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Increased STDs & HIV Transmission; HCV/HIV Coinfection
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Topics:
--Increased Prevalence of STDs & Risky Sex Facilitate HIV Transmission,
Despite HAART Reducing Transmission Risk;
--Problems with Treating HCV/HIV Coinfected Patients for HCV
--The Affect of CD4 Count & Viral Load on Response to Hep A & B Vaccines
At IDSA in SF in Dec 2001 several researchers discussed these problems. Dr.
Myron Cohen of the University of North Carolina at Chapel Hill discussed
sexual transmission of HIV (abstract S79). Plasma viral load is a reliable
predictor of the probability of HIV transmission; a viral load <3500
copies/ml is associated with a low risk. the lower the viral load the lower
the risk of transmission is, but a low or undetectable viral load does not
eliminate the risk for transmission. Sexual transmission is strongly
influences by the seminal viral load with transmission likely at viral load
levels at or above 4.5 log copies/ml of semen.
Inflammatory sexually transmitted diseases (STDs) facilitate transmission of
HIV not only by increasing the viral load in the genital tract of the
infected person, but by also increasing the number of cells available for
infection (that is, as in the HIV- partner). Gonococcal urethritis may be
associated with a 5-fold increase in transmission risk, and herpes simplex
lesions with as much as a 12-fold elevation in risk. Transmission rates
decline with successful treatment of the inflammatory diseases and resolution
of their lesions. HAART reduces transmission by reducing viral load in
genital secretions as well as in blood.
In one European study cited by Cohen AZT reduced HIV transmission from
infected persons by 50% vs transmission from untreated persons, However, this
is not a simple equation. Although ART is associated with reduced
infectivity, it may also be associated with a rise in risk behaviors.
Patients unduely feel they are protected from transmitting HIV if viral load
is undetectable. 50% of patients on HAART may have drug resistance and so
being on therapy can also have the effect of increasing drug resistance and
consequent transmission of resistant virus. A cucial period for HIV
transmission is early in infection, when transmitters usually are not aware
of their infected state but viral load is high. To improve prevention efforts
perhaps we should focus on better testing, education, and treatment of STDs,
condom use, diaphragm use, and other methods.
Dr. Connie Celum of the University of Washington summarized recent data on
STDs among men who have sex with men (MSM) [Abstract S81]. The incidence of
STDs has risen appreciably, as high as 60% in some populations of HIV+ men
who have sev with men. Rates of gonococcal infection have recently tripled in
some populations of MSM, although syphilis is more common than infection with
gonococcal or chlamydia.
The rise of STDs, particularly of bacterial origin (syphilis, gonorrhea) has
been quanified in major US cities, but it is also generally acknowledged to
be widespread outside urban areas as well. Cities are easier to study because
of the concentration of populations at risk and the presence of facilities
where people may gather not only to engage in social activities and risk
behaviors, but also to seek healthcare and counseling. the resurgance of STDs
among HIV-infected MSM is a certain indicator of unprotected sex. This has
been attributed to a permissive atmosphere nourished by several
interdependent factors, not least of which is the increased use of
recreationsl drugs, particularly crystal methamphetamine and sildenafil
(which is developing a reputation as a "part drug" in some populations).
Surveillance data from several urban centers in the U.S. and Europe has
described multiple syphilis outbreaks among MSM in the last half of the
1990šs. To study determinants of sexual risk-taking and STDs among MSM in
Seattle, approximately 1000 MSM (30% were HIV-seropositive) were recruited
from STD clinics and HIV primary care clinics. Overall, HIV-infected MSM were
not sexually safer, with 31% reporting meeting partners anonymously at bath
houses or sex clubs, compared to 22% of HIV-seronegative men reporting this
behavior. The prevalence of gonorrhea or chlamydia (isolated from oral, anal,
or rectal sites) was 10% among HIV-infected MSM and 13% among HIV-uninfected
MSM, with most infections being asymptomatic. These findings have significant
implications for HIV clinical providers: Discussion of sexual risk behaviors,
especially specific types of sexual practices and the use of anonymous venues
to meet partners, along with periodic screening for bacterial STDs should be
a consistent standard in clinical practice.
Dr. Steven Morin presented recent epidemiologic trends in San Francisco that
demonstrate a new rise in HIV incidence over each successive quarter of 2000
[Abstract S82]. To design effective prevention interventions to address this
trend, focus groups comprised of MSM in San Francisco were assembled.
The questions presented to the focus groups were as follows:
- Why have HIV infections increased?
- What has changed in the past 10 years that may have contributed to this
increase?
- What can be done about it?
The groups identified the following as factors contributing to HIV
transmission, but that had not changed significantly over the past several
years:
- Denial of risk, especially among adolescents.
- Sense of inevitability of getting HIV infection.
