Evaluation of the effect of human immunodeficiency virus-related structural interventions: the connect to protect project.

IMPORTANCE: With the emphasis on structural-level interventions that target social determinants of human immunodeficiency virus (HIV) transmission to curb the HIV epidemic, there is a need to develop evaluation models that can detect changes in individual factors associated with HIV-related structural changes. OBJECTIVE: To describe whether structural changes developed and achieved by community coalitions are associated with an effect on individual factors associated with the risk of contracting HIV. DESIGN, SETTING, AND PARTICIPANTS: In this serial cross-sectional survey design, data were collected from 8 cities during 4 rounds of annual surveys from March 13, 2007, through July 29, 2010. Study recruitment took place at venues where the population of focus was known to congregate, such as clubs, bars, community centers, and low-income housing. The convenience sample of at-risk youth (persons aged 12-24 years) included 5337 individuals approached about the survey and 3142 (58.9%) who were screened for eligibility. Of the 2607 eligible participants, 2559 (98.2%) ultimately agreed to participate. INTERVENTIONS: Achievement of locally identified structural changes that targeted public and private entities (eg, federal agencies, homeless shelters, and school systems) with the goal of fostering changes in policy and practice to ultimately facilitate positive behavioral changes aimed at preventing HIV. MAIN OUTCOMES AND MEASURES: Number of sexual partners, partner characteristics, condom use, and history of sexually transmitted infections and HIV testing. RESULTS: Exposure to structural changes was not statistically significantly associated with any of the outcome measures, although some results were in the direction of a positive structural change effect (eg, a 10-unit increase in a structural change score had an odds ratio of 0.88 [95% CI, 0.76-1.03; P = .11] for having an older sexual partner and an odds ratio of 0.91 [95% CI, 0.60-1.39; P = .39] for using a condom half the time or less with a casual partner). CONCLUSIONS AND RELEVANCE: This study evaluated a broad representation of at-risk individuals and assessed the effect of numerous structural changes related to various HIV risk factors. No structural changes as measured in this study were associated with a statistically significant reduction in risk behaviors. These null findings underscore the need for a long-term approach in evaluating structural interventions and the development of more nuanced methods of quantifying and comparing structural-change initiatives and determining the appropriate strategies for evaluating effect.

Profiles of Risk Among HIV-Infected Youth in Clinic Settings.

Despite the rising number of new HIV infections among youth, few tailored interventions for youth living with HIV (YLH) have been developed and rigorously tested. Developing tailored interventions necessitates identifying different profiles of YLH and understanding how risk and protective factors cluster together. Obtaining this critical information requires accessing a sufficiently large sample of YLH from diverse geographic settings such as those available through the Adolescent Trials Network for HIV Interventions (ATN). We recruited a cross-sectional sample of 1,712 YLH from ATN clinics; participants completed a survey on psychosocial and health factors. Using latent class analysis on nine composite variables representing risk factors, we identified five classes distinguished by substance use, sexual behavior, and pregnancy history and differing on health outcomes. Findings suggest a need for tailored interventions addressing multiple risky behaviors of HIV-infected youth and research to clarify how intervention effectiveness may differ by risk profile.

A comparison of network-based strategies for screening at-risk Hispanic/Latino adolescents and young adults for undiagnosed asymptomatic HIV infection.

PURPOSE: Hispanic/Latino adolescents and young adults are disproportionately impacted by the HIV/AIDS epidemic; yet little is known about the best strategies to increase HIV testing in this group. Network-based approaches are feasible and acceptable means for screening at-risk adults for HIV infection, but it is unknown whether these approaches are appropriate for at-risk young Hispanics/Latinos. Thus, we compared an alternative venue-based testing (AVT) strategy with a social and sexual network-based interviewing and HIV testing (SSNIT) strategy. METHODS: All participants were Hispanics/Latinos aged 13-24 years with self-reported HIV risk; they were recruited from 11 cities in the United States and Puerto Rico and completed an audio computer-assisted self-interview and underwent HIV screening. RESULTS: A total of 1,596 participants (94.5% of those approached) were enrolled: 784 (49.1%) through AVT and 812 (50.9%) through SSNIT. HIV infection was identified in three SSNIT (.37%) and four AVT (.51%) participants (p = .7213). CONCLUSIONS: Despite high levels of HIV risk, a low prevalence of HIV infection was identified with no differences by recruitment strategy. We found overwhelming support for the acceptability and feasibility of AVT and SSNIT for engaging and screening at-risk young Hispanics/Latinos. Further research is needed to better understand how to strategically implement such strategies to improve identification of undiagnosed HIV infection.

