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Biomedical subjects

George R Seage

Publications and source records attributed to George R Seage.

At least 19 recordsLinked to original sources
PubMed2006

The Pediatric AIDS Severity Score (PASS): a multidimensional AIDS-severity adjustment for pediatric HIV infection.

BACKGROUND: A severity staging system predictive of mortality for perinatally HIV-infected children is needed for clinical and research purposes. METHODS: A pediatric AIDS severity score (PASS) was developed using baseline sociodemographic, clinical, immunologic, and functional measures obtained from 786 perinatally HIV-infected children enrolled into a prospective cohort study (PACTG 219) in the pre-highly active antiretroviral therapy (HAART) era (pre-1996). PASS was then validated among 392 perinatally HIV-infected children randomly sampled from the original source population (n = 1178). Survival estimates and hazard ratios (HRs) were obtained using the Kaplan-Meier method and proportional hazards models, respectively. The most predictive models were determined using Harrell's "C" statistic. RESULTS: Overall survival was 95% and 90% at 1 and 2 years of follow-up, respectively. The most comprehensive model for predicting mortality, termed the "Full" PASS, included CD4% <15 (HR = 3.9), CDC category C (HR = 2.6), BMI <10% (HR = 2.4), a low (<70) neuropsychological score (HR = 2.6), a general health rating <5 (HR = 2.4), and an elevated symptoms score (HR = 1.9). These determinants were highly predictive of mortality (C statistic = 0.841). CONCLUSIONS: PASS will be helpful in assessing the effectiveness of ART among children with HIV infection, particularly when randomized clinical trials are not possible due to ethical and feasibility concerns.

Acquired Immunodeficiency Syndrome↗
PubMed2006

Simple Pediatric AIDS Severity Score (PASS): a pediatric severity score for resource-limited settings.

BACKGROUND: A multidimensional pediatric AIDS severity score (PASS) has been developed for severity adjustment and as a predictive model for mortality in a pediatric HIV-infected population. While the prognostic value of PASS is relevant in the US setting, there is a need to develop a simpler model of PASS for use in resource-limited settings where CD4% values and HIV RNA levels may not be available to assess prognosis and guide treatment decisions. METHODS: A Simple PASS model was developed including baseline weight percentile, WHO stage, symptoms, a general health rating, total lymphocyte count, packed-cell volume, and albumin measures from 1178 perinatally HIV-infected children enrolled into a prospective cohort study (PACTG 219). This prognostic model was then validated among 952 perinatally HIV-infected children enrolled in other PACTG research studies at the same sites. Survival estimates and Hazard Ratios (HR) were obtained using the Kaplan-Meier method and proportional hazards models, respectively. The predictive ability of the models was determined using Harrell's "C" statistic. RESULTS: Of the clinical measures and assays considered in this study, weight percentile, WHO stage, symptomatology, general health rating, total lymphocyte count, packed-cell volume, and albumin were found to be predictive of mortality. The simple PASS model including only the simple clinical measures and assays was found to be predictive of mortality (C statistic = 0.852). Its discriminative ability for mortality was comparable to a model consisting of the Simple PASS plus CD4% (C statistic = 0.871). CONCLUSION: The Simple PASS scoring system provides a reasonable alternative to CD4% values and HIV viral-load levels to assess prognosis and guide decisions about antiretroviral therapy initiation in resource-limited settings.

Acquired Immunodeficiency Syndrome↗
PubMed2006

Expanded HIV screening in the United States: effect on clinical outcomes, HIV transmission, and costs.

