U.S. prisons have a court-affirmed mandate to provide health care to prisoners. Given this mandate, we sought to determine whether use of prison health care was equitable across race using a nationally-representative sample of Black and White male state prisoners. We first examined the prevalence of health conditions by race. Then, across all health conditions and for each of 15 conditions, we compared the proportion of Black and White male prisoners with the condition who received health care. For most conditions including cancer, heart disease, and liver-related disorders, the age-adjusted prevalence of disease among Blacks was lower than among Whites (p<.05). Blacks were also modestly more likely than Whites to use health care for existing conditions (p<.05), particularly hypertension, cerebral vascular accident/brain injury, cirrhosis, flu-like illness, and injury. The observed racial disparities in health and health care use are different from those among non-incarcerated populations.
Prisoners; health disparities; access to health care; health care systems
Simplification of antiretroviral therapy in patients with suppressed viremia may minimize long-term adverse effects. The study’s primary objective was to determine whether abacavir/lamivudine + atazanavir (ABC/3TC+ATV) was virologically non-inferior to tenofovir/emtricitabine + atazanavir/ritonavir (TDF/FTC+ATV/r) over 24 weeks in a population of virologically suppressed, HIV-1 infected patients.
This open-label, multicenter, non-inferiority study enrolled antiretroviral experienced, HIV-infected adults currently receiving a regimen of TDF/FTC+ATV/r for ≥6 months with no history of virologic failure and whose HIV-1 RNA had been ≤75 copies/mL on 2 consecutive measurements including screening. Patients were randomized 1∶2 to continue current treatment or simplify to ABC/3TC+ATV.
The primary endpoint was the proportion of patients with HIV-RNA<50 copies/mL at Week 24 by the Time to Loss of Virologic Response (TLOVR) algorithm. Secondary endpoints included alternative measures of efficacy, adverse events (AEs), and fasting lipids. Exploratory endpoints included inflammatory, coagulation, bone, and renal biomarkers.
After 24 weeks, ABC/3TC+ATV (n = 199) was non-inferior to TDF/FTC+ATV/r (n = 97) by both the primary analysis (87% in both groups) and all secondary efficacy analyses. Rates of grade 2–4 AEs were similar between the two groups (40% vs 37%, respectively), but an excess of hyperbilirubinemia made the rate of grade 3–4 laboratory abnormalities higher in the TDF/FTC+ATV/r group (30%) compared with the ABC/3TC+ATV group (13%). Lipid levels were stable except for HDL cholesterol, which increased significantly in the ABC/3TC+ATV group. Bone and renal biomarkers improved significantly between baseline and Week 24 in patients taking ABC/3TC+ATV, and the difference between groups was significant at Week 24. No significant changes occurred in any inflammatory or coagulation biomarker within or between treatment groups.
After 24 weeks, simplification to ABC/3TC+ATV from TDF/FTC+ATV/r maintained viral suppression was well-tolerated, and led to improvements in bone and renal biomarkers and HDL cholesterol.
GlaxoSmithKline Clinical Study Register #113734
Young black men who have sex with men (MSM) bear a disproportionate burden of HIV. Rapid expansion of mobile technologies, including smartphone applications (apps), provides a unique opportunity for outreach and tailored health messaging. We collected electronic daily journals and conducted surveys and focus groups with 22 black MSM (age 18–30) at three sites in North Carolina to inform the development of a mobile phone-based intervention. Qualitative data was analyzed thematically using NVivo. Half of the sample earned under $11,000 annually. All participants owned smartphones and had unlimited texting and many had unlimited data plans. Phones were integral to participants' lives and were a primary means of Internet access. Communication was primarily through text messaging and Internet (on-line chatting, social networking sites) rather than calls. Apps were used daily for entertainment, information, productivity, and social networking. Half of participants used their phones to find sex partners; over half used phones to find health information. For an HIV-related app, participants requested user-friendly content about test site locators, sexually transmitted diseases, symptom evaluation, drug and alcohol risk, safe sex, sexuality and relationships, gay-friendly health providers, and connection to other gay/HIV-positive men. For young black MSM in this qualitative study, mobile technologies were a widely used, acceptable means for HIV intervention. Future research is needed to measure patterns and preferences of mobile technology use among broader samples.
