Institutionen för klinisk vetenskap / Department of Clinical Sciences
Abstract
During the last 20 years HIV-1 infection has changed from being an
unknown disease to being a widespread pandemic, in some areas affecting a
large proportion of the human population. Mother-to-child transmission
(MTCT) is the predominant route of transmission in children, who thus
become infected during a period when their immune system is immature and
developing. This thesis is based on a prospective follow-up of a
population-based cohort of children to HIV-1-infected women in Sweden
since the start of the HIV-1 epidemic.
We followed a total of 419 mother-child pairs between 1982 and 2003, 355
of them prospectively. The MTCT rate decreased during the period from
24.7% 1984-93 to 5.7% 1994-98 and 0.7% 1999-2003. The proportion of
children born to women who received antiretroviral treatment or
prophylaxis increased from 2.3% to 91.5%, and the elective caesarean
section rate from 8.0% to 80.1%. Seventy-two children, 31 of whom were
born in Sweden, were vertically infected. Eleven infected children died.
Ten out of 51 children living in Sweden in 2003 had had an AIDS diagnosis
and 29 were on antiretroviral treatment. Eleven lived with a non-parental
caregiver.
In 24 prospectively followed HIV-1-infected children born during 1985-98,
the disease progressed faster to severe immunodeficiency, AIDS or death
in children with early symptoms related to HIV-1 than in those without
early symptoms. Detectable virus during the first four days of life was
not shown to affect disease progression. Two children developed symptoms
suggestive of primary HIV-1 infection.
HIV-1 RNA load was determined in 32 infected children. The median HIV-1
RNA level was highest at 1.5-3 months of age, decreased between 1 and 8
years and then increased slightly. This pattern was not seen in all
individuals. Both symptomatic and asymptomatic children displayed a
varying pattern of viral load.
Stored samples from 24 infected children were analysed for genetic
subtype and coreceptor use of the virus. The virus belonged to subtypes
A, B, C, D, G and CRF01_AE. All isolates from the first year of life used
chemokine receptor CCR5 as coreceptor. In virus from four patients, the
coreceptor use changed from CCR5 to CXCR4. The change was associated with
a decreased CD4+ cell count and disease progression, but appeared after
immunological deterioration.
Infectious viral loads by limiting dilution culture and days-to-culture
positivity (infectious index) and HIV-1 RNA were determined in 16
children. Limiting dilution correlated to the infectious index. The
median HIV-1 RNA and infectious indices of plasma and PBMC rose rapidly
to 6-8 weeks of age to a plateau level. The median index in plasma
declined to zero by 2 years of age in contrast to that in PBMC and to
HIV-1 RNA. A high-peak plasma index correlated with clinical progression.
Children who progressed to AIDS had higher median plasma indices than
those who did not. In children displaying a coreceptor change in plasma,
there was a simultaneous reappearance of infectious virus, which was not
related to changes in RNA.
In summary, the virological studies contribute to a better knowledge of
the natural course and interaction between virus and host in perinatally
HIV-1 infected children. The epidemiological study shows that good
results can be achieved if prophylactic measures against MTCT of HIV-1
are used consistently, which highlights the importance of antenatal
screening programmes