Evidence-based Medicine: Time for a change? - Journal of Medical ...

ORIGINAL ARTICLE
behavioral characteristics of HIV-infected
South Indian patients in concordant and
discordant heterosexual relationships. 839
concordant patients were compared with 996
discordant patients in his study. Concordant
patients had significantly higher CD4 cell
counts than discordant patients at the time of
enrolling to care. Their study concluded that
couple-based interventions in addition to
proper provision for HAART will decrease the
HIV transmission among discordant South
Indian married couples. 7
A study from Canada has postulated that a
cumulative effect due to cellular immunity, viral
characteristics, and co receptor integrity could
be the reason behind the seronegativity results
after studying 11 discordant couples. There
is no single reason behind the resistance to
HIV infection 8 . Immunoglobulin A (IgA)
responses found in the cervico-vaginal fluids
of sex workers in Thailand as well as in other
discordant groups, suggests that local
mucosal immune responses might be the
reason behind the persistent seronegativity . It
has been studied that purified IgA from HIV
resistant sex workers have a neutralizing effect
towards HIV isolates from different clades and
inhibit HIV infection of susceptible cells in vitro.
This provides further evidence that IgA may
be an important part of the immune defense
against HIV 9, 10 . In literature there is evidence
of elevated levels of IgA, IgG and IgM which
are believed to suppress HIV, in the
cervicovaginal secretions of a cohort of HIVseronegative
African sex workers, suggesting
that the immune response may not be limited
to just IgA (Belec et al.) 11 .
It is postulated that cytotoxic T-lymphocytes
(CTLs) might have a role in resistance to HIV
infection although the resistance is believed
to be dependent on persistent exposure to
HIV. 12 This type of responses have been
found in babies born to infected mothers,
regular sexual partners of HIV-infected
individuals, and sex workers with high levels
of exposure to HIV. 13 Rowland-Jones et al in
their work on sex workers in Nairobi who were
HIV seronegative had discovered CTL
responses targeting epitopes defined by HIV
clade B. 14 A study in HIV seronegative Kenyan
sex workers, found that HIV-specific CD8+ T
cells in the genital mucosa of the sex workers,
suggesting that CTL responses were
protective against heterosexual transmission
of HIV infection (Kaul et al). 15 Another study
by the same author among a cohort of
exposed-uninfected Kenyan sex workers, a
subset who seroconvert for HIV infection were
found to have had lapses in sex work. This
apparent interruption in HIV exposure might
have lead to loss of HIV-specific CD8+
responses, suggesting that constant or
frequent exposure to HIV is needed to
maintain a protective CTL response. 16
A study among the Chinese males had shown
that 30% of the persistently negative
individuals have HIV-1 specific T cell immune
responses. 17 Though various studies explains
the evidence for CTL involvement in resistance
to HIV infection there is no conclusive
evidence, leaving the possibility that CTLs are
surrogate markers of some other
mechanism. Thomas et al in their study have
confirmed the reduced expression of CCR5
in HIV-1 resistance. This reduced expression
of CCR5 could be the reason for the
seronegativity. 18 A study among high risk
individuals of Indian origin had concluded that
single nucleotide polymorphism (SNP) in
Stromal Derived factor (SDF-1); a ligand for
CXCR4 could be a protective factor towards
HIV infection. 19, 20 Another study by Sangok et
al showed a high expression of CD26/DPPIV
enzymes in exposed seronegative individuals.
This opens a new dimension of CD26/DPPIV
in protection against HIV infection in vivo. 21
DPPIV enzymes are the enzymes which are
implicated in the carbohydrate metabolism.
Stanford et al in their study had observed a
strong non-cytotoxic CD81-cell anti-HIV
response in discordant persons suggesting
that this might be a contributing factor for the
reason towards the persistent negativity
Though various postulates have been given
for the persistent seronegativity or HIV
resistance /susceptibility, we could not
evaluate the reason for the discordance in our
patients due to lack of resources. An insight
towards the resistance or susceptibility to HIV-
1 infection is important in the context of future
treatment modalities and research towards
22 JMS * JMS Vol 25 * Vol * No. 25 3 * No. * September, 1 * June, 2010 2011