Association between efavirenz as initial therapy for HIV-1 infection and increased risk for suicidal ideation or attempted or completed suicide: an analysis of trial data.

BACKGROUND: The relationship between efavirenz use and suicidality is not well-defined. OBJECTIVE: To compare time to suicidality with efavirenz-containing versus efavirenz-free antiretroviral regimens for initial treatment of HIV. DESIGN: Participant-level data were analyzed from 4 AIDS Clinical Trials Group, antiretroviral-naive studies conducted from 2001 to 2010. Within each study, participants were randomly assigned to an efavirenz-containing (n = 3241) or efavirenz-free (n = 2091) regimen. (ClinicalTrials.gov: NCT00013520 [A5095], NCT00050895 [A5142], NCT00084136 [A5175], and NCT00118898 [A5202]). SETTING: AIDS Clinical Trials Group sites; 74% of participants enrolled in the United States. PATIENTS: Antiretroviral-naive participants. INTERVENTION: Efavirenz versus efavirenz-free regimens. MEASUREMENTS: Suicidality was defined as suicidal ideation or attempted or completed suicide. Groups were compared with a hazard ratio and 95% CI estimated from a Cox model, stratified by study. RESULTS: Seventy-three percent of participants were men, the median age was 37 years, and 32% had documented psychiatric history or received psychoactive medication within 30 days before entering the study. Median follow-up was 96 weeks. Suicidality incidence per 1000 person-years was 8.08 (47 events) in the efavirenz group and 3.66 (15 events) in the efavirenz-free group (hazard ratio, 2.28 [95% CI, 1.27 to 4.10]; P = 0.006). Incidence of attempted or completed suicide was 2.90 (17 events) and 1.22 (5 events) in the efavirenz and efavirenz-free groups, respectively (hazard ratio, 2.58 [CI, 0.94 to 7.06]; P = 0.065). Eight suicides in the efavirenz group and 1 in the efavirenz-free group were reported. LIMITATION: There was not a standardized questionnaire about suicidal ideation or attempt. Efavirenz was open-label in 3 of 4 studies. CONCLUSION: Initial treatment with an efavirenz-containing antiretroviral regimen was associated with a 2-fold increased hazard of suicidality compared with a regimen without efavirenz. PRIMARY FUNDING SOURCE: National Institutes of Health.

Plasma apolipoprotein L1 levels do not correlate with CKD.

Polymorphisms in APOL1 are associated with CKD, including HIV-related CKD, in individuals of African ancestry. The apolipoprotein L1 (APOL1) protein circulates and is localized in kidney cells, but the contribution of APOL1 location to CKD pathogenesis is unclear. We examined associations of plasma APOL1 levels with plasma cytokine levels, dyslipidemia, and APOL1 genotype in a nested case-control study (n=270) of HIV-infected African Americans enrolled in a multicenter prospective observational study. Patients were designated as having CKD when estimated GFR (eGFR) decreased to <60 ml/min per 1.73 m(2) (eGFR<60 cohort) or protein-to-creatinine ratios became >3.5 g/g (nephrotic proteinuria cohort). Circulating APOL1 levels did not associate with APOL1 genotype, CKD status, or levels of proinflammatory cytokines, but did correlate with fasting cholesterol, LDL cholesterol, and triglyceride levels. At ascertainment, CKD-associated polymorphisms (risk variants) in APOL1 associated with the eGFR<60 cohort, but not the nephrotic-range proteinuria cohort. Of note, in both the eGFR<60 and nephrotic proteinuria cohorts, CKD cases with two APOL1 risk variants had significant declines in eGFR over a median of 4 years compared with individuals with one or no risk variants. APOL1 risk genotype was not associated with changes in proteinuria. Higher circulating proinflammatory cytokine levels were independently associated with CKD but not APOL1 genotype. In conclusion, the function of variant APOL1 proteins derived from circulation or synthesized in the kidney, but not the level of circulating APOL1, probably mediates APOL1-associated kidney disease in HIV-infected African Americans.

No risk of myocardial infarction associated with initial antiretroviral treatment containing abacavir: short and long-term results from ACTG A5001/ALLRT.

