Lower immune response to the qHPV vaccine in HIV positive girls

1 February 2014. Related: Conference reports, Women's health, Paediatric care, Intl Workshop on HIV and Women 4th 2014.

Polly Clayden, HIV i-Base

Lower immune response was observed in HIV adolescent girls compared to HIV negative girls given the human papillomavirus quadrivalent (qHPV) vaccine. But the response was comparable to that in older negative women for whom this level of response gives efficacy against HPV.

The qHPV vaccine was approved for use in HIV negative adolescents in 2006. HIV negative girls aged 9 to 13 years have the highest level of antibody response to the vaccine. There is limited information on who well the vaccine will perform in HIV positive adolescents.

Deborah Money presented data from a sub-analysis of 9 to 13 year old girls in a Canadian study to evaluate the safety and immunogenicity of the vaccine, at the 4th International Workshop on HIV & Women.

The study was conducted at 11 Canadian sites between November 2008 and December 2012, and enrolled 407 HIV positive girls and women.

Girls included in the substudy (n=26) were a minimum of 9 years, able to consent, and with a cervix present. The duration of the study for each participant was 27 months during which they received three doses of the qHPV vaccine at months 0, 2 and 6.

Geometric mean antibody titers (GMT) before receiving the vaccine and at months 7, 12, 18 and 24, were evaluated to HPV types 6,11,16 and 18. Results were compared to the 3-dose arm of a previous 2-dose vs 3-dose study in HIV negative girls in the same age group receiving qHPV vaccine (n=252).

There were 32 HIV positive girls enrolled in the 9 to 13 year age group; 1 was seropositive to HPV18 at baseline and all others were seronegative to all four types in the quadrivalent vaccine. All girls completed the vaccine schedule. No adverse events related to the vaccine were reported.

The HIV positive girls were a mean age of 11 years, 4% white, 70% black and 26% Asian. The mean time since HIV diagnosis was 9 (5 to11) years. Median baseline CD4 was 692 mm3 (IQR 557 to 960), 76% were receiving ART and 59% had an undetectable viral load.

The investigators compared GMTs in HIV positive and HIV negative girls (from the previous study) in an age-adjusted analysis at month 7 and found statistically significantly lower peak GMTs against each HPV type in HIV positive girls. See Table 1.

Table 1. Month 7 GMTs (mMu/mL) in HIV positive vs HIV negative girls aged 9 to 13
HPV type	HIV positive	HIV negative	p-value
16	4382	7650	<0.01
18	640	1703	<0.0001
6	830	1856	<0.001
11	977	2096	<0.0001

The investigators noted that the GMTs were in the HIV positive girls were comparable to those in HIV negative 18 to 26 year old women for whom the vaccine efficacy has been demonstrated to be effective.

A subset of HIV positive girls (n=16), with 24 week follow up data showed considerably reduced efficacy against all HPV types – the GMTs for the HIV negative were also reduced but the differences were significant. See Table 2.

Table 2. Month 24 GMTs (mMu/mL) in HIV positive vs HIV negative girls aged 9 to 13
HPV type	HIV positive	HIV negative	p-value
16	628	1739	<0.01
18	55	267	<0.0001
6	101	359	<0.0001
11	105	422	<0.0001

Month 7 GMTs against all four HPV types were significantly higher in HIV positive girls with an undetectable viral load <50 copies/mL (n=19) compared to those whose viral load was detectable (n=13). See Table 3.

Table 3. Month 7 GMTs (mMu/mL) in HIV positive girls aged 9 to 13 with undetectable vs detectable viral load
HPV type	<50 c/mL	>50 c/mL	p-value	Ratio of GMTs
16	5851	1739	0.05	2.02
18	1032	330	0.03	3.11
6	1083	562	0.09	1.9
11	1307	639	0.05	2.01

But in conclusion the investigators noted that: “Until an immune correlate of protection is defined in HIV negative and HIV positive persons, understanding of the meaning of antibody levels remains limited.”

Comment

The role of booster dosing needs to be investigated for girls and women with HIV.

Reference:

Money D et al. Lower immune response in HIV positive girls to the qHPV vaccine. 4th International Workshop on HIV & Women, 13-14 January 2014, Washington DC. Oral abstract_15.
http://regist2.virology-education.com/2014/4hivwomen/docs/21_Money.pdf