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Background: Individuals infected with human immunodeficiency virus (HIV) are at increased risk for severe influenza, yet immune responses to standard-dose intramuscular (IM) influenza vaccine are suboptimal in this population. Intradermal (ID) delivery of influenza vaccine might improve immune response through enhanced stimulation of dendritic cells., Methods: We conducted a randomized, double-blind, controlled trial to compare the immunogenicity of off-label standard-dose (15 µg) ID vs standard-dose (15 µg) IM inactive influenza vaccine in HIV-infected men in Bangkok, Thailand. The primary study outcome was seroconversion (minimum titer of 1:40 and ≥4-fold rise in antibody titer) at 1 month postvaccination based on serum hemagglutination inhibition antibody titers against each vaccine strain. Adverse events (AEs) in the 7 days following vaccination were also assessed., Results: We enrolled 400 HIV-infected participants; 200 were randomly assigned to receive IM and 200 ID vaccine. Vaccine arms were well-balanced with respect to age, CD4 cell count, HIV RNA load, and antiretroviral treatment. Percentage of seroconversion to all (ID 14% vs IM 15%; P = .8) or at least 1 (ID 69% vs IM 68%; P = .7) of the 3 vaccine strains did not differ significantly between ID vs IM vaccine recipients. A higher proportion of participants who received ID vaccine had mild injection-site AEs compared with participants who received IM vaccine (77% vs 27%)., Conclusions: There were no significant differences in the immunogenicity of standard-dose ID vs IM influenza vaccine in this HIV-infected population in Thailand. Additional strategies to enhance immune responses to influenza vaccine among HIV-infected persons are needed., Clinical Trials Registration: NCT01538940., (© The Author 2015. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com.)

Background: Tenofovir disoproxil fumarate (tenofovir) has been associated with renal dysfunction in people infected with human immunodeficiency virus (HIV) receiving combination antiretroviral therapy. We reviewed data from an HIV preexposure prophylaxis trial to determine if tenofovir use was associated with changes in renal function in an HIV-uninfected population., Methods: During the trial, 2413 HIV-uninfected people who inject drugs were randomized to receive tenofovir or placebo. We assessed the renal function of trial participants with the Cockcroft-Gault, Modification of Diet in Renal Disease (MDRD), and Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equations using t tests for cross-sectional analysis and linear regression for longitudinal analysis., Results: Creatinine clearance and glomerular filtration rate (GFR) results were lower at 24, 36, 48, and 60 months in the tenofovir group compared with the placebo group. Results declined more in the tenofovir group than in the placebo group during follow-up using the Cockcroft-Gault (P < .001) and CKD-EPI (P = .007) equations, but not MDRD (P = .12). Creatinine clearance measured when study drug was stopped was lower in the tenofovir group than the placebo group (P < .001), but the difference resolved when tested a median of 20 months later (P = .12)., Conclusions: We found small but significant decreases in cross-sectional measures of creatinine clearance and GFR in the tenofovir group compared with the placebo group and modest differences in downward trends in longitudinal analysis using the Cockcroft-Gault and CKD-EPI equations. These results suggest that with baseline assessments of renal function and routine monitoring of creatinine clearance during follow-up, tenofovir can be used safely for HIV preexposure prophylaxis. Clinical Trials Registration. NCT00119106., (Published by Oxford University Press on behalf of the Infectious Diseases Society of America 2014. This work is written by (a) US Government employee(s) and is in the public domain in the US.)

Factors increasing genital human immunodeficiency virus (HIV) shedding may increase female-to-male HIV transmission risk. We examined HIV shedding in 67 women with HIV type 1 and herpes simplex virus type 2 coinfection, during 2 menstrual cycles. Shedding occurred in 60%, 48%, and 54% of samples during the follicular, periovulatory, and luteal phases, respectively (P = .01). Shedding declined after menses until ovulation, with a slope -0.054 log10 copies/swab/day (P < .001), corresponding to a change of approximately 0.74 log10 copies between peak and nadir levels. Shedding increased during the luteal phase only among women with CD4 counts of <350 cells/µL. In reproductive-aged women, shedding frequency and magnitude are greatest immediately following menses and lowest at ovulation.

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.