BACKGROUND: Observational and retrospective clinical trial cohorts have reported conflicting results for the association of abacavir use with risk of myocardial infarction (MI), possibly related to issues that may bias estimation of treatment effects, such as time-varying confounders, informative dropout, and cohort loss due to competing events. METHODS: We analyzed data from 5056 individuals initiating randomized antiretroviral treatment (ART) in AIDS Clinical Trials Group studies; 1704 started abacavir therapy. An intent-to-treat analysis adjusted for pretreatment covariates and weighting for informative censoring was used to estimate the hazard ratio (HR) of MIs after initiation of a regimen with or without abacavir. RESULTS: Through 6 years after ART initiation, 36 MI events were observed in 17,404 person-years of follow-up. No evidence of an increased hazard of MI in subjects using abacavir versus no abacavir was seen (over a 1-year period: P=.50; HR, 0.7 [95% confidence interval {CI}, 0.2-2.4]); over a 6-year period: P=.24; HR, 0.6 [95% CI, 0.3-1.4]); these results were robust over as-treated and sensitivity analyses. Although the risk of MI decreased over time, there was no evidence to suggest a time-dependent abacavir effect. Classic cardiovascular disease (CVD) risk factors were the strongest predictors of MI. CONCLUSION: We find no evidence to suggest that initial ART containing abacavir increases MI risk over short-term and long-term periods in this population with relatively low MI risk. Traditional CVD risk factors should be the main focus in assessing CVD risk in individuals with human immunodeficiency virus infection.

Treatment responses in antiretroviral treatment-naive premenopausal and postmenopausal HIV-1-infected women: an analysis from AIDS Clinical Trials Group Studies.

Menopause may affect antiretroviral treatment (ART) response. Immunologic and virologic responses to ART were compared in 220 premenopausal and 47 postmenopausal women enrolled in 2 studies involving ART-naive persons. Changes in CD4 counts or human immunodeficiency virus type 1 RNA levels were similar at 24, 48, and 96 weeks after treatment initiation. ART-naive women should respond to ART regardless of menopausal status.

Statin therapy and changes in hip circumference among HIV-infected participants in the ALLRT Cohort.

BACKGROUND: We aimed to determine whether statin exposure in antiretroviral-treated individuals is associated with increases in hip circumference compared with HIV treatment without concomitant statin use. METHODS: This was a prospective multicentre cohort study involving individuals who had received antiretroviral therapy for at least 40 weeks and who were enrolled in the AIDS Clinical Trials Group Longitudinal Linked Randomized Trials cohort. There were 2,223 participants in the statin-unexposed group and 371 in the statin-exposed group. The main outcome measure was change in hip circumference at week 32. RESULTS: The 32-week change in hip circumference in the statin-exposed group was 0.60 cm greater (95% confidence interval 0.11-1.10; P=0.02) than in the statin-unexposed group after adjustment for age, gender, race, baseline body mass index and thymidine analogue exposure. CONCLUSIONS: Our findings support the hypothesis that statins might be beneficial in lipoatrophy. Given the limited treatment options for this important problem, further studies are needed to confirm this effect and to determine its clinical significance.

The effects of HIV type-1 viral suppression and non-viral factors on quantitative proteinuria in the highly active antiretroviral therapy era.

BACKGROUND: Proteinuria is associated with progressive renal disease and overall mortality in HIV-infected patients; however, the prevalence and correlates of quantitative proteinuria in the highly active antiretroviral therapy era are unknown. METHODS: Spot urine protein to creatinine (P/Cr) ratios, an accepted measure of quantitative daily proteinuria, were measured annually since 2002 in participants of the AIDS Clinical Trials Group Longitudinal Linked Randomized Trials cohort. We used linear regression models with general estimating equations to identify factors associated with the abnormal P/Cr thresholds of >/=0.2 and >/=1.0. RESULTS: Of the 2,857 participants (most of whom were receiving antiretroviral therapy) analysed, 16% and 3% had P/Cr levels >/=0.2 and >/=1.0, respectively, at first measurement. P/Cr levels did not change during a median follow-up of 3 years (interquartile range 2-4). Factors associated with P/Cr>/=0.2 at any measurement included greater age, lower glomerular filtration rate, female sex, antiretroviral therapy prior to entry into parent randomized trial, HIV type-1 RNA level >/=400 copies/ml, lower CD4(+) T-cell count and history of hypertension, diabetes or hepatitis C coinfection (all P<0.04). Black race and higher non-high-density lipoprotein cholesterol levels were associated with P/Cr levels >/=1.0, but not with P/Cr levels >/=0.2. Hepatitis B coinfection and current use of adefovir, indinavir and tenofovir were not associated with either of the P/Cr thresholds. CONCLUSIONS: Both HIV-1 and non-HIV-1-related factors are associated with abnormal levels of proteinuria and identify those who are at a greater risk of worse clinical outcomes. Several of these factors are differentially associated with lower and higher proteinuria thresholds.