- Comodification of HIV (i.e., more chance to get social services, housing
assistance), especially among the poor.
- Loneliness and low self esteem.
- Drug use, including metamphetamines.
The following were phenomena that the groups identified as having changed in
the past several years and may be contributing to the recent increase in HIV
incidence:
- Decreased perception of HIV as a health threat among the HIV-uninfected.
- Decreased communication, either with friends or in the media, about HIV
- A gradual shift in community norms about sex, including peer pressure to
be unsafe, and a celebration of "barebacking."
The focus groups endorsed health promotion advertisements that focused on
friends talking to friends about safer sex, that provided facts on the rising
rates of HIV in San Francisco, that explained that HIV still had very
negative health consequences, and that promoted safer sex as "still the
norm."
Problems Associated With Treating HCV/HIV Coinfected Persons for HCV
As we move into the fourth decade of the HIV/AIDS epidemic without a
prophylactic vaccine, improved STD control is as important as ever in
preventing the spread of HIV. New data indicate that clinical trials of
genital herpes suppression, along with a more aggressive focus on STD
screening and prevention services in HIV clinical practice, should now be
high priority items on the HIV prevention agenda.
At IDSA, the problems associated with treating HCV/HIV coinfected patients
were highlighted. Although several small studies suggest patients infected
with HCV/HIV respond as well to interferon+ribavirin therapy as patients
infected with HCV only, initial results from larger studies suggest response
rates may not be the same. There is a higher rate of genotype 1 among
coinfected IVDUs and among African-Americans, and persons with genotype 1
have lower response rates than persons with genotype. The response by
African-Americans is lower than that of whites. This could be due to higher
prevalence of genotype 1 and perhaps genetic differences. A large NIH study
is starting which will explore the response to HCV therapy for
African-Americans.
At IDSA, Fleming and colleagues presented data from their clinic at Boston
University echoing these difficulties in clinical practice [Abstract 755]. Of
93 co-infected patients in their clinic who completed evaluation for HCV
treatment, only 31 (33%) were offered HCV therapy. Of the 62 who were not
suitable for therapy, 26% were non-adherent with clinic visits, 24% had
active psychiatric disease, 22% were actively using drugs or alcohol, and 23%
had decompensated liver disease or medical contraindications to therapy. Of
the 31 offered therapy, only 9 have commenced therapy at this point (6 have
refused and 16 are deferring therapy). Thus, only 10% of those evaluated for
HCV co-infection were eligible and agreed to start treatment.
Response to Vaccination in HIV-infected Individuals
Studies in the pre-HAART era focused on the association between CD4 count and
response to vaccines in HIV-infected patients. However, there is considerable
ambiguity about what factors predict serological response to vaccines in
patients on HAART, and which patients would be most likely to benefit.
Huprikar and collaborators presented data at IDSA suggesting that suppression
of the viral load is an important predictor of response to vaccination,
regardless of the CD4 cell count [Abstract 380]. The study was a
retrospective review of 41 HIV-infected patients who received the 3-dose
hepatitis B vaccine series and had follow-up hepatitis B serology performed.
The results in this small study also find patients with >200 Cd4s respond
better to the vaccine than those with <200 CD4s.
When viral load was <400, 8/14 (57%) of patients <200 cd4s and 2/4 (50%) with
>200 CD4s seroconverted suggesting that having an undetectable viral load is
protective despite the CD4 count. When viral load was >400 4/17 (24%) of
patients with >200 CD4s seroconverted to HBV after exposure compared to 0/6
(0%) of patients with <200 CD4s, suggesting CD4s add protectivity when viral
load is detectable. This was a small study but results from other studies
suggest the HBV vaccine may not be as effective for patients with a low CD4
count. But I believe this is the first study suggesting an undetectable viral
load may be protective even if CD4 count is low.
Huprikar noted there may be a few confounding factors in the way the study
was conducted. The low seroconversion rate overall may have been a byproduct
of the retrospective design and the broad time interval (2-14 months) between
vaccination and determination of serologic response. The group is planning a
larger, prospective study to better explore these issues.
Wallace reported at IDSA (abstract 379) seroconversion after the first in
athe series of two Hep A vaccines was 98% in HIV- persons and 100% after the
2nd booster vaccine. But in HIV+ persons, when CD4s were >400 the
seroconversion rate was 90% after the first vaccine and 100% after the
booster. When CD4s were <200 the seroconversion rate was 70% after the first
vaccine and 87% after the booster shot, suggesting the Hep A vaccine had less
protection when CD4s were below 300. Wallace also said that as CD4s declined
increasingly below 300 seroconversion rates declined at a similar rate.
References
1. HIV Information Network. University of Alabama-Birmingham. World Health
Communications. IDSA 2001.
2. Johns Hopkins AIDS Service website: www.hopkins-aids.edu
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