Background: World Health Organization guidelines for prevention of mother-to-child transmission of human immunodeficiency virus type 1 (HIV-1) recommend administration of zidovudine and single-dose nevirapine (NVP) for HIV-1-infected women who are not receiving treatment for their own health or if complex regimens are not available. This study assessed antiretroviral resistance patterns among HIV-infected women and infants receiving single-dose NVP in Thailand, where the predominant circulating HIV-1 strains are CRF01&#95;AE recombinants and where the minority are subtype B., Methods: Venous blood samples were obtained from (1) HIV-infected women who received zidovudine from 34 weeks' gestation and single-dose NVP plus oral zidovudine during labor and (2) HIV-infected infants who received single-dose NVP after birth plus zidovudine for 4 weeks after delivery. HIV-1 drug resistance testing was performed using the TruGene assay (Bayer HealthCare)., Results: Most mothers and infants were infected with CRF01&#95;AE. NVP resistance was detected in 34 (18%) of 190 women and 2 (20%) of 10 infants. There was a significantly higher proportion of NVP mutations in women with delivery viral loads of >50,000 copies/mL (adjusted odds ratio, 8.5; 95% confidence interval, 2.2-32.8, P = .002 for linear trend) and in those with subtype B rather than CRF01&#95;AE infections (38% vs. 16%; adjusted odds ratio, 3.6; 95% confidence interval, 1.1-11.8; P = .038)., Conclusions: The lower frequency of NVP mutations among mothers infected with subtype CRF01&#95;AE, compared with mothers infected with subtype B, suggests that individuals infected with subtype CRF01&#95;AE may be less susceptible to the induction of NVP resistance than are individuals infected with subtype B.

Background: GB virus C (GBV-C) is an apathogenic virus that inhibits human immunodeficiency virus (HIV) replication in vitro. Mother-to-child transmission (MTCT) of GBV-C has been observed in multiple small studies. Our study examined the rate and correlates of MTCT of GBV-C in a large cohort of GBV-C-HIV-coinfected pregnant women in Thailand., Methods: Maternal delivery plasma specimens from 245 GBV-C-HIV-infected women and specimens from their infants at 4 or 6 months of age were tested for GBV-C RNA. Associations with MTCT of GBV-C were examined using logistic regression., Results: One hundred one (41%) of 245 infants acquired GBV-C infection. MTCT of GBV-C was independently associated with maternal antiretroviral therapy (adjusted odds ratio [AOR], 5.21 [95% confidence interval {CI}, 2.12-12.81]), infant HIV infection (AOR, 0.05 [95% CI, 0.01-0.26]), maternal GBV-C load (8.0 log(10) copies/mL: AOR, 86.77 [95% CI, 15.27-481.70]; 7.0-7.9 log(10) copies/mL: AOR, 45.62 [95% CI, 8.41-247.51]; 5.0-6.9 log(10) copies/mL: AOR, 9.07 [95% CI, 1.85-44.33]: reference, <5 log(10) viral copies/mL), and caesarean delivery (AOR, 0.26 [95% CI, 0.12-0.59])., Conclusions: Associations with maternal GBV-C load and mode of delivery suggest transmission during pregnancy and delivery. Despite mode of delivery being a common risk factor for virus transmission, GBV-C and HIV were rarely cotransmitted. The mechanisms by which maternal receipt of antiretroviral therapy might increase MTCT of GBV-C are unknown.

Background: Prolonged coinfection with GB virus C (GBV-C) has been associated with improved survival in human immunodeficiency virus (HIV)-infected adults. We investigated whether maternal or infant GBV-C infection was associated with mother-to-child transmission (MTCT) of HIV-1 infection., Methods: The study population included 1364 HIV-infected pregnant women enrolled in 3 studies of MTCT of HIV in Bangkok, Thailand (the studies were conducted from 1992-1994, 1996-1997, and 1999-2004, respectively). We tested plasma collected from pregnant women at delivery for GBV-C RNA, GBV-C antibody, and GBV-C viral genotype. If GBV-C RNA was detected in the maternal samples, the 4- or 6-month infant sample was tested for GBV-C RNA. The rates of MTCT of HIV among GBV-C-infected women and infants were compared with the rates among women and infants without GBV-C infection., Results: The prevalence of GBV-C RNA in maternal samples was 19%. Of 245 women who were GBV-C RNA positive, 101 (41%) transmitted GBV-C to their infants. Of 101 infants who were GBV-C RNA positive, 2 (2%) were infected with HIV, compared with 162 (13%) of 1232 infants who were GBV-C RNA negative (odds ratio [OR] adjusted for study, 0.13 [95% confidence interval {CI}, 0.03-0.54]). This association remained after adjustment for maternal HIV viral load, receipt of antiretroviral prophylaxis, CD4(+) count, and other covariates. MTCT of HIV was not associated with the presence of GBV-C RNA (adjusted OR [aOR], 0.94 [95% CI, 0.62-1.42]) or GBV-C antibody (aOR, 0.90 [95% CI, 0.54-1.50]) in maternal samples., Conclusions: Reduced MTCT of HIV was significantly associated with infant acquisition of GBV-C but not with maternal GBV-C infection. The mechanism for this association remains unknown.