AIDS clinical trials group longitudinal linked randomized trials (ALLRT): rationale, design, and baseline characteristics.

PURPOSE: ALLRT is a longitudinal cohort study of HIV-infected subjects prospectively randomized into selected clinical trials for antiretroviral (ARV) treatment-naïve and ARV treatment-experienced individuals conducted by the AIDS Clinical Trials Group (ACTG). We describe the rationale, design, and baseline characteristics of the ALLRT cohort and its potential to address important research questions related to ARV therapy. METHOD: Standardized visits occur every 16 weeks to evaluate long-term clinical, virologic, and immunologic outcomes associated with ARV treatment. RESULTS: A total of 4,371 subjects enrolled in ALLRT from January 2000 through June 2007. Of these, 3,146 (72%) were ARV naïve at parent study entry (18% female, 44% white, 32% black, 21% Hispanic; median age 37 years, CD4 count 218 cells/microL, follow-up 3.6 years; 343 [11%] followed > or = 8 years) and 1,225 (28%) were treatment experienced (13% female, 59% white, 20% black, 17% Hispanic; median age 42 years, CD4 count 325 cells/microL, follow-up 5.7 years). CONCLUSIONS: ALLRT provides the opportunity to understand long-term ramifications of therapeutic ARV choices and determine whether these vary by treatment regimen, timing of treatment initiation, or treatment changes over long-term follow-up. Investigations based on uniform data and specimen collection in the context of randomized ARV treatments will be critical to developing more successful long-term therapeutic strategies for HIV treatment.

The prevalence and incidence of neurocognitive impairment in the HAART era.

OBJECTIVES: HAART suppresses HIV viral replication and restores immune function. The effects of HAART on neurological disease are less well understood. The aim of this study was to assess the prevalence and incidence of neurocognitive impairment in individuals who initiated HAART as part of an AIDS clinical trial. DESIGN: A prospective cohort study of HIV-positive patients enrolled in randomized antiretroviral trials, the AIDS Clinical Trials Group (ACTG) Longitudinal Linked Randomized Trials (ALLRT) study. METHODS: We examined the association between baseline and demographic characteristics and neurocognitive impairment among 1160 subjects enrolled in the ALLRT study. RESULTS: A history of immunosuppression (nadir CD4 cell count < 200 cells/microl) was associated with an increase in prevalent neurocognitive impairment. There were no significant virological and immunological predictors of incident neurocognitive impairment. Current immune status (low CD4 cell count) was associated with sustained prevalent impairment. CONCLUSION: The association of previous advanced immunosuppression with prevalent and sustained impairment suggests that there is a non-reversible component of neural injury that tracks with a history of disease progression. The association of sustained impairment with worse current immune status (low CD4 cell count) suggests that restoring immunocompetence increases the likelihood of neurocognitive recovery. Finally, the lack of association between incident neurocognitive impairment and virological and immunological indicators implies that neural injury continues in some patients regardless of the success of antiretroviral therapy on these laboratory measures.

Key components of a theory-guided HIV prevention outreach model: pre-outreach preparation, community assessment, and a network of key informants.

Although outreach frequently is used to provide community-based HIV prevention services to members of underserved populations, researchers may not be familiar with the specific components of and factors influencing outreach and how systematic community outreach methods can be used to recruit participants for research purposes. This article describes key components of a theory and PRECEDE-based outreach model developed and used as part of a broader study examining the feasibility of enhancing access to STD clinical services for sexually transmitted diseases in order to reduce HIV incidence. We present a three-part outreach model and describe lessons learned from implementing it. Factors that improved access to key informants who could facilitate participant recruitment during the outreach process included sustained project visibility in the community, outreach worker affiliation with trusted community-based organizations, and development of a reliable network of key informants. This model enabled a systematic approach to reaching community members and documenting the steps taken to do so.

