (2) readiness assessment; (3) disclosure; and (4) follow-up. Disclosure occurred after agreement of both providers and caretakers. Among 438 children who were screened, 398 (89%) were eligible. Readiness assessment was completed for 353 (91%) of eligible children and 216 (61%) were determined ready. Disclosure was done for 186 children. The mean age at eligibility screening was 10.5 years (range: 6.8-15.8 years); the mean age at disclosure was 11.7 years (range: 7.6-17.7 years). The mean duration between eligibility screening and disclosure was 15.2 months. There were no significant negative behavioral or emotional outcomes reported in children following disclosure. This HIV diagnosis disclosure model was feasible to implement and had no negative outcomes. As the time for preparation process was over 1 year for most cases, the disclosure process can be initiated as early as age 7 to allow enough time for disclosure to be completed by the age of adolescence.

Compliance with and outcomes of CD4-based national guidelines for prevention of mother-to-child transmission of HIV for Thailand, 2006-2007.

The 2006 Thailand national prevention of mother-to-child transmission of HIV (PMTCT) guidelines recommended antiretroviral (ARV) regimen use during antenatal care (ANC) be based on CD4 results: highly active antiretroviral therapy (HAART) should be used for a CD4 < 200 cells/mm(3) and zidovudine/single-dose nevirapine should be used for a CD4 count > or = 200 cell/mm(3). We evaluated compliance with and outcomes of these guidelines. We conducted a retrospective chart review of HIV-infected women and their infants born during October 2006 - December 2007 at 27 hospitals in 11 provinces of Thailand. The infant HIV-infection status was determined using laboratory test results and death reports. Mother-infant pairs were classified as fully, partially, or non-compliant with PMTCT guidelines based on CD4 testing history and ARV received. Factors associated with compliance were analyzed using univariate and multivariate generalized estimating equations (GEE). Among 875 mother-infant pairs reviewed, 387 mothers (44%) had ANC CD4 testing done, of whom 75 (19%) had a CD4 count < 200 cells/mm(3). Proportions of pairs fully, partially and non-compliant with guidelines were 38, 34 and 28%, respectively. A definitive infant HIV-infection status was determined in 578 infants (66%). The overall mother-to-child transmission (MTCT) rate was 5.1% [95% confidence interval (95%(CI): 3.8-6.9] and the MTCT rates for the fully, partially and non-compliant groups were 1.2% (95% CI: 0.4-3.3), 6.0% (95% CI: 3.7-9.5) and 9.5% (95% CI: 6.2-14.0; p<0.001). Factors associated with compliance were: have ANC, awareness of the mothers' HIV status before delivery, and having first ANC prior to 24 weeks gestation. Compliance with the 2006 national PMTCT guidelines was low, and the MTCT rates were high among non- and partially compliant mother-infant pairs. The simplified PMTCT guidellines introduced in 2010, might increase compliance with and improve outcomes for Thailand's PMTCT program.

Successful clinical outcomes following decentralization of tertiary paediatric HIV care to a community-based paediatric antiretroviral treatment network, Chiangrai, Thailand, 2002 to 2008.

INTRODUCTION: Most paediatric antiretroviral treatments (ARTs) in Thailand are limited to tertiary care hospitals. To decentralize paediatric HIV treatment and care, Chiangrai Prachanukroh Hospital (CRH) strengthened a provincial paediatric HIV care network by training community hospital (CH) care teams to receive referrals of children for community follow-up. In this study, we assessed factors associated with death and clinical outcomes of HIV-infected children who received care at CRH and CHs after implementation of a community-based paediatric HIV care network. METHODS: Clinical records were abstracted for all children who initiated ART at CRH. Paired Wilcoxon signed rank tests were used to assess CD4% and virological change among all children. Cox proportional hazard models were used to assess factors associated with death. Treatment outcomes (CD4%, viral load (VL) and weight-for-age Z-score (WAZ)) were compared between CRH and CH children who met the criteria for analysis. RESULTS: Between February 2002 and April 2008, 423 HIV-infected children initiated ART and 410 included in the cohort analysis. Median follow-up for the cohort was 28 months (interquartile range (IQR)=12 to 42); 169 (41%) children were referred for follow-up at CH. As of 31 March 2008, 42 (10%) children had died. Baseline WAZ (< -2 (p=0.001)) and baseline CD4% (<5% (p=0.015)) were independently associated with death. At 48 months, 86% of ART-naïve children in follow-up had VL<400 copies/ml. For sub-group analysis, 133 children at CRH and 154 at CHs were included for comparison. Median baseline WAZ was lower in CH children than in CRH children (p=0.001); in both groups, WAZ, CD4% and VL improved after ART with no difference in rate of WAZ and CD4% gain (p=0.421 and 0.207, respectively). CONCLUSIONS: Children at CHs had more severe immunological suppression and low WAZ at baseline. Community- and tertiary care-based paediatric ART follow-ups result in equally beneficial outcomes with the strengthening of a provincial referral network between tertiary and community care. Nutrition interventions may benefit children in community-based HIV treatment and care.