We evaluated local reactions at 1, 2, and 4 months of age to bacille Calmette-Guérin vaccine given at birth to 1058 infants who were exposed to human immunodeficiency virus (HIV). No scar was discernible in 12 (12.4%) of 97 HIV-infected infants and 20 (2.1%) of 961 uninfected infants (relative risk, 5.9; 95% confidence interval, 3.0-11.8). This difference may reflect poorer immunogenicity in HIV-infected infants.

Palmtop-assisted self-interviewing (PASI) may provide a cheaper and more mobile alternative to audio-computer-assisted self-interviewing (ACASI) for collecting sensitive behavioral data. To evaluate PASI, in late 2002 the authors enrolled 1,283 Thai students aged 15-21 years in a randomized trial. Data collection used PASI, ACASI, self-administered questionnaire, and face-to-face interview in combination with drug-use urine testing. By use of reported levels of behaviors and agreement between self-reports of smoking and urine test results, PASI and ACASI (alpha = 0.05) were compared for noninferiority, and PASI and interview were compared for superiority (alpha = 0.05). Noninferiority of PASI was demonstrated by use of self-reports of the most sensitive areas of sexual behavior (e.g., oral sex, sexual intercourse, commercial sex, history of genital ulcers, pregnancy), as well as self-reports of less sensitive behaviors (e.g., alcohol use, dietary behaviors, symptoms of depression). Data generally showed noninferiority of PASI, ACASI, and self-administered questionnaires when compared with each other and superiority of PASI, ACASI, and self-administered questionnaires when compared with interviews. PASI agreements between self-reports of tobacco smoking and presence of nicotine metabolites in urine were noninferior to ACASI and superior to interviews. The establishment of PASI noninferiority and superiority using behavioral and biologic measures suggests that PASI is a scientifically acceptable alternative for collecting sensitive behavioral data.

The Bangkok (Thailand) Metropolitan Administration cohort of injecting drug users (IDUs) consisted of 1,209 IDUs initially seronegative for human immunodeficiency virus (HIV) who were followed from 1995 to 1998 at 15 Administration drug treatment clinics. At enrollment and approximately every 4 months thereafter, participants were assessed for HIV seropositivity. As of December 1998, there were 133 HIV type 1 seroconversions and approximately 2,300 person-years of follow-up. Of the 133 observed seroconversions, specimens from 126 persons were available for subtyping (27 subtype B, 99 subtype E). In this analysis, the authors assessed differences in subtype-specific transmission while controlling for important risk factors. The methodology used accounts for left truncation, interval censoring, and competing risks as well as for time-varying covariates such as each IDU's history of reported frequency of injection and of incarceration. Using plausible epidemiologic assumptions and controlling for behavioral risks, the authors found that a significantly higher transmission probability was associated with subtype E compared with subtype B in this population. Since many epidemiologic, virologic, and host factors can influence HIV transmission, it was difficult to conclude whether these differences in transmission probabilities were due to biologic properties associated with subtype.

Human immunodeficiency virus (HIV) levels in cervicovaginal lavage (CVL) and plasma samples were evaluated in relation to perinatal transmission in a randomized placebo-controlled trial of brief antenatal zidovudine treatment. Samples were collected at 38 weeks' gestation from 310 women and more frequently from a subset of 74 women. At 38 weeks, after a 2-week treatment period, CVL HIV-1 was quantifiable in 23% and 52% of samples in the zidovudine and placebo groups, respectively (P<.001). The perinatal transmission rate was 28.7% among women with quantifiable CVL HIV-1 and high plasma virus levels (>10,000 copies/mL) and 1% among women without quantifiable CVL HIV-1 and with low plasma virus levels (P<.001). A 1-log increase in plasma HIV-1 increased the transmission odds 1.8 and 6.1 times (95% confidence interval, 0.9-3.5 vs. 2.4-15.4) for women with and without quantifiable CVL HIV-1, respectively (P=.03). CVL HIV-1 is an independent risk factor for perinatal HIV-1 transmission.

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.

Both plasma and dietary measures of vitamin A status were investigated along with previously established risk factors (number of sexual partners, age at first intercourse, smoking, and oral contraceptive use) in a study of 117 in situ cervical cancer patients and 196 matched community controls in Sydney, Australia. Neither total calories nor retinol from foods was related to cancer risk, nor was plasma retinol. When plasma and dietary indexes were considered together, vitamin C, fruit juices, and plasma beta-carotene showed protective effects. Plasma beta-carotene reduced risk from top to bottom quartile by 80%, vitamin C by 60%, and fruit juices by 50%. Thus the evidence suggests that cancer risk is associated with some aspect of diet that is reflected in the effect of plasma beta-carotene. There is no clear effect of any one nutrient but fruit juices appear protective. Thus vitamin C and beta-carotene are likely candidates.