Allen McCutchan

Effect of brief safer-sex counseling by medical providers to HIV-1 seropositive patients: a multi-clinic assessment.

Objective: To test the efficacy of brief, safer-sex counseling by medical providers of HIV-positive patients during medical visits. Setting: Six HIV clinics in California. Design: Clinics were randomized to intervention arms evaluated with cohorts of randomly selected patients measured before and after the intervention. Participants: Five-hundred and eighty-five HIV-positive persons, sexually active prior to enrollment. Interventions: Prevention counseling from medical providers supplemented with written information. Two clinics used a gain-framed approach (positive consequences of safer-sex), two used a loss-frame approach (negative consequences of unsafe sex), and two were attention-control clinics (medication adherence). Interventions were given to all patients who attended the clinics. Outcome measure: Self-reported unprotected anal or vaginal intercourse (UAV). Results: Among participants who had two or more sex partners at baseline, UAV was reduced 38% (P < 0.001) among those who received the loss-frame intervention. UAV at follow-up was significantly lower in the loss-frame arm [odds ratio (OR), 0.42; 95% confidence interval (CI), 0.19–0.91; P = 0.03] compared with the control arm. Using generalized estimating equations (GEE) to adjust for clustering did not change the conclusions (OR, 0.34; 95% CI, 0.24–0.49; P = 0.0001). Similar results were obtained in participants with casual partners at baseline. No effects were seen in participants with only one partner or only a main partner at baseline. No significant changes were seen in the gain-frame arm. Conclusions: Brief provider counseling emphasizing the negative consequences of unsafe sex can reduce HIV transmission behaviors in HIV-positive patients presenting with risky behavioral profiles.

Are HIV care providers talking with patients about safer sex and disclosure?: A multi-clinic assessment

Objectives: To examine HIV-positive patients’ reports of whether HIV care providers ever talked with them about practicing safer sex and disclosing seropositive status to sex partners. Design: Cross-sectional survey (1998–1999) of HIV-positive men and women sampled randomly at six public HIV clinics in California. Methods: Participants were interviewed and asked whether applicable clinic providers (physician, physician assistant, nurse practitioner, nurse, social worker, health educator, psychologist, psychiatrist) ever talked with them about safer sex or disclosure. Responses were analyzed by clinic site, HIV medical status (viral load), demographic, and behavioral variables (unprotected intercourse, non-disclosure). Results: The sample (n = 839) included heterosexual men (n = 127), men who have sex with men (MSM; n = 607), and women (n = 105). Thirty-nine percent were white, 36% Hispanic, 17% black, and 8% other/mixed ethnicity. Overall, 71% reported that an applicable provider had talked with them at least once about safer sex (range across clinics, 52–94%); 50% reported discussion of disclosure (range across clinics, 31–78%). Discussion of safer sex was more prevalent with physicians than with other clinic staff. In multivariate analyses, in addition to significant clinic differences, MSM (versus heterosexual men) and whites (versus blacks or Hispanics) were less likely to receive prevention messages on these topics. Patients’ behaviors (unsafe sex, non-disclosure) and HIV medical status were not independently associated with provider communication. Conclusions: HIV clinics differed substantially in the percentage of patients who reported that they received prevention messages from clinic staff. Care providers should assess and overcome barriers to providing prevention messages to patients.

The roles of dispositional optimism and pessimism in hiv disease progression

Relationships between dispositional optimism and pessimism and the course of HIV infection, determined by changes in viral load and CD4 counts, were studied in a longitudinal cohort of 412 patients on antiretroviral therapy (ART). Multiple regression analyses controlling for baseline levels of disease status, ethnicity, and depressive symptoms demonstrated that higher pessimism at baseline was associated with higher viral load at follow-up (average of 18 months later). Optimism at baseline had a curvilinear relationship with CD4 counts at follow-up. Moderate levels of optimism at baseline predicted the highest CD4 counts at follow-up. Although optimism and pessimism were associated with specific health behaviors (e.g., ART adherence, cigarette use, drug use, dietary practices), none of these behaviors mediated the optimism/pessimism effects. The biologic and behavioral mediators of associations of personality variables with the course of treated HIV infection deserve continued investigation.

