HCV:
The Correctional Conundrum
(continued)
Initiating Antiretroviral
Therapy in Women
The HHS guidelines rely
heavily on HIV-1 viral load as a predictor of disease progression; and
much of the data linking viral load to development of AIDS comes from longitudinal
studies of male populations, such as the MACS cohort.7, 8 However, multiple
studies have shown that women at all stages of HIV infection have lower
mean HIV-1 viral loads than men, even after controlling for CD4 count.9,
10 Researchers at Johns Hopkins University (JHU) and the National
Institute of Allergy and Infections Disease (NIAID) recently published
results in the New England Journal of Medicine from one of the largest
studies ever to examine gender-specific difference in HIV infection, the
AIDS Linked to the Intravenous Experience or ALIVE cohort. The study found
that women who developed AIDS had a median initial viral load of 17,149
copies/mL, compared to 77,822 copies/mL in men. This sex difference in
viral load means that the same viral load measurement does not convey the
same risk of AIDS in women and men. Under current treatment guidelines,
which suggest initiation of antiretroviral therapy when viral load exceeds
50,000, many women in the ALIVE cohort would have been excluded from HIV
therapy. The results of the NIAID and JHU study suggest that decisions
concerning the initiation of HIV therapy should emphasize CD4+ count more
than viral load.11
A possible mechanism for
this gender-based discrepancy is a difference in the expression of the
HIV virion target on T-cells (CCR5 co-receptor) in women versus men. Portales
and others have demonstrated a lower membrane density of CCR5 in women,
which they postulate may be caused by the inhibitory effects of progesterone
on CCR5 expression.12 Because the membrane density of CCR5 determines
the in vitro infectability of a target cell by an HIV-1 R5 strain, this
finding could account for the gender difference seen in HIV-1 viral loads.
Thus, clinicians caring for the HIV infected woman should probably emphasize
CD4 T cell count over viral load when making decisions about initiating
HIV treatment.
Pregnancy
Pregnancy presents another
set of considerations for HIV treatment, where there is the additional
goal of preventing vertical transmission. Given the decrease in vertical
transmission seen with a zidovudine (AZT, Retrovir) alone regimen in PACTG
076, it is generally agreed that zidovudine should be part of any antiretroviral
regimen prescribed during pregnancy unless absolutely contraindicated.13
The 2001 HHS Treatment Guidelines recommend treatment with combination
HAART (updated treatment guidelines, specific to pregnancy, are available
at http://hopkins-aids.edu/publications/report/may01_1).
It is less clear how to manage
the HIV infected pregnant woman who has a high CD4 count and low HIV-1
viral load. There is no data to suggest that combination therapy
would be better than zidovudine monotherapy in preventing vertical transmission,
but combination therapy does have the advantage of better virologic suppression
for the mother and less chance of developing resistance mutations that
might limit options for treatment in the future. The pros and cons of limiting
fetal exposure to multiple agents versus preserving options for the mother
in the future should be discussed in detail with the patient. The physician
and patient should also discuss the potential benefit of ceasarian section.
If treatment is to be initiated
for the first time during pregnancy, initiation of antiretroviral therapy
should wait until the second trimester to minimize teratogenicity and avoid
gastrointestinal toxicity during the early stage of pregnancy. Clinicians
should avoid using efavirenz (Sustiva) in pregnancy because of evidence
of teratogenicity in primate studies. The combination of didanosine (DDI,
Videx) and stavudine (D4T, Zerit) should also be avoided because of multiple
case reports of hepatic steatosis with lactic acidosis in pregnant women,
including three deaths.
Other GYN Considerations
HIV-infected incarcerated
women have particularly high rates of cervical cytological abnormalities,
sexually transmitted diseases and certain gynecologic infections.14,15
Research indicates that vaginal infections are slightly more common among
HIV-infected incarcerated women than noninfected incarcerated women, while
the prevalence rates of STDs are high among incarcerated women compared
to free-living women overall.16
Furthermore, high rates of
HPV infection, of cervical cytological abnormalities and of invasive cervical
cancer, have been found among high-risk HIV-seronegative women and HIV-infected
incarcerated women.17 Most correctional HIV programs have adopted an increased
level of vigilance for cervical cancer, leading to the institution of performing
pap smears every six months as a routine component of care for HIV-infected
women (See HIV 101, page 7).
-Human Papilloma Virus
(HPV) and Cervical Cancer
A womanís lifetime risk
of HPV infection is 80%. Certain types of HPV are associated with increased
risk for cervical cancer. As a consequence of cervical cytology screening
programs, cervical cancer is typically diagnosed in early stages. While
patients with stage I disease can be treated effectively with either surgery
or radiation therapy, patients with stages II-IVa disease usually receive
radiation therapy as the primary treatment modality. Forty percent of patients
develop persistent, recurrent or widely metastatic disease for which there
is currently no consistently effective therapy. (See HIV 101) for treatment
recommendations.
-Abnormal Menstruation
Although the Womenís Interagency
HIV Study data suggests a similar rate of menstrual irregularities in HIV-infected
and uninfected women, there is data to suggest that prolonged anomenorrhea
is more common in HIV-infected women.
CONTINUE...
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