Topics in HIV Medicine® - International AIDS Society-USA
Topics in HIV Medicine® - International AIDS Society-USA
Topics in HIV Medicine® - International AIDS Society-USA
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Conference Highlights - Advances <strong>in</strong> Antiretroviral Therapy Volume 11 Issue 3 May/June 2003<br />
ma<strong>in</strong>ta<strong>in</strong><strong>in</strong>g a plasma <strong>HIV</strong>-1 RNA level<br />
of less than 5000 copies/mL.<br />
Hecht and colleagues presented data<br />
on behalf of the Acute Infection Early<br />
Disease Research Program (Abstract<br />
519). They compared those who started<br />
antiretroviral therapy with<strong>in</strong> 6 months<br />
of seroconversion and later underwent<br />
STI with those choos<strong>in</strong>g to defer<br />
antiretroviral therapy. After adjust<strong>in</strong>g for<br />
basel<strong>in</strong>e plasma <strong>HIV</strong>-1 RNA level and<br />
estimated number of weeks s<strong>in</strong>ce <strong>in</strong>fection,<br />
subjects start<strong>in</strong>g antiretroviral therapy<br />
had a lower plasma <strong>HIV</strong>-1 RNA level<br />
and a higher CD4+ cell count off<br />
antiretroviral therapy than did those<br />
deferr<strong>in</strong>g antiretroviral therapy.<br />
However, the unadjusted analysis did<br />
not show a clear benefit, and the<br />
authors suggested that a randomized<br />
trial is necessary to def<strong>in</strong>itively assess<br />
the role of treatment <strong>in</strong> primary <strong>HIV</strong><br />
<strong>in</strong>fection.<br />
Super<strong>in</strong>fection<br />
Several studies concerned so-called<br />
super<strong>in</strong>fection with viral variants phylogenetically<br />
dist<strong>in</strong>ct from preced<strong>in</strong>g <strong>HIV</strong><br />
isolates. Wong and colleagues (Abstract<br />
485) described 2 cases <strong>in</strong> which new<br />
clade B stra<strong>in</strong>s were retrospectively<br />
identified by phylogenetic analysis of<br />
env clones <strong>in</strong> female sexworkers who<br />
were also <strong>in</strong>jection drug users. Allen and<br />
colleagues (Abstract 307) described a<br />
s<strong>in</strong>gle <strong>in</strong>dividual who received HAART<br />
at primary <strong>in</strong>fection and later went on<br />
to 4 cycles of STI. Phylogenetic analysis<br />
of gag sequences from 4 time po<strong>in</strong>ts<br />
demonstrated emergence of a stra<strong>in</strong><br />
with 12% heterogeneity from the stra<strong>in</strong><br />
at seroconversion. This second stra<strong>in</strong><br />
persisted dur<strong>in</strong>g the second and third<br />
STIs despite the presence of an immunodom<strong>in</strong>ant<br />
CD8+ T-cell epitope <strong>in</strong> p24<br />
common to both viruses. Subbarao and<br />
colleagues (Abstract 486) described cellfree<br />
<strong>HIV</strong> RNA and proviral DNA levels<br />
us<strong>in</strong>g a real-time reverse transcriptase<br />
polymerase cha<strong>in</strong> reaction method<br />
adapted to dist<strong>in</strong>ctly quantify subtypes<br />
B and CRF01_AE <strong>in</strong> a co<strong>in</strong>fected <strong>in</strong>dividual.<br />
Initially, the plasma virus was a<br />
subtype B stra<strong>in</strong>. Subtype CRF01_AE<br />
was detected at 8 and 20 months <strong>in</strong><br />
plasma and proviral DNA, respectively.<br />
The plasma <strong>HIV</strong>-1 RNA level for subtype<br />
B ranged from 7484 to 237,649<br />
copies/mL over 44 months but for<br />
CRF01_AE was consistently lower, rang<strong>in</strong>g<br />
from 3320 to 18,348 copies/mL over<br />
33 months, respectively.<br />
Treatment Strategies<br />
Results of select studies of STIs <strong>in</strong><br />
antiretroviral-experienced patients are<br />
summarized <strong>in</strong> Table 4.<br />
STIs <strong>in</strong> Persons with Virologic<br />
Suppression<br />
Ananworanich and colleagues presented<br />
the 48-week results of <strong>HIV</strong>-NAT 001.4<br />
(Abstract 64), a prospective, open-label,<br />
randomized trial conducted <strong>in</strong> Thailand<br />
that evaluated <strong>HIV</strong> disease progression<br />
and safety of a STI undertaken <strong>in</strong><br />
patients with chronic <strong>HIV</strong> <strong>in</strong>fection. A<br />
total of 74 Thai patients who had<br />
received 1 year of dual nRTIs followed by<br />
PI-based therapy (saqu<strong>in</strong>avir soft gel<br />
capsule 1600 mg/ritonavir 100 mg once<br />
daily) for 3 years were enrolled. The trial<br />
exam<strong>in</strong>ed STIs based upon a CD4+<br />
count decl<strong>in</strong>e versus 1 week on/1 week<br />
off antiretroviral therapy. When CD4+<br />
count was greater than 350 cells/µL and<br />
plasma <strong>HIV</strong>-1 RNA was less than 50<br />
copies/mL for at least 6 months, subjects<br />
were randomized to 1 of 3 study arms:<br />
cont<strong>in</strong>uous antiretroviral therapy<br />
(n=25), CD4+ count-guided arm<br />
(n=23), or 1 week on/1 week off arm<br />
(n=26). The STI <strong>in</strong> the CD4+countguided<br />
arm was based on a CD4+ count<br />
of 350 cells/µL or less or a 30% drop or<br />
rise <strong>in</strong> CD4+ cell count. Treatment failure<br />
was def<strong>in</strong>ed as plasma <strong>HIV</strong>-1 RNA<br />
levels greater than 1000 copies/mL or<br />
CD4+ count of 350 cells/µL or less <strong>in</strong><br />
the cont<strong>in</strong>uous and week on/week off<br />
study arms. Basel<strong>in</strong>e characteristics<br />
were similar between arms with regard<br />
to sex (49% male), mean age (34 years),<br />
and mean CD4+ count (644 cells/µL).<br />
Preantiretroviral therapy and pre-HAART<br />
plasma <strong>HIV</strong>-1 RNA levels were higher <strong>in</strong><br />
the CD4+ count-guided arm (4.8 and<br />
3.2 log 10 copies/mL, respectively) and <strong>in</strong><br />
the week on/week off arm (4.9 and 3.4<br />
log 10 copies/mL, respectively) than <strong>in</strong> the<br />
cont<strong>in</strong>uous arm (4.3 and 2.6 log 10<br />
copies/mL, respectively; P