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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

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