Intersectional stigma and the non-communicable disease syndemic in the context of HIV: protocol for a multisite, observational study in the USA.

INTRODUCTION: The increasing burden of non-communicable diseases, such as hypertension, diabetes and dyslipidaemia, presents key challenges to achieving optimal HIV care outcomes among ageing people living with HIV. These diseases are often comorbid and are exacerbated by psychosocial and structural inequities. This interaction among multiple health conditions and social factors is referred to as a syndemic. In the USA, there are substantial disparities by social position (ie, racial, ethnic and socioeconomic status) in the prevalence and/or control of non-communicable diseases and HIV. Intersecting stigmas, such as racism, classism and homophobia, may drive these health disparities by contributing to healthcare avoidance and by contributing to a psychosocial syndemic (stress, depression, violence victimisation and substance use), reducing success along the HIV and non-communicable disease continua of care. Our hypothesis is that marginalised populations experience disparities in non-communicable disease incidence, prevalence and control, mediated by intersectional stigma and the psychosocial syndemic. METHODS AND ANALYSIS: Collecting data over a 4 year period, we will recruit sexual minority men (planned n=1800) enrolled in the MACS/WIHS Combined Cohort Study, a long-standing mixed-serostatus observational cohort in the USA, to investigate the following specific aims: (1) assess relationships between social position, intersectional stigma and the psychosocial syndemic among middle-aged and ageing sexual minority men, (2) assess relationships between social position and non-communicable disease incidence and prevalence and (3) assess relationships between social position and HIV and non-communicable disease continua of care outcomes, mediated by intersectional stigma and the psychosocial syndemic. Analyses will be conducted using generalised structural equation models using a cross-lagged panel model design. ETHICS AND DISSEMINATION: This protocol is approved as a single-IRB study (Advarra Institutional Review Board: Protocol 00068335). We will disseminate results via peer-reviewed academic journals, scientific conferences, a dedicated website, site community advisory boards and forums hosted at participating sites.

Incident hepatitis C virus infection in men who have sex with men: a prospective cohort analysis, 1984-2011.

BACKGROUND: Prospective characterization of hepatitis C virus (HCV) transmission in both human immunodeficiency virus (HIV)-infected and -uninfected men who have sex with men (MSM) over the entire HIV epidemic has not been comprehensively conducted. METHODS: To determine the trends in and risk factors associated with incident HCV in MSM since 1984, 5310 HCV antibody (anti-HCV)-negative MSM in the Multicenter AIDS Cohort Study were prospectively followed during 1984-2011 for anti-HCV seroconversion. RESULTS: During 55 343 person-years (PYs) of follow-up, there were 115 incident HCV infections (incidence rate, 2.08/1000 PYs) scattered throughout the study period. In a multivariable analysis with time-varying covariates, older age (incidence rate ratio [IRR], 1.40/10 years, P < .001), enrollment in the later (2001-2003) recruitment period (IRR, 3.80, P = .001), HIV infection (IRR, 5.98, P < .001), drinking >13 alcoholic drinks per week (IRR, 1.68, P < .001), hepatitis B surface antigen positivity (IRR, 1.68, P < .001), syphilis (IRR, 2.95, P < .001), and unprotected receptive anal intercourse with >1 male partner (IRR, 3.37, P < .001) were independently associated with incident HCV. Among HIV-infected subjects, every 100 cell/mm(3) increase in CD4 count was associated with a 7% (P = .002) decrease in the HCV incidence rate up to a CD4 count of 500 cells/mm(3), whereas there was no association with highly active antiretroviral therapy. CONCLUSIONS: The spread of HCV among both HIV-infected and -uninfected MSM in the United States has been ongoing since the beginning of the HIV epidemic. In HIV-infected men with <500 CD4(+) T cells, the HCV incidence rate was inversely proportional to CD4 T-cell count.

HIV monoinfection is associated with increased aspartate aminotransferase-to-platelet ratio index, a surrogate marker for hepatic fibrosis.

