Journal of acquired immune deficiency syndromes and human retrovirology : official publication of the International Retrovirology Association最新文献

We have examined the effect of potent antiretroviral regimens on the latent reservoirs of HIV-1. The HIV-1 DNA in the peripheral blood mononuclear cells (PBMC) of 10 patients with undetectable plasma HIV-1 RNA (<20 copies/ml) who had received combination antiretroviral therapy was assayed every 12 weeks. No evidence of residual viral replication was found in the PBMC after 24 weeks of treatment. Although HIV-1 DNA remained detectable in all patients, it decreased significantly from 3.5 log copies/10(6) cells (range, 1.8-4.7 log copies/10(6) cells) to 2.3 log copies/10(6) cells (range, 0.6-3.1 log copies/10(6) cells) after 60 weeks of suppressive therapy. Analysis based on 6 patients who reached 60 weeks showed a slow decline with an estimated half-life of 40 weeks (range, 26-163 weeks). Genotypic analysis by sequencing the HIV-1 pol gene revealed no changes in the reverse transcriptase or protease coding regions after 48 to 60 weeks of therapy. The findings suggest that, in addition to potent antiretroviral regimens, new strategies must be developed to ensure eradication of the latent reservoir of provirus, and hence of the virus itself.

To investigate the protective efficacy of various gp130 vaccine preparations, rhesus monkeys were immunized with gp130 oligomers (O-gp130) or two different gp130-monomer preparations (M1-gp130; M2-gp130) and challenged with 50 MID50 of simian immunodeficiency virus (SIV)mac32H. Following challenge the control animals and all animals of the M1- and M2-gp130 group and 1 animal of the O-gp130 group were productively infected, whereas 3 animals of the O-gp130 group resisted the productive virus replication. The protection was correlated with high neutralizing antibodies and a long-lasting immune response to the transmembrane protein gp41. Whereas none of the O-gp130 animals had developed disease symptoms, 3 M1-gp130 animals, 1 M2-gp130 animal, and 2 control animals died as a result of AIDS within 18 months after challenge. Therefore, immunization with virion-derived gp130 oligomers of SIVmac32H can confer protection against the productive infection with SIVmac32H and suppress the development of the AIDS-like disease.

The temporal course of the humoral immune response to T-cell-dependent and T-cell-independent type 2 antigens was evaluated in HIV-infected patients. In all, 26 seropositive patients were vaccinated with tetanus toxoid and 23-valent pneumococcal vaccines; total IgG and IgG1 antibodies to tetanus toxoid (Ttox) and total IgG and IgG2 antibodies against 23 Streptococcus pneumoniae capsular antigens (PPS) were measured at baseline, 2 months, and 12 months after vaccination. For the Ttox, baseline levels of IgG1 (Ttox-IgG1) increased from 11.0 to 19.5 mg/L at 2 months postimmunization. Overall only 6 patients (23%) showed a significant response. At 12 months postvaccination, Ttox-IgG and T-tox-IgG1 were significantly lower than baseline levels (Ttox IgG basal; 11.0 mg/L, 12 months; 0.8 mg/L, Ttox IgG1 baseline; 13.1 mg/L, Ttox IgG1 12 months; 2.4 mg/L) and in 10 patients, antibodies that fell below protective levels (0.6 mg/L). In contrast with PPS, a significant response was observed at 2 and 12 months (PPS-IgG basal; 35.9 U/ml, 2 months; 151.4 U/ml, 12 months; 59.7 U/ml; PPS-IgG2 baseline 20.3 U/ml, 2 months; 113.2 U/ml, 12 months; 51.9 U/ml). Overall, 19 patients (76%) showed an immune response to pneumococcal polysaccharides antigens. Immunization with the Ttox T-cell-dependent antigen fails to elicit a significant immune response and may induce inhibition of antibody production in HIV-infected patients. In contrast, immunization with a T-cell-independent type 2 antigen can cause the pneumococcal polysaccharides to induce significant immune response in a high proportion of HIV-infected patients.

Context: Preventive HIV vaccines can temporarily cause uninfected individuals to have positive results on HIV testing. As preparations are underway to mount larger efficacy trials, the social risks of trial participation should be studied.

Objective: To describe frequency of HIV testing and discrimination among participants in a preventive phase II HIV vaccine trial.

Participants: 266 vaccine trial volunteers were eligible; 247 participated in a confidential survey.

Results: 63 volunteers (26% of respondents) reported 185 HIV tests during the prior 12 to 24 months; most tests were for other research studies, health care, insurance, incarceration, or employment. Only 5 volunteers reported having positive HIV test results. Volunteers reported 99 adverse social incidents or problems, 53 of which were related to the trial. The most common type of event occurred when volunteers disclosed their trial participation and were mistakenly presumed to be infected with HIV. Few reported difficulty obtaining insurance, job loss, and inadvertent disclosure of their participation in the trial.