HIVQUAL-T: monitoring and improving HIV clinical care in Thailand, 2002-08.

OBJECTIVE: We report experience of HIVQUAL-T implementation in Thailand. DESIGN: Program evaluation. SETTING: Twelve government hospital clinics. PARTICIPANTS: People living with HIV/AIDS (PLHAs) aged ≥15 years with two or more visits to the hospitals during 2002-08. INTERVENTION: HIVQUAL-T is a process for HIV care performance measurement (PM) and quality improvement (QI). The program includes PM using a sample of eligible cases and establishment of a locally led QI infrastructure and process. PM indicators are based on Thai national HIV care guidelines. QI projects address needs identified through PM; regional workshops facilitate peer learning. Annual benchmarking with repeat measurement is used to monitor progress. MAIN OUTCOME MEASURE: Percentages of eligible cases receiving various HIV services. RESULTS: Across 12 participating hospitals, HIV care caseloads were 4855 in 2002 and 13 887 in 2008. On average, 10-15% of cases were included in the PM sample. Percentages of eligible cases receiving CD4 testing in 2002 and 2008, respectively, were 24 and 99% (P< 0.001); for ARV treatment, 100 and 90% (P= 0.74); for Pneumocystis jiroveci pneumonia prophylaxis, 94 and 93% (P= 0.95); for Papanicolau smear, 0 and 67% (P< 0.001); for syphilis screening, 0 and 94% (P< 0.001); and for tuberculosis screening, 24 and 99% (P< 0.01). PM results contributed to local QI projects and national policy changes. CONCLUSIONS: Hospitals participating in HIVQUAL-T significantly increased their performance in several fundamental areas of HIV care linked to health outcomes for PLHA. This model of PM-QI has improved clinical care and implementation of HIV guidelines in hospital-based clinics in Thailand.

Kinetics of nevirapine and its impact on HIV-1 RNA levels in maternal plasma and breast milk over time after perinatal single-dose nevirapine.

OBJECTIVE: To determine kinetics after single-dose nevirapine and the impact on HIV RNA [viral load (VL)] in maternal plasma and breast milk (BM). METHODS: Cohort of 120 HIV-1-infected pregnant Ugandan women received perinatal single-dose nevirapine alone and followed up with their infants through 24 weeks postdelivery. We assessed the relationship of nevirapine concentration (tandem mass spectroscopy) and HIV-1 VL (Roche AMPLICOR HIV-1 Kit, version 1.5) in maternal plasma and BM over time. RESULTS: At week 1 postpartum, NVP (≥10 ng/mL) was detected in all 53 plasma and 47 of 51 (92.2%) BM samples with median (interquartile ranges) of, respectively, 171 (78-214) ng/mL and 112 (64-158) ng/mL, P = 0.075, which decreased subsequently with traces persisting through week 4 in plasma. Plasma and BM VL dropped by week 1 and were highly correlated at delivery (R = 0.71, P < 0.001) and week 1 (R = 0.69, P < 0.001) but not thereafter. At week 1, VL correlated inversely with NVP concentration in plasma (R = 0.39, P = 0.004) and BM (R = 0.48, P = 0.013). There was a VL rebound in both compartments, which peaked at week 4 to levels greater than those at week 1 [significantly in plasma (P < 0.001) but not in BM] and remained stable thereafter. Median VL was consistently greater (11- to 50-fold) in plasma than BM at all time points (all P < 0.001). CONCLUSIONS: After single-dose nevirapine, NVP concentration was comparably high through week 1, accompanied by suppression of plasma and BM VL. A longer "tail" (>1 week) of potent postnatal antiretroviral drugs is warranted to minimize the observed VL rebound and potential for NVP resistance as a result of persistent NVP traces.

