We evaluated phenotypic and functional parameters of immune restoration of 27 HIV-infected patients on highly active antiretroviral therapy (HAART) (HIV-cases) with HIV-RNA levels below detectable limits at least during 18 months, and CD4+ cell per microliter higher than 500 at the moment of the study and lower than 300 anytime before. These patients were compared with 11 HIV-controls that never had less than 500 CD4+ cell per microliter and 20 healthy-controls (HIV seronegative subjects) in a cross-sectional study. HIV-cases had lower counts of naïve CD4+ than HIV-controls and healthy-controls. HIV-patients (both HIV-cases and HIV-controls) showed higher values of naïve and memory CD8+ counts than healthy-controls. TREC-bearing cell levels were significantly lower in HIV-cases than in healthy-controls. Peripheral blood mononuclear cells (PBMC) cultures, HIV-cases had lower values in proliferation to streptokinase (SK) and tetanus toxin (TT) than in healthy-controls. HIV-cases had lower IFN-gamma and higher IL-5 production with pokeweed than healthy-controls ( P < 0.01). However, IL-5 production of HIV-cases after TT stimulation was lower than in HIV-controls and healthy-controls. Total IgG and IgG1 levels were significantly higher in HIV-cases than in HIV-controls and healthy-controls. Also, IgM levels were significantly higher in HIV-cases than in healthy-controls. Nevertheless, IgG2 levels were significantly lower in HIV-cases and HIV-controls than in healthy-controls. The levels of specific Igs antipneumococcal capsular polysaccharide and TT were significantly lower in HIV-cases than in healthy-controls. HIV-patients with a previous state of severe-moderate immunosuppression normalizing their CD4+ counts have a incomplete immune reconstitution after HAART. Long-term consequences of this subclinical immune deficiency remain to be determined.
Most HIV behavioral interventions provide participants with preventive information emphasizing how not to behave, and have neglected to provide attractive and feasible alternatives to risky behavior. Interventions that emphasize cultural strengths may have more powerful effects and may help remove the stigma of HIV, which has hampered prevention efforts among African American communities. Starting in 1997, the SHIELD (Self-Help in Eliminating Life-Threatening Diseases) intervention trained injection drug users (N=250) to conduct risk reduction outreach education among their peers. Many participants saw their outreach as "work," which gave them a sense of meaning and purpose and motivated them to make other positive changes in their lives.
Bloodborne pathogens continue to be a source of occupational infection for healthcare workers, but particularly for surgeons. Over 1 per cent of the U.S. population has one or more chronic viral infections. Hepatitis B is the infection that has the longest known role as an occupational pathogen, but infection with this virus is largely preventable with the use of the effective hepatitis B vaccine. Hepatitis C affects the largest number of people in the United States, and there is no vaccine available for the prevention of this infection. HIV infection still has not been associated with a documented transmission in the operating room environment, but six cases of probable occupational transmission have been reported. A total of 57 healthcare workers have had documented occupational infection since the epidemic of HIV infection began. Infection of blood-borne pathogens to patients from infected surgeons remains a concern. Surgeons who are e-antigen-positive for hepatitis B have been well documented to be an infection risk to patients in the operating room. Only four surgeons have been documented to transmit hepatitis C, although other transmissions have occurred in the care of patients when practices of infection control have been violated. No surgical transmission of HIV to a patient has been identified at this time. Prevention of occupational infection requires use of protective barriers, avoidance of exposure risk by modification of techniques, and a constant awareness of sharp instruments in the operating room. Blood exposure in the operating room carries risk of infection and should be avoided. It is likely that other infectious agents will emerge as operating room threats. Surgeons must maintain vigilance in avoiding blood exposure and percutaneous injury.
To determine the frequency and spectrum of neurological illnesses in Black South African hospital-based HIV infected (clade C) patients.
A prospective audit of 506 consecutive HIV infected medical inpatients at the Helen Joseph Hospital, Johannesburg, South Africa.
The patients had a mean age of 37 years; a male:female ratio of 1.2:1; a mean CD4 count of 107 cells/ml. Eighty four percent of patients had AIDS defining CD4 counts (less than 200 cells/ml). Seventy five percent of patients had a neurological illness. In 64% the neurological illness occurred in association with a non-neurological (systemic) illness. Eleven percent of patients had an isolated neurological illness. The predominant systemic illness was tuberculosis (TB), occurring with a frequency of 46%. The neurological spectrum in our patients was similar to that described in the literature, (clade B virus data) other than for a greater frequency of infectious illnesses.
The neurological profile of HIV infection is a function of the environment and the immunological state of the patient (CD4 count) rather than an influence of the clade.