Drug-resistant HIV complicates management of HIV infection. Although an estimated 14% of all HIV-positive persons pass through a prison or jail in the United States each year, little is known about the overall prevalence of antiretroviral (ARV) resistance in incarcerated persons. All genotypic sequence data on HIV-positive prisoners in the North Carolina (NC) Department of Corrections (DOC) were obtained from LabCorp. Screening for major resistance mutations in protease (PI) and reverse transcriptase (NRTI and NNRTI) was done using Genosure and the Stanford HIV Database. For subjects with multiple genotype reports, each mutation was counted only once and considered present on all subsequent genotypes. Between October 2006 and February 2010, the NC DOC incarcerated 1,911 HIV+ individuals of whom 19.2% (n=367) had at least one genotype performed. The overall prevalence of a major resistance mutation was 28.3% (95% CI 23.7, 33.0). Among prisoners ever exposed to an ARV during incarceration (n=329) prevalence of a major resistance mutation was 29.8% (95% CI 24.9, 34.7); resistance by class was 20.4% (95% CI 16.0, 24.7) for NRTIs, 19.8% (95% CI 15.5, 24.1) for NNRTIs, and 8.8% (95% CI 5.8,11.9) for PIs. Single class drug resistance was most prevalent at 14.2% (10.2,17.7) followed by dual 12.5% (I8.9,16.0) and triple class 3.3% (1.4,5.3) resistance. The three most prevalent mutations were K103N 15.8% (12.0, 20.2), M184V 14.3% (10.7,18.5), and M41L 4.9% (2.8,7.8). In the NC DOC ARV resistance prevalence, dual and triple class drug resistance was moderate over the study period. Resistance to PIs was lower than NNRTIs and NRTIs, likely reflecting higher usage of these two classes or a lower barrier to resistance.
Abacavir has been associated with myocardial infarction in several studies. This may be related to inflammation and endothelial cell activation. We compared changes in inflammation and endothelial activation markers between antiretroviral-naive adults initiating zidovudine, lamivudine, abacavir, and nonnucleoside reverse transcriptase inhibitor (NNRTI) or this regimen without abacavir. Changes in soluble tumor necrosis factor receptors-I, -II (sTNFR-I, -II), high sensitivity C-reactive protein, and soluble vascular cell adhesion molecule-1 (sVCAM-1) from baseline (pre-ART) to a second time point about 24 weeks after initiating antiretroviral therapy (ART) were compared between groups using multivariable linear regression. A total of 37 met eligibility criteria; 12 received abacavir. The median (interquartile range) age was 37 years (27–45). Most were men (32/37), African-American (15/37), or white (15/37). The median nadir CD4+ and baseline HIV-1 RNA were 230 cells/mm3 (180–301) and 82,642 copies/ml (34,400–204,703). In all, 15/30 smoked, 7/37 had hypertension, 1/37 had diabetes, and 1/37 had hyperlipidemia. None had coronary or renal disease. Changes in CD4+ and HIV-1 RNA level and timing of stored samples with regard to ART initiation were not different between groups. In univariable analysis, log transformed percent change in sTNFR-I (p=0.05) and -II (p=0.04) showed significant between-group differences and trended toward significance for sVCAM-1 (p=0.08). These markers decreased less in the abacavir group. After adjustment for confounders, significantly less decrease for sTNFR-II and sVCAM-1 was seen for those receiving the abacavir-containing regimen. When taken with an NNRTI, abacavir induced a smaller decrease in inflammation biomarkers in this cohort, suggesting a possible proinflammatory effect of this nucleoside analogue.
Despite the efficacy and tolerability of modern antiretroviral therapy (ART), many patients with advanced AIDS prescribed these regimens do not achieve viral suppression or immune reconstitution as a result of poor adherence, drug resistance, or both. The clinical outcomes of continued ART prescription for such patients have not been well characterized.
We examined the causes and predictors of all-cause mortality, AIDS-defining conditions, and serious non-AIDS-defining events among a cohort of participants in a clinical trial of pre-emptive therapy for CMV disease. We focused on participants who, despite ART had failed to achieve virologic suppression and substantive immune reconstitution.
233 ART-receiving participants entered with a median baseline CD4+ T cell count of 30/mm3 and plasma HIV RNA of 5 log10 copies/mL. During a median 96 weeks of follow-up, 24.0% died (a mortality rate of 10.7/100 patient-years); 27.5% reported a new AIDS-defining condition, and 22.3% a new serious non-AIDS event. Of the deaths, 42.8% were due to an AIDS-defining condition, 44.6% were due to a non-AIDS-defining condition, and 12.5% were of unknown etiology. Decreased risk of mortality was associated with baseline CD4+ T cell count ≥25/mm3 and lower baseline HIV RNA.