Total Raltegravir Concentrations in Cerebrospinal Fluid Exceed the 50-Percent Inhibitory Concentration for Wild-Type HIV-1

ABSTRACT HIV-associated neurocognitive disorders continue to be common. Antiretrovirals that achieve higher concentrations in cerebrospinal fluid (CSF) are associated with better control of HIV and improved cognition. The objective of this study was to measure total raltegravir (RAL) concentrations in CSF and to compare them with matched concentrations in plasma and in vitro inhibitory concentrations. Eighteen subjects with HIV-1 infection were enrolled based on the use of RAL-containing regimens and the availability of CSF and matched plasma samples. RAL was measured in 21 CSF and plasma pairs by liquid chromatography-tandem mass spectrometry, and HIV RNA was detected by reverse transcription-PCR (RT-PCR). RAL concentrations were compared to the 50% inhibitory concentration (IC50) for wild-type HIV-1 (3.2 ng/ml). Volunteers were predominantly middle-aged white men with AIDS and without hepatitis C virus (HCV) coinfection. The median concurrent CD4+ cell count was 276/μl, and 28% of CD4+ cell counts were below 200/μl. HIV RNA was detectable in 38% of plasma specimens and 4% of CSF specimens. RAL was present in all CSF specimens, with a median total concentration of 14.5 ng/ml. The median concentration in plasma was 260.9 ng/ml, with a median CSF-to-plasma ratio of 0.058. Concentrations in CSF correlated with those in with plasma (r2, 0.24; P, 0.02) but not with the postdose sampling time (P, >0.50). RAL concentrations in CSF exceeded the IC50 for wild-type HIV in all specimens by a median of 4.5-fold. RAL is present in CSF and reaches sufficiently high concentrations to inhibit wild-type HIV in all individuals. As a component of effective antiretroviral regimens or as the main antiretroviral, RAL likely contributes to the control of HIV replication in the nervous system.

Localized Osteomyelitis Due to Mycobacterium avium Complex in Patients with Human Immunodeficiency Virus Receiving Highly Active Antiretroviral TherapyLocalized Osteomyelitis Due to Mycobacterium avium Complex in Patients with Human Immunodeficiency Virus Receiving Highly Active Antiretroviral Therapy

We describe 3 patients who developed atypical manifestations of Mycobacterium avium complex (MAC) infection >10 months (range, 3-16 months) after attaining sustained CD4(+) T cell counts of >100 cells/microL while receiving antiretroviral therapy and not receiving MAC prophylaxis. The common features of these cases include the degree of immune reconstitution, the unusual locations of the infections, and the absence of a systemic inflammatory response. The low rate of these unusual MAC infections does not warrant continuation of primary or secondary prophylaxis after presumed immune reconstitution.

Dynamics of monocyte chemoattractant protein type one (MCP-1) and HIV viral load in human cerebrospinal fluid and plasma

BACKGROUND Increased expression of monocyte chemoattractant protein type 1 (MCP-1) is associated with HIV CNS disease. This study evaluated the temporal relationships between MCP-1 expression and HIV replication in the CNS. METHODS MCP-1 and HIV viral load (VL) were measured in serially obtained samples of plasma and cerebrospinal fluid (CSF) in subjects either interrupting (TI) or starting (TS) antiretroviral therapy. RESULTS Following TI, plasma VL rebounded first, followed by increases in CSF MCP-1, which immediately preceded or coincided with a rebound of CSF VL. CONCLUSION The close temporal relationship of the increase of MCP-1 and CSF VL suggests that they are co-regulated, or that one is a stimulus for the other.

Effect of a brief antiretroviral adherence intervention delivered by HIV care providers.

Antiretroviral therapy (ART) is effective in controlling viral load in many people infected with HIV, but high levels of adherence to ART are needed for prolonged viral suppression. This study evaluated a brief adherence intervention delivered to HIV-positive patients by primary care providers during routine medical examinations. Six clinics were randomly allocated to deliver an intervention focusing on ART adherence (2 clinics) or safer sex (4 clinics). Interventions included written information (posters, brochures, and flyers) and brief counseling from providers and were evaluated with cohorts of randomly selected patients (n = 437) measured before and after a 10-month intervention. Among those 95% or greater adherent at baseline, 91% of patients who received the adherence intervention remained 95% or greater adherent at follow-up compared with 75% of the patients who received the safer sex intervention (χ2 = 12.59, P < 0.01). This difference was significant in a logistic regression analysis (odds ratio = 2.26; 95% confidence interval = 1.27-4.04), adjusting for baseline adherence, demographics, and HIV medical status. The adherence intervention did not significantly increase the prevalence of 95% or greater adherence among patients less than 95% adherent at baseline. Similar but nonsignificant results were observed for viral load. A brief intervention delivered to HIV patients by their primary providers helped to maintain adequate adherence to ART regimens. More intensive intervention is needed to improve adherence among patients who are initially less than 95% adherent.

