Unintegrated circular HIV-1 DNA in the peripheral mononuclear cells of HIV-1-infected subjects: association with high levels of plasma HIV-1 RNA, rapid decline in CD4 count, and clinical progression to AIDS.

We observed 36 HIV-infected patients to evaluate whether the presence of tandem 2-long terminal repeat circular unintegrated HIV-1 DNA (2-LTR) in peripheral blood mononuclear cells (PBMC) at baseline was associated with acceleration of HIV disease. Detection of 2-LTR at baseline correlated with high plasma HIV-1 RNA levels (p < .01), recovery of culturable HIV-1 from plasma (p = .02), and progression to AIDS during follow-up (p = .01). More patients with 2-LTR (68%) than without 2-LTR (31%) had a decline in CD4 levels of >50 cells/mm3 over the first 18 months of follow-up (p = .04), and the average annual CD4 decline was 35% in patients with 2-LTR compared with 16% in those without 2-LTR (p = 0.06). Detection of 2-LTR in PBMC at baseline was an independent predictor of high plasma HIV-1 RNA levels and subsequent CD4 cell decline in this cohort of patients with predominantly nonsyncytium-inducing (NSI) isolates at baseline. The presence of 2-LTR in PBMC appears to be reflective of ongoing HIV-1 replication, as measured by plasma HIV-1 RNA levels, and identifies persons at risk for immunologic and clinical decline.

Intermittent shedding of human immunodeficiency virus in semen: implications for sexual transmission.

PURPOSE: We attempt to increase our understanding of human immunodeficiency virus (HIV) shedding in semen. MATERIALS AND METHODS: We followed 16 seropositive men for up to 27 months by HIV cocultivation, with a subset evaluated using the polymerase chain reaction. RESULTS: The proportion with at least 1 HIV positive semen culture increased from 3 of 16 subjects (19%) at visit 1 to 10 (63%) by visit 5. Overall, HIV was cultured from 25 of 114 specimens (22%). Shedding was intermittent for each of the 10 men with at least 1 positive culture and seminal shedding patterns were highly variable. CONCLUSIONS: By culture and polymerase chain reaction, HIV is shed intermittently in the semen. If cultures are performed often enough most seropositive men shed HIV in the semen.

The effects of high-dose recombinant soluble CD4 on human immunodeficiency virus type 1 viremia.

In vitro, low-passage clinical human immunodeficiency virus type 1 (HIV-1) isolates require up to 1000 times greater serum levels of recombinant soluble CD4 (rsCD4) than have ever been given. To determine if sufficient serum levels of rsCD4 provide in vivo inhibition of HIV-1, 4 HIV-1 plasma-viremic subjects were given single-dose boluses of 2, 4, 6, 8, and 10 mg/kg intravenous rsCD4. Plasma HIV-1 cultures were done after infusion. Three subjects demonstrated a dose-dependent reduction in plasma HIV-1 viremia. The inhibitory effect of rsCD4 on plasma HIV-1 viremia was associated with the in vitro ID90-95 of the isolate, not the ID50. These data demonstrate that extremely high doses of rsCD4 inactivate cell-free HIV-1 in vivo and suggest that high doses of rsCD4 may have some short-term therapeutic utility, such as with accidental or occupational HIV-1 exposure.

A multinomial model for estimating the size of a whale population from incomplete census data.

This paper adapts the removal method of population size estimation to the problem of estimating the size of the western Arctic stock of bowhead whales. The whales are counted during their spring migration as they pass two census camps located near Point Barrow, Alaska. Whales seen at the first camp are "removed" from the population of concern to the second camp, where only whales missed by the first camp are counted. If both camps were in operation throughout the migration and if the probability of missing a whale were constant, the removal method would provide a population size estimate based on a trinomial model in which the size of the population would be the number of trials, whales counted by each camp would provide the observed cell totals, and whales missed by both camps would represent an unobserved cell total. Since the probability of missing a whale depends on visibility, we model the population size as the sum of the number of trials of several independent trinomial distributions, each of which represents a particular visibility condition occurring during the census. To account for the fact that watch cannot be maintained at both camps throughout the migration, we derive a confidence interval estimate of the number of trials under a more general model allowing for incomplete observation of totals within particular cells as well as for completely unobserved cells.