Among patients with advanced AIDS prescribed modern ART who achieve neither virologic suppression nor immune reconstitution, crude mortality percentages appear to be lower than reported in cohorts of patients studied a decade earlier. Also, in contrast to the era before modern ART became available, nearly half of the deaths in our modern-era study were caused by serious non-AIDS-defining events. Even among the most advanced AIDS patients who were not obtaining apparent immunologic and virologic benefit from ART, continued prescription of these medications appears to alter the natural history of AIDS—improving survival and shifting the causes of death from AIDS- to non-AIDS-defining conditions.
Racial differences in antiretroviral treatment responses remain incompletely explained and may be a consequence of differential pharmacokinetics (PK) associated with race. Raltegravir, an inhibitor of HIV-1 integrase, is commonly used in the treatment of HIV-infected patients, many of whom are African-American. However, there are few data regarding the PK of raltegravir in African-Americans. HIV-infected men and women, self-described as African-American and naive to antiretroviral therapy were treated with raltegravir (RAL) at 400 mg twice a day, plus a fixed dose of tenofovir-emtricitabine (TDF/FTC) at 300 mg/200 mg once daily. Intensive PK sampling was conducted over 24 h at week 4. Drug concentrations at two trough values of 12 and 24 h after dosing (C12 and C24), area under the concentration-curve values (AUC), maximum drug concentration (Cmax), and the time at which this concentration occurred (Tmax) in plasma were estimated with noncompartmental pharmacokinetic methods and compared to data from a subset of white subjects randomized to the RAL twice a day (plus TDF/FTC) arm of the QDMRK study, a phase III study of the safety and efficacy of once daily versus twice daily RAL in treatment naive patients. A total of 38 African-American participants were enrolled (90% male) into the REAL cohort with the following median baseline characteristics: age of 36 years, body mass index (BMI) of 23 kg/m2, and a CD4 cell count of 339/ml. Plasma HIV RNA levels were below 200 copies/ml in 95% of participants at week 4. The characteristics of the 16 white QDMRK study participants were similar, although fewer (69%) were male, the median age was higher (45 years), and BMI was lower (19 kg/m2). There was considerable interindividual variability in RAL concentrations in both cohorts. Median C12 in REAL was 91 ng/ml (range, 10 to 1,386) and in QDMRK participants was 128 ng/ml (range, 15 to 1,074). The Cmax median concentration was 1,042 ng/ml (range, 196 to 10,092) for REAL and 1,360 ng/ml (range, 218 to 9,701) for QDMRK. There were no significant differences in any RAL PK parameter between these cohorts of African-American and white individuals. Based on plasma PK, and with similar adherence rates, the performance of RAL among HIV-infected African-Americans should be no different than that of infected patients who are white.
Improving testing and uptake to care among highly impacted populations is a critical element of Seek, Test, Treat and Retain strategies for reducing HIV incidence in the community. HIV disproportionately impacts prisoners. Though, incarceration provides an opportunity to diagnose and initiate therapy, treatment is frequently disrupted after release. Though model programs exist to support linkage to care on release, there is a lack of scalable metrics with which to assess adequacy of linkage to care after release. The linking data from Ryan White program Client Level Data (CLD) files reported to HRSA with corrections release data offers an attractive means of generating these metrics. Identified only by use of a confidential encrypted Unique Client Identifier (eUCI) these CLD files allow collection of key clinical indicators across the system of Ryan White funded providers. Using eUCIs generated from corrections release data sets as a linkage tool, the time to the first service at community providers along with key clinical indicators of patient status at entry into care can be determined as measures of linkage adequacy. Using this strategy, high and low performing sites can be identified and best practices can be identified to reproduce these successes in other settings.
HIV; incarceration; linkage to care; minorities; treatment interruptions
Incarceration is associated with sexually transmitted infections (STIs) including human immunodeficiency virus (HIV). Incarceration may contribute to STI/HIV by disrupting primary intimate relationships that protect against high-risk partnerships.
In an urban sample of men (N=229) and women (N=104) in North Carolina, we assessed how commonly respondents experienced the dissolution of a primary intimate relationship at the time of their own (among men) or their partner’s (among women) incarceration, and we measured the association between dissolution of relationships during incarceration and STI/HIV-related risk behaviors.