Implementing asthma guidelines using practice facilitation and local learning collaboratives: a randomized controlled trial.

PURPOSE: Guideline implementation in primary care has proven difficult. Although external assistance through performance feedback, academic detailing, practice facilitation (PF), and learning collaboratives seems to help, the best combination of interventions has not been determined. METHODS: In a cluster randomized trial, we compared the independent and combined effectiveness of PF and local learning collaboratives (LLCs), combined with performance feedback and academic detailing, with performance feedback and academic detailing alone on implementation of the National Heart, Lung and Blood Institute's Asthma Guidelines. The study was conducted in 3 primary care practice-based research networks. Medical records of patients with asthma seen during pre- and postintervention periods were abstracted to determine adherence to 6 guideline recommendations. McNemar's test and multivariate modeling were used to evaluate the impact of the interventions. RESULTS: Across 43 practices, 1,016 patients met inclusion criteria. Overall, adherence to all 6 recommendations increased (P ≤.002). Examination of improvement by study arm in unadjusted analyses showed that practices in the control arm significantly improved adherence to 2 of 6 recommendations, whereas practices in the PF arm improved in 3, practices in the LLCs improved in 4, and practices in the PF + LLC arm improved in 5 of 6 recommendations. In multivariate modeling, PF practices significantly improved assessment of asthma severity (odds ratio [OR] = 2.5, 95% CI, 1.7-3.8) and assessment of asthma level of control (OR = 2.3, 95% CI, 1.5-3.5) compared with control practices. Practices assigned to LLCs did not improve significantly more than control practices for any recommendation. CONCLUSIONS: Addition of PF to performance feedback and academic detailing was helpful to practices attempting to improve adherence to asthma guidelines.

Immunogenicity and safety of the human papillomavirus 6, 11, 16, 18 vaccine in HIV-infected young women.

BACKGROUND: The objective of this study was to determine whether the 3-dose quadrivalent human papillomavirus (HPV) vaccine series (HPV-6, -11, -16, -18) is immunogenic and safe in young women infected with human immunodeficiency virus (HIV). METHODS: We enrolled 99 women aged 16-23 years in a phase 2, open-label, multicenter trial, conducted from 2008 to 2011 by the Adolescent Medicine Trials Network for HIV/AIDS Interventions. Outcome measures were immunogenicity 4 weeks after dose 3, measured by (1) geometric mean titers (GMTs) and (2) seroconversion rates for HPV-6, -11, -16, and -18, among those seronegative and HPV DNA negative for each type. Immune responses were compared to those of a historical comparison group of HIV-negative women (n = 267) using univariate methods. Clinical and laboratory adverse events were assessed after each dose. RESULTS: The mean age of subjects was 21.4 years; 80% were non-Hispanic black, 69 were not taking antiretroviral therapy (ART), and 30 were taking ART. No differences in GMTs were noted among participants taking ART vs the comparison group, but GMTs were lower in participants not taking ART vs the comparison group for HPV-16 (2393 vs 3892 milli-Merck units per milliliter [mMU/mL], P = .012) and HPV-18 (463 vs 801 mMU/mL, P = .003). Seroconversion rates were 100% for HPV-6, -11, -16, and -18 among participants taking ART. Rates ranged from 92.3% (for HPV-18) to 100.0% (for HPV-6) among participants not taking ART. One severe adverse event (fatigue) was noted. CONCLUSIONS: In a sample of HIV-infected women who were HPV DNA and HPV seronegative, immune responses to HPV vaccination were generally robust and the vaccine was well tolerated.

Prevalence and risk factors for HPV in HIV-positive young women receiving their first HPV vaccination.