BACKGROUND: An extensive literature supports expanded HIV screening in the United States. However, the question of whom to test and how frequently remains controversial. OBJECTIVE: To inform the design of HIV screening programs by identifying combinations of screening frequency and HIV prevalence and incidence at which screening is cost-effective. DESIGN: Cost-effectiveness analysis linking simulation models of HIV screening to published reports of HIV transmission risk, with and without antiretroviral therapy. DATA SOURCES: Published randomized trials, observational cohorts, national cost and service utilization surveys, the Red Book, and previous modeling results. TARGET POPULATION: U.S. communities with low to moderate HIV prevalence (0.05% to 1.0%) and annual incidence (0.0084% to 0.12%). TIME HORIZON: Lifetime. PERSPECTIVE: Societal. INTERVENTIONS: One-time and increasingly frequent voluntary HIV screening of all adults using a same-day rapid test. OUTCOME MEASURES: HIV infections detected, secondary transmissions averted, quality-adjusted survival, lifetime medical costs, and societal cost-effectiveness, reported in discounted 2004 dollars per quality-adjusted life-year (QALY) gained. RESULTS OF BASE-CASE ANALYSIS: Under moderately favorable assumptions regarding the effect of HIV patient care on secondary transmission, routine HIV screening in a population with HIV prevalence of 1.0% and annual incidence of 0.12% had incremental cost-effectiveness ratios of 30,800 dollars/QALY (one-time screening), 32,300 dollars/QALY (screening every 5 years), and 55,500 dollars/QALY (screening every 3 years). In settings with HIV prevalence of 0.10% and annual incidence of 0.014%, one-time screening produced cost-effectiveness ratios of 60,700 dollars/QALY. RESULTS OF SENSITIVITY ANALYSIS: The cost-effectiveness of screening policies varied within a narrow range as assumptions about the effect of screening on secondary transmission varied from favorable to unfavorable. Assuming moderately favorable effects of antiretroviral therapy on transmission, cost-effectiveness ratios remained below 50,000 dollars/QALY in settings with HIV prevalence as low as 0.20% for routine HIV screening on a one-time basis and at prevalences as low as 0.45% and annual incidences as low as 0.0075% for screening every 5 years. LIMITATIONS: This analysis does not address the difficulty of determining the prevalence and incidence of undetected HIV infection in a given patient population. CONCLUSIONS: Routine, rapid HIV testing is recommended for all adults except in settings where there is evidence that the prevalence of undiagnosed HIV infection is below 0.2%.

Adult↗
PubMed2006

Incidence of opportunistic and other infections in HIV-infected children in the HAART era.

CONTEXT: Combination anti-retroviral therapy or highly active antiretroviral therapy (HAART) has resulted in a dramatic decline in the incidence of opportunistic and other infections in human immunodeficiency virus (HIV)-infected adults and children. OBJECTIVES: To estimate the incidence of 29 targeted opportunistic and other infections occurring in the era of HAART-between January 1, 2001, and December 31, 2004-in HIV-infected infants, children, and adolescents followed up in Pediatric AIDS Clinical Trials Group (PACTG) 219C; to compare incidence rates in the HAART era to those of the pre-HAART era; and to test for linear trends over time in the HAART era. DESIGN, SETTING, AND PARTICIPANTS: Ongoing, multicenter, prospective cohort study designed to examine long-term outcomes in HIV-infected children. The study population included 2767 children enrolled between September 15, 2000, and December 31, 2004, with information entered in the database up to August 1, 2005, when data analysis was conducted. The pre-HAART era comparison population included 3331 children enrolled in 13 PACTG protocols from October 1988 to August 1998. MAIN OUTCOME MEASURES: First occurrence of each of the 29 targeted infections. RESULTS: Seventy-five percent of the children were enrolled in 2000 and 2001, 90% acquired HIV perinatally, 52% were girls, and 59% were black. The median age was 8.2 years (range, 6-13 years). The median duration of follow-up was 3.4 years. Overall, 553 first episodes of a specific infection occurred among 395 (14%) of the study participants. The number of events for the 4 most common first-time infections and their incidence rates (IRs) per 100 person-years were 123 bacterial pneumonia (IR, 2.15; 95% confidence interval [CI], 1.79-2.56), 77 herpes zoster (IR, 1.11; 95% CI, 0.88-1.39), 57 dermatophyte infections (IR, 0.88; 0.67-1.14), and 52 oral candidiasis (IR, 0.93; 95% CI, 0.70-1.22). Incidence rates of first bacteremia, Pneumocystis jeroveci pneumonia, disseminated Mycobacterium avium complex, lymphoid interstitial pneumonitis, systemic fungal infection, cytomegalovirus retinitis, and tuberculosis were all less than 0.50 per 100 person-years. There were no statistically significant linear trends in incidence for any of the 29 infections over the 4 calendar years. However, infection rates were significantly lower than those reported in the PACTG in the pre-HAART era. The pre-HAART IRs were as follows: for bacterial pneumonia, IR, 11.1; 95% CI, 10.3-12.0; bacteremia, IR, 3.3; 95% CI, 2.9-3.8; herpes zoster, IR, 2.9; 95% CI, 2.6-3.3; disseminated M avium complex, IR, 1.8; 95% CI, 1.5-2.1; P jeroveci, IR, 1.3; 95% CI, 1.1-1.6; oral candidiasis, IR, 1.2; 95% CI, 1.0-1.5; cytomegalovirus retinitis, IR, 0.5; 95% CI, 0.3-0.6; and tuberculosis, IR, 0.2; 95% CI, 0.1-0.4. CONCLUSIONS: Opportunistic infections and other related infections are uncommon in children in the HAART era, and infection rates continue to be lower than those reported in the pre-HAART era. Continued surveillance is important to assess the long-term effect of HAART on the occurrence of opportunistic and other related infections in children.