Among men who had ever been incarcerated for one month or longer (N=72), 43% (N=31) had a marital or non-marital primary partner at the time of the longest prior sentence. Among women, 22% (N=31) had ever had a primary partner who had been incarcerated for one month or longer. Of men and women who were in a relationship at the time of a prior incarceration of one month or longer (N=62), 40% reported the relationship ended during the incarceration. In analyses adjusting for socio-demographic characteristics and crack/cocaine use, loss of a partner during incarceration was associated with nearly three times the prevalence of having two or more new partners in the four weeks prior to the survey (prevalence ratio: 2.80, 95% confidence interval: 1.13–6.96).
These findings indicated that incarceration disrupts substantial proportions of primary relationships and that the dissolution of relationships during incarceration is associated with subsequent STI/HIV risk. The results highlight the need for further research into the effects of incarceration on relationships and health.
incarceration; disruption; sexual risk behavior; STI/HIV; North Carolina
Imprisonment provides opportunities for the diagnosis and successful treatment of HIV, however, the benefits of antiretroviral therapy are frequently lost following release due to suboptimal access and utilization of health care and services. In response, some have advocated for development of intensive case-management interventions spanning incarceration and release to support treatment adherence and community re-entry for HIV-infected releasees. We conducted a randomized controlled trial of a motivational Strengths Model bridging case management intervention (BCM) beginning approximately 3 months prior to and continuing 6 months after release versus a standard of care prison-administered discharge planning program (SOC) for HIV-infected state prison inmates. The primary outcome variable was self-reported access to post-release medical care. Of the 104 inmates enrolled, 89 had at least 1 post-release study visit. Of these, 65.1% of BCM and 54.4% of SOC assigned participants attended a routine medical appointment within 4 weeks of release (P >0.3). By week 12 post-release, 88.4% of the BCM arm and 78.3% of the SOC arm had at attended at least one medical appointment (P = 0.2), increasing in both arms at week 24–90.7% with BCM and 89.1% with SOC (P >0.5). No participant without a routine medical visit by week 24 attended an appointment from weeks 24 to 48. The mean number of clinic visits during the 48 weeks post release was 5.23 (SD = 3.14) for BCM and 4.07 (SD = 3.20) for SOC (P >0.5). There were no significant differences between arms in social service utilization and re-incarceration rates were also similar. We found that a case management intervention bridging incarceration and release was no more effective than a less intensive pre-release discharge planning program in supporting health and social service utilization for HIV-infected individuals released from prison.
Prisoners; Access to care; Case management
We compared mortality rates among state prisoners and other state residents to identify prisoners’ healthcare needs
We linked North Carolina prison records with state death records for 1995-2005 to estimate all-cause and cause-specific death rates among Black and White male prisoners aged 20-79 years, and used standardized mortality ratios (SMRs) to compare these observed deaths with the expected number based on death rates among state residents
The all-cause SMR of Black prisoners was 0.52 (95%CI: 0.48 0.57), with fewer deaths than expected from accidents, homicides, cardiovascular disease and cancer. The all-cause SMR of White prisoners was 1.12 (95%CI: 1.01, 1.25) with fewer deaths than expected for accidents, but more deaths than expected from viral hepatitis, liver disease, cancer, chronic lower respiratory disease, and HIV.
Mortality of Black prisoners was lower than that of Black state residents for both traumatic and chronic causes of death. Mortality of White prisoners was lower than that of White state residents for accidents, but higher for several chronic causes of death. Future studies should investigate the effect of prisoners’ pre-incarceration and in-prison morbidity, the prison environment, and prison healthcare on prisoners’ patterns of mortality.
Mortality; Prisoners; Minority Health
Places where people meet new sex partners can be venues for the delivery of individual and environmental interventions that aim to reduce transmission of HIV and other sexually transmitted infections (STI). Using the Priorities for Local AIDS Control Efforts (PLACE) methodology we identified and characterized venues where people in a southeastern US city with high prevalence of both HIV and STI go to meet new sexual partners. A total of 123 community informants identified 143 public, private and commercial venues where people meet sex partners. Condoms were available at 14% of the venues, although 48% of venue representatives expressed a willingness to host HIV prevention efforts. Interviews with 373 people (229 men, 144 women) socializing at a random sample of 54 venues found high rates of HIV risk behaviors including concurrent sexual partnerships, transactional sex and illicit substance abuse. Risk behaviors were more common among those at certain venue types including those that may be overlooked by public health outreach efforts. The systematic methodology used was successful in locating venues where risky encounters are established and reveal opportunities for targeted HIV prevention and testing programs as well as research.