Conclusion: In this vaccine trial, few serious social harms were reported. Those who conduct HIV tests for insurance, employment, health care, or other reasons should be made aware that HIV vaccines can cause false-positive HIV test results. Those planning future trials must continue to provide needed support to volunteers. Social harms should be monitored with the same vigilance accorded to physical harms.

Data from three epidemiologic studies of heterosexual transmission of HIV among monogamous couples are used to assess evidence for time variation in HIV infectivity, possibly related to varying levels of infectiousness following infection in the primary infected partner. Analyses are based on statistical techniques that account for the inherent incompleteness of exposure information from such studies, and that allow direct assessment of the hypotheses that infectivity varies with time since infection and across partnerships. Data include findings from 302 couples from the California Partners' Study and 51 and 31 couples, respectively, from two U.S. Center for Disease Control and Prevention (CDC)-sponsored studies of infection in partners of transfusion recipients. Results indicate weak evidence for higher infectivity following infection of the primary partner, decreasing to relatively lower levels from 2 to 10 years after. Although these findings are consistent with biologic observations of time variation in viral levels, other explanations of the observed pattern (e.g., heterogeneity of infectivity) are equally plausible, pointing out some inherent limitations of data from such studies.

Septicemia is a frequent cause of death in HIV-infected adults in developing countries. Additional prospective studies are needed to determine the etiology of bloodstream infections (BSI) in febrile HIV-infected adults and guide initial evaluation and treatment in this setting. We assessed the prevalence and etiology of community-acquired BSI among 299 consecutive febrile adult medical admissions to Mulago Hospital, Kampala, Uganda, over a 4-month period in 1997. The median age of our patients was 30 years, 159 (53%) were male, and 227 (76%) HIV-1-seropositive. Overall, prevalence of bacteremia or fungemia (1 patient) was 24%. Bacteremia was more frequent in HIV-infected than in uninfected patients (27% versus 15%, respectively; p = .04). Mycobacterium tuberculosis (n = 28), Streptococcus pneumoniae (n = 15) and Salmonella species (n = 13) were the most frequent isolates. All Salmonella and mycobacterial isolates were recovered from HIV-infected patients. Pneumococcal bacteremia was not associated with HIV seropositivity. M. avium complex and M. simiae were isolated from two HIV-infected patients. The rate of mycobacteremia among febrile HIV-infected adults presenting for hospitalization was 13%. Bacteremia and disseminated tuberculosis are frequent causes of morbidity in febrile HIV-infected Ugandan adults. Initial empiric antibiotic coverage in this setting should be targeted toward the pneumococcus and gram-negative enteric bacilli, especially nontyphi Salmonella species. All patients presenting with chronic cough should be evaluated for tuberculosis.

To study the epidemiology of HTLV-I-associated myelopathy/tropical spastic paraparesis (HAM/TSP) in Brazil, we conducted a nationwide survey between March 1994 and April 1995. Five centers from three regions of the country participated, enrolling 163 patients. Most patients came from the northeastern and southeastern regions (93.2%). Most enrollees were white women, 42.9% and 64.4%, respectively. The most common risk factors for infection included a history of venereal diseases (30.6%) and blood transfusion (21.6%). The median age at the beginning of the disease was 42 years. The main neurologic findings were spastic paraparesis, widespread brisk tendon jerks, bilateral Babinski's sign, and bladder dysfunction. Some interregional differences reached statistical significance. The ratio of females over males increased from south to north. In addition, in both southern and southeastern regions, whites prevailed, whereas in the northeast, mulattos predominated. This follows the normal distribution of the population in these regions. A significantly higher rate of venereal diseases was found in the southeast compared with the other regions studied. A history of intravenous drug use was more frequent among patients as the sample moves south. Finally, a fluctuating course of the disease was proportionally more frequent in the southern region.

To assess the incidence of HIV infection and risk factors associated with HIV seroconversion among patients attending clinics for sexually transmitted diseases (STD), medical record reviews were conducted in 12 clinics in 7 U.S. cities. The records of all patients who initially tested negative for HIV from 1991 through 1996 and who received at least one additional HIV test during the study period were reviewed. In each of 7 cities, 5 to 112 patients seroconverted. Of the 286 seroconverters identified in total, 53% (152 of 286) were heterosexual men and 28% (81 of 286) were women. HIV incidence rates among men who have sex with men (MSM) ranged by city from 0.81 to 7.0 new infections/100 person-years. Rates among heterosexual men and women ranged from 0.018 to 1.2 infections/100 person-years. Multivariate analyses showed that drug use was associated with HIV seroconversion only among heterosexuals. Most new HIV infections in these clinics are being transmitted heterosexually and are associated with drug use. Nevertheless, MSM, particularly young MSM, are at greatest risk for HIV in this population: 1 of 47 seroconvert/year. The effective use of targeted prevention efforts depends upon the continued ability to monitor the incidence of HIV infection.