Association of Nevirapine Levels with Rash or Hepatotoxicity Among HIV-Infected Thai Women.

BACKGROUND: We performed a nested case-control study of Thai women prescribed nevirapine-based antiretroviral therapy (ART) to determine if development of rash or hepatotoxicity during the first 24 weeks of treatment is associated with plasma nevirapine concentrations. METHOD: From May 2005-January 2007, we enrolled 217 women initiating nevirapine-based ART in Thailand. Cases (n = 54) were women who during the first 24 weeks of treatment with nevirapine developed rash (any grade, n = 42) or hepatotoxicity (≥grade 2, n = 22, [10 had both]). Controls were the next enrolled woman who was confirmed not to meet the case definition during the first 24 weeks. Nevirapine concentrations after the two week lead-in dose of 200 mg once daily were compared between cases and controls by Wilcoxon rank-sum tests. RESULTS: We found no difference in Week 2 pre-dose nevirapine concentrations: cases median = 3,528 ng/mL (n = 24), controls median = 3,150ng/mL (n = 30), p = 0.5. Cases had higher post-dose nevirapine concentrations (median = 6,150 ng/mL, n = 21) than controls (median = 4,746 ng/mL, n = 20, p = 0.02). When limited to cases who developed a rash at Week 2, we found no differences in the pre-dose (median = 3,270 ng/mL, n = 12, p = 0.9) or post-dose nevirapine concentration (median = 5,443 ng/mL, n = 9, p = 0.4) compared with controls. CONCLUSIONS: We cannot conclude definitively that nevirapine concentrations at two weeks of therapy are associated with rash or hepatotoxicity. It is unlikely that therapeutic drug monitoring at that time will improve identification of patients at risk for rash or hepatotoxicity.

Optimization of a low cost and broadly sensitive genotyping assay for HIV-1 drug resistance surveillance and monitoring in resource-limited settings.

UNLABELLED: Commercially available HIV-1 drug resistance (HIVDR) genotyping assays are expensive and have limitations in detecting non-B subtypes and circulating recombinant forms that are co-circulating in resource-limited settings (RLS). This study aimed to optimize a low cost and broadly sensitive in-house assay in detecting HIVDR mutations in the protease (PR) and reverse transcriptase (RT) regions of pol gene. The overall plasma genotyping sensitivity was 95.8% (N = 96). Compared to the original in-house assay and two commercially available genotyping systems, TRUGENE® and ViroSeq®, the optimized in-house assay showed a nucleotide sequence concordance of 99.3%, 99.6% and 99.1%, respectively. The optimized in-house assay was more sensitive in detecting mixture bases than the original in-house (N = 87, P<0.001) and TRUGENE® and ViroSeq® assays. When the optimized in-house assay was applied to genotype samples collected for HIVDR surveys (N = 230), all 72 (100%) plasma and 69 (95.8%) of the matched dried blood spots (DBS) in the Vietnam transmitted HIVDR survey were genotyped and nucleotide sequence concordance was 98.8%; Testing of treatment-experienced patient plasmas with viral load (VL) ≥ and <3 log10 copies/ml from the Nigeria and Malawi surveys yielded 100% (N = 46) and 78.6% (N = 14) genotyping rates, respectively. Furthermore, all 18 matched DBS stored at room temperature from the Nigeria survey were genotyped. Phylogenetic analysis of the 236 sequences revealed that 43.6% were CRF01_AE, 25.9% subtype C, 13.1% CRF02_AG, 5.1% subtype G, 4.2% subtype B, 2.5% subtype A, 2.1% each subtype F and unclassifiable, 0.4% each CRF06_CPX, CRF07_BC and CRF09_CPX. CONCLUSIONS: The optimized in-house assay is broadly sensitive in genotyping HIV-1 group M viral strains and more sensitive than the original in-house, TRUGENE® and ViroSeq® in detecting mixed viral populations. The broad sensitivity and substantial reagent cost saving make this assay more accessible for RLS where HIVDR surveillance is recommended to minimize the development and transmission of HIVDR.