BACKGROUND: Although liver disease commonly causes morbidity and mortality among human immunodeficiency virus (HIV)-infected individuals, data are limited on its prevalence in HIV monoinfection. We used the aspartate aminotransferase-to-platelet ratio index (APRI) as a surrogate marker of hepatic fibrosis to characterize liver disease in the Multicenter AIDS Cohort Study. METHODS: Men were categorized based on their HIV and viral hepatitis status: uninfected (n = 1170), HIV monoinfected (n = 509), viral hepatitis monoinfected (n = 74), and HIV-viral hepatitis coinfected (n = 66). RESULTS: The median APRI in the HIV-monoinfected group was similar to that in the hepatitis-monoinfected group (0.42 vs 0.43; P > .05), higher than in the uninfected group (0.42 vs 0.27; P < .001) but lower than in the coinfected group (0.42 vs 1.0; P < .001). On multivariable analysis, HIV infection (1.39-fold increase [FI]; P < .001), viral hepatitis infection (1.52-FI; P < .001), and the interaction between HIV and viral hepatitis infections were independently associated with a higher APRI (1.57-FI; P < .001). Among the HIV-infected men, viral hepatitis coinfection (2.34-FI; P < .001), HIV RNA ≥100 000 copies/mL (1.26-FI; P = .007), and CD4 count ≤200 cells/mL (1.23-FI; P = .022) were independently associated with a higher APRI. CONCLUSIONS: HIV and viral hepatitis are independently associated with an increased APRI. Further studies are needed to understand the biological basis for the association between HIV and liver disease.

Comparative risk of liver-related mortality from chronic hepatitis B versus chronic hepatitis C virus infection.

BACKGROUND: It is not known whether chronic hepatitis B (CH-B) or chronic hepatitis C (CH-C) carries a greater risk of liver-related mortality. This study compared rates of liver-related mortality between these 2 groups in the Multicenter AIDS Cohort Study (MACS). METHODS: Six hundred eighty men with CH-B (n = 337) or CH-C (n = 343) at study entry into the MACS were prospectively followed to death, last follow-up visit, or 30 March 2010, whichever came first. Four hundred seventy-two (69.4%) of these men were infected with human immunodeficiency virus type 1 (HIV-1). Causes of death were obtained from death registry matching and death certificates. Liver-related and all-cause mortality rates (MRs) were compared between groups using Poisson regression and adjusted for potential confounders and competing risks. RESULTS: In 6728 person-years (PYs) of follow-up, there were 293 deaths from all causes (43.5 per 1000 PYs), of which 51 were liver-related (7.6 per 1000 PYs). The all-cause MR was similar between those with CH-B and CH-C; however, the liver-related MR was significantly higher in those with CH-B (9.6 per 1000 PYs; 95% confidence interval [CI], 6.9-13.2) than those with CH-C (5.0 per 1000 PYs; 95% CI, 3.0-8.4). In the HIV-infected subgroup, which had 46 (90.2%) of the liver-related deaths, the liver-related MR remained higher from CH-B after adjusting for potential confounders (incidence rate ratio, 2.2; P = .03) and competing risks (subhazard rate ratio, 2.4; P = .02). Furthermore, among HIV-infected subjects, CD4 cell counts <200 cells/mm(3) were associated with a 16.2-fold (95% CI, 6.1-42.8) increased risk of liver-related death compared with CD4 cell counts >350 cell/mm(3). CONCLUSIONS: Chronic hepatitis B carries a higher risk of death from liver disease than does CH-C, especially in HIV-infected men with greater immunosuppression.

Epidemiology of COVID-19 vs. influenza: Differential failure of COVID-19 mitigation among Hispanics, Cook County Health, Illinois.

BACKGROUND: During the early phases of the COVID-19 pandemic in the U.S., African-American or Hispanic communities were disproportionately impacted. To better understand the epidemiology and relative effects of COVID-19 among hospitalized Hispanic patients, we compared individual and census-tract level characteristics of patients diagnosed with COVID-19 to those diagnosed with influenza, another viral infection with respiratory transmission. We evaluated temporal changes in epidemiology related to a shelter-in-place mandate. METHODS: We evaluated patients hospitalized at Cook County Health, the safety-net health system for the Chicago metropolitan area. Among self-identified hospitalized Hispanic patients, we compared those with influenza (2019-2020 season) to COVID-19 infection during March 16, 2020-May 11, 2020. We used multivariable analysis to identify differences in individual and census-tract level characteristics between the two groups. RESULTS: Relative to non-Hispanic blacks and whites, COVID-19 rapidly increased among Hispanics during promotion of social-distancing policies. Whereas non-Hispanic blacks were more likely to be hospitalized for influenza, Hispanic patients predominated among COVID-19 infections (40% relative increase compared to influenza). In the comparative analysis of influenza and COVID-19, Hispanic patients with COVID-19 were more likely to reside in census tracts with higher proportions of residents with the following characteristics: Hispanic; no high school diploma; non-US citizen; limited English speaking ability; employed in manufacturing or construction; and overcrowding. By multivariable analysis, Hispanic patients hospitalized with COVID-19 compared to those with influenza were more likely to be male (adjusted OR = 1.8; 95% CI 1.1 to 2.9), obese (aOR = 2.5; 95% CI 1.5 to 4.2), or reside in a census tract with ≥40% of residents without a high-school diploma (aOR = 2.5; 95% CI 1.3 to 4.8). CONCLUSIONS: The rapid and disproportionate increase in COVID-19 hospitalizations among Hispanics after the shelter-in-place mandate indicates that public health strategies were inadequate in protecting this population-in particular, for those residing in neighborhoods with lower levels of educational attainment.

