S. Yerlya; S. Voraa; P. Rizzardib; J.-P. Chavef; P. L. Vernazzac; M. Fleppd;
A. Telentib; M. Battegaye; A.-L. Veutheyg; J.-P. Bru h; M. Rickenbachi; B.
Hirschela; L. Perrina; and the Swiss HIV Cohort Study*
From the University Hospitals of aGeneva, bLausanne, cSt Gallen, dZurich and
eBasel, fLa Source Hospital, Lausanne and the gSwiss Institute of
Bioinformatics, CMU, Geneva,Switzerland, hAnnecy Hospital, France and the
iCoordination and Data Centre, Swiss HIV Cohort Study, Lausanne, Switzerland.
Objective: To assess the impact of primary HIV infection (PHI) on the spread
of HIV and the temporal trends in transmission of HIV drug resistance between
1996 and 1999 in Switzerland.
Methods: Sequencing of the genes for reverse transcriptase (RT) and protease
was performed for 197 individuals with documented PHI. Phylogenetic analyses
were confronted with epidemiological data.
Results: Significant clustering was demonstrated for 29% of the RT sequences.
All these cases occurred closely together in place and time; contact tracing
demonstrated transmission at the time of PHI in 30% of them. Genotypic drug
resistance was detected in 8.6% of PHI individuals in 1996, 14.6% in 1997,
8.8% in 1998 and 5.0% in 1999. Drug-resistant variants were identified in
11.3% of individuals infected by homosexual contacts, 6.1% by heterosexual
contacts, 13% of intravenous drug users and more frequently in men (10.4%)
than women (2.6%). Potential factors involved in the recent decrease of
transmission of drug-resistant variants include increase of HIV non-B
subtypes from 23% in 1996 to 35% in 1999 (only one non-B subtype had
resistance mutations) and a steady increase of patients with undetectable
viraemia as documented in Swiss
HIV Cohort Study (10% in 1996 vs 53% in 1999). editorial note: it's been
suggested that the Swiss are better at getting more people under car & in
therapy and in success with achieving undetectable viral load. Its suggested
that plays an important role in reduced rates.
Conclusions: Phylogenetic and epidemiological analyses underline the impact
of PHI in the spread of HIV. Moreover, this study indicates that drug
resistance transmission may have decreased recently in Switzerland through
the increased frequency of infection with HIV non-B subtypes and the steady
increase of patients with undetectable viraemia.
The study included all individuals with documented PHI identified in six AIDS
centres of University Hospitals in Switzerland (Basel, Geneva, Lausanne,
Lugano, St Gallen and Zurich) and two AIDS Centres of Hospitals close to
Geneva (Annemasse and Annecy, France). For each patient, the clinician in
charge completed an epidemiological questionnaire labelled with a code
number. In the total of 197 individuals infected between January 1996 and
January 2000, PHI was documented by evolving HIV antibody response and/or
symptoms consistent with an acute retroviral syndrome  within 3 months in
70% of individuals and by seroconversion within 12 months of presentation in
30%. Sequence analyses were performed on plasma samples collected at the
first visit, before initiation of antiretroviral treatment.
In this large and systematic study, a peak in transmission of antiretroviral
drug-resistant variants, reaching nearly 15%, was observed in 1997, followed
by decreased prevalence in 1998 (8.8%) and 1999 (5.0%). As in previous
studies, genotypic resistance to RT inhibitors was more frequent than to PI
[16-22]. The prevalence of transmission of drug-resistant variants was higher
in IDU (13%) and in the homosexual group (11%) than in the heterosexual group
(6%). The high transmission rate of drug-resistant variants in the first two
risk groups is likely because of the initial spreading of HIV-1 infection
and, therefore, earlier antiretroviral treatment within these two risk
groups. The lower transmission rate observed in the heterosexual risk group
is also partially explained by the high percentage of women infected with
HIV-1 non-B subtypes (41%).
New guidelines favour a less aggressive strategy for initiation of treatment,
based more on CD4 cell counts than on viraemic levels, and treatment
interruptions within or outside clinical trials are increasingly popular
because of drug adverse events. This obviously leads to an increased number
of infectious individuals. Measures to prevent HIV transmission should,
reinforced. Finally, if mutations conferring multiple drug resistance result
in reduced viral fitness , the limitations in the replication capacity
might also reduce the risk of transmission.
The data presented here underline two main points: first, it is not
inevitability that transmission of antiretroviral drug resistance will
increase, since preventive programmes and treatment availability may decrease
it; second, individuals with acute HIV infection are
frequently involved in the spread of HIV in a geographical area where newly
diagnosed infections decreased over recent years. Hence, the identification
infected individuals and contact tracing should be considered as an important
public health measure to reduce HIV transmission further.
Eleven (5.8%) individuals harboured variants with mutations associated with
resistance to zidovudine and or stavudine (M41L, D67N, K70R, L210W and
T215Y/F). The lamivudine-resistant mutation M184V was detected in three
(1.6%) individuals and mutations associated with
resistance to non-nucleoside reverse transcriptase inhibitors (G190A and/or
Y181C) were detected in two (1.1%) individuals. Major mutations associated
with PI resistance were detected in 6/176 (3.4%) individuals: the V82A/F
mutation was detected in four of these and the L90M mutation in two. In these
six individuals, two to five of the minor mutations associated
with PI resistance (L10I, K20R, M36I, I54V, L63P, A71T/V and I84V) were also