BACKGROUND: The objectives of this study were to describe the prevalence and risk factors for HPV infection among HIV-infected young women receiving their first quadrivalent HPV (HPV-6, -11, -16, and -18) vaccine dose. METHODS: We recruited 16- to 23-year-old women from 14 sites for an HPV vaccine trial. At the first visit, they completed a questionnaire and were tested for cervicovaginal HPV DNA (41 types) and HPV serology (4 vaccine types). Factors associated with any HPV, type-specific HPV, and high-risk (cancer-associated) HPV infections were identified using univariate and multivariable logistic regression. RESULTS: The mean age of participants (N = 99) was 21.4 years, 30.3% were on antiretroviral therapy, 74.7% were positive for ≥1 HPV DNA type, 53.5% for ≥1 high-risk type, 12.1% for HPV-16, and 5.1% for HPV-18. Most were HPV DNA negative and seronegative for HPV-16 (55.6%) and HPV-18 (73.7%); 45.5% were HPV DNA negative and seronegative for both HPV-16 and -18. Three variables were associated with high-risk HPV DNA in multivariable analysis: non-Hispanic black versus Hispanic ethnicity (adjusted odds ratio [AOR]: 7.06, 95% CI: 1.63 to 30.5), HIV viral load ≥ 400 versus <400 copies/mL (AOR: 3.47, 95% CI: 1.28 to 9.43), and frequency of vaginal sex in the past 90 days (AOR: 5.82, 95% CI: 1.30 to 26.11 for ≥6 vs 0 times). CONCLUSIONS: The prevalence of ≥1 HPV type was high in these young women, demonstrating the importance of vaccinating before sexual initiation. However, most women were HPV DNA negative and seronegative for high-risk vaccine-type HPV infection, supporting vaccination of sexually experienced HIV-positive young women.

Risk perceptions after human papillomavirus vaccination in HIV-infected adolescents and young adult women.

PURPOSE: To examine risk perceptions (perceived risk of human papillomavirus [HPV], perceived risk of other sexually transmitted infections [STIs], and need for safer sexual behaviors) and to determine factors associated with these risk perceptions after HPV vaccination. METHODS: Data were collected at the baseline visit of an HPV-6, -11, -16, -18 vaccine clinical trial in 16-23-year-old HIV-infected young women (N = 99). Immediately after receiving the first vaccine dose, participants completed a confidential questionnaire that included three 5-item scales measuring perceived risk of HPV, perceived risk of other STIs, and need for safer sexual behaviors. Linear and logistic regression models were used to examine associations between baseline characteristics (demographic characteristics; cluster of differentiation antigen 4 (CD4(+)) count; HIV viral load; knowledge about HPV and HPV vaccines; sexual behaviors; and STI diagnosis) and each measure of risk perceptions. RESULTS: Most participants perceived themselves to be at lower risk for HPV (mean scale score = 19.5/50), most perceived that they were not at lower risk for other STIs (mean = 31.2/50), and the vast majority reported that there was still a need for safer sexual behaviors after vaccination (mean = 43.1/50). Multivariate analyses indicated that knowledge about HPV and HPV vaccines was associated with perceived need for safer sexual behaviors (OR = 1.05, 95% CI = 1.0-1.1). CONCLUSIONS: Although almost all young women in this study believed that safer sexual behaviors were still important after HPV vaccination, a subset believed they were at less risk for STIs other than HPV. Educational interventions are needed to prevent misperceptions and promote healthy behaviors after vaccination.

Lipid levels in the second year of life among HIV-infected and HIV-exposed uninfected Latin American children.

BACKGROUND: Dyslipidemia is observed among older children and adults with HIV. We examined nonfasting cholesterol and triglycerides in two groups of 12-23-month-old Latin American children - HIV-infected vs. HIV-exposed but uninfected (HEU). METHODS: HIV-infected and HEU children in Latin America and Jamaica were enrolled in an observational cohort. Eligibility for this analysis required having cholesterol and triglyceride results available during the second year of life. RESULTS: HIV-infected (n = 83) children were slightly older at the time of lipid testing than the HEU (n = 681). Forty percent of the HIV-infected children were on protease inhibitor-based antiretroviral therapy (ART); 41% were not on ART. There was no statistically significant difference in mean cholesterol concentrations (mg/dl) by HIV status; however, the HIV-infected children had higher mean triglyceride concentrations. The prevalence of high cholesterol (>200  mg/dl) and high triglycerides (>110 mg/dl) was higher among the HIV-infected vs. HEU. Among the HIV-infected children, mean cholesterol and triglyceride concentrations varied by ART. Children receiving no ART had a significantly lower mean cholesterol concentration. Those receiving protease inhibitor-containing ART had a significantly higher mean triglyceride concentration compared to the other two antiretroviral regimen groups. CONCLUSION: A greater proportion of HIV-infected children at 12-23 months have hyperlipidemia when compared to HEU children, with the highest triglyceride concentrations observed among those receiving protease inhibitor-containing ART, and the lowest cholesterol levels among those not receiving ART. Implications of these findings will require continued follow-up of HIV-infected children who initiate therapy early in life.

