8th Annual Retrovirus Conference
Highlights from the 8th Annual Retrovirus Conference
(simpler easier-to-read version)
Written for NATAP by Kathleen Squires, MD, Medical Director of the University of Southern California HIV Clinic, Los Angeles, CA; edited by Jules Levin, NATAP
There are many unanswered questions regarding HIV and its course (pathogenesis) of development in women. Increasingly studies are suggesting that there are differences in pathogenesis between men & women. New studies presented at Retrovirus have findings that continue to suggest this. So, more studies in women are needed to answer these questions.
One of the biggest questions is --do women respond to HIV therapy (HAART) differently than men regarding safety, side effects and antiviral effect. Several studies have found that early in disease stage women have lower viral loads than men, but after 5 years, the viral loads are the same. And the longer-term disease progression appears to be the same for men & women. But, does this affect when to begin therapy for women? Should women begin therapy at a different point (depending on CD4 & viral load) than men? We don't have an answer to this question, but the current Federal Treatment Guidelines recommend women & men should use the same guidelines for when to begin therapy.
The ACTG (AIDS Clinical Trials Group) is considering proposals to try to answer many of these questions, which are crucial for women. Dr. Squires is a leader in the effort in the ACTG to design studies to answer these questions.
Why do some women get HIV following unprotected sex and others do not?
If the man has a high viral load, this may increase risk of transmitting HIV to the woman. If either the man or woman has or has previously had a STD, this increases the risk of transmission. If the woman is able to produce a certain type of immune response that is capable of fighting HIV, this immune response can help prevent HIV infection. This response is called an HIV-specific CD4/CD8 response. This is an ability for the immune system to produce special CD8 cells called CTLs (cytotoxic lymphocyte cells) which may be capable of fighting HIV & protecting against it. If the CTL response is strong this may offer a better capacity to fight infection, while if the response is weaker it may not be able to prevent infection.
Topical Creams To Prevent HIV Infection
Two products are in early stages of research and were discussed at the Retrovirus Conference. PRO 2000 is a gel that was used in monkeys in a study and was found to prevent HIV -infection to most of the monkeys after the monkeys were exposed to a monkey form of HIV called SHIV. B-cyclodextrin is a compound (drug) that was studied in the test tube and in mice. It was found to be safe in mice and inhibited vaginal transmission of HIV in the mice. The hope is that one day we can have a cream that a woman can use during sex to prevent infection with HIV. This would allow the woman to have more control of the situation since some men don't want to use contraceptives.
Drug Use and HIV Disease Progression
In the Women's and Infant Transmission Study (WITS), women were asked if they used illegal drugs. Women who used hard drugs (heroin, methadone, cocaine, IVDU) did not have lower CD4s or higher viral loads than woman who did not use hard drugs. This suggests that women who used hard drugs (IV coke/heroin) did not suffer accelerated HIV disease progression compared to women who did not use hard drugs.
Postmenopausal CD4 Counts
Women who were postmenopausal had lower CD4 counts than women who were pre-menopausal, in a study presented at the Retrovirus Conference. This difference seen, if reproducible in other studies, may reflect changes in reproductive hormones and could reflect why cd4 differences have been seen between men & women. However, in a separate study reported on at Retrovirus CD4 cell counts in HIV-infected & uninfected female newborn babies were higher than CD4 counts in male infected & uninfected newborn babies, suggesting a non-hormonal mechanism. It's possible the cause for the differences in cd4 counts may be different for newborns than for adult women.
CD4 Count in Pregnant Women
In a study, pregnant women were found to have lower CD4 counts than non-pregnant women, but in other studies lower CD4 counts during pregnancy return to their original level after delivery.
Women Will Enroll & Stay in Studies: Women's First Study
The Women's First study was designed to enroll women only in a study of nelfinavir/saquinavir + d4T/3TC comparing a twice or three times per day regimen. Enrollment was successful because the study was designed to answer questions of concern to women & because special unique efforts were made improve enrollment by meeting the needs of women. The study looked at the viral suppression achieved by HAART in blood and in the genital tract. Dr Cu-Uvin demonstrated that 1) suppression of viral load by HAART in blood & in the genital tract was better in ART-naive than NRTI-experienced patients, 2) there was concordance (agreement) between plasma and genital tract viral loads in patients with undetectable viral load and 3) HIV RNA was detected more frequently in the plasma than genital tract of patients failing ART. A separate study has found that drug resistant mutations are different in the blood than in the cervico-vaginal secretions.
Complications in Women
In a study conducted in South Africa, 10% of the patients receiving nevirapine experienced grade 4 elevations in liver enzymes. The incidence of grade 4 elevations in women was twice that of men. Two women died of liver complications. Study participants all received d4T, either FTC or 3TC, and either nevirapine or efavirenz. The reported that no one receiving efavirenz had grade 3 or 4 liver enzyme elevations. In a study in the USA, women were reported to have a higher incidence of rash from nevirapine, but this was not accompanied by hepatotoxicity (grade 3/4 elevated liver enzymes). So, researchers are scratching their heads in trying to figure out why the South African women experienced the hepatotoxicity. Several possible ideas have been offered. Diet, water and overall nutrition are different in South Africa than in the US. It's possible that the South African women were drinking some sort of juice or other formulation of liquids or juices. The juices may interact with HIV medications or cause some unhealthy situation. It's also been suggested that different genetics between South African women & US women may play a role. Another possible reason is that women in the USA study may have been instructed to stop nevirapine within the first month, because they were monitored by bloodwork and were able to detect the elevated liver enzymes very quickly. And in the African study it's possible this was not done. It's also been proposed that a rash on black skin may not be as noticeable, and so if the African women had a rash this might not be noticed. Surely, this will receive follow-up attention. So, if a person has been on nevirapine for 2 years and has hepatitis C but their liver enzyme counts are low, should they remain on nevirapine? Speak to your doctor, as we don't have an answer to this question.
A study found that using hydroxyurea in combination with ddI, or ddi+d4T led to a higher incidence of pancreatitis than without hydroxyurea. And it was found that women had more risk than men did in developing pancreatitis if they were using hydroxyurea with these combinations.
An ACTG study found that nandrolone deconoate increased weight and lean body mass in HIV-infected women with weight loss, but side effects were seen. Although the side effects were rarely seen, they were hoarseness in the voice, excessive facial & body hair) and clitoral enlargement.
HAART Improves Cervical Intraepithelial Neoplasia (CIN); biopsy
In a study reported at Retrovirus, women with biopsy-proven CIN reverted back to normal or improved by using HAART. The study also found a higher than previously seen rate of CIN in HIV-infected women. Studies are trying to better understand how much HAART can improve CIN. Results from the WIHS study suggests that biopsy should be routinely considered for women with abnormal cervical smears.
Transmission of HIV from pregnant woman to newborn is low when antiretroviral therapy is used. When looking at 7 studies and 1200 mothers, if viral load was <1000 copies/ml at or near delivery, the transmission rate was 1% for women receiving therapy and 10% for women not receiving treatment. Depending on a woman's viral load, HAART is more likely to reduce viral load to below 1000 copies/ml than AZT alone. But a woman should speak with her doctor about the various treatment options and what is appropriate for her situation. The use of caesarian section has increased: in the United States, the proportion of deliveries by caesarian section increased from 19% in 1994 to 44% in 2000 with the greatest increase in 1999. It has been found in studies conducted in Africa that when a single dose of nevirapine was used to prevent mother-to-child HIV transmission, the woman & the child could develop nevirapine resistance. However, in the USA single-dose or short-term nevirapine use for preventing mother-to-child transmission is not standard.