Prevalence and correlates of GB virus C infection in HIV-infected and HIV-uninfected pregnant women in Bangkok, Thailand.

GB virus C (GBV-C) is an apathogenic virus that has been shown to inhibit HIV replication. This study examined the prevalence and correlates of GBV-C infection and clearance in three cohorts of pregnant women in Thailand. The study population consisted of 1,719 (1,387 HIV-infected and 332 HIV-uninfected) women from three Bangkok perinatal HIV transmission studies. Stored blood was tested for GBV-C RNA, GBV-C antibody, and if RNA-positive, genotype. Risk factors associated with the prevalence of GBV-C infection (defined as presence of GBV-C RNA and/or antibody) and viral clearance (defined as presence of GBV-C antibody in the absence of RNA) among women with GBV-C infection were examined using multiple logistic regression. The prevalence of GBV-C infection was 33% among HIV-infected women and 15% among HIV-uninfected women. GBV-C infection was independently associated (AOR, 95% CI) with an increasing number of lifetime sexual partners (referent-1 partner, 2 partners [1.60, 1.22-2.08], 3-10 partners [1.92, 1.39-2.67], >10 partners [2.19, 1.33-3.62]); injection drug use (5.50, 2.12-14.2); and HIV infection (3.79, 2.58-5.59). Clearance of GBV-C RNA among women with evidence of GBV-C infection was independently associated with increasing age in years (referent <20, 20-29 [2.01, 1.06-3.79] and ≥30 [3.18, 1.53-6.60]), more than 10 lifetime sexual partners (3.05, 1.38-6.75), and HIV infection (0.29, 0.14-0.59). This study found that GBV-C infection is a common infection among Thai women and is associated with HIV infection and both sexual and parenteral risk behaviors.

National program scale-up and patient outcomes in a pediatric antiretroviral treatment program, Thailand, 2000-2007.

BACKGROUND: There are limited reports of public sector scale-up of antiretroviral treatment (ART) for HIV-infected children. We describe patient outcomes for HIV-infected children initiating ART in Thailand from 2000 to 2005. METHODS: ART-naive patients <15 years old initiating ART from January 2000 to December 2005 were included; follow-up was through March 2007. Survival probabilities were estimated with Kaplan-Meier and hazard ratios for death and loss to follow-up (LTFU) with Cox proportional hazards models. RESULTS: Analysis included 3409 children. Median follow-up time was 1.7 years (interquartile range = 1.0-2.5). Median age at ART initiation was 7.3 years, weight-for-age z score was -2.0, CD4% was 5.0%. ART was initiated in 1428 (41.9%) children at regional/university hospitals and in 689 (20.2%) at district/community hospitals. At last visit, 346 (10.1%) were LTFU and 305 (9.0%) had died. Age <1 (P = 0.008), weight-for-age z score <-2.0 (P < 0.001), CD4% <5% (P < 0.001), and clinical stage C (P < 0.001) were associated with death; district/community hospital patients had a lower hazard of death (P = 0.011). Clinical stage C (P = 0.052) and regional/university hospital (P < 0.001) were associated with increased LTFU. CONCLUSIONS: Pediatric ART has been successfully scaled-up in Thailand, including to district/community hospitals. Late entry to care is associated with poorer outcomes, and earlier ART initiation should be prioritized.

Effectiveness of non-nucleoside reverse-transcriptase inhibitor-based antiretroviral therapy in women previously exposed to a single intrapartum dose of nevirapine: a multi-country, prospective cohort study.