AIDS-Related Opportunistic Infections↗
PubMed2006

Risk factors for opportunistic illnesses in children with human immunodeficiency virus in the era of highly active antiretroviral therapy.

OBJECTIVE: To examine the relationship between the use of highly active antiretroviral treatment (HAART) and the occurrence of opportunistic illnesses (OIs) among children perinatally infected with human immunodeficiency virus. DESIGN: Prospective cohort study. SETTING: Pediatric AIDS Clinical Trials Group 219C cohort. PARTICIPANTS: From September 15, 2000, to August 31, 2003, 1927 children perinatally infected with human immunodeficiency virus and receiving HAART were followed up. Main Exposures Age at initiating HAART, duration of HAART use, CD4+ T-lymphocyte percentage, and human immunodeficiency virus 1 viral load. MAIN OUTCOME MEASURES: Incidence rates for Centers for Disease Control and Prevention OI category B and OI category C events were calculated. The association between main exposures and OI occurrence was estimated using proportional hazards regression. RESULTS: Of 1927 subjects, 226 (12.7%) developed OIs during follow-up. Incidence rates were 4.99 per 100 person-years (95% confidence interval, 4.30-5.76) for first OI category B events and 1.47 per 100 person-years (95% confidence interval, 1.12-1.91) for first OI category C events. Duration of HAART use was not related to OI risk. Older age (age >10 years) at HAART initiation was associated with increased risk of a first OI (hazard ratio, 2.48; 95% confidence interval, 1.23-5.00) compared with initiating HAART in children younger than 2 years. This increased risk diminished after adjusting for CD4+ T-lymphocyte percentage and Centers for Disease Control and Prevention disease category at HAART initiation. More children with OIs than without OIs had a CD4+ T-lymphocyte percentage of less than 15% at HAART initiation (49.6% of children with OIs vs 23.7% of children without OIs), at enrollment (41.2% of children with OIs vs 7.7% of children without OIs), and at the end of follow-up (41.2% of children with OIs vs 8.3% of children without OIs). CONCLUSIONS: Opportunistic illnesses are occurring in the pediatric human immunodeficiency virus population in the HAART era, mainly in children with persistently low CD4+ T-lymphocyte percentages. Lack of a sustained response to HAART rather than age at or duration of HAART use is predictive of OI risk.

AIDS-Related Opportunistic Infections↗
PubMed2006

Sexual behavior, psychosocial and knowledge differences between consistent, inconsistent and non-users of condoms: a study of female bar and hotel workers in Moshi, Tanzania.

