Durban World AIDS Conference
July 9-14, Durban, South Africa

REPORT 31

Reported by Mike Norton, PA, Greenwich House, NYC

1. HPV in HIV-Infected Women
2. Effect of HAART on Clinical Outcome of HPV-related Lesions in HIV+ Women
3. Once Daily Regimen: Efavirenz+DDI+3TC
4. Double NNRTI Once Daily Regimen: Efavirenz+ Nevirapine+DDI

HPV in HIV-Infected Women-- In an interesting report from San Francisco, J Palefshky and colleagues looked at anal HPV infection in both HIV positive and HIV negative women at high risk and compared the prevalence between the two groups.  There were 223 HIV positive women and 57 HIV negative women who attended high-risk clinics in SF.  This study found that there was a high rate of anal HPV among both groups.   Among the 57 HIV negative women 24 were found to be positive.  Among the HIV positive 170 or 76% were found to be positive.  The most common subtype of HPV found was 16, which along with subtype 18, 31, 33, and 45 are strongly correlated with high oncogenic potential.  Other results of the study were that the prevalence among the HIV positive women increased as cd4 decreased, and if you had cervical HPV you were more likely to have anal HPV.  There was also a higher risk of HPV in Caucasians among this cohort.  There was no such association found with viral load.  Finally, the authors noted that women have higher rates of anal cancer than men do.  Abstract # TuPeB3161

Commentary:  Rectal PAP smears were not performed as part of this study. Therefore it is difficult to say whether this means a looming increase in anal cancer among this group of women, but it not unreasonable to assume such.  Consider that anal cancer rates have been on the rise.  And in this group, one does expect that if rectal PAP smears were performed that there would be a high rate of ASIL (Anal squamous intraepithelial lesions) which does precede anal Ca.  One confounding fact of this and other studies like it is that while there is a correlation between being cervically positive for HPV and rectally positive for HPV, the subtypes of HPV found at the different locations are often different.  Knowing what to make of this is a bit of a quandary.  Perhaps it points to multiple infections or one infection with multiple subtypes were one becomes predominant in a specific location.  That remains to be answered by future work in this area.  What is becoming increasingly clear is that anal PAP smears should become a regular part of primary care for patients at high risk, even if at this juncture it is an exercise in monitoring patients.  Hopefully in the near future there will be consensus on what procedures are needed and effective at preventing the progression of ASIL to anal cancer.  Until then these ASIL+ patients will be ideal candidates to enroll in studies attempting to answer the questions surrounding rectal HPV.

Effect of HAART on Clinical Outcome of HPV-related Lesions in HIV+ Women--  

Following up on same theme of HPV infection, and in accordance with a report filed from Day 1 of the conference, C. Uberti-Foppa and colleagues from Italy presented a longitudinal study on the effect of highly active antiretroviral therapy on the clinical outcome of HPV-related lesions in HIV positive women.  In this study, 26 women had taken no antiretroviral therapy for HIV, 60 were taking antiretrovirals that are not considered HAART, and 73 women were on HAART.  The mean follow up was approximately 1 year.  During this time period the women not on therapy lost an average of 5 T-cells as a group.  The women on therapy but not HAART gained 14 T-cells as a group.  And the women on HAART gained an average of 88 T-cells.  Still what was found was that the improvement in immune function related to taking antiretrovirals does not influence the evolution of HPV infection and related disease. 

Commentary:  As noted earlier, in a report filed yesterday by a separate group, they also found that regression of cervical HPV lesions did not take place due to HAART therapy.