A randomized, placebo controlled, double masked phase IB study evaluating the safety and antiviral activity of aprepitant, a neurokinin-1 receptor antagonist in HIV-1 infected adults.

BACKGROUND: Neurokinin-1 receptor (NK1R) antagonists have anti-HIV activity in monocyte-derived macrophages, decrease CCR5 expression and improve natural killer cell function ex vivo. Aprepitant is a NK1R antagonist approved by FDA as an antiemetic. METHODS: We conducted a phase IB randomized, placebo controlled, double masked study to evaluate the safety, antiviral activity, pharmacokinetics and immune-modulatory effects of aprepitant in HIV-infected adults not receiving antiretroviral therapy, with CD4+ cell count ≥350 cells/mm(3) and plasma viral load ≥2,000 copies/ml. Subjects were stratified by viral load (< vs. ≥20,000 copies/ml) and randomized within each stratum to receive aprepitant at 125 mg QD(Low), or 250 mg QD(High), or placebo(PL) for 14 days, and followed for 42 days. RESULTS: Thirty subjects were randomized and 27 completed treatment (9, 8, 10 subjects in 125 (Low), 250 (High), and PL groups). 63% were male; 37% white; mean (SD) age 43 (9.3) years. Geometric mean baseline viral load (copies/ml) for Low, High, and PL was 15,709, 33,013, and 19,450, respectively. Mean (95%CI) change in log10 viral load at day 14 for Low, High, and PL was -0.02(-0.24,+0.20), -0.05(-0.21,+0.10), and +0.04(-0.08,+0.16), respectively. The number of subjects with AEs was 4(44.4%), 5(62.5%), and 1(10%) for Low, High, and PL. No Grade 4 AEs occurred. CONCLUSIONS: Adverse events of aprepitant were more common in the treated groups. At the dose used in this two-week phase IB study, aprepitant showed biological activity, but no significant antiviral activity. TRIAL REGISTRATION: ClinicalTrials.gov NCT00428519.

A retrospective analysis of outcomes by age in a three-arm phase III trial of gemcitabine in combination with carboplatin or paclitaxel vs. paclitaxel plus carboplatin for advanced non-small cell lung cancer.

PURPOSE: Sufficient data are currently unavailable to assist in defining suitable regimens for patients ≥ 70 years with advanced non-small cell lung cancer (NSCLC). METHODS: Chemonaïve patients with a performance status (PS) of 0 or 1 and stage IIIB or IV NSCLC were randomized to gemcitabine 1000mg/m(2) on days 1 and 8 plus carboplatin area under the curve (AUC) 5.5 on day 1; the same schedule of gemcitabine plus paclitaxel 200mg/m(2) on day 1; or paclitaxel 225mg/m(2) on day 1 plus carboplatin AUC 6.0 on day 1. Cycles were every 21 days up to 6. Efficacy and toxicity results were compared by age groups. RESULTS: Overall survival (OS) between patients <70 years (8.6 months, 95% CI: 7.9, 9.5) and ≥ 70 years (7.9 months, 95% CI: 7.1, 9.5) was similar. OS was 8.8 months (95% CI: 7.5, 10.3) among patients 70-74 years, 6.5 months (95% CI: 5.6, 9.3) among patients 75-79 years, and 7.9 months (95% CI: 6.3, 10.3) among patients ≥ 80 years. OS was lower among patients 75-79 years compared with patients 70-74 years (P=0.04). Compared with patients <70 years, patients ≥ 70 years experienced similar rates of myelosuppresion, but younger patients experienced more vomiting and nausea. There was no clear pattern with respect to differences in efficacy by treatments across age groups. CONCLUSIONS: Based on the similarity of patient outcomes across age groups, doublet chemotherapy is feasible among carefully selected elderly patients with good PS.