Understanding psychosocial, sexual behavior and knowledge differences between never, inconsistent and consistent condom users can improve interventions to increase condom use in resource-poor countries, but they have not been adequately studied. We examined these differences in a cohort of 961 female hotel and bar workers in Moshi, Tanzania. Forty-nine percent of women reported no condom use; 39% reported inconsistent use, and 12% reported consistent use. Women with multiple sexual partners in the past five years were less likely to be consistent rather than inconsistent users as were women who had ever exchanged sex for gifts or money. Inconsistent users had higher condom knowledge and higher perceived acceptability of condom use than did never users, but they did not differ from consistent users by these factors. There are important differences between women by level of condom use. These findings can help inform interventions to increase condom use.

Adolescent↗
PubMed2006

The lifetime cost of current human immunodeficiency virus care in the United States.

OBJECTIVE: We sought to project the lifetime cost of medical care for human immunodefiency virus (HIV)-infected adults using current antiretroviral therapy (ART) standards. METHODS: Medical visits and hospitalizations for any reason were from the HIV Research Network, a consortium of high-volume HIV primary care sites. HIV treatment drug regimen efficacies were from clinical guidelines and published sources; data on other drugs used were not available. In a computer simulation model, we projected HIV medical care costs in 2004 U.S. dollars. RESULTS: From the time of entering HIV care, per person projected life expectancy is 24.2 years, discounted lifetime cost is Dollars 385,200, and undiscounted cost is Dollars 618,900 for adults who initiate ART with CD4 cell count < 350/microL. Seventy-three percent of the cost is antiretroviral medications, 13% inpatient care, 9% outpatient care, and 5% other HIV-related medications and laboratory costs. For patients who initiate ART with CD4 cell count < 200/microL, projected life expectancy is 22.5 years, discounted lifetime cost is Dollars 354,100 and undiscounted cost is Dollars 567,000. Results are sensitive to drug manufacturers' discounts, ART efficacy, and use of enfuvirtide for salvage. If costs are discounted to the time of infection, the discounted lifetime cost is Dollars 303,100. CONCLUSIONS: Effective ART regimens have substantially improved survival and have increased the lifetime cost of HIV-related medical care in the U.S.

AIDS-Related Opportunistic Infections↗
PubMed2006

Human immunodeficiency virus type 1 among bar and hotel workers in northern Tanzania: the role of alcohol, sexual behavior, and herpes simplex virus type 2.

GOALS: We assessed baseline prevalence of human immunodeficiency virus type 1 (HIV-1) and other STDs, as well as behavioral and biologic risk factors for HIV-1 in a population of female bar/hotel workers in Moshi, Tanzania. STUDY DESIGN: Between 2002 and 2003, we enrolled 1042 female bar/hotel workers in an ongoing prospective cohort study. We analyzed data collected at baseline to assess the associations between alcohol, sexual behavior, STDs, and HIV-1 infection. RESULTS: The prevalence of HIV-1 infection was 19.0% (95% confidence interval [CI] = 16.6%-21.4%). Consistent condom use was low (11.1%). HIV-1 was associated with genital ulcers on examination (adjusted odds ratio [AOR] = 2.08, 95% CI = 1.16-3.74), herpes simplex virus type 2 (HSV-2) (AOR = 3.80, 95% CI = 2.42-5.97), and problem drinking (AOR = 1.92, 95% CI = 1.06-3.47). Other independent predictors of HIV-1 were increasing age, number of sex partners, cohabitating, formerly married, location of employment, and having a husband with another wife. CONCLUSIONS: These findings suggest that programs designed to control HSV-2, reduce the number of sexual partners and alcohol use, and promote condom use could be effective in reducing transmission of HIV-1 in this population.

Adolescent↗
PubMed2005

The development and utility of a clinical algorithm to predict early HIV-1 infection.