Disparities and Temporal Trends in COVID-19 Exposures and Mitigating Behaviors Among Black and Hispanic Adults in an Urban Setting.

Importance: COVID-19, caused by SARS-CoV-2 virus, has disproportionately affected Black and Hispanic communities in the US, which can be attributed to social factors including inconsistent public health messaging and suboptimal adoption of prevention efforts. Objectives: To identify behaviors and evaluate trends in COVID-19-mitigating practices in a predominantly Black and Hispanic population, to identify differences in practices by self-reported ethnicity, and to evaluate whether federal emergency financial assistance was associated with SARS-CoV-2 acquisition. Design, Setting, and Participants: This survey study was conducted by telephone from July 1 through August 30, 2020, on a random sample of adults who underwent SARS-CoV-2 testing at a safety-net health care system in Chicago during the surge in COVID-19 cases in the spring of 2020. Behaviors and receipt of a stimulus check were compared between participants testing positive and negative for SARS-CoV-2. Differences in behaviors and temporal trends were assessed by race and ethnicity. Main Outcomes and Measures: SARS-CoV-2 infection was assessed using nasopharyngeal quantitative reverse transcriptase-polymerase chain reaction testing. Mitigating behaviors and federal emergency financial assistance were assessed by survey. Race and ethnicity data were collected from electronic health records. Results: Of 750 randomly sampled individuals, 314 (41.9%) consented to participate (169 [53.8%] women). Of those, 159 (51%) self-reported as Hispanic and 155 (49%) as non-Hispanic (120 [38.2%] Black), of whom 133 (84%) and 76 (49%) tested positive for SARS-CoV-2, respectively. For all participants, consistent mask use (public transport: adjusted odds ratio [aOR], 0.00; 95% CI, 0.00-0.34; social gatherings: aOR, 0.10; 95% CI, 0.00-0.50; running errands: aOR, 0.18; 95% CI, 0.07-0.42; at work: aOR, 0.23; 95% CI, 0.07-0.79) and hand sanitizer use (aOR, 0.26; 95% CI, 0.13-0.52) were associated with lower odds of infection. During 3 sampled weeks, mitigation practices were less frequent among Hispanic compared with non-Hispanic participants (eg, mask use while running errands: aOR, 0.26; 95% CI, 0.15-0.46). Hispanic participants were at high risk of infection (aOR, 5.52; 95% CI, 4.30-7.08) and more likely to work outside the home (aOR, 2.05; 95% CI, 1.27-3.30) compared with non-Hispanic participants, possibly because of limited receipt of stimulus checks (aOR, 0.03; 95% CI, 0.02-0.07) or unemployment benefits (aOR, 0.36; 95% CI, 0.16-0.74). Conclusions and Relevance: In this survey study of adults in a large US city, public health messaging improved preventive behaviors over time but lagged among Hispanic participants; messaging tailored to Hispanic communities, especially for mask use, should be prioritized. Hispanic individuals were at higher risk for infection, more often worked outside the home, and were less likely to have received a stimulus check; this suggests larger studies are needed to evaluate the provision of economic support on SARS-CoV-2 transmission dynamics in low-income populations.

Early development of non-hodgkin lymphoma following initiation of newer class antiretroviral therapy among HIV-infected patients - implications for immune reconstitution.

