Bridging the Gap: Conference Record [Abstract book, International Conference on AIDS (12th: 1998: Geneva, Switzerland)]

420 Abstracts 23391-23394

12th World AIDS Conference

The median ratio of log BP to SP HIV-1 RNA was 1.59 which is higher than
that previously reported in subtype B and C populations. Weak but significant
correlations were seen between BP and SP HIV-1 RNA and between CD4 count
and BP HIV-1 RNA. Evaluation of the correlation between HIV-1 transmission and
viral load in both blood and semen is ongoing and will be discussed.
Conclusions: High levels of HIV-1 were seen in the blood of the Thai men
in this study. Semen HIV-1 levels were comparable to those seen in subtype
B populations as was the correlation between BP and SP RNA. However, the
ratios of BP to SP RNA were higher than those previously reported in subtype
B and C populations. The correlations of viral load with HIV-1 transmission and
the implications of these findings for the dynamics of HIV-1 transmission will be
discussed.
23391 Changes in HIV-1 viral load after discontinuation of oral
AZT given to pregnant Ugandan women
J. Brooks Jackson1, Laura Guay1, A. Murarka1, C. Nakabiito2, J. Nakakande2,
P. Musoke2, F.A. Nmiro2. 1Johns Hopkins University, Baltimore MD, USA;
2Makerere University, Kampala, Uganda
Objectives: To determine if significant post-partum HIV-1 viral load changes
occur after cessation of a short course of oral AZT therapy in pregnant Ugandan
women from 37 weeks gestation until delivery.
Methods: Twenty HIV-1 infected pregnant Ugandan women with plasma HIV-1
RNA levels of >2000 copies/ml and equally distributed between CD4 cell count
>500 cells/pl and CD4 cell count <500 cells/il were enrolled. Women received
300 mg AZT orally BID starting at 37 weeks gestation until the onset of labor. A
600 mg oral AZT bolus was given at the onset of labor, followed by 300 mg every
3 hours until delivery. Plasma HIV-1 RNA (Roche RT PCR), CD4 cell counts, and
complete blood counts were monitored at enrollment, delivery, and post-partum.
A greater than three fold change in HIV-1 RNA was considered a biologically
significant difference.
Results: The study women delivered from 5 to 38 days (mean 21.9 days)
after initiation of AZT therapy. The median plasma HIV-1 RNA level was 10,119
copies/ml at baseline (37 weeks gestation), 3,720 copies/ml at delivery, 24,000
copies/mi at 72 hours post-partum, and 13,790 copies/ml at 6 weeks post-partum.
As compared to baseline:
- 8 of 19 women (42%) had >3 fold decrease in HIV-1 RNA by delivery (5 with
CD4 < 500);
- 6 of 20 women (30%) had >3 fold increase in HIV-1 RNA by 72 hours
post-partum (2 with CD4 < 500);
- 4 of 20 women (20%) had >3 fold increase in HIV-1 RNA by 6 weeks
post-partum (2 with CD4 < 500).
Overall none of the changes in plasma HIV-1 RNA levels associated with initiation or termination of oral AZT therapy were significant using log-transformed
data.
Conclusion: A short course of oral AZT in twenty pregnant Ugandan women
produced variable changes in plasma HIV-1 RNA levels from initiation of therapy to timepoints after termination of therapy. While a minority of women had
persistent increased viremia up to six weeks post-partum, overall there was no
significant viral overshoot response to termination of therpy.
S23392 Influencing HIV infectivity: The effect of antiviral
treatment on the shedding of cell-free and
cell-associated HIV in semen
Pietro Vernazza1, F. Roth2, K. Boggian3, M. Flepp4, J. Gron5. 'Department of
Medicine Cantonal Hospital, 9007 St. Gallen; 21 Km St. Gallen 9007 St Gallen;
3 Kantonsspital 9007 St Gallen; 4 University Hospital Zurich, Switzerland; 5Chapel
Hill Nc, USA
Background: Shedding of cell free HIV in semen is associated with parameters
that influence HIV infectivity. Only little data is available on the cellular viral load
in semen. We have studied the effect of antiviral therapies on the shedding of
cell-free and cell-associated HIV in semen of HIV infected individuals.
Methods: Patients starting a new antiretroviral treatment were asked to provide
a semen and blood sample at baseline and at 3-monthly intervals. The effect of
antiviral treatment was measured by the reduction of HIV-RNA in blood plasma
and compared to the effect of treatment on the shedding of HIV in semen. Cell-free
virus was measured by NASBA as described previously. Proviral HIV-DNA was
quantified in the seminal cell pellet using an in-house quantitative competitive
DNA-PCR.
Results: Fifty-two patients were included in the study. Follow up information is
available from 41 patients. The median HIV-RNA level in blood at baseline was
5.1 loglo cp/ml. HIV-RNA and DNA was detectable in semen from 64% and 37%
of the patients, respectively. On treatment, the detection rate dropped to 24% and
31%, respectively. The measurement of HIV-DNA in seminal cells correlated well
with CD4 lymphocyte count in semen (r = 0.47, p = 0.003) and with HIV-RNA in
seminal plasma (r = 0.55, p < 0.001). At the first follow up (week 8-14), treatment
resulted in a suppression of detectable HIV RNA in blood (<200 cp/ml) in 27%

of the subjects. In patients with detectable HIV-DNA in semen at baseline, the
median drop of HIV-DNA was 0.31 loglo copies/ejaculate. In the eleven patients,
in whom antiviral treatment resulted in a complete suppression of detectable
HIV-RNA in blood, HIV-DNA remained detectable in semen samples from three
patients.
Conclusion: Potent antiretroviral treatment results in a marked suppression of
HIV-RNA in seminal plasma as well as in a reduced shedding of cell associated