The association between self-reported clinical factors and recent HIV-1 seroconversion was evaluated in a prospective cohort of 4652 high-risk participants in the HIV Network for Prevention Trials (HIVNET) Vaccine Preparedness Study. Eighty-six individuals seroconverted, with an overall annual seroconversion rate of 1.3 per 100 person-years. Four self-reported clinical factors were significantly associated with HIV-1 seroconversion in multivariate analyses: recent history of chlamydia infection or gonorrhea, recent fever or night sweats, belief of recent HIV exposure, and recent illness lasting > or =3 days. Two scoring systems, based on the presence of either 4 or 11 clinical factors, were developed. Sensitivity ranged from 2.3% (with a positive predictive value of 12.5%) to 72.1% (with a positive predictive value of 1%). Seroconversion rates were directly associated with the number of these clinical factors. The use of scoring systems comprised of clinical factors may aid in detecting early and acute HIV-1 infection in vaccine and microbicide trials. Organizers can educate high-risk trial participants to return for testing during interim visits if they develop these clinical factors. Studying individuals during early and acute HIV-1 infection would allow scientists to investigate the impact of the intervention being studied on early transmission or pathogenesis of HIV-1 infection.

Adolescent↗
PubMed2005

Antiretroviral treatment in pediatric HIV infection in the United States: from clinical trials to clinical practice.

CONTEXT: Antiretroviral therapy (ART) for pediatric human immunodeficiency virus (HIV) infection has evolved from simple nucleoside reverse transcriptase inhibitor (NRTI) regimens to complex combination therapies based largely on evidence from clinical trials. However, the integration of novel ART into the clinical care of pediatric HIV infection has not been examined. OBJECTIVES: To describe changes in the treatment of pediatric HIV infection in the United States from 1987-2003, to assess concordance of initial regimens with US pediatric guidelines, and to identify predictors of the first regimen switch. DESIGN, SETTING, AND PARTICIPANTS: The study population included 766 perinatally HIV-infected children in the Pediatric AIDS Clinical Trials Group 219C cohort born before January 1, 2004, who had not participated in an ART clinical trial at 219C enrollment or during follow-up. MAIN OUTCOME MEASURES: Proportion of children receiving specific ART regimens, proportion of children initiating ART according to pediatric guidelines, and time to first regimen switch (risk of switching). RESULTS: Single and dual NRTI regimens were used most frequently through 1997. In 1998, 2 years after protease inhibitors were approved for adult HIV infection and at the time pediatric guidelines were issued, regimens of highly active antiretroviral therapy including a protease inhibitor became most frequently used. From 1998-2003, 22% of children initiated ART with a regimen not recommended by pediatric guidelines. In multivariate regression, the risk of switching decreased with age at ART initiation (hazard ratio [HR], 0.96; 95% confidence interval [CI], 0.94-0.99) and increased with year of initiation (HR, 1.28; 95% CI, 1.23-1.33). The risk of switching was higher in children who started with 1 NRTI (HR, 8.05; 95% CI, 5.80-11.18), 2 NRTIs (HR, 4.08; 95% CI, 3.08-5.40), or an unconventional regimen (HR, 6.23; 95% CI, 3.36-11.54) vs children who started with a protease inhibitor-containing regimen; and in children who initiated ART at CD4 T lymphocyte percentages less than 15 vs 15 or greater (HR, 2.90; 95% CI, 1.03-8.13). CONCLUSIONS: There was a short lag between the identification of novel ART and its adoption in the pediatric community. A variety of regimens were used, including some unorthodox therapies. Important predictors of first regimen switch were identified.

Adolescent↗
PubMed2005

Sexual risk, nitrite inhalant use, and lack of circumcision associated with HIV seroconversion in men who have sex with men in the United States.

