Important note: Information in this article was accurate in April 1999. The state of the art may have changed since the publication date.
Women and Viral Load
Last November a critical study by researchers at the Johns Hopkins School of Public Health was published in the Lancet. Findings of the study, which was first presented at the 12th World AIDS Conference in Geneva in 1998, suggest that HIV viral load tests may be causing infection levels in women to be underrated.
Researchers examined 650 men and women with HIV and a history of injection drug use. They found that viral loads in women were lower than those in men at the same stage(s) of HIV disease: women therefore had a 60% (1.6 times) greater chance of developing AIDS than men with the same viral load levels. This study prompted researchers as well as clinicians and patients to ask if viral load testing (at least according to current guidelines, established largely from studies in gay white men) is reliable for guiding treatment decisions in women. Perhaps viral load data gathered in men cannot be directly applied to women.
U.S. Public Health Service recommendations suggest that women and men with HIV viral loads of 10,000 copies/mL of blood or higher receive anti-HIV treatment. However, the Johns Hopkins report indicated that a viral load level of 5,000 copies/mL in women may be equivalent to 10,000 copies/mL in men.
At the time, Kathryn Anastos, MD, of the Catholic Medical Centers in Queens, New York, commented that "the study raises the question of whether we should consider gender in establishing treatment guidelines. But it doesn't answer the question." Below is a report by Anastos on the results of another study on gender and viral load.
Women Are Not Receiving Timely HIV Treatment
At the 6th Conference on Retroviruses and Opportunistic Infections (CROI) in Chicago, conducted January 31 through February 4, 1999, Anastos reported results of a study that analyzed viral load levels in nearly 1,300 women and 1,600 men with HIV. This study confirmed the results reported in the November 1998 issue of the Lancet that suggested that women's viral load levels were 20% lower than men's at comparable HIV disease stages.
Anastos stated that HIV positive women in the U.S. are not receiving treatment early enough. "Official treatment guidelines, which are based on the course of the disease in men, are causing women to begin treatment later than they should," she said. "The treatment guidelines need to be adjusted to lower the treatment threshold by 20%." Reducing treatment guideline levels by 20% for women would increase the number of women needing treatment from two to five percent.
Diabetes in Women Taking Protease Inhibitors
Investigators with the Women's Interagency HIV Study (WIHS), an ongoing multicenter study of the natural history of HIV infection in women, evaluated the rate of diabetes mellitus (DM) in their cohort of HIV positive women. J. Justman reported findings at the 6th CROI.
Of nearly 2,000 HIV positive and 500 HIV negative women, there was a prevalence rate of 4% at entry. Those women with pre-existing DM were excluded from consideration. Among the others, none reported pregnancy, or use of pentamidine or prednisone, any of which can increase blood sugar levels. Median age was 36 years and a majority were African-American (approximately 53%). Slightly more than a quarter were Latina or Asian/Pacific Islander, and slightly less than one-fifth were Caucasian.
The women were further divided into groups for comparison. There were 426 HIV negative (confirmed HIV negative during the entire follow-up period) and 1,615 HIV positive women eligible for analysis. HIV positive women received either 1) no antiretroviral therapy, 2) therapy with reverse transcriptase inhibitors, or 3) therapy with one or two protease inhibitors. In addition, some of the women who took protease inhibitors also took reverse transcriptase inhibitors.
Women were followed at regular intervals for four years. Among the 2,041 women followed, 71 new cases of diabetes mellitus were reported, as follows: HIV positive women taking protease inhibitors (22 of 629), HIV positive women taking reverse transcriptase inhibitors only (17 of 1,035), HIV positive women receiving no antiretroviral therapy (18 of 1,055), and HIV negative women (14 of 426). The incidence was highest in those taking protease inhibitors, which was statistically significant and associated with a two-three times greater increase in risk of diabetes, compared with HIV negative women.
In the cohort overall, diabetes was considered rare. Independent risk factors for the development of diabetes were found to be protease inhibitor use, age, and baseline weight--weight among DM cases was consistently higher. However, there was a lack of association between protease inhibitor use and weight gain.
Gender Differences in Nevirapine Rash
Another presentation at the 6th CROI on gender differences, by S.J. Bersoff-Matcha and colleagues, reflected a gender bias in nevirapine rash. In response to nevirapine use, ten percent of 358 study participants (72 women and 286 men) developed rash as a side effect. Women were significantly more likely than men to develop rash in response to nevirapine (12% vs. 8%, respectively). Severe rash developed in nine women and three men, giving women a significantly greater--8.3 times--risk of developing severe rash than men.
HIV Prevalence Remains Stable in U.S. Women through 1994
The prevalence of HIV in U.S. women of childbearing age, about 1.6 cases per 1,000 women, remained stable between 1989 and 1994, say researchers from the CDC. While the HIV infection rate declined in the Northeast through the early 1990s, despite the region's typically high prevalence rate of HIV, the southern U.S. saw a marked increase in the rate of HIV infection through 1991. Rates in the South leveled off except in black southern women, who continued to experience a rising rate of HIV. Rates remained low for women in the West and Midwest.
The researchers say that, overall, "the number of HIV positive women who have not yet developed AIDS 'changed relatively little' for the time period studied," due to treatment advances. Lead researcher Susan Davis, MD, notes that "new infections among women of reproductive age are occurring at a rate that offsets losses from this population as a result of aging, disease progression and death."