Nurse versus doctor management of HIV-infected patients receiving antiretroviral therapy (CIPRA-SA): a randomised non-inferiority trial.

BACKGROUND: Expanded access to combination antiretroviral therapy (ART) in resource-poor settings is dependent on task shifting from doctors to other health-care providers. We compared outcomes of nurse versus doctor management of ART care for HIV-infected patients. METHODS: This randomised non-inferiority trial was undertaken at two South African primary-care clinics. HIV-positive individuals with a CD4 cell count of less than 350 cells per microL or WHO stage 3 or 4 disease were randomly assigned to nurse-monitored or doctor-monitored ART care. Patients were randomly assigned by stratified permuted block randomisation, and neither the patients nor those analysing the data were masked to assignment. The primary objective was a composite endpoint of treatment-limiting events, incorporating mortality, viral failure, treatment-limiting toxic effects, and adherence to visit schedule. Analysis was by intention to treat. Non-inferiority of the nurse versus doctor group for cumulative treatment failure was prespecified as an upper 95% CI for the hazard ratio that was less than 1.40. This study is registered with ClinicalTrials.gov, number NCT00255840. FINDINGS: 408 patients were assigned to doctor-monitored ART care and 404 to nurse-monitored ART care; all participants were analysed. 371 (46%) patients reached an endpoint of treatment failure: 192 (48%) in the nurse group and 179 (44%) in the doctor group. The hazard ratio for composite failure was 1.09 (95% CI 0.89-1.33), which was within the limits for non-inferiority. After a median follow-up of 120 weeks (IQR 60-144), deaths (ten vs 11), virological failures (44 vs 39), toxicity failures (68 vs 66), and programme losses (70 vs 63) were similar in nurse and doctor groups, respectively. INTERPRETATION: Nurse-monitored ART is non-inferior to doctor-monitored therapy. Findings from this study lend support to task shifting to appropriately trained nurses for monitoring of ART. FUNDING: National Institutes of Health; United States Agency for International Development; National Institute of Allergy and Infectious Diseases.

Clinical performance of an in-house real-time RT-PCR assay using a fluorogenic LUX primer for quantitation of human immunodeficiency virus type-1 (HIV-1).

The South African National Antiretroviral Treatment Guideline recommends the use of HIV viral load assays for routine monitoring of HIV-1 positive patients on Highly Active Antiretroviral Therapy (HAART). Approved commercial HIV-1 viral load assays are expensive for developing countries where a large number of patients are treated in the public sector. The evaluation of an in-house HIV-1 viral load assay (LUX assay) is described using 458 plasma specimens. Good specificity of the LUX assay was demonstrated using 50 seronegative plasma specimens. A group of 142 HIV-1 positive patients was used to assess the agreement between the LUX assay and the COBAS Amplicor assay. An intra class correlation (ICC) coefficient of 0.85 (CI 95%) indicated good agreement between the assays. The Bland-Altman model showed good agreement between the assays for approximately 87% of the results (mean 0.03 [-1.26; 1.32], CI 95%). In a cohort of 55 patients followed-up longitudinally the LUX assay showed similar declines in viral load to the COBAS Amplicor assay in response to therapy. Viral rebound was detected in 5 patients out of 55 by both assays. Thus, the LUX assay compares well to the gold standard and represents an affordable alternative for high volume testing in resource limited settings.

Maternal antiretroviral drugs during pregnancy and infant low birth weight and preterm birth.