BACKGROUND: In the HAART era, the incidence of HIV-associated non-Hodgkin lymphoma (NHL) is decreasing. We describe cases of NHL among patients with multi-class antiretroviral resistance diagnosed rapidly after initiating newer-class antiretrovirals, and examine the immunologic and virologic factors associated with potential IRIS-mediated NHL. METHODS: During December 2006 to January 2008, eligible HIV-infected patients from two affiliated clinics accessed Expanded Access Program antiretrovirals of raltegravir, etravirine, and/or maraviroc with optimized background. A NHL case was defined as a pathologically-confirmed tissue diagnosis in a patient without prior NHL developing symptoms after starting newer-class antiretrovirals. Mean change in CD4 and log10 VL in NHL cases compared to controls was analyzed at week 12, a time point at which values were collected among all cases. RESULTS: Five cases occurred among 78 patients (mean incidence = 64.1/1000 patient-years). All cases received raltegravir and one received etravirine. Median symptom onset from newer-class antiretroviral initiation was 5 weeks. At baseline, the median CD4 and VL for NHL cases (n = 5) versus controls (n = 73) were 44 vs.117 cells/mm3 (p = 0.09) and 5.2 vs. 4.2 log10 (p = 0.06), respectively. The mean increase in CD4 at week 12 in NHL cases compared to controls was 13 (n = 5) vs. 74 (n = 50)(p = 0.284). Mean VL log10 reduction in NHL cases versus controls at week 12 was 2.79 (n = 5) vs. 1.94 (n = 50)(p = 0.045). CONCLUSIONS: An unexpectedly high rate of NHL was detected among treatment-experienced patients achieving a high level of virologic response with newer-class antiretrovirals. We observed trends toward lower baseline CD4 and higher baseline VL in NHL cases, with a significantly greater decline in VL among cases by 12 weeks. HIV-related NHL can occur in the setting of immune reconstitution. Potential immunologic, virologic, and newer-class antiretroviral-specific factors associated with rapid development of NHL warrants further investigation.

Utility of repeat genotypic resistance testing and clinical response in patients with three class resistance and virologic treatment failure.

We sought to determine the utility of repeat genotypic resistance testing (GRT) and the clinical response in HIV-1-infected patients with known resistance to three of the major classes of antiretroviral drugs. The HIV-1 genetic sequences for 20 patients who had high-level 3 class resistance demonstrated on a prior GRT (3C-GRT 1) measured during the period from November 1, 2000 through July 1, 2004 were retrospectively evaluated. At the time of 3C-GRT 1, the median CD4 count and HIV-1 RNA viral load were 168 cells/mm(3) and 4.5 log copies per milliliter, respectively. The median time to the second GRT (3C-GRT 2) was 17 months. At that time, the median CD4 count and VL were 140 cells/mm(3) and 4.9 log copies per milliliter (p = 0.8 and p = 0.12, respectively). On 3C-GRT 2, all patients retained essentially identical mutations, with the exception of the loss of the M184V mutation in 6 patients. After 3C-GRT 2, all patients continued on protease inhibitor-containing highly active antiretroviral therapy (HAART) regimens. At 24 weeks after 3C-GRT 2, there was no significant change in CD4 count or HIV-1 RNA viral load (p = 0.68 and p = 0.30, respectively). Repeat GRT in patients with documented high-level 3 class resistance does not provide new or clinically useful information. Under continued antiretroviral selective pressure, the viral genetic sequences in this patient population remained stable. In addition, continuing HAART regimens containing protease inhibitors appeared to forestall further immunological and virologic deterioration in patients with multiple resistance mutations. Providers should focus on obtaining access to combinations of novel agents for patients with 3 class resistance rather than repeated GRT.

How does expert advice impact genotypic resistance testing in clinical practice?

The Havana trial, a randomized, prospective study, demonstrated that expert interpretation of genotypic resistance test (GRT) results improved virological outcomes in human immunodeficiency virus type 1 (HIV-1)-infected patients for whom highly active antiretroviral therapy (HAART) was failing. The impact of expert advice in routine clinical practice is unknown. We retrospectively evaluated the virological outcomes of 74 patients for whom HAART was failing and whose clinical providers accepted or rejected HAART regimens recommended by an expert panel who routinely reviewed GRT results. Fifty (68%) of 74 patients received regimens recommended by the expert panel ("advice accepted" [AA]), and 24 patients (32%) received regimens per the clinician's preference ("advice rejected" [AR]). After 24 weeks, AA and AR groups had median decreases in the plasma HIV-1 RNA viral load of 2.6 and 1.3 log(10) copies/mL, respectively (P=.0001). Twenty-six (52%) of 50 patients in the AA group and 5 (21%) of 24 patients in the AR group had a plasma HIV-1 RNA viral load of <50 copies/mL (P=.01). Consideration should be given to enlisting expert assistance in the interpretation of GRT results in routine clinical practice.

