NATAP/IAC: Gardasil Effective in CD4 Count >200 & >350

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Subject: NATAP/IAC: Gardasil Effective in CD4 Count >200 & >350

Quadrivalent HPV Vaccine Immunogenic

in HIV+ Women With CD4s Over 200

XIX International AIDS Conference, July 22-27, 2012, Washington, DC

Mark Mascolini

A vaccine designed to protect against four human papillomavirus (HPV) types (6,

11, 16, and 18) proved highly immunogenic in HIV-positive women with a CD4

count above 200, according to results of an ongoing three-country trial [1]. No

serious safety problems have developed.

HPV is the most frequently transmitted sexual infection in the United States and

many other countries [2]. It can cause cervical cancer in women and other cancers

and anogenital diseases in women and men. HPV disproportionately affects women

with HIV infection, and two studies of the quadrivalent HPV vaccine (Gardasil)

are under way in HIV-positive women. (Results of the other study, which confirm

findings in the current trial in a younger population, are reported separately

by NATAP.)

ACTG study 5240 involves 319 HIV-positive women in the United States, Brazil,

and South Africa who receive the vaccine in three doses, at study weeks 0, 8,

and 24. Women were 13 to 45 years old and could not have anal, cervical, or

vulvar cancer. Other exclusion criteria were pregnancy or breastfeeding, use of

immunomodulatory agents, serious illness requiring hospital admission,

hemophilia, thrombocytopenia, and hysterectomy.

This analysis involved (1) stratum A, 130

women with a CD4 count above 350 when they entered the study and (2) stratum B, 95 women with a CD4 count of

200 to 350 at study entry. The trial is also evaluating the vaccine in 94 women

with a CD4 count of 200 or less, but results in those women were not presented

at the International AIDS Conference.

Four weeks after the last dose, ACTG investigators measured immunogenicity as

the proportion of women who seroconverted for each of the four HPV types and

geometric mean titers for each type.

When women entered the trial, their median age stood at 37 years and ranged

from 19 to 45. More than half of women (57%) were black, 29% were Hispanic, and

13% were white. Median lowest-ever CD4 count stood at 262, 41% of women had an

undetectable viral load, and 63% had a load at or below 10,000 copies. Ninety-three

women (42%) were not taking antiretrovirals. Only 13% of women came from Brazil

or South Africa.

Among women with a baseline CD4 count above 350, 46% were seropositive for

HPV-6 at baseline, 19% seropositive for HPV-11, 37% seropositive for HPV-16,

and 24% seropositive for HPV-18. Respective seropositive proportions of women

with 201 to 350 CD4s at baseline were 36%, 23%, 32%, and 13%. Overall, 39% of

women were seronegative for all HPV types and only 4% were seropositive for all

four types.

No serious safety problems arose. Twenty of 127 women (16%) in stratum A and 19

of 95 (20%) in stratum B had a grade 3 or 4 adverse event, none of which were

judged related to vaccination. In stratum A one adverse event (chest pain) was

judged possibly or definitely related to vaccination. In stratum B two adverse

events (back pain and rash) were judged possibly or definitely related to

vaccination.

Seroconversion rates and geometric mean titers for each genotype were generally

high in both CD4 strata:

Stratum A: CD4s

above 350:

-- HPV-6: seroconversion rate 96%, geometric mean titer 425

-- HPV-11: seroconversion rate 97.6%, geometric mean titer 461

-- HPV-16: seroconversion rate 98.4%, geometric mean titer 1120

-- HPV-18: seroconversion rate 90.7%, geometric mean titer 164

Stratum B: CD4s 201 to 350:

-- HPV-6: seroconversion rate 100%, geometric mean titer 327

-- HPV-11: seroconversion rate 98.3%, geometric mean titer 388

-- HPV-16: seroconversion rate 98.2%, geometric mean titer 1077

-- HPV-18: seroconversion rate 84.3%, geometric mean titer 166

The researchers proposed that low prevaccination seroprevalence of HPV types

covered by the vaccine "suggests that the majority of HIV-infected women

would benefit from vaccination."

The CDC recommends HPV vaccination for (1) all teen girls and women through age

26 who did not get all three doses of the vaccine when they were younger, (2)

all teen boys and men through age 21 who did not get all three doses of the

vaccine when they were younger, and (3) any man who has sex with men, and men

with compromised immune systems (including HIV-positive men) through age 26 if

they did not get fully vaccinated when they were younger [3].

References

1. Kojic EM, Cespedes M, Umbleja T, et al. Safety and immunogenicity of the

quadrivalent human papillomavirus vaccine in HIV-positive women. XIX

International AIDS Conference. July 22-27, 2012. Abstract WEAB0203. Slides for this

report can be found at http://pag.aids2012.org/session.aspx?s=217.

2. Centers for Disease Control and Prevention. Human papillomavirus (HPV). http://www.cdc.gov/hpv/.

3. Centers for Disease Control and Prevention. HPV vaccines. http://www.cdc.gov/hpv/vaccine.html.