HIV/AIDS; HIV prevention; Sexual behavior; US south
Mortality and morbidity from HIV have dramatically decreased in both high- and low-income countries. However, some patients may not benefit from combination antiretroviral therapy (cART) because of inadequate access to HIV care, including attrition after care initiation.
The study population included all HIV-infected patients receiving cART through the Chinese National Free Antiretroviral Treatment Program from 1 January 2003 to 31 December 2010 (n = 106,542). We evaluated retention in HIV care and used multivariable Cox proportional hazard models to identify independent factors predictive of attrition. The cumulative probability of attrition from cART initiation was 9% at 12 months, 13% at 18 months, 16% at 24 months and 24% at 60 months. A number of factors were associated with attrition, including younger age, male gender, and being single or divorced. Patients with higher CD4 cell counts at cART initiation were more likely to drop out of HIV care. The proportion of patients remaining in HIV care increased in more recent calendar years and among patients who initiated modern cART regimens.
Retention in HIV care is essential for optimizing individual and public health outcomes. Attrition, even the degree observed in our study, can lead to premature morbidity and mortality, and possibly affect further transmission of HIV and HIV resistant drug variants. Effective strategies to promote retention in HIV care programs are needed. In China these strategies may include focusing particularly on younger male patients and those with higher CD4 cell counts at therapy initiation.
Incarceration is associated with sexually transmitted infections (STIs) including human immunodeficiency virus (HIV). Incarceration may contribute to STI/HIV by disrupting primary intimate relationships that protect against high-risk relationships. Research on sexual network disruption during incarceration and implications for post-release sexual risk behavior is limited. We interviewed a sample of HIV-positive men incarcerated in North Carolina to assess how commonly inmates leave partners behind in the community; characteristics of the relationships; and the prevalence of relationship dissolution during incarceration. Among prison inmates, 52% reported having a primary intimate partner at the time of incarceration. In the period prior to incarceration, 85% of men in relationships lived with and 52% shared finances with their partners. In adjusted analyses, men who did not have a primary cohabiting partner at the time of incarceration, versus those did, appeared to have higher levels of multiple partnerships (adjusted prevalence ratio (PR), 1.5; 95% confidence interval (CI) 0.9–2.6; p = 0.11) and sex trade, defined as giving or receiving sex for money, goods, or services (adjusted PR, 2.1; 95% CI 0.9–4.8; p = 0.08) in the 6 months prior to incarceration. Involvement in financially interdependent partnerships appeared to be associated with further reductions in risk behaviors. Of men in primary partnerships at the time of prison entry, 55% reported their relationship had ended during the incarceration. The findings suggest that involvement in primary partnerships may contribute to reductions in sexual risk-taking among men involved in the criminal justice system but that many partnerships end during incarceration. These findings point to the need for longitudinal research into the effects of incarceration-related sexual network disruption on post-release HIV transmission risk.
Incarceration; Disruption; Sexual networks; Primary partnerships; Sexual behavior; African Americans; Southern US; North Carolina
The incarcerated population has increased to unprecedented levels following the 1970 US declaration of war on illicit drug use. A substantial proportion of people with or at risk for HIV infection, including those with substance use and mental health disorders, have become incarcerated. The overlapping epidemics of incarceration and HIV present a need for academic medical centers to collaborate with the criminal justice system to improve the health of incarcerated populations. With coordinated collaboration and new programmatic initiatives it is possible to reduce HIV-associated risk behaviors and the likelihood of acquisition and transmission of HIV. Centers for AIDS Research (CFAR), funded by the National Institutes of Health, have proactively responded to this need through Collaboration on HIV in Corrections (CHIC) to improve the diagnosis, treatment, linkage to care, and prevention of HIV. This collaboration serves as a model for aligning academic expertise with criminal justice to confront this challenge to individual and public health. This is especially relevant given recent evidence of the effectiveness of antiretroviral therapy in reducing HIV transmission
HIV/AIDS; Corrections; Prison; Jail; Collaboration; Academic
Microalbuminuria is associated with increased risk of cardiovascular disease and mortality. The objective of the study was to evaluate if HIV infection was an independent risk factor for microalbuminuria.
The relationship between HIV infection and microalbuminuria was assessed using subjects enrolled in the study of Fat Redistribution and Metabolic Change in HIV Infection, which consists of HIV-positive and control men and women. Participants with proteinuria (dipstick ≥1+) were excluded.