Men who have sex with men (MSM) continue to account for the largest number of new HIV infections in the United States, but limited data exist on independent risk factors for infection beyond the early 1990s. The HIV Network for Prevention Trials Vaccine Preparedness Study enrolled 3257 MSM in 6 US cities from 1995 to 1997. HIV seroincidence was 1.55 per 100 person-years (95% confidence interval: 1.23-1.95) over 18 months of follow-up. On multi-variable analysis using time-dependent covariates, independent risk factors for HIV seroconversion were increased number of reported HIV-negative male sex partners (adjusted odds ratio (AOR) = 1.14 per partner, population attributable risk (PAR) = 28%), nitrite inhalant use (AOR = 2.2, PAR = 28%), unprotected receptive anal sex with an HIV unknown serostatus partner (AOR = 2.7, PAR = 15%) or HIV-positive partner (AOR = 3.4, PAR = 12%), protected receptive anal sex with an HIV-positive partner (AOR = 2.2, PAR = 11%), lack of circumcision (AOR = 2.0, PAR = 10%), and receptive oral sex to ejaculation with an HIV-positive partner (AOR = 3.8, PAR = 7%). Having a large number of male sex partners, nitrite inhalant use, and engaging in receptive anal sex explained the majority of infections in this cohort and should be targeted in prevention strategies for MSM.

Administration, Inhalation↗
PubMed2005

Expanded screening for HIV in the United States--an analysis of cost-effectiveness.

BACKGROUND: Although the Centers for Disease Control and Prevention (CDC) recommend routine HIV counseling, testing, and referral (HIVCTR) in settings with at least a 1 percent prevalence of HIV, roughly 280,000 Americans are unaware of their human immunodeficiency virus (HIV) infection. The effect of expanded screening for HIV is unknown in the era of effective antiretroviral therapy. METHODS: We developed a computer simulation model of HIV screening and treatment to compare routine, voluntary HIVCTR with current practice in three target populations: "high-risk" (3.0 percent prevalence of undiagnosed HIV infection; 1.2 percent annual incidence); "CDC threshold" (1.0 percent and 0.12 percent, respectively); and "U.S. general" (0.1 percent and 0.01 percent). Input data were derived from clinical trials and observational cohorts. Outcomes included quality-adjusted survival, cost, and cost-effectiveness. RESULTS: In the high-risk population, the addition of one-time screening for HIV antibodies with an enzyme-linked immunosorbent assay (ELISA) to current practice was associated with earlier diagnosis of HIV (mean CD4 cell count at diagnosis, 210 vs. 154 per cubic millimeter). One-time screening also improved average survival time among HIV-infected patients (quality-adjusted survival, 220.7 months vs. 219.8 months). The incremental cost-effectiveness was 36,000 dollars per quality-adjusted life-year gained. Testing every five years cost 50,000 dollars per quality-adjusted life-year gained, and testing every three years cost 63,000 dollars per quality-adjusted life-year gained. In the CDC threshold population, the cost-effectiveness ratio for one-time screening with ELISA was 38,000 dollars per quality-adjusted life-year gained, whereas testing every five years cost 71,000 dollars per quality-adjusted life-year gained, and testing every three years cost 85,000 dollars per quality-adjusted life-year gained. In the U.S. general population, one-time screening cost 113,000 dollars per quality-adjusted life-year gained. CONCLUSIONS: In all but the lowest-risk populations, routine, voluntary screening for HIV once every three to five years is justified on both clinical and cost-effectiveness grounds. One-time screening in the general population may also be cost-effective.

Anti-Retroviral Agents↗
PubMed2005

Routine human immunodeficiency virus testing: an economic evaluation of current guidelines.