Fc gamma receptor 3A polymorphism and risk for HIV-associated cryptococcal disease.

UNLABELLED: Cryptococcus neoformans is one of the most common causes of fungal disease in HIV-infected persons, but not all of those who are infected develop cryptococcal disease (CD). Although CD4(+) T cell deficiency is a risk factor for HIV-associated CD, polymorphisms of phagocytic Fc gamma receptors (FCGRs) have been linked to CD risk in HIV-uninfected persons. To investigate associations between FCGR2A 131 H/R and FCGR3A 158 F/V polymorphisms and CD risk in HIV-infected persons, we performed PCR-based genotyping on banked samples from 164 men enrolled in the Multicenter AIDS Cohort Study (MACS): 55 who were HIV infected and developed CD and a matched control group of 54 who were HIV infected and 55 who were HIV uninfected. Using additive and allelic statistical models for analysis, the high-affinity FCGR3A 158V allele was significantly associated with CD status after adjusting for race/ethnicity (odds ratio [OR], 2.1; P = 0.005), as was the FCGR3A 158 VV homozygous genotype after adjusting for race/ethnicity, rate of CD4(+) T cell decline, and nadir CD4(+) T cell count (OR, 21; P = 0.005). No associations between CD and FCGR2A 131 H/R polymorphism were identified. In binding studies, human IgG (hIgG)-C. neoformans complexes exhibited more binding to CHO-K1 cells expressing FCGR3A 158V than to those expressing FCGR3A 158F, and in cytotoxicity assays, natural killer (NK) cells expressing FCGR3A 158V induced more C. neoformans-infected monocyte cytotoxicity than those expressing FCGR3A 158F. Together, these results show an association between the FCGR3A 158V allele and risk for HIV-associated CD and suggest that this polymorphism could promote C. neoformans pathogenesis via increased binding of C. neoformans immune complexes, resulting in increased phagocyte cargo and/or immune activation. IMPORTANCE: HIV-associated CD4(+) T cell deficiency is a sine qua non for HIV-associated cryptococcal disease (CD), but not all patients with CD4(+) T cell deficiency develop CD despite serological evidence of previous infection. At present, there are no biomarkers that predict HIV-associated CD risk. The goal of our study was to understand whether Fc gamma receptor (FCGR) polymorphisms that have been shown to portend CD risk in HIV-uninfected people are associated with CD risk in HIV-infected people. Such biomarkers could identify those who would benefit most from targeted prophylaxis and/or earlier treatment, particularly in sub-Saharan Africa, where there are nearly a million cases of HIV-associated CD annually. A biomarker of risk could also identify potential candidates for immunization, should there be a vaccine for Cryptococcus neoformans.

Evaluation of adherence and factors affecting adherence to combination antiretroviral therapy among White, Hispanic, and Black men in the MACS Cohort.

OBJECTIVES: This study investigated levels of adherence to antiretroviral therapy in white, Hispanic, and black men and isolated factors associated with adherence among each racial group. METHODS: Data were collected from 1102 men enrolled in the Multicenter AIDS Cohort Study followed between April 2002 and October 2006. Self-reported 100% adherence was defined as taking all doses and pills over the previous 4-day period, reporting not typically skipping any medications, and reporting always following the medication schedule. Variables associated with adherence were determined by multilevel logistic regression for each racial group. Adherence was also analyzed by ethnicity within racial groups. RESULTS: After controlling for confounders, we found that Hispanics were 2.16 times and blacks were 1.37 times more likely than whites to not report 100% adherence (95% confidence interval 1.47 to 3.18 and 1.05 to 1.79, respectively). Hispanics with ethnic backgrounds from Central and South America and the Caribbean had lower rates of adherence. Blacks with ethnic backgrounds from the Caribbean had lower rates of adherence than those from other regions.

IgM(+) memory B cell expression predicts HIV-associated cryptococcosis status.

