[Show abstract][Hide abstract] ABSTRACT: We conducted a prospective cohort study of 795 outpatients, many of whom were human immunodeficiency virus-infected men who have sex with men, to characterize risk of skin and soft-tissue infection (SSTI) associated with methicillin-resistant Staphylococcus aureus (MRSA) nares and perianal colonization. Multivariate analysis revealed that perianal colonization, drug use, and prior SSTIs were strongly associated with development of an SSTI. Of the patients who were colonized with MRSA at study entry, 36.7% developed an SSTI during the ensuing 12 months, compared with 8.1% of persons who were not colonized with MRSA.
[Show abstract][Hide abstract] ABSTRACT: To evaluate the recognition of computationally designed, centralized HIV-1 antigens derived from clade B, C and group M sequences by individuals infected with HIV-1-M clades B and C.
Three centralized sequences have been described - consensus, ancestor and center-of-tree - each of which attempts to minimize the genetic distance to circulating viruses. It is unclear whether any of these sequences affords an advantage for T cell recognition. The ability of centralized clade B and C and group M peptides to be targeted in ELISpot assays was assessed using samples from the United States, Peru, Barbados and South Africa.
Each of the clade-specific centralized peptide sets was equally powerful in detecting cytotoxic T cell (CTL) responses. Importantly, combination of these sets detected significantly broader responses. Although broad responses were observed in populations from which few sequences informed the design of these centralized sequences, the genetic distance between local sequences and the respective test set was inversely associated with response rates. Furthermore, the CTL reactivity in clade C-infected subjects using clade B peptides was reduced relative to within-clade peptide responses, while responses to group M peptides were comparable to within-clade peptide responses in these individuals.
All tested centralized antigens provided a similarly potent set of antigenic peptides. However, the significantly broader responses detected using the combination of sets highlight the importance of maximizing coverage of HIV-1 sequence diversity in vaccine preparations, as well as in the evaluation of CTL responses in HIV-1-infected individuals and those vaccinated.
AIDS (London, England) 03/2008; 22(4):447-56. DOI:10.1097/QAD.0b013e3282f42412 · 5.55 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Large clinical trials have repeatedly proven the effectiveness of highly active antiretroviral therapy (HAART) in achieving virological suppression; however, subsequent increases in CD4 cell counts (i.e., immunological rebound) do not always follow. Thus, it remains unclear to what extent persons living with HIV/AIDS may expect significant increases in CD4 cell count upon HAART initiation, particularly outside of the highly structured environment of a clinical trial. We analyzed the patterns of CD4 and plasma viral load (PVL) change in 170 HIV-infected individuals who were ART naive and initiated HAART between 1997 and 2003. Immunological success (>50 CD4 cells/mm(3) increase) was evaluated using Kaplan-Meier survival analysis and Cox proportional hazard models. Of individuals, 80% experienced a confirmed CD4 cell count increase of >50 cells/mm(3) after HAART initiation. Multivariate analysis showed that patients with pre-HAART PVL >or=100,000 copies/ml were more likely to achieve immunological success when compared with patients with baseline PVL <10,000 copies/ml, suggesting that individuals with the highest HIV viral load levels may benefit the most from HAART initiation. Future studies of immunological rebound are warranted to further define and characterize immune responses to HAART in diverse populations in order to optimize guidelines for initiation of treatment and assessment of successful responses.
AIDS Research and Human Retroviruses 03/2008; 24(3):499-504. DOI:10.1089/aid.2007.0099 · 2.33 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Infection with multidrug-resistant, community-associated, methicillin-resistant Staphylococcus aureus (MRSA) has been reported but seems to be isolated.
To determine the incidence of a multidrug-resistant MRSA clone (USA300) in San Francisco, and to determine risk factors for the infection.
Population-based survey and cross-sectional study using chart review.
9 hospitals in San Francisco (population-based survey) and 2 outpatient clinics in San Francisco and Boston (cross-sectional study).
Persons with culture-proven MRSA infections in 2004 to 2006.
Annual incidence, spatial clustering, and risk factors for multidrug-resistant USA300 infection. Pulsed-field gel electrophoresis, polymerase chain reaction assays, and DNA sequencing were used to characterize MRSA isolates.
