symptoms during primary HIV infection (PHI) is associated with subsequent disease
progression, results of a study published in PLoS One show. People who had severe clinical symptoms and a lower CD4 count during PHI had a significantly
reduced period without AIDS-related illnesses. The researchers hope their findings
will help develop guidelines for the use of antiretroviral therapy during
The research was
undertaken because of ongoing uncertainties about the relationship between the
severity of clinical and immunologic symptoms during primary HIV infection –
the period when the body first produces antibodies in response to infection
with HIV – and the subsequent risk of HIV disease progression. The best way of
managing primary infection is unclear, and there is debate concerning the risks
and benefits of antiretroviral therapy at this time.
the international CASCADE collaboration therefore analysed the relationship
between severity of clinical and immunologic symptoms during primary infection
and the subsequent rate of disease progression. Their study sample comprised 1108
participants with a known approximate date of seroconversion.
seroconversion illness was defined as the presence in the first six months
after seroconversion of clinical symptoms such as thrush in the mouth or
throat, bronchitis, pneumonia or a low platelet count. Immunologic markers of a
severe seroconversion illness were a single CD4 cell count below 350 cells/mm3
or two counts below 500 cells/mm3.
compared the subsequent risk of progression to an AIDS diagnosis or death between participants
with severe and non-severe symptoms during primary HIV infection.
three-quarters (71%) of participants were men who have sex with men and the median
CD4 cell count during PHI was 511 cells/mm3. Clinical
progression was observed in 366 participants, comprising 326 who developed an AIDS-defining illness and 40
who died. The overall rate of disease progression was 7.4 per 100 person-years
and the median AIDS-free survival time was eight years.
Information on the
severity of clinical symptoms during primary HIV infection was available for
865 participants, and this was severe in 127 (15%) individuals.
The median period
of AIDS-free survival was significantly shorter for participants with severe
symptoms during PHI, compared to participants without (6.3 vs 8.3 years; p = 0.003). After
controlling for potential confounders, participants with a severe seroconversion
illness had a two-fold increase in their risk of disease progression compared
to those without severe illness during PHI (OR = 2.1; 95% CI, 1.4-3.2).
Data on CD4 cell
count in the first six months of care were available for 740 participants. During
this period, a CD4 count below 500 cells/mm3 was observed in 54% of participants and 28% had a count below 350 cells/mm3.
individuals with CD4 cells above 500 cells/mm3, individuals with
either a count below 350 cells/mm3 or 500 cells/mm3 were
twice as likely to progress to an AIDS diagnosis or death.
Analysis was then
limited to the 443 individuals with two CD4 counts available from the first six months
after seroconversion. Participants with no CD4 cell count below 350 cells/mm3
during this period had a median AIDS-free survival time of 8.1 years. This fell
to 5.4 years for participants with one count below 350 cells/mm3 and 3.9
years for individuals with two measurements below this threshold (comparison, p
who maintained a CD4 count above 500 cells/mm3 during this six-month
period had a longer period of AIDS-free survival compared to individuals with
two or one test results below this level (7.5 vs 6.7 vs 4.8 years; p <
Participants with a
combination of severe symptoms and a CD4 cell count below 350 cells/mm3 or 500
cells/mm3 had a two-fold increase in their risk of an AIDS-related illness or death,
compared to participants who had a severe illness alone.
suggests that one or more CD4 < 350 cells/mm3 and/or severe
seroconversion illness, may be a useful indicator for identifying patients who
are likely to benefit from early treatment and initial close monitoring,”
conclude the authors. “More evidence from RCT [randomised controlled trials] is
needed to establish the beneficial value of treatment initiation in [primary