HIV-provirus in semen. However, in a small number of patients with treatment
induced suppression of detectable HIV-RNA in blood, HIV provirus can still be
detectable in the cellular fraction of semen samples.
23393 Antiretroviral therapy and HIV-1 shedding from anorectal
mucosa
Thomas Lampinen, C.W. Critchlow, J. Kuypers, S.E. Hawes, C. Hurt,
K.K. Holmes, N.B. Kiviat. University of Washington Dept of Epidemology,
University of Washington Seattle, WA, USA
Background: Decreasing levels of HIV-1 shed from the anorectal mucosa may
reduce the risk of transmission via anal intercourse. The association between
highly active antiretroviral therapy (HAART) and HIV-1 shedding is not known.
Objectives: To determine whether antiretroviral therapy is associated with reduced levels of proviral (DNA) and genomic (RNA) HIV-1 shed from the anorectal
mucosa of homosexual men.
Methods: Clinic and community-recruited HIV+ homosexual men (N = 256,
mean age 39, with peripheral blood median 356 CD4 cells/mm3, median 4181
copies plasma HIV-1 RNA/mm3) were enrolled into a longitudinal study between
July 1996 and December 1997. Visits every 4 months included a structured
questionnaire, physical and anal exams, lymphocyte count, and Roche PCR
quantitation of plasma and anorectal swab HIV-1 DNA and RNA.
Results: Analysis of 213 baseline anorectal swab specimens showed that 122
(57%) had detectable HIV DNA or RNA: 45 (21%) were anorectal DNA+/RNA+, 52
(24%) were anorectal DNA+/RNA-, and 25 (12%) were anorectal DNA-/RNA+.
Significant associations between antiretroviral therapy and detection of anorectal HIV DNA (p <.01)and HIV RNA (p < 0.001) were observed:

Not on therapy
Non-HAART therapy
HAART

No. Men (%) Median plasma
RNA level
111 (43) 18,633 copies/mm3
85 (33) 1,822 copies/mm3
60 (23) 0 copies/mm3

~

% Anorectal
HIV DNA+
58
39
37

% Anorectal
HIV RNA+
50
27
17

Detection of anorectal HIV RNA was strongly related to plasma RNA level,
with an inflection point apparent at 10,000 copies plasma HIV RNA/mm3 (below
which 13% were anorectal HIV RNA+ and above which 61% were anorectal HIV
RNA+). These relationships were also observed over 500 follow-up visits (mean
of 2.7 returns over an average 350 days).
Conclusions: Detection of HIV DNA and RNA shed from anorectal mucosa is
markedly decreased at reduced plasma RNA levels observed with antiretroviral
therapy. These data may be useful in risk reduction counseling of seropositive individuals. Moreover, they suggest that individual benefits of HAART may
be complemented by public health benefits resulting from reductions in HIV-1
transmission via anal intercourse.
S23394 HIV quantification in semen: Evidence for a group at
higher risk for sexual transmission
Anne Tachet1, Emmanuel Dulioust2, D. Salmon3, M. de Almeida2
L. Finkielsztejn3, D. Sicard3, P. Jouannet2, C. Rouzioux1. Laboratoire de
Virologie-Hospital Necker - 149, Rue de Serves 75015 Paris; 2Biologie de la
Reproduction - Hop. Cochin, Paris 75; 3Medicine Interne, Hospital Cochin, Paris
75, France
Objective: To quantify HIV in the different fractions of the semen from infected
men.
Methods: We combined three viral markers to evaluate the total cellular and
acellular viral burden in semen and to compare it with plasma HIV-RNA quantified
by the HIV Monitor kit (Roche). Paired blood and semen samples were obtained
from 38 HIV-1 seropositive men (21 naive patients). Semen fractions were separated on Percoll gradient. Seminal plasma and spermatozoa-associated HIV-RNA
were quantified using the HIV Monitor technique combined with an RNA extraction step on silica (detection thresholds respectively: 200 copies/ml and 5 to 20
copies/106 cells). HIV-DNA presence was assessed by PCR (gag region) in non
spermatozoal cells enriched fractions (NSCF) and in purified spermatozoa (spz)
(detection threshold: 5 to 25 copies/106 cells).
Results: Seminal HIV-RNA (range: <1.2 to 6.6 log copies/ml) was detected
in 32 (84%) out of 38 patients (and correlated to CD4 count in the naive patients group), HIV-RNA in spermatozoa pellets in 5 out of 29 patients (17%) and
HIV-DNA in NSCF in 17 out of 37 patients (46%). We identified two groups of men
with distinct patterns: the first one (n = 24) with undetectable HIV-RNA in seminal
plasma or difference (d) between plasmatic and seminal HIV-RNA values superior
to 0.3 log and the second one (n = 14) with d values inferior to 0.3 log. In this
second group, a high frequency of positive viral detection in the cellular fractions
was obtained: 77% of positive HIV-DNA in NSCF (30% in the first group), 50%
of positive HIV-RNA in purified spermatozoa pellets, from 5 to 40 copies/106 spz,
(0% in the first group). Genomic sequences analysis of the viruses from blood or
from semen are under progress for several patients of each group.
Conclusion: Patients presenting with a seminal HIV-RNA equal to or higher
than the plasmatic HIV-RNA, a feature which may be linked to viral replication in
the genital tract, are at higher risk to have both numerous free HIV particles in
seminal plasma and detectable cell-associated virus (including spermatozoa) in
semen, with an increased risk for sexual transmission of HIV.