Impact of aging on neurocognitive performance in previously antiretroviral-naive HIV-infected individuals on their first suppressive regimen.

BACKGROUND: Despite treatment with virologically suppressive antiretroviral therapy (ART), neurocognitive impairment may persist or develop de novo in aging HIV-infected individuals. We evaluated advancing age as a predictor of neurocognitive impairment in a large cohort of previously ART-naive individuals on long-term ART. DESIGN: The AIDS Clinical Trials Group Longitudinal Linked Randomized Trials was a prospective cohort study of HIV-infected individuals originally enrolled in randomized ART trials. This analysis examined neurocognitive outcomes at least 2 years after ART initiation. METHODS: All participants underwent annual neurocognitive testing consisting of Trail making A and B, the wechsler adult intelligence scale-revised Digit Symbol and Hopkins Verbal Learning Tests. Uni and multivariable repeated measures regression models evaluated factors associated with neurocognitive performance. Predictors at parent study entry (ART naive) included entry demographics, smoking, injection drug use, hepatitis B surface antigen, hepatitis C virus serostatus, history of stroke, ART regimen type, pre-ART nadir CD4 cell count, and plasma viral load and as well as time-updated plasma viral load and CD4 cell count. RESULTS: The cohort comprised 3313 individuals with median pre-ART age of 38 years, 20% women; 36% Black, non-Hispanic; 22% Hispanic. Virologic suppression was maintained at 91% of follow-up visits. Neurocognitive performance improved with years of ART. After adjusting for the expected effects of age using norms from HIV-negative individuals, the odds of neurocognitive impairment at follow-up visits among the HIV infected increased by nearly 20% for each decade of advancing age. CONCLUSION: Despite continued virologic suppression and neurocognitive improvement in the cohort as a whole, older individuals were more likely to have neurocognitive impairment than younger individuals.

Failure to return for HIV posttest counseling in an STD clinic population.

This study assessed the extent of and characteristics associated with FTR for HIV posttest counseling in persons undergoing an HIV test during their visit to a sexually transmitted disease (STD) clinic. The study population included all 101 newly diagnosed HIV-infected subjects and 411 matched HIV-uninfected subjects, identified over a 5-year period in a publicly funded STD clinic in the southeastern United States. Overall, 55% of subjects failed to return for their test results. HIV testing history, demographic characteristics, and STD diagnosis were associated with FTR. Of clients testing HIV-positive, 58% failed to return. A median of 12 days was required for disease intervention specialists (DIS) to locate HIV-infected subjects who failed to return. The proportion of persons returning for HIV antibody test results is low among patients tested while seeking STD services. Considerable time and effort is required to find and notify those subjects testing HIV-positive who fail to return. To maximize the potential benefit of counseling and testing, interventions need to be designed to target those at highest risk of not returning.

Barriers to asymptomatic screening and other STD services for adolescents and young adults: focus group discussions.

BACKGROUND: Sexually transmitted diseases (STDs) are a major public health problem among young people and can lead to the spread of HIV. Previous studies have primarily addressed barriers to STD care for symptomatic patients. The purpose of our study was to identify perceptions about existing barriers to and ideal services for STDs, especially asymptomatic screening, among young people in a southeastern community. METHODS: Eight focus group discussions including 53 White, African American, and Latino youth (age 14-24) were conducted. RESULTS: Perceived barriers to care included lack of knowledge of STDs and available services, cost, shame associated with seeking services, long clinic waiting times, discrimination, and urethral specimen collection methods. Perceived features of ideal STD services included locations close to familiar places, extended hours, and urine-based screening. Television was perceived as the most effective route of disseminating STD information. CONCLUSIONS: Further research is warranted to evaluate improving convenience, efficiency, and privacy of existing services; adding urine-based screening and new services closer to neighborhoods; and using mass media to disseminate STD information as strategies to increase STD screening.

Virologic and serologic outcomes of mono versus dual HBV therapy and characterization of HIV/HBV coinfection in a US cohort.