OBJECTIVE: To determine the relationship between maternal antiretroviral regimens during pregnancy and adverse infant outcomes [low birth weight (LBW) and preterm birth]. The a priori hypothesis was that protease inhibitor (PI)-containing regimens are associated with an increased risk of LBW and preterm birth. DESIGN: Prospective cohort study of HIV-1-infected women and their infants (NISDI Perinatal Study). METHODS: Data were analysed from 681 women receiving at least one antiretroviral drug [in order of increasing complexity: one or two nucleoside reverse transcriptase inhibitors (1-2 NRTI), two NRTI plus one non-nucleoside reverse transcriptase inhibitor (NNRTI) (HAART/NNRTI), or two NRTI plus one PI (HAART/PI)] for at least 28 days during pregnancy, and who delivered live born, singleton infants with known birth weight and gestational age by 1 March 2005. Multivariable logistic regression modeling was used to assess the relationship of maternal ART with LBW and with preterm birth, adjusting for covariates. RESULTS: The incidence of LBW and preterm birth, respectively, was 9.6% and 7.4% (1-2 NRTI), 7.4% and 5.8% (HAART/NNRTI), and 16.7% and 10.6% (HAART/PI). There was no statistically significant increased risk of LBW [adjusted odds ratio (AOR), 1.5; 95% confidence interval (95% CI), 0.7-3.2] or preterm birth (AOR, 1.1; 95% CI, 0.5-2.8) among women who received HAART/PI compared with women receiving 1-2 NRTI. CONCLUSIONS: Among a population of HIV-1-infected women in Latin America and the Caribbean, maternal receipt of PI-containing ART regimens during pregnancy was not associated with a statistically significant increase in risk of LBW or preterm birth.

Temporal trends and drug exposures in pulmonary hypertension: an American experience.

BACKGROUND: Reports have linked anorexigen intake to an increased risk of pulmonary arterial hypertension (PAH). With the rise in anorexigen use in the latter half of the last decade, we established a surveillance network within the United States to monitor temporal trends in the number of reported cases of PAH. We also studied whether use of anorexigens and other drugs differed among patients with pulmonary hypertension of different etiologies. METHODS: Newly diagnosed subjects (N = 1335) at 13 tertiary pulmonary hypertension centers were enrolled between January 1998 and June 2001. Patient-reported medication use was obtained by a telephone interview. Patients were classified as to the type of pulmonary hypertension. Poisson regression models were fitted to monthly case counts, and logistic regression methods were used to assess the association between type of pulmonary hypertension and medication use. RESULTS: The average monthly number of reported cases of PAH and other categories of pulmonary hypertension did not change over the study period. Fenfluramine or dexfenfluramine use during the 5 years before the time of the interview was preferentially associated with PAH. Fenfluramine/dexfenfluramine use was particularly common in cases referred but found not to have pulmonary hypertension. CONCLUSIONS: No epidemic of anorexigen-related PAH was evident during the study period. As persons who had taken fenfluramine or dexfenfluramine were particularly likely to be referred for evaluation of pulmonary hypertension, it is unlikely that the failure to detect an anorexigen-induced rise in primary pulmonary hypertension was because of underascertainment. The association between fenfluramine derivatives and PAH is consistent with the risk elevations previously reported.

Mode of delivery and postpartum morbidity in Latin American and Caribbean countries among women who are infected with human immunodeficiency virus-1: the NICHD International Site Development Initiative (NISDI) Perinatal Study.

OBJECTIVE: The purpose of this study was to test whether cesarean delivery before labor and before ruptured membranes is associated with a higher risk of postpartum morbidity than vaginal delivery among women who are infected with human immunodeficiency virus-1 in Latin America and the Caribbean. STUDY DESIGN: Data from a prospective cohort study (National Institute of Child Health and Human Development International Site Development Initiative Perinatal Study) were analyzed. The study population consisted of women who were followed for > or = 6 to 12 weeks after delivery, who had singleton infants, and with a known mode of delivery. RESULTS: Of 819 enrollees, 697 women met inclusion criteria (299 vaginal deliveries, 260 cesarean deliveries before labor and before ruptured membranes, 138 cesarean deliveries after labor and/or after ruptured membranes); 36 women (5%) had postpartum morbidity (18 major, 18 minor). Mode of delivery was associated with postpartum morbidity (P = .02). Unadjusted odds ratios (95% CIs) for postpartum morbidity according to mode of delivery were cesarean delivery before labor and before ruptured membranes (odds ratio, 1.16 [95% CI, 0.5, 2.7]), cesarean delivery after labor and/or after ruptured membranes (odds ratio, 2.96 [95% CI, 1.3, 6.7]), and vaginal delivery (reference). These results did not differ appreciably with covariate adjustment. CONCLUSION: The rate of postpartum morbidity was low. Mode of delivery was associated with postpartum morbidity, possibly reflecting the larger proportion of minor postpartum morbidity events among those with cesarean delivery after labor and/or after ruptured membranes.

