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Molecular and Epidemiological Characteristics of Primary HIV-1 Infections among a Cohort of Predominantly Men Who Have Sex with Men in a Defined Geographical Area: Transmission Events Associated with High Risk Activity and STD
D Pao*1, M Fisher1, S Hué2, G Dean1, P Cane3, C Sabin4, and D Pillay2
1Brighton and Sussex Univ. Hospitals, UK; 2Univ. Coll. London, UK; 3Univ. of Birmingham Med. Sch., UK; and 4Royal Free and Univ. Coll. Med. Sch., London, UK
Background: It is postulated
that onward transmission of HIV-1 is increased during primary HIV infection (PHI) due to high viral load, high-risk sexual
behavior and increased rates of concurrent sexually transmitted diseases (STD). In a treatment center with a high population
of MSM and high rates of both HIV
and STD, we have studied primary
infections combining molecular and epidemiological approaches in order to more
precisely assess correlates of transmission.
Methods: Subjects were recruited from a cohort of 1000
HIV+ individuals under follow-up in a discrete geographical area. PHI was diagnosed by one of: negative HIV antibody test within 18 months,
evolving antibody response or negative detuned antibody assay. Sequencing of
the pol gene was undertaken at time of diagnosis with subsequent
genotypic resistance and phylogenetic clustering analyses performed. Epidemiological
data was collected (surrogate markers, HIV acquisition group, frequency/risk
nature of sexual contacts and frequency/nature of concurrent STD. Clinical and phylogenetic data were linked in
an irretrievable fashion where informed consent was obtained. Statistical
analysis was with SPSS software.
Results: Of the 125 subjects with PHI diagnosed between 1999 and 2003, 95% were men
with a median age of 36 (range 21 to 71) of whom 82.8% were MSM. Of 125 pol sequences, 15 (12%) had primary
antiretroviral resistance associated mutations. Viruses from 32 individuals
(25%) appeared within 14 transmission clusters, according to the topology of the
neighbor-joining phylogenetic tree. These comprised 1 cluster of 5 individuals,
2 of 3 and 11 of 2.
High
rates of acute bacterial STD (NSU,
gonorrhea, chlamydia, primary syphilis) at the time of PHI
were seen, with a trend toward higher rates in those individuals with viruses
within a cluster (35.7% vs 25%; p = ns).
The reporting of 3 or more sexual partners in the 3 months prior to diagnosis
showed the same trend (55.6% vs 42.3%; p
= ns). Unprotected anal intercourse in the 3 months prior to diagnosis was
significantly higher in the cluster group (85.2% vs 68.6%; p <0.05).
Conclusions: We demonstrate high
rates of viral clustering in individuals with PHI
in a defined geographical area. The high rates of partner change, unprotected
anal intercourse, and concomitant STD
are all factors that can facilitate onward transmission. Targeted
identification of individuals during PHI,
appropriate management of STD, and treatment with HAART may all be useful
methods to break transmission networks.
Keywords: Primary HIV Infection; Sexually Transmitted Infections; Phylogenetics