OBJECTIVES: To characterize HIV/hepatitis B virus (HBV) coinfection in the AIDS Clinical Trials Group Longitudinal Linked Randomized Trials cohort and compare long-term HBV outcomes between regimens with 1 (MONO) or 2 (DUAL) anti-HBV agents. DESIGN: A retrospective study of coinfected AIDS Clinical Trials Group Longitudinal Linked Randomized Trials subjects who received regimens containing anti-HBV agent(s). METHODS: Stored samples at baseline and weeks 16, 32, 48, 144, and 240 were tested for HBV DNA, HBV e antigen (HBeAg), HBV e antibody (HBeAb), and hepatitis D virus (HDV) antibody. Resistance and genotype were tested in samples with HBV DNA >600 IU/mL. MONO versus DUAL analyses were limited to HBV treatment-naive subjects (Naive-MONO, Naive-DUAL). RESULTS: Of 150 study subjects, median age was 40 years, 96% were male; 57% white, 26% black, 13% Hispanic. Baseline median CD4 was 224 cells per cubic millimeter, HIV RNA 4.48 log10 copies/mL, HBV DNA 6.30 log10 IU/mL; 59% HBeAg positive and 65% HBeAb negative; HBV genotypes A = 69%, G = 18%, D = 7%, <2% for A/G, B, C, F, H. Coinfection with HDV was 2%. There were 49 Naive-MONO (lamivudine) and 22 Naive-DUAL (11 lamivudine + tenofovir, 11 emtricitabine + tenofovir) with detectable HBV DNA. In the 240-week follow-up, HBV DNA suppression was not significantly higher in Naive-DUAL (P = 0.14); lower baseline HBV DNA (P < 0.01) was associated with suppression. Among 32 Naive-MONO subjects with detectable HBV DNA at baseline and results at week 48, 41% suppressed; among such 15 Naive-DUAL subjects, 53% suppressed. HBeAg and HBeAb analyses showed similar trends. CONCLUSIONS: While consistent trends toward increased HBV DNA suppression, HBeAg loss and HBeAb seroconversion were observed in Naive-DUAL compared with Naive-MONO, they were not statistically significant. Overall, HDV coinfection was low.

Factors associated with remaining on initial randomized efavirenz-containing regimens.

OBJECTIVE: Efavirenz (EFV) along with two nucleoside reverse transcriptase inhibitors (NRTIs) is a recommended initial antiretroviral regimen. Understanding characteristics related to EFV success is clinically useful. DESIGN: Data from 2220 antiretroviral-naive participants randomized to EFV and two to three NRTIs in four ACTG trials as well as a long-term cohort were analysed. METHODS: Logistic regression, using inverse probability of censoring weighting to address selective-follow-up bias, was used to identify factors associated with EFV success (no treatment interruptions of >30 days, HIV RNA < 200 copies/ml) 1 year post initiation and at years 2-5 if successful at year 1. RESULTS: Pretreatment characteristics were median age 38 years, 82% male, 40% white, 10% history of IDU (HxIDU), median CD4+ T-lymphocyte 227 cells/µl and 33% HIV RNA more than 100 ,000 copies/ml. In a multivariable model, factors associated with year 1 EFV success were race [white odds ratio (OR) 1.5; P < 0.001; Hispanic OR 1.5; P = 0.003 vs. black], no pretreatment sign/symptom grade 3 or higher (OR 1.7; P = 0.008) and no HxIDU (OR 1.7; P = 0.001). Predictors of EFV success at years 2-5 were no HxIDU (years 2-5; ORs 1.9-2.2); self-reported complete (4 days prior to study visit) adherence during year 1 (years 2-4; ORs 1.6-1.9); fewer missed visits during year 1 (years 2, 4, 5; ORs 0.92-0.98/1% increase); HIV RNA less than 50 copies/ml at year 1 (years 2, 3; ORs 1.9-2.2); and older age (>50 vs. ≤30 years) (years 2-4: ORs 2.3-3.7). CONCLUSION: Characteristics predictive of EFV success in the short-term and longer term differed except for HxIDU. Behaviours occurring during year 1 were associated with EFV success over 5 years.

Effects of central nervous system antiretroviral penetration on cognitive functioning in the ALLRT cohort.

