A third of women living with HIV subtype C have a fall in their CD4 count to below
350 cells/mm3 within a year of seroconversion, investigators report
in the online edition of Clinical
Infectious Diseases. The World Health Organization (WHO) now recommends
that antiretroviral therapy (ART) should be initiated at a CD4 count of 500 cells/mm3
and 69% of women had a CD4 count below this level within twelve months of acquiring HIV.
The study was
conducted in South Africa and the investigators suggest their findings have
major implications for ART programmes.
progression observed in this cohort provides additional motivation to implement
earlier ART initiation,” comment the authors. “This study suggests that earlier
treatment initiation carries many benefits including the potential for major
impact on individual health by increasing survival and on public health by
little is known about the rate of disease progression in people living with
HIV subtype C – the dominant strain of HIV in sub-Saharan Africa. It is
important to gain a clearer understanding of this question so that ART roll-out
programmes in the region can be properly planned and resourced.
team of investigators therefore designed a study to determine the rate of CD4
cell loss among women with a known date of HIV seroconversion.
place between August 2004 and May 2005. The study population comprised sex
workers and women reporting a high number of sexual partners. The participants were
monitored for acute HIV infection at monthly or three-monthly intervals.
A total of 62
women were identified with recent HIV infection and their rate of CD4 count
loss was monitored over three years.
The median age at
HIV infection was 25 years. The mean CD4 count at the first post-seroconversion
follow-up was 520 cells/mm3. This was significantly lower than the
pre-infection count of 993 cells/mm3 (available for 23 women).
Almost a third of
participants (31%) reached a CD4 count below 350 cells/mm3 six to twelve months after acquiring HIV, 44% within 24 months and 55% within 36 months.
In 2013, WHO
increased its recommended CD4 count threshold for ART initiation to 500 cells/mm3.
Applying this criterion would have resulted in 69% of women requiring therapy
within twelve months, 79% within 24 months and 81% within 36 months.
The first mean
viral load measurement after seroconversion was approximately 65,000 copies/ml.
Three months after infection, rapid progressors had a significantly higher
viral load compared to non-rapid progressors (72,000 copies/ml vs 13,000
copies/ml, p < 0.001).
a viral load of 100,000 copies/ml or higher three months post-infection were
more likely to experience a fall in their CD4 count below 350 cells/mm3
sooner, compared to women with a lower viral load.
At month 24, 77%
of women with a high viral load at the three-month follow-up point had a CD4
count below 350 cells/mm3 compared to 35% of women with a lower
early viral load.
The median time to
CD4 cell decline to below 350 cells/mm3 was seven months
post-infection for women with a high viral load compared to 35 months for women
with a low viral load.
predictors of CD4 decline and rapid disease progression were CD4 count three
months after seroconversion (HR = 2.07; 95% CI, 1.31-3.28 per 100 cell/mm3
decrease), high viral load during early infection (HR = 3.82; 95% CI, 1.51-9.67
per 1 log10 increase) and hepatitis B virus co-infection (HR = 4.54;
95% CI, 1.31-15.69).
slower disease progression was associated with carrying certain HLA genotypes
(B*1302, B*27, B*57, B*5801, B*8101).
“We show nearly
half of the clade C-infected women met our conservative definition for rapid
disease progression (CD4 decline < 350 cells/mm3 within 2 years
of HIV-1 infection),” comment the investigators. “This finding supports the argument
of starting ART early…given the new WHO guidelines of ART initiation at 500
cells/mm3, more effort should be placed on diagnosing acute HIV
infection to ensure that the large proportion of women requiring treatment
within the first year of infection are not missed.”