The overall incidence of multidrug-resistant USA300 infection in San Francisco was 26 cases per 100,000 persons (95% CI, 16 to 36 cases per 100,000 persons); the incidence was higher in 8 contiguous ZIP codes with a higher proportion of male same-sex couples. Male-male sex was a risk factor for multidrug-resistant USA300 infection (relative risk, 13.2 [CI, 1.7 to 101.6]; P < 0.001) independent of past MRSA infection (relative risk, 2.1 [CI, 1.2 to 3.7]; P = 0.007) or clindamycin use (relative risk, 2.1 [1.2 to 3.6]; P = 0.007). The risk seemed to be independent of HIV infection. In San Francisco, multidrug-resistant USA300 manifested most often as infection of the buttocks, genitals, or perineum. In Boston, the infection was recovered exclusively from men who had sex with men.
The study was retrospective, and sexual risk behavior was not assessed.
Infection with multidrug-resistant USA300 MRSA is common among men who have sex with men, and multidrug-resistant MRSA infection might be sexually transmitted in this population. Further research is needed to determine whether existing efforts to control epidemics of other sexually transmitted infections can control spread of community-associated, multidrug-resistant MRSA.
Annals of internal medicine 03/2008; 148(4):249-57. · 17.81 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Men who have sex with men (MSM) receiving non-occupational post-exposure prophylaxis (NPEP) to prevent HIV transmission completed interview-assisted questionnaires regarding high-risk behavior in the 6 months prior to NPEP and during the 28-day NPEP period. 21% of participants reported unprotected sex during NPEP, and 11% reported unprotected sex with HIV-positive or HIV status unknown partners. In univariate analyses, unprotected sex during NPEP was associated with prevention fatigue, depression, loss of loved ones to HIV, and a history of engagement with HIV/AIDS service organizations, e.g., receiving services from an HIV-related agency, donating money to HIV-related causes, and reading HIV-related magazines. Logistic regression analyses revealed that the strongest predictor of risk-taking during NPEP was HIV engagement. These data underscore the importance of combining chemoprophylaxis with behavioral interventions that support risk-reduction. Such interventions should not assume that those most engaged with HIV/AIDS service organizations are less likely to engage in risk behavior.
AIDS and Behavior 09/2007; 12(6):852-9. DOI:10.1007/s10461-007-9286-8 · 3.49 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: HIV primary care is determined by the intersection of the unique aspects of the infection and its treatment, the unique aspects of the populations affected by HIV, and the challenges of disease prevention and health maintenance in the general population. Any primary care provider may be called on to care for a patient living with HIV, and it is incumbent on all medical providers to become proficient in the management of this complex infection. This proficiency includes an awareness of local resources for referral, including medical and surgical specialists, mental health providers, and social service organizations. Given the complexity of HIV care in the twenty-first century and the potential for involvement of multiple consultants, the role of primary care provider is perhaps more critical for the HIV-infected patient than for the average patient.
Infectious Disease Clinics of North America 04/2007; 21(1):49-70, viii. DOI:10.1016/j.idc.2007.01.001 · 2.73 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: CD8+ T cells impact control of viral infections by direct elimination of infected cells and secretion of a number of soluble factors. In HIV-1 infection, persistent HIV-1 specific IFN-gamma+ CD8+ T cell responses are detected in the setting of disease progression, consistent with functional impairment in vivo. Recent data suggest that impaired maturation, as defined by the lineage markers CD45RA and CCR7, may contribute to a lack of immune control by these responses.
We investigated the maturation phenotype of epitope-specific CD8+ T cell responses directed against HIV-1 in 42 chronically infected, untreated individuals, 22 of whom were "Controllers" (median 1140 RNA copies/ml plasma, range<50 to 2520), and 20 "progressors" of whom had advanced disease and high viral loads (median 135,500 RNA copies/ml plasma, range 12100 to >750000). Evaluation of a mean of 5 epitopes per person revealed that terminally differentiated CD8+ T cells directed against HIV-1 are more often seen in HIV-1 Controllers (16/22; 73%) compared to HIV-1 progressors (7/20; 35%)(p = 0.015), but the maturation state of epitope-specific responses within a given individual was quite variable. Maturation phenotype was independent of the HLA restriction or the specificity of a given CD8+ T cell response and individual epitopes associated with slow disease progression were not more likely to be terminally differentiated.
These data indicate that although full maturation of epitope-specific CD8+ T cell responses is associated with viral control, the maturation status of HIV-1 specific CD8+ T cell responses within a given individual are quite heterogeneous, suggesting epitope-specific influences on CD8+ T cell function.
