Showing papers by "Jeffrey L. Lennox published in 2001"
TL;DR: Peak level HIV replication is established in blood, oropharyngeal tissues and genital tract, but potentially not in CSF, by the time patients are commonly diagnosed with primary HIV infection, and antiretroviral therapy is unlikely to limit initial virus spread to most tissue compartments.
Abstract: Objective To describe initial viral dissemination to peripheral tissues and infectious body fluids during human primary HIV infection. Design Observational cohort study. Methods Blood plasma, cerebrospinal fluid (CSF), seminal plasma, cervicovaginal lavage fluid and/or saliva were sampled from 17 individuals with primary HIV infection (range of time from symptoms onset to sampling, 8--70 days) and one individual with early infection (168 days). Subjects' HIV-1 RNA levels in each fluid were compared with levels from antiretroviral-naive controls with established HIV infection. For study subjects, correlations were assessed between HIV-1 RNA levels and time from symptoms onset. Responses to antiretroviral therapy with didanosine + stavudine + nevirapine +/- hydroxyurea were assessed in each compartment. Results HIV-1 RNA levels were highest closest to symptoms onset in blood plasma (18 patients) and saliva (11 patients). CSF HIV-1 RNA levels (five patients) appeared lower closer to symptoms onset, although they were higher overall in primary versus established infection. Shedding into seminal plasma (eight patients) and cervicovaginal fluid (two patients) was established at levels observed in chronic infection within 3--5 weeks of symptoms onset. High-level seminal plasma shedding was associated with coinfection with other sexually transmitted pathogens. Virus replication was suppressed in all compartments by antiretroviral therapy. Conclusions Peak level HIV replication is established in blood, oropharyngeal tissues and genital tract, but potentially not in CSF, by the time patients are commonly diagnosed with primary HIV infection. Antiretroviral therapy is unlikely to limit initial virus spread to most tissue compartments, but may control genital tract shedding and central nervous system expansion in primary infection.
178 citations
TL;DR: In a double-blinded, randomized trial, human immunodeficiency virus (HIV)-infected adults with > or = 200 CD4 cells/microl received placebo (PL), 7-valent conjugate, or 23-Valent pneumococcal polysaccharide (PS) vaccine in one of the following two-dose combinations given 8 weeks apart.
151 citations
TL;DR: Cervical inflammation and ulceration are associated with local human immunodeficiency virus 1 expression, which increases as much as 10,000-fold the amount of virus shed into genital secretions, which may explain why sexually transmitted diseases are important risk factors for human immunosuppressive virus transmission.
85 citations
TL;DR: Prolonged survival was associated with receiving therapy that including clarithromycin and receiving combination antiretroviral therapy that included a protease inhibitor and with receiving antimicrobial prophylaxis, but 32 (89%) of 36 patients did not adhere to the proPHylaxis regimen.
Abstract: Disseminated Mycobacterium avium complex disease remains a substantial cause of morbidity and mortality among patients with acquired immunodeficiency syndrome. From 1985 through 2000, we studied 1458 consecutive patients at Grady Memorial Hospital, Atlanta, with disseminated M. avium complex disease. There was a peak of 198 patients in the 1995, which decreased to 66 patients in 2000. In 1997, significantly more patients than in 1991 or 1994 were female (P<.001) or black (P<.001) and significantly fewer had acquired human immunodeficiency virus through homosexual contact (P<.001). In 1997, 50 (51%) of 99 of patients acquired M. avium complex disease despite receiving antimicrobial prophylaxis, but 32 (89%) of 36 patients did not adhere to the prophylaxis regimen. The median duration of survival of patients in 1991 was 110 days, whereas in 1994 it was 185 days, and in 1997 it was 339 days (P<.001). Prolonged survival was associated with receiving therapy that included clarithromycin and receiving combination antiretroviral therapy that included a protease inhibitor.
82 citations
TL;DR: It is indicated that cellular replication of HIV-1 occurs in vaginal secretions and can result in a virus population with important differences from that in blood.
Abstract: Most human immunodeficiency virus type 1 (HIV-1) transmission worldwide is the result of exposure to infectious virus in genital secretions. However, current vaccine candidates are based on virus isolates from blood. In this study, vaginal secretions from HIV-1-infected women were examined for evidence of cellular viral replication that produced virus with properties different from that in blood. Multiply spliced HIV-1 messenger RNA, which is found only in cells replicating virus, was detected in all vaginal lavage samples tested. There was a strong correlation between the amounts of multiply spliced HIV-1 messenger RNA and of cell-free HIV-1 RNA in the lavage samples. In addition, significant genotypic differences were found in cell-free virus from matched blood plasma and vaginal secretions. Moreover, drug resistance-associated mutations appeared in plasma virus several months before appearing in vaginal virus. These findings indicate that cellular replication of HIV-1 occurs in vaginal secretions and can result in a virus population with important differences from that in blood.
55 citations