OBJECTIVE: Differences in antiretroviral distribution into the central nervous system (CNS) may impact neurocognitive status. We assessed the relationship between estimates of antiretroviral therapy penetration into the CNS, using a published ranking system, and neurocognitive status in HIV-positive participants with plasma HIV-1 RNA (vRNA) suppression. DESIGN: Participants with at least 6 weeks ongoing antiretroviral drug use and vRNA less than 50 copies/ml (N = 2636; 83% male, median baseline CD4 T cells: 244 cells/µl) had at least one neuroscreen assessment [Trail Making Test, Part A and B; Wechsler Adult Intelligence Scale-Revised (WAIS-R) Digit Symbol] at 10 413 neurovisits. Neuroscreen test scores were demographically adjusted and converted to Z-scores (NPZ3: lower scores imply more impairment). Central nervous system penetration effectiveness (CPE) ranks of 0.0 (low), 0.5 (medium), or 1.0 (high) were assigned to antiretrovirals and summed per regimen, per neurovisit. METHODS: Multivariate linear regression models using generalized estimating equations assessed NPZ3 scores with respect to antiretroviral regimen. Covariates were retained if P ≤ 0.1. RESULTS: A final model demonstrated that better NPZ3 scores were associated with higher CPE among participants taking more than three antiretroviral drugs (+0.07 per one unit increase in CPE score; P = 0.004) but not among participants with three or less antiretroviral drugs in the regimen (+0.01; P = 0.5). Results were adjusted for demographics, injection drug use, hepatitis C virus serostatus, CD4 cell count (current and nadir), baseline vRNA, antiretroviral experience, and years since first antiretroviral drug use. CONCLUSION: Use of antiretroviral drugs with better estimated CNS penetration may be associated with better neurocognitive functioning; some people may require more than three antiretroviral drugs to treat HIV in the CNS. Clinically this means antiretroviral regimens could be designed to optimize estimated CNS penetration without sacrificing virologic and immunologic benefits.

Relationship between CD4+ T-cell counts/HIV-1 RNA plasma viral load and AIDS-defining events among persons followed in the ACTG longitudinal linked randomized trials study.

BACKGROUND: AIDS-defining events (ADEs) decreased in the era of highly active antiretroviral therapy but still lead to hospitalizations and deaths. Understanding factors related to ADEs is important to mitigate events. METHODS: We examined the relationship between demographics, behaviors, comorbidities, laboratory, clinical measurements, and ADEs diagnosed among subjects randomized to antiretroviral treatments (ART)/strategies and followed prospectively. Logistic regression models using generalized estimating equations generated odds ratios (ORs) focusing on the relationship between current CD4 T-cell count (CD4)/HIV-1 RNA viral load (VL) and ADEs in the subsequent 16-week study period. RESULTS: Among the 2948 subjects in the analysis, overall incidence of ADEs was 1.53 per 100 person-years. Multivariate regression models adjusted for demographics, body mass index, and ADE history. A 6-level time-varying variable examined VL (>100,000 copies/mL, < or =100,000) at CD4 levels (0-50, 51-200, >200 cells/microL); reference level was CD4 >200/VL < or =100,000. Among ART naives, odds of having an ADE in the subsequent 16-week interval were greater among subjects with lower CD4 counts; this relationship was modified by VL level (CD4 < or =50/VL >100,000: OR 37.2; CD4 < or =50/VL < or =100,000: OR 30.5; CD4 51-200/VL >100,000: OR 13.0; CD4 51-200/VL < or =100,000: OR 4.5; all P values <0.001). Similar results were seen among ART-experienced subjects. CONCLUSIONS: Recent CD4 and VL values are closely associated with development of ADEs even after examining a multitude of potential factors.

Suppression of HIV-1 replication by antiretroviral therapy improves renal function in persons with low CD4 cell counts and chronic kidney disease.

OBJECTIVE: To examine the association between changes in glomerular filtration rates (GFR) and antiretroviral therapy (ART)-mediated suppression of plasma HIV-1 viremia. DESIGN: : Observational, prospective, multicenter cohort study. INTERVENTION: ART regimens or treatment strategies in HIV-1-infected subjects were implemented through randomized clinical trials; 1776 ambulatory subjects from these trials also enrolled in this cohort study. METHOD: The association between suppression of viremia and GFR changes from baseline was examined using the abbreviated Modification of Diet and Renal Disease equation in mixed effects linear models. RESULTS: GFR improvement was associated with ART-mediated suppression of plasma viremia in subjects with both chronic kidney disease stage > or = 2 and low baseline CD4 cell counts (< 200 cells/microl). In this subset, viral suppression (by > 1.0 log10 copies/ml or to < 400 copies/ml) was associated with an average increase in GFR of 9.2 ml/min per 1.73 m(2) from baseline (95% confidence interval, 1.6-16.8; P = 0.02) over a median follow-up of 160 weeks. The magnitude of this association increased in subjects who had greater baseline impairment of renal function, and it did not depend on race or sex. CONCLUSIONS: Viral suppression was associated with GFR improvements in those with both low CD4 cell counts and impaired baseline renal function, supporting an independent contribution of HIV-1 replication to chronic renal dysfunction in advanced HIV disease. GFR improvement not associated with viral suppression also was observed in subjects with higher CD4 cell counts.

