Reports for NATAP

1st International AIDS Society (IAS) Conference on HIV Pathogenesis and Treatment

July 7-11, 2001 Buenos Aires, Argentina

HPV Infection in Women and Men
Highlights from the first IAS Conference
     Written for NATAP by Danielle Milano, MD

HPV Infection in Women

There were 5 posters on Human Papilloma Virus infections (HPV) in women. Only 1 of the 5 presenters was actually present to discuss the data during the scheduled poster session.

Dr. Eduardo Franco of the Federal University of San Paulo in Brazil, was available to discuss his poster "HPV Induced Lesions in a Population of Pregnant Women Infected with HIV" (poster #795). 166 pregnant women were evaluated with Pap smears, colposcopy with directed biopsies, and HPV DNA testing using the Hybrid Capture II. Pap Smears missed half of the HPV infections: prevalence HPV, 57.2% by Hybrid Capture II, 47% by Colpo and 25.9% by Pap smear.

Dr. Franco also reported that women with CD4 < 200 had nearly double the risk of being infected with a high-risk HPV (HR-HPV) when compared to women with CD4 > 200 (84.2% vs 43.7%).

The effect of HIV VL was similarly significant. Women with HIV VL < 10K were half as likely to be positive for HR-HPV when compared to women with HIV VL > 10K (25.3% vs 58.5%).

Discussion
The report was an eye opener for me because in our clinic we have gynecologists who perform the pelvic exams and Pap smears on our patients. I knew that they were testing for HPV but, I did not know what assay they were using, what the sensitivity of the assay was, and what prompted them to test for HPV. Sure enough, we use the Hybrid Capture II which indicates whether the HPV is of a HR or Low-Risk(LR) sub-type, but does not indicate the actual sub-type. So I called one of our Nurse Practitioners in the GYN department and asked her what test they use to test for HPV. She though they the lab did a culture. She didn't know that we use a PCR based assay, let alone what specific assay.

The point is that we are so compulsive in our treatment of our HIV positive patients, yet we leave something this importance up to chance. We assume that our Gynecologists are familiar with diagnosis and treatment of HPV in our HIV+ women. In addition, we trust that the laboratory will use an assay with a high sensitivity and specificity. Our clinic is associated with a major medical center; therefore we have little control over what assays are used. We can not assume the laboratory directors keep current, for example, I called the medical director of our lab to inquire about the Roche 1.5 for HIV VL, since we have a number of patients with HIV-2 or HIV-1 Non-B. He had no idea what I was talking about. I called the administrative director of the lab to find out the sensitivity and specificity of the Hybrid Capture II. He had no idea, nor could he tell me who had made the decision to use that test.

Whether the presence of HPV in the presence of a normal Pap and/or a normal Colpo is of any significance is not clear. It's presence does indicate that we should be vigilant in our follow-up of those patients. As to the shift from LR-HPV to HR-HPV as the CD4 drops, this has also been seen in MSM with anal HPV infection.

The remainder of the 4 posters can be summarized briefly:

A group from Badalona, Spain presented "Cervical Squamous Intraepithelial lesions (SIL) in a Spanish HIV+ Womens Cohort. Prevalence, Incidence Rate and Effect of HAART on Cytological Changes" (#794). They found a correlation of both low CD4 and high HIV VL with SIL. More importantly, HAART increased the number of mean days to progression of the cervical lesions from 571 ± 156 to 1018 ± 109.

A group from Milan, Italy reported "HPV and Associated Cervical Disease in HIV Infected Women: Effect of HAART" (#797). This group found a CD4 < 350 the only variable associated with the persistence of HR-HPV. Persistence of HPV and progression of SIL were equivalent in the groups of women on or not on HIV therapy. This would seem to indicate that HIV therapy has no impact on HPV; however, there were a number of problems with their data or lack thereof. Since HIV-VL was not reported, we cannot make a conclusion that HAART has no impact. What we should take home from this poster; however, is to use a CD4 cut off of 350 if not higher, to increase our vigilance.

"Prevalence of Pap Smear Abnormalities HIV+ Women in the STD/AIDS Municipal Center of Porto Alegre, Brazil" (#793) reported that not only was a CD4 < 200 associated with an increased RR of an abnormal Pap, but also there was a higher prevalence of abnormal Pap's in women on ARV than in women not on ARV (25% vs 6%) for a RR = 4.10. We have no other information on the patients taking ARV: what were the CD4's, were the HIV VL’s controlled, were they on HAART, etc. Therefore, I’m not sure there is a take home message from this poster.

Lastly, a group from Palermo presented "Follow-up of Cervical Lesions and Viral Load Levels in HIV Infected Women" (#796). 26 women with SIL were followed over time to track progression of the lesions. The researchers formed a correlation between higher HIV VL and progression. They did not find a relationship between CD4 and progression. P Values were not given; therefore, it is likely that the data is not statistically significant given the small number of subjects. This study would never be done in America and I have some issues with ethics of following a group of women with SIL in lieu of treatment.

Conclusions:

< Pap smears miss half of HPV infections in HIV+ women (although the significance of HR-HPV in the presence of a normal Pap is not clear)

< Higher VL may be associated with HR-HPV and SIL.

< HAART decreases the time to progression of cervical lesions.

< Lower CD4 is associated with HR-HPV and SIL

There were a total of 8 posters on women out of 829, not including the posters that dealt with Maternal - Fetal Transmission. Therefore, although our female patients complain about the lack of research in America directed at women, the landscape is far worse in Europe and South America.

Anal HPV in Male IVDU

It is well documented that HPV infections and anal SIL occur in HIV+ MSM. This small study looked at the prevalence of anal HPV in male IVDU.

117 patients were enrolled (67 MSM, 50 IVDU). The IVDU reported in a self-administered questionnaire that they never experienced receptive anal intercourse with a man. Both groups provided anal samples for cytology, HPV testing, and histology.

HPV DNA was detected in 46% of IVDU (vs 82% in MSM). Anal cytology was abnormal in 36% (18/50) of IVDU vs 72% of the MSM. If you include only those with HPV infection, 78% (18/23) of the IVDU with anal HPV infection had an abnormal histology.

Of the 18 IVDU with abnormal cytology, 9 had high grade SIL and 8 low grade SIL.

Risk factors for the presence of anal SIL included cigarette smoking, HIV VL > 1.7 log, prior AIDS defining illness, CD4 < 250 and Hepatitis Virus. (The definition of "Hepatitis Virus" was not clarified).

Dr. Marcus Conant of San Francisco was able to ask one question that dealt with how to be sure patients tell the truth on self-administered questionnaires. Did those IVDU really have a history of MSM despite denying it? Time was short so we didn't get much of an answer, but Dr. Conant and I were able to discuss it later. The point is that it really doesn’t matter if your patient is withholding information. 46% of patients who are identified as IVDU will have anal HPV infections, and will be at risk for SIL.