We used participatory research to develop a theoretically based online STD/HIV and pregnancy prevention intervention that would be entertaining and captivating for 15-25 year olds while delivering key messages about condom use. We conducted six focus groups with 15-25 year olds attending reproductive health clinics and completed a content analysis with focus group data. Youth had expectations that websites contain features such as graphics and flash technology. They would participate in research online if their confidentiality was assured and if they could receive an instant incentive. Limited access to high-end bandwidth capability requires use of compressed graphics and music to reach diverse audiences. Youth suggested approaches to frame role-model delivered messages about HIV/STD and pregnancy risk, condom attitudes, norms and self-efficacy for negotiation. These data allowed for development of a dynamic, interactive and relatively low bandwidth site that retains fidelity to key theoretical constructs in STD/HIV and pregnancy prevention.
We explored healthcare provider perspectives and practices regarding safer conception counseling for HIV-affected clients.
We conducted semistructured interviews with 38 providers (medical and clinical officers, nurses, peer counselors, and village health workers) delivering care to HIV-infected clients across 5 healthcare centres in Mbarara District, Uganda. Interview transcripts were analyzed using content analysis.
Of 38 providers, 76% were women with median age 34 years (range 24-57). First, we discuss providers' reproductive counseling practices. Emergent themes include that providers (1) assess reproductive goals of HIV-infected female clients frequently, but infrequently for male clients; (2) offer counseling focused on "family planning" and maternal and child health; (3) empathize with the importance of having children for HIV-affected clients; and (4) describe opportunities to counsel HIV-serodiscordant couples. Second, we discuss provider-level challenges that impede safer conception counseling. Emergent themes included the following: (1) providers struggle to translate reproductive rights language into individualized risk reduction given concerns about maternal health and HIV transmission and (2) providers lack safer conception training and support needed to provide counseling.
Tailored guidelines and training are required for providers to implement safer conception counseling. Such support must respond to provider experiences with adverse HIV-related maternal and child outcomes and a national emphasis on pregnancy prevention.
CXCR4 is a G protein-coupled receptor with excellent potential as a therapeutic target for a range of clinical conditions, including stem cell mobilization, cancer prognosis and treatment, fibrosis therapy, and HIV infection. We report here the development of a fully human single-domain antibody-like scaffold termed an "i-body," the engineering of which produces an i-body library possessing a long complementarity determining region binding loop, and the isolation and characterization of a panel of i-bodies with activity against human CXCR4. The CXCR4-specific i-bodies show antagonistic activity in a range of in vitro and in vivo assays, including inhibition of HIV infection, cell migration, and leukocyte recruitment but, importantly, not the mobilization of hematopoietic stem cells. Epitope mapping of the three CXCR4 i-bodies AM3-114, AM4-272, and AM3-523 revealed binding deep in the binding pocket of the receptor.
Integrase inhibitors are the most recently approved family of antiretroviral agents for the treatment of HIV infection. As with other antiretroviral agents, under pharmacological pressure, the virus selects resistance mutations if viral suppression is incomplete. Mutations are selected in the integrase gene, specifically in positions proximal to the catalytic center. Because clinical experience with these drugs is scarce, information on resistance is limited. Virologic failure with raltegravir is associated with selection of primary mutations such as N155H (40%) and distinct changes in position Q148 (28%). Less frequently, Y143R (6.6%) and E92Q are selected. The most frequently observed mutations in failure with elvitegravir are E92Q, E138K, Q148R/K/H and N155H, and less frequently S147G and T66A/I/K. The most common resistance pattern seems to be E138K + E147G + Q148R. There is a high grade of cross resistance between raltegravir and elvitegravir, making sequencing between these two drugs impossible.
The goals of this study were to examine trends, risk factors, and survival rates of people diagnosed with HIV/AIDS. We used national surveillance data reported to the Taiwan Center for Disease Control (Taiwan CDC). The subjects of this study were all confirmed HIV and AIDS cases in Taiwan. From 1990 through 2005, the number of people that have been reported to have HIV/AIDS is 9961. Among individuals with HIV/AIDS, the male-to-female ratio was 11:1, the median age was 32 years. The number of HIV and AIDS diagnoses increased significantly for both men and women during the study period. The number of HIV cases among men who have sex with men (MSM) increased from 24 in 1990 to 527 in 2005, while diagnoses among injection drug users (IDUs) rose rapidly from 3 in 1990 to 2450 in 2005. The incidence-to-prevalence ratio (IPR) has risen sharply in recent years and has exceeded the epidemic threshold (IPR(t) = 0.1) for IDUs, indicating a growing epidemic. The corresponding hazard ratios for the highly active antiretroviral therapy (HAART) era versus pre-HAART era in the earlier and late HIV diagnosis groups were 0.45 (95% confidence interval [CI] 0.36-0.54) and 0.39 (95% CI 0.31-0.49), respectively. There was no significant difference in the survival rate of HIV testers. The increasing number of HIV infection places Taiwan among the worst IDU-concentrated epidemic areas in Asia. HIV intervention and prevention strategies, especially targeting IDUs, are urgently needed to reduce the ongoing spread of HIV infections in Taiwan.