BACKGROUND: The Centers for Disease Control and Prevention guidelines recommend human immunodeficiency virus (HIV) counseling, testing, and referral for all patients in hospitals with an HIV prevalence of >or=1%. The 1% screening threshold has not been critically examined since HIV became effectively treatable in 1995. Our objective was to evaluate the clinical effect and cost-effectiveness of current guidelines and of alternate HIV prevalence thresholds. METHODS: We performed a cost-effectiveness analysis using a computer simulation model of HIV screening and disease as applied to inpatients in U.S. hospitals. RESULTS: At an undiagnosed inpatient HIV prevalence of 1% and an overall participation rate of 33%, HIV screening increased mean quality-adjusted life expectancy by 6.13 years per 1000 inpatients, with a cost-effectiveness ratio of 35,400 dollars per quality-adjusted life-year (QALY) gained. Expansion of screening to settings with a prevalence as low as 0.1% increased the ratio to 64,500 dollars per QALY gained. Increasing counseling and testing costs from 53 dollars to 103 dollars per person still yielded a cost-effectiveness ratio below 100,000 dollars per QALY gained at a prevalence of undiagnosed infection of 0.1%. CONCLUSION: Routine inpatient HIV screening programs are not only cost-effective but would likely remain so at a prevalence of undiagnosed HIV infection 10 times lower than recommended thresholds. The current HIV counseling, testing, and referral guidelines should now be implemented nationwide as a way of linking infected patients to life-sustaining care.

Centers for Disease Control and Prevention, U.S.↗
PubMed2005

Malignancy in perinatally human immunodeficiency virus-infected children in the United States.

OBJECTIVES: To determine the incidence of and factors associated with malignancy in perinatally human immunodeficiency virus (HIV)-infected children in the United States. METHODS: Included were 2969 children followed in the Pediatric AIDS Clinical Trials Group (PACTG) 219/219C cohort from 1993 through 2003. Cancer incidence by sex, race, age, histology and highly active antiretroviral therapy (HAART) era (pre-HAART, 1993-1997; HAART, 1998-2003) was estimated, and the standardized incidence ratio contrasting infected and uninfected children was determined. Poisson regression was used to further investigate the relation between HAART use (> or =3 drugs of > or =2 classes, 1 of which was a protease inhibitor), CD4% and cancer. RESULTS: There were 37 cancers (17 prevalent and 20 incident) diagnosed in 2969 children for a prevalence of 0.6% [95% confidence interval (CI), 0.3, 0.9] and an incidence of 1.56/1000 person-years (95% CI 0.95, 2.41). Compared with uninfected children, the standardized incidence ratio was 10.08 (95% CI 5.87, 16.14). Incidence did not significantly differ by sex, race, age or HAART era. Of the cases, 35% were immunocompetent (CD4 > or =25%), 25% were moderately immunosuppressed (15%< or = CD4 < or =24%) and 40% were severely immunosuppressed (CD4 <15%) at diagnosis. In multivariate regression, the cancer rate was 3.09 (95% CI 1.22, 7.85) times higher in children with < or =2 years of HAART use than in children with >2 years of HAART and 3.20 (95% CI 1.32, 7.76) times higher in children with CD4 <15% at cohort enrollment than in children with CD4 > or =15%. CONCLUSION: Cancer incidence in this U.S. pediatric cohort was lower than that of European cohorts but was markedly higher than that of HIV-uninfected children. Cancer incidence was highest in children who were severely immunosuppressed and in children who received HAART for < or =2 years.

Age Distribution↗
PubMed2004

A therapeutic HIV vaccine: how good is good enough?

The goal of a therapeutic HIV vaccine is to attenuate HIV disease progression in those already infected. Our objective was to establish comparative efficacy and cost-effectiveness thresholds at which a therapeutic vaccine would make a valuable contribution to HIV care. Using an HIV computer simulation model, we compared therapeutic vaccination with HIV standard of care without vaccination. Input data were obtained from the literature. Base case and sensitivity analyses related to vaccine magnitude, penetrance, durability, and cost. In the base case (0.5 log magnitude, 25% penetrance, 3-year durability, and US$ 4000 per series), vaccination increased quality-adjusted life expectancy (QALE) by 0.50 months compared to no vaccination (cost-effectiveness ratio US$ 89,900 per quality-adjusted life year (QALY)). Increasing vaccine penetrance to 50% increased the projected QALE benefit to 0.91 months (cost-effectiveness ratio US$ 45,500/QALY). Even modestly effective therapeutic HIV vaccines may produce small but meaningful increases in life expectancy and compare favorably to alternative uses of scarce HIV care resources.