BACKGROUND: Intrapartum and neonatal single-dose nevirapine (NVP) reduces the risk of mother-to-child HIV transmission but also induces viral resistance to non-nucleoside reverse transcriptase inhibitor (NNRTI) drugs. This drug resistance largely fades over time. We hypothesized that women with a prior single-dose NVP exposure would have no more than a 10% higher cumulative prevalence of failure of their NNRTI-containing antiretroviral therapy (ART) over the first 48 wk of therapy than would women without a prior exposure. METHODS AND FINDINGS: We enrolled 355 NVP-exposed and 523 NVP-unexposed women at two sites in Zambia, one site in Kenya, and two sites in Thailand into a prospective, non-inferiority cohort study and followed them for 48 wk on ART. Those who died, discontinued NNRTI-containing ART, or had a plasma viral load >or=400 copies/ml at either the 24 wk or 48 wk study visits and confirmed on repeat testing were characterized as having failed therapy. Overall, 114 of 355 NVP-exposed women (32.1%) and 132 of 523 NVP-unexposed women (25.2%) met criteria for treatment failure. The difference in failure rates between the exposure groups was 6.9% (95% confidence interval [CI] 0.8%-13.0%). The failure rates of women stratified by our predefined exposure interval categories were as follows: 47 of 116 women in whom less than 6 mo elapsed between exposure and starting ART failed therapy (40%; p<0.001 compared to unexposed women); 25 of 67 women in whom 7-12 mo elapsed between exposure and starting ART failed therapy (37%; p = 0.04 compared to unexposed women); and 42 of 172 women in whom more than 12 mo elapsed between exposure and starting ART failed therapy (24%; p = 0.82 compared to unexposed women). Locally weighted regression analysis also indicated a clear inverse relationship between virologic failure and the exposure interval. CONCLUSIONS: Prior exposure to single-dose NVP was associated with an increased risk of treatment failure; however, this risk seems largely confined to women with a more recent exposure. Women requiring ART within 12 mo of NVP exposure should not be prescribed an NNRTI-containing regimen as first-line therapy.

Emergence and persistence of nevirapine resistance in breast milk after single-dose nevirapine administration.

OBJECTIVE: Single-dose nevirapine (NVP) (sdNVP) can reduce the risk of HIV vertical transmission. We assessed risk factors for NVP resistance in plasma and breast milk from sdNVP-exposed Ugandan women. METHODS: Samples were analyzed using the Roche AMPLICOR HIV-1 Monitor Test Kit, version 1.5, and the ViroSeq HIV-1 Genotyping System. NVP concentrations were determined by liquid chromatography with tandem mass spectroscopy. RESULTS: HIV genotypes (plasma and breast milk) were obtained for 30 women 4 weeks after sdNVP (HIV subtypes: 15A, 1C, 12D, two recombinant). NVP resistance was detected in 12 (40%) of 30 breast milk samples. There was a nonsignificant trend between detection of NVP resistance in breast milk and plasma (P = 0.06). There was no association of HIV resistance in breast milk with median maternal pre-NVP viral load or CD4 cell count, median breast milk viral load at 4 weeks, breast milk sodium more than 10 mmol/l, HIV subtype, or concentration of NVP in breast milk or plasma. CONCLUSION: NVP resistance was frequently detected in breast milk 4 weeks after sdNVP exposure. In this study, we were unable to identify specific factors associated with breast milk NVP resistance.

Pediatric HIVQUAL-T: measuring and improving the quality of pediatric HIV care in Thailand, 2005-2007.

BACKGROUND: As increasing numbers of children initiate antiretroviral treatment (ART), a systematic process is needed to measure and improve pediatric HIV care quality. METHODS: Pediatric HIVQUAL-T, a model for performance measurement and quality improvement (QI), was adapted from the U.S. HIVQUAL model by incorporating Thai national guidelines as standards. In each of five pilot-site hospitals in Thailand in 2005-2007, clinical data abstracted from patient records were used to identify priority areas for QI. Improvement strategies were designed by clinic teams in different care system areas, and indicators were remeasured in 2006 and 2007. RESULTS: At the five hospitals, 1119 HIV-infected children younger than 15 years of age received care in 2005, 1183 in 2006, and 1,341 in 2007--of whom 460, 435, and 418, respectively, were selected for chart abstraction. Of the eligible children, > or = 95% received clinical monitoring, annual CD4 count monitoring, ART, and adherence and growth assessments; 60%-90% received Pneumocystis jiroveci pneumonia (PCP) prophylaxis, tuberculosis (TB) screening, oral health assessments, and HIV disclosure. Indicators with a score < or = 40% in 2005 but with significant improvement (p < .05) in 2006-2007 following QI activities were Mycobacterium avium complex (MAC) prophylaxis, and cytomegalovirus (CMV) retinitis and immunization screenings. CONCLUSIONS: Despite the promulgation of national guidelines, performance rates of some pediatric HIV indicators needed improvement. The pediatric HIVQUAL-T model facilitates use of hospital data for pediatric HIV care improvement and indicates that the U.S. HIVQUAL model is adaptable to developing countries.