BACKGROUND: The role of B cells in resistance to Cryptococcus neoformans disease (i.e., cryptococcosis) is unknown. Given evidence that IgM(+) memory B cells are required for immunity to other encapsulated pathogens, we hypothesized that these cells might contribute to resistance to cryptococcosis. METHODS: We compared levels of IgM expression on memory B cells in 29 HIV-infected individuals who had a history of cryptococcosis (the HIV+CN+ group) with levels in 30 human immunodeficiency virus (HIV)-infected subjects who had no history of cryptococcosis (the HIV+CN- group) and 20 HIV-uninfected subjects who had no history of cryptococcosis (the HIV- group) (cohort 1). We also determined levels of IgM expression on memory B cells in banked samples obtained before cryptococcosis onset from 31 participants in the Multicenter AIDS Cohort Study, of whom 8 had HIV infection and subsequently developed cryptococcosis (the HIV+CN+ group), 8 had HIV infection and did not develop cryptococcosis (the HIV+CN- group), and 15 did not have HIV infection and did not develop cryptococcosis (the HIV- group) (cohort 2). RESULTS: In cohort 1, the percentage of memory B cells that expressed IgM was lower among HIV+CN+ subjects, compared with HIV+CN- subjects (P < .01) and HIV- subjects (P < .05); expression of IgM on 50% of memory B cells was a significant predictor of C. neoformans disease status (odds ratio, 5.5; P = .03). In cohort 2, the percentage of memory B cells that expressed IgM was lower in HIV+CN+ subjects than in HIV+CN- subjects (P = .02) and HIV- subjects (P < .01); an IgM(+) memory B cell percentage of 38.5% was a significant predictor of future development of cryptococcosis (odds ratio, 14; P = .02). CONCLUSIONS: These findings suggest that HIV-infected persons in whom the percentage of memory B cells that express IgM is decreased might be at greater risk for the development of cryptococcosis.

Metabolic syndrome in older HIV-infected patients: data from the CORE50 cohort.

Metabolic abnormalities and cardiovascular disease are increasingly recognized in HIV-infected patients. While HIV-infected patients older than 50 years of age account for up to 25% of HIV cases in the United States, there are limited data on these individuals. To determine the prevalence and predictors of the metabolic syndrome among a cohort of older, HIV-infected patients and to calculate their 10-year Framingham cardiac risk (FCR) score a cross-sectional study of HIV patients older than 50 years of age was conducted at the CORE Center, Chicago, Illinois, between May 2005 and February 2006. There were 121 HIV-infected patients with a median age of 54 years, of whom 79% were male, 83% African American, 9% Hispanic, and 6% Caucasian. Thirty-four percent of patients had the metabolic syndrome, 49% had a moderate-high (>10%) 10-year FCR, and 13% had a high (>20%) 10-year FCR. Patients with the metabolic syndrome were significantly more likely to have a greater than 20% 10-year FCR. Sixty-five percent of all patients were current smokers and 55% of patients with the metabolic syndrome were current smokers. There were significant differences in the components of the metabolic syndrome by gender with women having significantly more components related to insulin resistance such as elevated waist circumference and diabetes, while men were more likely to have low high-density lipoprotein (HDL) levels. This study shows a high prevalence of the metabolic syndrome in older HIV-infected patients and an association between the metabolic syndrome and FCR in our study population. As the HIV population ages, attention to modifiable cardiac risk factors will become increasingly important.

Interruption and discontinuation of highly active antiretroviral therapy in the multicenter AIDS cohort study.

OBJECTIVE: Identify the determinants and consequences of interrupting and discontinuing highly active antiretroviral therapy (HAART) among a population-based cohort of HIV-infected men. METHODS: Longitudinal analyses were applied to 2916 person-visit pairs (589 men) of continuous HAART use, 243 person-visit pairs (154 men) during which HAART was interrupted, and 151 person-visit pairs (130 men) in which HAART was discontinued by the second visit. HIV RNA increase was defined as > or =1 log10 copies/mL across the visit pairs. RESULT: : Younger age, black race, geographic location, higher HIV RNA level, depression, shorter time on HAART, lower medication adherence, and not taking a lamivudine-containing regimen predicted interrupting HAART use. Younger age, higher HIV RNA level, depression, and taking an abacavir- or lopinavir-containing regimen predicted discontinuing HAART. Among men with < or =1000 HIV RNA copies/mL, approximately 5% of those who interrupted HAART for < or =7 days and those who continued HAART had an HIV RNA increase. Men with longer interruptions and HAART discontinuers had significantly higher rates of HIV RNA increases (35.7% and 70.5%, respectively). Discontinuation and long interruptions resulted in lower CD4 cell counts. CONCLUSIONS: Host characteristics play a role in short interruptions, whereas longer interruptions may be clinically indicated. These longer stoppages had further virologic and immunologic consequences, however.