Once Daily Regimen: Efavirenz+DDI+3TC

Franco Magggiolo and colleagues presented a once a day study.  They enrolled 70 patients.  Median baseline viral load was 122,500 copies/ml.  Mean cd4+ cells were 264.  The regimen was DDI 300mg qd with 3TC 300mg qd and EFV 600mg qd.  There were 12 drop-outs, 2 due to rash, 1 due to DDI intolerance, 1 for CNS symptoms, 3 for non-adherence, and 3 due to virological failure and resistance.  Using the more stringent intent to treat analysis, approximately 60% were <50 copies after 48 weeks, which compares favorably with bid and tid HAART studies.  There was a median decline of HIV RNA of 3.39 log over the 48 weeks.  There was a 254 cell increase seen in cd4ís.  The authors concluded that the once a day therapy was readily accepted by the patients.  The therapy was well tolerated.  CNS observations were observed in approximately of all patients but that they were usually mild, self-limited and did not cause interruption of treatment.  Commentary:  Unfortunately the authors were not available to answer questions regarding this paper.  DDI was a lower dose than has been approved, but appears to have been effective.  Also DDI is typically dosed alone and on an empty stomach with nothing added to the stomach for 30 minutes in order to achieve DDI absorption.  We cannot ascertain if this was done or if all meds were taken at the same time.

Double NNRTI Once Daily Regimen: Efavirenz+ Nevirapine+DDI

A second once a day regimen was presented by WC Jordon and colleagues at the King-Drew Medical Center in Los Angeles.  It combined NVP 400mg qd with EFV 600mg qd, with DDI 400mg qd.  26 patients enrolled.  15 were treatment naÔve at entry.  11 were treatment-experienced who wanted to simplify their existing regimen.  On entry the mean viral load was 4.59 log or 38,603  copies/ml among the treatment naÔve group and was 3.31 log or 2,025 copies/ml among the treatment experienced group.  It should be noted that 9 out of the 11 treatment experienced group were <400 copies/ml upon entry.  CD4+ cells in the naÔve group were a median of 312 at entry and 310 in the treatment experienced group.  5 out of the 26 patients dropped out over the course of the study.  3 who were treatment naÔve.  Reasons for discontinuations were: 2 cases of intractable insomnia, 2 rash, and 1 for CNS toxicity.  Of the remaining 12 patients in the treatment naÔve group 11 out of 12 were <400 copies/ml at 12 months.  1 took a drug holiday.  Of the remaining 9 who were treatment experienced 8 were <400 copies/ml with one in this group also taking a drug holiday.  There were no virologic failures in either group.  In both groups cd4+ cells increased.  The naÔve group saw a 438 cell increase after 1 year and the treatment experienced group saw a 367 cell increase.  Abstract #TuPeB3207 

Commentary:  Once again the authors have not given us any information about the important question: Was DDI taken with the other two meds simultaneously?  Or, was there a delay after taking DDI before taking NVP & EFV?  Or, were the NVP & EFV taken at different times of the day?  This is yet another small study showing synergy and durability among patients using dual NNRTIís.  One could think of reasons why this combination is beneficial.  If a person starts with a combination such as this, one would be starting with a reasonably easy regimen, especially if all meds could be taken together, and one could then, if virologic failure arises move onto 2 nucs and a PI.  If that first PI was NFV one could conceivably salvage a future NFV failure with dual PI therapy.  And this scenario doesnít even address ABT-378rís place.  On the contrary, we need larger studies to address the durability of such a regimen in larger numbers because the genetic barrier to two of the drugs in this regimen is 1 mutation away, K103N.

Note: At the Retrovirus Conference in Feb. 2000, the DONUT Study reported on interaction they found between NVP & EFV (excerpted from Retrovirus Summaries on NATAP web site: Authors concluded NVP PK are not affected by the coadministration of EFV. The exposure to EFV, however, is significantly decreased by approximately 22% (measured as AUC), and 36% (measured as C-min) when combined with NVP. It may be appropriate to increase the dose of EFV to 800 mg qd. Possibly, increasing EFV to 900 mg may be more appropriate. What about individuals whose AUC or Cmin is affected differently than the median PK effects seen above?

Veldkamp, Hoetelmans, Lange and others reported on this study which was conducted to investigate the PK of NVP and EFV when administered in combination. HIV-1-infected individuals who already used EFV (600 mg qd) for at least two weeks were included. The PK of EFV were determined during 24 hours at baseline. Subsequently, NVP was added to the regimen: the first 2 weeks at 200 mg qd, followed by 400 mg qd. The PK of EFV and NVP were assessed on day 29.