PLoS ONE 03/2007; 2(3):e321. DOI:10.1371/journal.pone.0000321 · 3.23 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To assess the prevalence of asymptomatic urethral gonorrhea and chlamydia men who have sex with men (MSM) living in greater Boston, 206 men attending routine medical appointments consented to urine-based chlamydia and gonorrhea screening using urine LCR amplification. Of those screened, 201 patients also completed a seven-question survey to assess sexual risk behaviors associated with urethral sexually transmitted infections. Less than 1% of the asymptomatic patients screened tested positive for urethral chlamydia; none tested positive for urethral gonorrhea. Forty-eight percent reported multiple sexual partners in the 30 days prior to screening, with HIV-infected patients reporting fewer partners and less unprotected insertive anal sex than HIV-uninfected patients. Almost 25% of patients screened used the Internet in the 30 days prior to screening to find a sexual partner. Internet use was associated with increased numbers of sexual partners in the 30 days prior to screening. Findings suggest that asymptomatic urethral chlamydia and gonorrhea may be uncommon in MSM living in the greater Boston area and that the recent rise in the prevalence of sexually transmitted infections may not be due to untreated asymptomatic infections. Increased awareness of STD symptoms among patients and medical providers is critical to timely diagnosis and treatment of STDs in MSM.
AIDS PATIENT CARE and STDs 03/2007; 21(3):205-11. DOI:10.1089/apc.2006.0051 · 3.50 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Community-acquired methicillin-resistant Staphylococcus aureus (MRSA) skin and soft tissue infections (SSTI) have become increasingly common. This study's objectives were to describe the clinical spectrum of MRSA in a community health center and to determine whether the use of specific antimicrobials correlated with increased probability of clinical resolution of SSTI. A retrospective chart review of 399 sequential cases of culture-confirmed S. aureus SSTI, including 227 cases of MRSA SSTI, among outpatients at Fenway Community Health (Boston, MA) from 1998 to 2005 was done. The proportion of S. aureus SSTI due to MRSA increased significantly from 1998 to 2005 (P<0.0001). Resistance to clindamycin was common (48.2% of isolates). At the beginning of the study period, most patients with MRSA SSTI empirically treated with antibiotics received a beta-lactam, whereas by 2005, 76% received trimethoprim-sulfamethoxazole (TMP-SMX) (P<0.0001). Initially, few MRSA isolates were sensitive to the empirical antibiotic, but 77% were susceptible by 2005 (P<0.0001). A significantly higher percentage of patients with MRSA isolates had clinical resolution on the empirical antibiotic by 2005 (P=0.037). Use of an empirical antibiotic to which the clinical isolate was sensitive was associated with increased odds of clinical resolution on empirical therapy (odds ratio=5.91), controlling for incision and drainage and HIV status. MRSA now accounts for the majority of SSTI due to S. aureus at Fenway, and improved rates of clinical resolution on empirical antibiotic therapy have paralleled increasing use of empirical TMP-SMX for these infections. TMP-SMX appears to be an appropriate empirical antibiotic for suspected MRSA SSTI, especially where clindamycin resistance is common.
[Show abstract][Hide abstract] ABSTRACT: The present study sought to investigate the prevalence of hepatitis C virus (HCV) among men who have sex with men (MSM) seen at a community health center, and to examine risk factors associated with infection. The study population included 218 MSM who were screened for HCV infection during routine clinic visits from May through December, 2001. Eighty-four percent of those screened (n = 183) agreed to complete a self-report questionnaire assessing drug use, sexual practices, and medical history. Participants ranged in age from 22 to 54 years. The majority of participants (82%) self-identified as Caucasian and 35% were HIV-positive. Prevalence of HCV infection was 11.5%. Men infected with HCV were more likely than HCV uninfected men to be coinfected with HIV and hepatitis B, and to have a history of rectal or urethral gonorrhea. HCV-infected men were more likely to have seen blood on shared cocaine straws and to have used crack cocaine in the past 6 months. Overall, 12% of HCV-infected men reported no parenteral risk factors for HCV infection. HCV seropositivity was significantly associated with an aggregate score representing high-risk behavior in the past six months. HCV prevention and screening should target MSM engaging in high-risk sex. Conversely, HIV and sexually transmitted infection risk reduction interventions should be targeted at MSM with HCV.