Predictors of repeat testing and HIV seroconversion in a sexually transmitted disease clinic population.

OBJECTIVE: This study assessed the extent of and characteristics associated with repeat HIV testing in persons presenting to a sexually transmitted disease (STD) clinic. METHODS: The study population included all 101 newly diagnosed HIV-infected subjects and 411 matched HIV-uninfected subjects identified over a 5-year period in a publicly funded STD clinic in the southeastern United States. RESULTS: Of the 508 subjects (99%) with available records, 160 (32%) had tested previously. Age, race, return for posttest counseling, and the client's stated reason for coming to the clinic were associated with repeat testing. Among the 160 subjects who had tested previously, self-identifying as a man who has sex with men or having a history of incarceration was strongly associated with HIV seroconversion (adjusted odds ratio [OR], 51.82; 95% confidence interval [CI], 9.10-295.13; adjusted OR, 83.98, 95% CI, 17.26-408.69, respectively). Presenting for STD-related reasons (STD symptoms or requesting an STD check) had a negative association with HIV seroconversion (adjusted OR, 0.07; 95% CI, 0.01-0.90) compared with presenting for the sole purpose of requesting an HIV test. CONCLUSIONS: Repeat HIV testing is common among patients receiving services at an STD clinic. The role of repeat testing in HIV prevention efforts is complex and poorly understood. Results from this study could be used to identify and target those testing previously at highest risk for contracting HIV for risk-reduction interventions.

Real-time, universal screening for acute HIV infection in a routine HIV counseling and testing population.

CONTEXT: Acute human immunodeficiency virus (HIV) infection cannot be diagnosed by routine antibody tests and is rarely diagnosed in clinical practice. However, HIV nucleic acid-based testing is widely used to screen for antibody-negative acute infection among low-risk blood donors. OBJECTIVE: To assess the feasibility of screening in high-volume laboratories for acute and long-term HIV infection in a routine HIV testing population, in which HIV infection prevalence is low, using specimen pooling and HIV RNA reverse transcriptase-polymerase chain reaction (RT-PCR) tests. DESIGN AND SETTING: Clinical diagnostic performance evaluation at a state-funded public health virology and serology laboratory. PARTICIPANTS: A total of 8505 consecutive individuals presenting for routine HIV counseling and testing during a total of 20 business days to simulate a month of testing in August and December 2001 at 110 publicly funded testing sites in North Carolina. MAIN OUTCOME MEASURES: Prevalence of acute and long-term HIV infection. Serum specimens negative by HIV enzyme immunoassay (EIA) were screened in pools by an ultrasensitive HIV RNA RT-PCR test. Results for individual HIV RNA-positive specimens were reclassified as true or false according to results of confirmatory testing. RESULTS: Of the 8505 individuals screened, 8194 had not previously tested HIV positive and had sufficient serum to complete the testing protocol. Of those, 39 had long-term HIV infection (prevalence, 47.6 per 10,000 at-risk persons [95% confidence interval, 33.8-65.0 per 10,000]). Of the 8155 at-risk individuals whose antibody tests were negative, 5 were HIV RNA positive. Four of those had true-positive acute infection (prevalence, 4.9 per 10,000 [95% confidence interval, 1.3-12.5 per 10,000]). All 4 were women; 2 developed symptoms consistent with an acute retroviral syndrome in the week after testing. Screening all specimens required 147 HIV RNA tests. Overall specificity of the strategy was 0.9999. CONCLUSIONS: These findings suggest the widespread diagnosis of acute HIV infections in a routine testing population is not only possible but feasible using specimen pooling and nucleic acid testing. These additional procedures may increase diagnostic yield by approximately 10% compared with conventional HIV antibody testing.