Microalbuminuria (urinary albumin/creatinine ratio, ACR>30 mg/g) was present in 11% of HIV infected, and 2% of control participants (P<0.001); a fivefold odds after multivariate adjustment (odds ratio, 5.11; 95% confidence interval, 1.97–13.31; P=0.0008). Several cardiovascular risk factors were associated with higher ACR in HIV participants: insulin resistance (HOMA>4; 32%, P<0.0001), systolic blood pressure (21%, P=0.01 for 120–140 versus <120 mmHg, and 43%, P <0.06 for >140 versus <120 mmHg), and family history of hypertension (17%, P=0.03). Higher CD4 cell count was associated with lower albumin/creatinine ratio (−24%, P=0.009 for 200–400 versus <200 cells/ml and −26%, P=0.005 for >400 versus <200 cells/ml).
HIV infection had a strong and independent association with microalbuminuria, the severity of which was predicted by markers of insulin resistance, hypertension, and advanced HIV infection. These associations warrant further investigation, as the increased prevalence of microalbuminuria in HIV infection may be a harbinger of future risk of cardiovascular and kidney diseases.
Microalbuminuria; kidney; urine protein; insulin resistance; lipodystrophy
HIV infection and antiretroviral therapy are associated with dyslipidemia, but the association between regional adipose tissue depots and lipid levels is not defined.
The association of MRI-measured visceral (VAT) and regional subcutaneous adipose tissue (SAT) volume with fasting lipid parameters was analyzed by multivariable linear regression in 737 HIV-infected and 145 control men from the study of Fat Redistribution and Metabolic Change in HIV Infection (FRAM).
HIV-infected men had higher median triglycerides (TG) (170mg/dl vs. 107mg/dl, p<0.0001), lower high density lipoprotein (HDL-C) (38mg/dl vs. 46mg/dl, p<0.0001) and lower low density lipoprotein (LDL-C) (105mg/dl vs. 125mg/dl, p<0.0001) than controls. After adjustment, greater VAT was associated with higher TG and lower HDL-C in both HIV-infected and control men, while greater leg SAT was associated with lower TG in HIV-infected men with a similar trend in controls. More upper trunk SAT was associated with higher LDL-C and lower HDL-C in controls, while more lower trunk SAT was associated with higher TG in controls. After adjustment, HIV infection remained strongly associated (p<0.0001) with higher TG (+76%, CI: 53, 103), lower LDL-C (−19%, CI: −25,−12), and lower HDL-C (−18%, CI: −22,−12).
HIV-infected men are more likely than controls to have higher TG and lower HDL-C, which promote atherosclerosis, but also lower LDL-C. Less leg SAT and more VAT are important factors associated with high TG and low HDL-C in HIV-infected men. The reduced leg SAT in HIV-infected men with lipoatrophy places them at increased risk for pro-atherogenic dyslipidemia.
BMS-488043 is a novel and unique oral small-molecule inhibitor of the attachment of human immunodeficiency virus type 1 (HIV-1) to CD4+ lymphocytes. The antiviral activity, pharmacokinetics, viral susceptibility, and safety of BMS-488043 were evaluated in an 8-day monotherapy trial. Thirty HIV-1-infected study subjects were randomly assigned to sequential, safety-guided dose panels of 800 and 1,800 mg BMS-488043 or a matched placebo in a 4:1 ratio, and the drug was administered every 12 h with a high-fat meal for 7 days and on the morning of day 8. Dose-related, albeit less-than-dose-proportional, increases in plasma BMS-488043 concentrations were observed. Mean plasma HIV-1 RNA decreases from the baseline for the BMS-488043 800- and 1,800-mg dose groups on day 8 were 0.72 and 0.96 log10 copies/ml, respectively, compared with 0.02 log10 copies/ml for the placebo group. A lower baseline BMS-488043 50% effective concentration (EC50) in the active-treatment groups was predictive of a greater antiviral response. Although absolute drug exposure was not associated with an antiviral response, the trough concentration (Ctrough), adjusted by the baseline EC50 (Ctrough/EC50), was associated with antiviral activity. During dosing, four subjects experienced >10-fold reductions in viral susceptibility to BMS-488043, providing further support of the direct antiviral mechanism of BMS-488043. BMS-488043 was generally safe and well tolerated. These results suggest that further development of this novel class of oral HIV-1 attachment inhibitors is warranted.
Patients who participate in clinical trials may experience better clinical outcomes than patients who initiate similar therapy within clinical care (trial effect), but no published studies have evaluated a trial effect in HIV clinical trials.