Cerebrospinal fluid human immunodeficiency virus viral load in patients with neurosyphilis.

Syphilis is a frequent coinfection with human immunodeficiency virus (HIV). Whereas systemic syphilis infection increases plasma HIV RNA levels (viral load; VL), effects of syphilis on cerebrospinal fluid (CSF) VL are unknown. We hypothesized that intrathecal immune activation in neurosyphilis would selectively increase CSF VL in coinfected patients. In this study, HIV-infected research subjects (N = 225) were categorized into three groups based on serum rapid plasma reagin (RPR), microhemaglutination for Treponema pallidum (MHA-TP) MHA-TP, and CSF VDRL: 23 with neurosyphilis (NS +; reactive serum RPR and MHA-TP and positive CSF VDRL); 42 with systemic syphilis but not neurosyphilis (Syph+; reactive serum RPR and MHA-TP; negative CSF VDRL), and 160 without syphilis (Syph−; nonreactive serum RPR). Plasma and CSF HIV VL were quantified by reverse transcriptase—ploymerase chain reaction (RT-PCR) (Amplicor, Roche) in log10 copies/ml. To adjust for covariates previously shown to influence CSF HIV VL (i.e., plasma VL, CD4, pleocytosis, and highly active antiretroviral therapy [HAART]), multivariable linear regression was used. Lumbar punctures (LP) done for research purposes diagnosed 23 with neurosyphilis; most (83%) of these reported prior syphilis treatment. Among subjects with detectable plasma VL, CSF VL was highest in NS+, followed by Syph+ and Syph− (P =.006). This relationship was independent of the level of plasma VL or CSF pleocytosis. By contrast, among subjects with undetectable plasma HIV VL, CSF VLs were similar in the three syphilis subgroups (P = .50). Neurosyphilis may amplify intrathecal HIV replication, possibly through immune activation that persists even after syphilis treatment. Because elevated CSF VL is associated with subsequent neurocognitive decline, future studies should evaluate the impact of neurosyphilis on the course of central nervous system (CNS) HIV infection.

Odor sensitivity is impaired in HIV-positive cognitively impaired patients

An estimated 7-28% of patients infected by the human immunodeficiency virus (HIV) develop dementia and at least 50% develop mild neurocognitive impairment. Past studies have shown odor identification impairments in HIV + neurocognitively impaired patients. It is difficult, however, based on an odor identification test to state with certainty that individuals with cognitive impairment have sensory olfactory deficits, because odor identification tests are known to draw upon cognitive skills. In the present study odor detection sensitivity was evaluated using an ascending, forced-choice, two-alternative, odor threshold test for butanol. Subjects were divided into three groups, HIV seropositive (HIV+) neurocognitively impaired, HIV+ neurocognitively unimpaired, and HIV negative, based on neurological and psychological testing. An analysis of variance revealed significantly poorer odor sensitivity for the HIV+ neurocognitively impaired group than for the two control groups. A significant negative correlation between degree of cognitive impairment and olfactory sensitivity was also found. We suspect that the olfactory deficits found in the HIV+ neurocognitively impaired subjects are primarily due to damage to the central nervous system; however, nasal infection may be a contributing etiology.

Abacavir and increased risk of myocardial infarction

This project was initiated as part of the Uganda Women’s Health Initiative (UWHI) involving the University College London Institute for Women’s Health, Mulago Hospital, Makerere University, and Hospice Africa, Uganda. We are grateful to Graham Evans (Project Manager UWHI) for his support and guidance. The UWHI and this project were supported by generous donations from Lee and Roger Myers and Ann-Margaret and John Walton. These funding sources had no involvement in study design, collection, analysis, and interpretation of data in the writing of report or the decision to submit the letter for publication. We declare that we have no confl ict of interest.