AIDS Vaccines↗
PubMed2003

Projecting the cost-effectiveness of adherence interventions in persons with human immunodeficiency virus infection.

PURPOSE: To explore the cost-effectiveness of interventions to improve adherence to combination antiretroviral therapy in patients with human immunodeficiency virus (HIV) infection. METHODS: A simulation model of HIV infection, incorporating CD4 cell count and HIV ribonucleic acid levels as predictors of disease progression, was used to estimate the lifetime costs and quality-adjusted life expectancy associated with clinical interventions to improve adherence to antiretroviral therapy (e.g., directly observed therapy, automatic medication dispensers, beepers, portable alarms) in a clinical trial cohort with early disease (mean CD4 count, 350 cells/microL), a clinical trial cohort with advanced disease (mean CD4 count, 87 cells/microL), and an urban cohort (mean CD4 count, 217 cells/microL). Data were from clinical trials, national databases, and published literature. RESULTS: For relatively healthy patients with early disease, interventions that reduced virologic failure rates by 10% increased quality-adjusted life expectancy by 3.2 months, whereas those that reduced failure by 80% increased quality-adjusted life expectancy by 34.8 months, as compared with standard care. The cost-effectiveness ratio was below 50000 US dollars per quality-adjusted life-year (QALY) for interventions costing 100 US dollars per month provided that failure rates were reduced by at least 10%, and for those costing 500 US dollars per month provided that failure rates were reduced by more than 50%. For both patients with advanced disease and those from an urban cohort, adherence interventions costing about 500 US dollars per month (e.g., directly observed therapy) had to reduce failure by about 25% to have cost-effectiveness ratios below 50000 US dollars per QALY. CONCLUSION: In patients with lower baseline levels of adherence or advanced disease, even very expensive, moderately effective adherence interventions are likely to confer cost-effectiveness benefits that compare favorably with other interventions.

Antiretroviral Therapy, Highly Active↗
PubMed2003

Delayed onset of pubertal development in children and adolescents with perinatally acquired HIV infection.

OBJECTIVE: To examine whether greater severity of HIV infection is associated with delayed initiation of pubertal development among perinatally HIV-infected children, and to compare sexual maturation of perinatally HIV-infected children with children in the general US population using the National Health and Nutrition Examination Survey III. METHODS: In a prospective cohort study, the authors studied 983 HIV-infected children aged 6 to 18 years, who had Tanner stage assessed on at least two occasions between 1995 and 2000. Analyses were conducted separately for girls and boys to identify factors associated with onset of puberty or adrenarche (progression beyond Tanner stage 1). RESULTS: Among children who were in Tanner stage 1 at their first assessment, 185 of 413 (45%) girls and 144 of 434 (33%) boys entered puberty during the observation period. In multivariate longitudinal regression analyses adjusted for age, race/ethnicity, time interval between study visits, and other clinical factors, girls with severe immunosuppression (CD4% <15) were significantly less likely to enter adrenarche (odds ratio [OR], 0.48; 95% confidence interval [CI], 0.29-0.83) and puberty (OR, 0.57; 95% CI, 0.33-0.96) compared with girls who were not immunosuppressed (CD4% > or =25). For boys, those with severe immunosuppression were significantly less likely to enter adrenarche (OR, 0.52; 95% CI, 0.28-0.96) and tended to be less likely to begin puberty (OR, 0.69; 95% CI, 0.39-1.22) compared with boys who were not immunosuppressed. Qualitative comparisons suggested that HIV-infected children may experience delayed puberty and adrenarche compared with similarly aged children in the general US population. CONCLUSIONS: Immunosuppression was associated with delayed pubertal onset in perinatally HIV-infected children. Further studies of perinatally HIV-infected and uninfected children are needed to better quantify the delay in pubertal onset and to compare the pace of pubertal maturation.

Adolescent↗