To examine a trial effect we compared virologic suppression (VS) among patients who initiated HAART in a clinical trial versus in routine clinical care. VS was defined as a plasma HIV RNA ≤400 copies/ml at six months after HAART initiation and was assessed within strata of early (1996–99) or current (2000–06) HAART periods. Risk ratios (RR) were estimated using binomial models.
Of 738 persons initiating HAART, 30.6% were women, 61.7% were black, 30% initiated therapy in a clinical trial and 67% (n = 496) had an evaluable six month HIV RNA result. HAART regimens differed between the early and current periods (p<0.001); unboosted PI regimens (55.6%) were more common in the early and NNRTI regimens (46.4%) were more common in the current period. Overall, 78% (95%CI 74, 82%) of patients achieved VS and trial participants were 16% more likely to achieve VS (unadjusted RR 1.16, 95%CI 1.06, 1.27). Comparing trial to non-trial participants, VS differed by study period. In the early period, trial participants initiating HAART were significantly more likely to achieve VS than non-trial participants (adjusted RR 1.33; 95%CI 1.15, 1.54), but not in the current period (adjusted RR 0.98; 95%CI 0.87, 1.11).
A clear clinical trial effect on suppression of HIV replication was observed in the early HAART period but not in the current period.
High rates of both HIV and depression are seen in prison populations; depression has been linked to disease progression in HIV, risky behaviors, and medication non-adherence. Despite this, few studies have examined HIV-infected inmates with depression. We therefore conducted an exploratory study of a sample of HIV-infected inmates in North Carolina prisons (N=101) to determine what proportion of this sample screened positive for depression and whether depression was associated with different pre-incarceration characteristics or post-release needs. A high proportion of HIV infected inmates (44.5%) screened positive for depression. Depressed inmates were significantly more likely have low coping self-efficacy scores (180 vs. 214), to report having had resource needs (OR=2.91) prior to incarceration and to anticipate needing income (OR=2.81), housing (OR=4.07), transportation (OR=9.15), and assistance with adherence (OR=8.67) post-release. We conclude by discussion the implications of our findings for prison based care and effective prison release planning for HIV infected inmates.
HIV; AIDS; prison; depression; reentry; coping self-efficacy
We identified factors associated with testing HIV positive in a prison system performing voluntary HIV testing on inmates and estimated the number of undetected HIV cases to evaluate the efficacy of risk-factor–based HIV testing.
We used logistic regression to estimate associations between HIV serostatus and HIV risk behaviors, mental health, coinfection status, and socio-demographic characteristics for prisoners entering the North Carolina Department of Correction from January 2004 through May 2006. We estimated the number of undetected HIV cases on the basis of age-, gender-, and race-specific HIV prevalences among prisoners and in the state.
Nearly 3.4% (718/21419) of tested prisoners were HIV positive. The strongest risk factors for infection among men were having sex with men (odds ratio [OR]=8.0), Black race (OR=6.2), other non-White race (OR=7.4), and being aged 35 to 44 years (OR=4.1). The strongest risk factor among women was Black race (OR=3.8). Among HIV-positive prisoners, 65% were coinfected with HCV. We estimated that between 24% (223) and 61% (1101) of HIV cases remained undetected.
The associations between HIV serostatus and a variety of factors highlight the potential limitations of risk-factor–based HIV testing in prisons, as do the high number of potential undetected HIV cases.
Incarceration may contribute to HIV transmission by disrupting stable partnerships and promoting high-risk partnerships. We investigated incarceration and high-risk partnerships among African Americans in North Carolina (NC).
We conducted a weighted analysis using the NC Rural Health Project (N=320), a population-based case-control study of HIV among African Americans. We measured associations between timing and duration of incarceration and high-risk partnerships (multiple partnerships or sex trade for money or drugs).
Duration of incarceration appeared to be more important than how long ago incarceration occurred. After adjustment for socio-demographic indicators, high-risk partnerships were associated with short-term (<1 month) incarceration of the respondent versus no respondent incarceration (men: adjusted prevalence ratio (aPR): 1.9, 95% confidence interval (CI): 1.2–2.8; women: aPR: 3.1, 95% CI: 1.2–8.3). High-risk partnerships were also associated with incarceration of a partner versus no partner incarceration (men: aPR: 1.8, 95% CI: 1.1–3.0; women: aPR: 2.0, 95% CI: 1.1–3.8). Among men, associations remained when adjusting for substance abuse. Among women, adjustment for substance abuse weakened estimates due to the strong correlation between substance abuse and incarceration.