Evaluation of two commercially available, inexpensive alternative assays used for assessing viral load in a cohort of human immunodeficiency virus type 1 subtype C-infected patients from South Africa.

Although human immunodeficiency virus type 1 (HIV-1) RNA is the acknowledged "gold standard" marker for monitoring disease activity in patients receiving highly active antiretroviral therapy (HAART), it remains unaffordable in resource-constrained settings. The present study investigated two commercially available kits for the detection of HIV-1 viral load markers as more affordable alternatives to HIV-1 RNA quantitation. The greatly improved heat-denatured, signal-boosted HiSens HIV-1 p24 Ag Ultra kit (Perkin-Elmer) and the ExaVir Load Quantitative HIV-RT kit (Cavidi Tech AB) were compared with the Amplicor HIV-1 Monitor (version 1.5) assay (Roche Molecular Systems Inc.). A total of 117 samples containing HIV-1 subtype C were analyzed by all three methodologies. Eighty-nine of these samples represented serial measurements from 20 patients receiving HAART. The remaining samples analyzed were from a group of treatment-naive patients. The association between the p24 antigen assay and the RNA assay was fairly strong (R(2) = 0.686). The association between the reverse transcriptase (RT) quantitation assay and the RNA assay was strong (R(2) = 0.810). Both alternative assays seemed most useful for the serial monitoring of patients receiving HAART (n = 89 plasma samples from 20 patients), as all assays showed a statistically significant downward trend over time, with the trend being either linear or curvilinear. In addition, all three assays showed negative correlations with the CD4 count (CD4 count versus RNA load, r = -0.336 and P = 0.001; CD4 count versus p24 antigen level, r = -0.541 and P < 0.0001; CD4 count versus RT level, r = -0.358 and P = 0.0006). Still of major concern are both the lack of sensitivity and the wide degrees of variability of both assays. However, both assays provide a less expensive alternative to the Roche viral load assay and demonstrate the same trends during treatment.

Controlled trials of very high dose folic acid, vitamins B12 and B6, intravenous folinic acid and serine for treatment of hyperhomocysteinemia in ESRD.

BACKGROUND: Hyperhomocysteinemia is seen in most hemodialysis (HD) patients and is an independent risk factor for cardiovascular disease. Homocysteine metabolism via remethylation requires activated folate and vitamin B12 and metabolism via transsulfuration requires serine and vitamin B6. Prior studies have shown highly variable effects of supplemental B vitamin and folate therapy for hyperhomocysteinemia. We undertook a fully controlled trial with abnormally high doses of folic acid alone or with supplemental vitamin B6 and B12 compared with active folate alone or with serine. METHODS: Two prospective studies were undertaken in hemodialysis patients. In the first study (protocol A), hyperhomocysteinemia was treated in 77 patients with 30 or 60 mg folic acid with or without vitamins B6 and B12 for eight weeks and compared with matching placebos. In the second study (protocol B), hyperhomocysteinemia was treated in 37 patients with intravenous folinic acid given alone or with serine and compared with matching placebos. All patients received the standard of care treatment with a multivitamin tablet before and throughout the protocol to test the hypothesis that additional therapy is required over and above the routine therapy for maximum reduction in total homocysteine (tHcy). RESULTS: Normal volunteers; The mean (SD) tHcy of 128 normal subjects was 6.5 (4) micromol/L. Protocol A; Plasma folate increased significantly in the groups given folic acid at both four and eight weeks (P = 0.0001 at both time points). Plasma vitamin B12 was significantly increased at four weeks (P = 0.0018) but not at eight weeks (P = 0.064) in those given Vitamin B12. However, tHcy did not differ between treatment groups at baseline (P = 0.63), four weeks (P = 0.79) or eight weeks (P = 0.74). Protocol B: Plasma folate increased significantly at four weeks in those receiving folinic acid (P = 0.0001) but tHcy was not significantly different between groups (P = 0.92). In neither study was there any significant change in tHcy comparing before and during any treatment intervention. CONCLUSIONS: In our studies high dose oral folic acid, intravenous folinic acid, vitamins B6 and B12 and oral serine were ineffective at lowering tHcy in patients on hemodialysis when given folic acid, folinic acid serine or B vitamins in addition to routine folic acid and B vitamin supplements.