With the recent advent of type-specific serologic assays for
the determination of herpes simplex virus type 1 (HSV-1) or HSV-2
antibody and the role that genital and rectal herpes infections
play in HIV transmission, there has been a renewed interest in herpes
epidemiology in MSM. Recent studies have documented higher prevalence
levels of HSV-2 antibody in MSM as compared with heterosexual men
(31% vs 18%) and a higher proportion of initial
genital herpes infections attributable to HSV-1 infection among
MSM as compared with women and heterosexual men (47% vs 21% and
15%, respectively). In a Canadian study, 54% of
genital herpes infections were caused by HSV-1, and a San Francisco
study showed that 22% of genital herpes infections among
STD clinic attendees resulted from HSV-1.
Genital herpes infections cause a substantial amount of morbidity
in MSM, with symptoms ranging from recurrent itching, redness, or
burning sensations to blisters and sores and genital neuropathic
pain. These manifestations can involve the penis, scrotum, perineal
area, anus, or rectum. Definitive diagnosis is often difficult because
it requires isolation by culture of HSV from the affected area.
Most laboratories upon isolation of HSV will routinely confirm the
subtype using direct fluorescent type-specific antibody. Serologic
testing may be helpful to rule out infection, because the seropositivity
of HSV-1 and HSV-2 in the general population is about 70% and
22%, respectively. A negative antibody test for both subtypes
thus makes infection unlikely. Recent data show that asymptomatic
viral shedding is common in HSV-2–infected MSM, similar
to prior data in women, occurring in more than 50% of men
an average of 1 day a month.
The most significant recent advance in the treatment of genital
herpes has been the approval by the Food and Drug Administration
of valacyclovir, 500 mg orally twice daily for 3 days, for recurrent
infections. Clinicians can prescribe the 1-g dose and order it scored
or split. The average wholesale cost of three 1-g tablets of valacyclovir
($23.25 in 2004) is less or similar to the cost of the
recommended dosage of acyclovir for recurrent infections (400 mg
orally twice daily for 5 days, [$30.90];
and 800 mg orally three times daily for 2 days [$24.00]).
Given the known role that HSV infection plays in the increased
risk of acquisition and spread of HIV infection, several studies
are underway to determine whether chronic herpes suppression (twice
daily acyclovir therapy) will reduce HIV transmission. Although
suppressive herpes therapy (valacyclovir, 500 mg by mouth daily)
was recently approved by the FDA for chronic suppression and reduction
of HSV transmission based on studies in heterosexual couples, chronic suppressive
therapy is likely effective in reducing HSV transmission between
MSM, as well.
Hepatitis infections are a major concern for MSM, because both
hepatitis A and hepatitis B are sexually transmitted via oral-anal
sex and anal intercourse. Current CDC guidelines for preventive
care in MSM recommend routine immunization against hepatitis A and
B; however, immunization coverage of this population has been low.
The recently FDA-approved combination hepatitis A and B vaccine
provides a simpler delivery system for immunization, given over
several months in three separate doses. Various immunization schedules
of 0, 1, and 4 months or 0, 2, and 6 months have been shown to be
equally immunogenic, and data demonstrate that even after a single
dose more than 50% of patients have demonstrable seroprotection.
Hepatitis A is most often a self-limited infection with rare
fatalities. The morbidity, however, can be substantial and, recently,
hepatitis A immunization in MSM has been shown to be cost-saving.
Treatment for chronic active hepatitis B is evolving. Recent
clinical data suggest that therapy with antiviral agents such as
lamivudine, 100 mg daily, and interferon alfa, 10 million units
three times per week, can suppress viral replication in 30–40% of
patients. The recent FDA approval of the oral drugs adefovir and
entecavir offers a promising new addition to treatment options for
patients with chronic hepatitis B.
Hepatitis C is an important sexually acquired infection for MSM,
particularly for HIV-infected MSM, because population-based prevalence
data document a higher risk of infection than in the general population.
Recent data controlling for past injection drug use suggest limited
risk for MSM and that the sexual transmission of hepatitis C virus
is rare among MSM. Hepatitis coinfections with type A or B virus
may accelerate the course of hepatitis C; thus, it is imperative
that persons with hepatitis C infection receive immunizations for
hepatitis A and B.
Human Papillomavirus & Anogenital Warts
Over 70 oncogenic and nononcogenic subtypes of human papillomavirus
(HPV) are associated with sexual transmission. In MSM these infections
can cause asymptomatic infection, external genital warts, internal
rectal warts, and anorectal (and rarely, penile) carcinoma. Exposure
to HPV through sexual activity is common, and population-based prevalence
studies document that more than 80% of sexually active
persons have been exposed to HPV. There is a clear relationship between
the number of sex partners and increased prevalence of HPV and infection
with an increasing number of different HPV subtypes.
External genital warts are a major reason why MSM present for
clinical care and evaluation. In men may present with warts on various
areas of the penis and anus. Anal condylomata acuminata should be
a clinical cue to receptive anal sex and should prompt further discussion
of risk behaviors and appropriate screening (ie, rectal gonorrhea,
rectal chlamydia, and syphilis testing). Most external genital warts
can be adequately diagnosed by visual inspection, but if the diagnosis
is uncertain biopsy may be indicated.
Patients may also complain of internal rectal warts, either self
diagnosed or recognized by a sex partner. Symptomatic rectal warts,
rectal obstruction, or significant bleeding are indications for referral
to a colorectal specialist for wart removal.
Treatment for external genital warts includes provider- or patient-applied
therapy such as liquid nitrogen, podophyllin 25%, trichloroacetic
acid, imiquimod 5%, or podofilox gel. Patient-applied topical
applications appear more efficacious on mucosal sites and other
areas that are less keratinized. One advantage of imiquimod 5% is
that it may be associated with a reduced recurrence rate, because
it activates host immunologic mechanisms to clear infection rather
than simple ablation of the wart.
Several observational studies have shown the relationship between
oncogenic subtypes of HPV and anorectal carcinoma. These studies
have led some experts to recommend routine anal Papanicolaou (Pap)
smear testing as a means to reduce the rate of anorectal carcinoma
in MSM. The current rate of anorectal carcinoma, at 50 cases per
100,000 MSM per year, is similar to the rate of cervical cancer
before the implementation of cervical cancer screening programs.
Although HIV-infected persons may have higher rates of abnormal
anal Pap smears, the impact of HAART on the reversion of abnormal
anal Pap smears is currently under study. Because HIV-infected patients are
living longer, one might expect the incidence of anal carcinoma
to increase in this population if HAART has no effect.
Anorectal carcinoma is a treatable, albeit not curable, condition
with substantial treatment-associated morbidity. At present there
are no national recommendations regarding male screening for anorectal
carcinoma (anal Pap smear testing).