HIV prevention programs targeting currently- and formerly-incarcerated individuals and their partners may decrease HIV in African American communities with high incarceration rates.
incarceration; poverty; sexual behavior; HIV; sexually transmitted infections; African Americans; Southern US; North Carolina
We examined the use of voluntary HIV testing among state prisoners in the North Carolina prison system.
We calculated system-wide and facility-specific proportions and rates of adult inmates tested for HIV and estimated associations between testing status and inmate characteristics for prisoners in North Carolina.
Of the 54016 inmates who entered prison between January 2004 and May 2006, 20820 (38%) were tested for HIV; of those tested, 18574 (89%) were tested at admission. Across the 8 intake prisons, more than 80% of inmates in both female facilities but less than 15% of inmates in 4 of 6 male facilities were tested. Prisoners with a documented history of heroin use, crack or cocaine use, conventional HIV risk behavior, or tuberculosis were at least 10% more likely to be tested than were inmates without these characteristics. However, more than 60% of men reporting conventional risk behaviors were not tested. Before covariate adjustment, Black men were 30% less likely than White men to be tested; in the multivariable regression model, this difference was attenuated to 13%.
Rates of HIV testing varied widely across intake prisons, and many male inmates with documented risk of infection were never tested.
Fish oil has been shown to reduce serum triglyceride (TG) concentrations. In HIV-infected patients on antiretroviral therapy, high TG concentrations likely contribute to increased risk of cardiovascular disease. AIDS Clinical Trials Group A5186 examined the safety and efficacy of fish oil plus fenofibrate in subjects not achieving serum TG levels ≤200 mg/dL with either agent alone.
One hundred subjects on highly active antiretroviral therapy with serum TG concentrations ≥400 mg/dL and low-density lipoprotein cholesterol ≤160 mg/dL were randomized to 3 g of fish oil twice daily or 160 mg of fenofibrate daily for 8 weeks. Subjects with a fasting TG level >200 mg/dL at week 8 received a combination of fish oil and fenofibrate in the same doses from week 10 to week 18.
Median baseline TG was 662 mg/dL in the fish oil group and 694 mg/dL in the fenofibrate group (P = not significant). Fish oil reduced TG levels by a median of 283 mg/dL (46%), fenofibrate reduced them by 367 mg/dL (58%), and combination therapy reduced them by 65.5%. Combination therapy achieved TG levels of ≤200 mg/dL in 22.7% subjects. Fish oil had no measurable effect on immunologic parameters or the pharmacokinetics of lopinavir.
Fish oil was safe when administered alone or combined with fenofibrate and significantly reduced TG levels in HIV-infected subjects with hypertriglyceridemia.
fenofibrate; fish oil; hypertriglyceridemia; low-density lipoprotein cholesterol; omega-3 fatty acids
Incarceration is strongly associated with HIV infection and may contribute to viral transmission by disrupting stable partnerships and promoting high-risk partnerships. We investigated incarceration and STI/HIV-related partnerships among a community-based sample recruited for a sexual behavior interview while frequenting venues where people meet sexual partners in a North Carolina city (N = 373). Men reporting incarceration in the past 12 months were more likely than men without recent incarceration to experience multiple new sexual partnerships (unadjusted prevalence ratio [PR] 1.8, 95% confidence interval [CI]: 1.1–3.1) and transactional sex defined as trading sex for money, goods, or services (unadjusted PR: 4.0, 95% CI: 2.3–7.1) in the past 4 weeks. Likewise, women who were ever incarcerated were more likely than never-incarcerated women to experience recent multiple new partnerships (unadjusted PR: 3.1, 95% CI: 1.8–5.4) and transactional sex (unadjusted PR: 5.3, 95% CI: 2.6–10.9). Sexual partnership in the past 12 months with someone who had ever been incarcerated versus with partners with no known incarceration history was associated with recent multiple new partnerships (men: unadjusted PR 2.0, 95% CI 1.4–2.9, women: unadjusted PR 4.8, 95% CI 2.3–10.1) and transactional sex (men: unadjusted PR 3.3, 95% CI 1.7–6.6, women: unadjusted PR 6.1, 95% CI 2.4–15.4). Adjustment for demographic and socioeconomic variables had minimal effect on estimates. However, the strong overlap between incarceration, partner incarceration, and substance abuse had substantial effects in multivariable models. Correctional-facility and community-based HIV prevention, with substance abuse treatment, should reach currently and formerly incarcerated individuals and their sexual partners.
Incarceration; Poverty; Sexual behavior; HIV; Sexually transmitted infections; African Americans; Southern U. S.; North Carolina