AIDS PATIENT CARE and STDs 09/2006; 20(8):557-64. DOI:10.1089/apc.2006.20.557 · 3.50 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Numerous studies now support that human immunodeficiency virus type 1 (HIV-1) evolution is influenced by immune selection pressure, with population studies showing an association between specific HLA alleles and mutations within defined cytotoxic T-lymphocyte epitopes. Here we combine sequence data and functional studies of CD8 T-cell responses to demonstrate that allele-specific immune pressures also select for mutations flanking CD8 epitopes that impair antigen processing. In persons expressing HLA-A3, we demonstrate consistent selection for a mutation in a C-terminal flanking residue of the normally immunodominant Gag KK9 epitope that prevents its processing and presentation, resulting in a rapid decline in the CD8 T-cell response. This single amino acid substitution also lies within a second HLA-A3-restricted epitope, with the mutation directly impairing recognition by CD8 T cells. Transmission of the mutation to subjects expressing HLA-A3 was shown to prevent the induction of normally immunodominant acute-phase responses to both epitopes. However, subsequent in vivo reversion of the mutation was coincident with delayed induction of new CD8 T-cell responses to both epitopes. These data demonstrate that mutations within the flanking region of an HIV-1 epitope can impair recognition by an established CD8 T-cell response and that transmission of these mutations alters the acute-phase CD8(+) T-cell response. Moreover, reversion of these mutations in the absence of the original immune pressure reveals the potential plasticity of immunologically selected evolutionary changes.
Journal of Virology 08/2004; 78(13):7069-78. DOI:10.1128/JVI.78.13.7069-7078.2004 · 4.44 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: We screened 651 human immunodeficiency virus (HIV)-1-infected subjects for hepatitis B surface antigen (HBsAg) and antibody to hepatitis B surface antigen (anti-HBs). Of a total of 387 subjects who tested negative for both HBsAg and anti-HBs, 142 underwent further testing for isolated presence of antibody to hepatitis B core antigen (anti-HBc). Of these 142 subjects, 60 (42%) tested positive for anti-HBc (isolated anti-HBc). Individuals coinfected with HIV-1 and hepatitis C virus (HCV) were more likely to have isolated anti-HBc than were subjects with HIV-1 alone (80% vs. 16%, respectively). Our findings suggest that individuals with HIV-1/HCV coinfection for whom there is no serological evidence for hepatitis B virus when screened with HBsAg and anti-HBs will be positive for anti-HBc in >75% of cases. A screening strategy that tests only for HBsAg and anti-HBs in HIV-1-infected patients will miss a large number of individuals with isolated anti-HBc.
[Show abstract][Hide abstract] ABSTRACT: Superinfection with multiple strains or subtypes of the human and simian immunodeficiency viruses has been documented. Recent increases in the prevalences of both unprotected anal intercourse and sexually transmitted diseases among men who have sex with men indicate that these men continue to practice unsafe sex and, therefore, are at risk for superinfection with the human immunodeficiency virus (HIV). Recurrent exposure to HIV among seropositive individuals who engage in high-risk behaviors can have serious consequences, because superinfection is a necessary first step for viral recombination to occur. Recombination may produce more virulent viruses, drug-resistant viruses, or viruses with altered cell tropism. Additionally, recombinant viruses and superinfection can accelerate disease progression and increase the likelihood of sexual transmission by increasing virus load in the blood and genital tract. The extent of superinfection and recombination in persons living with HIV is unknown. The implications of HIV superinfection and the generation of recombinant viruses are discussed.
[Show abstract][Hide abstract] ABSTRACT: Infection with human immunodeficiency virus (HIV) results in inevitable progressive deterioration of the immune system in the majority of untreated patients. Prospects for virus eradication are remote, because HIV establishes long-lived reservoirs during the earliest stages of infection that are impervious to available antiviral therapies. Understanding how the immune system copes with this illness and other chronic viral infections is the key to designing future strategies for long-term control of viremia. Valuable insights have been gained from 2 populations in particular: patients with chronic, long-term, nonprogressing infections, in whom viremia is controllable in the absence of antiviral medications, and acutely infected patients, in whom the initial HIV-specific immune response might be preserved and augmented by timely intervention. These cases of immune control of HIV provide hope for the development of improved vaccine products that may eventually produce vaccine-induced immunity that will enhance durable control of HIV infection.