Women's Responses to Nelfinavir
Preliminary results of Women First, a multicenter, two-year study of women with HIV, discussed at the 6th CROI, included a report on the utility of the protease inhibitor nelfinavir (Viracept) in women. In summary: at the end of one year on therapy, 91% of women who took 1,250 mg of nelfinavir twice daily and 73% of women who took 750 mg of nelfinavir three times daily had undetectable HIV viral levels.
Study to Address Effects of Antiretroviral Therapy on Women
Although women comprise 45% of new HIV infections, they account for only 9% to 20% of clinical research participants. To address this imbalance, Hoffmann-La Roche is conducting what they call "the first investigational study ever" to evaluate potential differences in response to antiretroviral drug therapy according to gender. The study will enroll 60 women and 20 men, all HIV positive, and compare their responses to the protease inhibitor saquinavir (Fortovase) in combination with two nucleoside reverse transcriptase inhibitors.
To determine if gender differences in treatment responses exist, researchers will look at immunologic measures including CD4 cell counts and viral suppression in vaginal secretions and blood. Investigators want to determine whether decreases in viral load in the blood are accompanied by similar decreases in genital tissues, or whether the vagina functions as "an HIV reservoir, hiding the virus from treatment."
To address the concerns of many women and their doctors about contraception, the trial will also evaluate the efficacy of both oral contraceptives and saquinavir when used simultaneously. For more information, call 1-800-TRIALS-A.
HAART and HPV Infection
A study by L. Andieh and others presented at the 6th CROI evaluated the influence of highly active antiretroviral therapy (HAART) on infection with the human papillomavirus (HPV), which causes warts including genital warts and is associated with the development of genital cancers. In the beginning of the study, 82% of 141 HIV positive women enrolled were taking HAART. Unfortunately, this study had a high attrition (dropout) rate, with few women going to all five scheduled clinic visits and exams. Therefore, general findings only are discussed, without specific conclusions.
Overall, 47% of women had an abnormal Pap smear at any visit, with 45% found at the first visit. Over two-thirds had detectable HPV DNA, and related tissue changes ranged from 23% with mild cell changes (atypical squamous cells of undetermined significance) to 17% with low-grade cervical dysplasia to 3.5% with high-grade dysplasia (cervical cancer). Yet half of women with normal Pap smears had detectable HPV DNA; nearly one-third with HPV had more than one type.
Over the course of the study, which lasted from March 1996 to January 1999, women tended to intensify their antiretroviral regimens, which led to elevated CD4 cell counts and decreased HIV viral load. Since HPV is detected more frequently at lower CD4 cell counts and with greater immune suppression, researchers hypothesize that increased use of HAART could effect decreased HPV infection and its cancerous consequences.
HPV and Neoplasia: Notes from CROI
Other reports at CROI confirmed earlier studies that show that women with HIV are more likely to have recurrent HPV infections and neoplasia (precancerous or cancerous tissue changes) than their HIV negative counterparts, and that women with advanced HIV are at elevated risk, compared to their healthier HIV positive counterparts.
One study looked at the occurrence of vaginal lesions and infections in women with HIV. Approximately 350 HIV positive and 350 HIV negative women all received regular exams that included a thorough pelvic exam and PCR tests for HPV infection. Women received colposcopy (examination of the cervix with a microscope) and other tests as needed. HIV positive women were far more likely than HIV negative women to have lesions (8% vs. 1%).
In addition, HIV positive women were more likely to have developed neoplasia (5 vs. 0 women). Women with fewer than 500 CD4 cells/mm³ and HPV at the beginning of the study were most likely to develop related lesions.
Vitamin A and HPV
Another study examined the relationship between immune suppression, vitamin A deficiency, and HPV-related cervical lesions. This study enrolled nearly 1,000 women who were either HIV positive or considered "at risk" for HIV infection; Pap smears were performed and CD4 cells and plasma retinol (a form of vitamin A) were measured. (Women in this study were all part of the larger WIHS cohort.)
Overall, 17% of the women had either low- or high-grade squamous intraepithelial lesions (SIL) and 15% were vitamin A-deficient. Women with fewer than 200 CD4 cells/mm³ showed a trend toward vitamin A deficiency. Injection drug use and an annual income of less than $12,000 were significantly associated with vitamin A deficiency.
The prevalence of SIL was highest in women with very decreased retinol levels, and lowest in women with higher levels. Previous studies in animals have associated low retinol levels with the development of precancerous lesions. While not determined in the study, the results suggest that vitamin A supplements in HIV positive women may decrease the rate of precancerous changes in the cervix.
5-FU for Maintenance Therapy of Cervical Lesions
In terms of treatment, another study, by M. Maiman, on cervical lesions (biopsy-proven CIN II or III) in HIV positive women compared maintenance treatment with intravaginal 5-fluorouracil (5-FU) to observation (i.e., no treatment). There were approximately 50 women in each arm of the study. Those who were randomized to receive 5-FU used 1 gram of 5% cream every two weeks for six months.
No high-grade (3 or 4) toxicities were reported and there were no systemic side effects. Local side effects were similar for both study arms. However, 28% of those in the 5-FU treatment arm had recurrent dysplasia, compared to 47% of those in the observation arm. Recurrence was also associated with having fewer than 200 CD4 cells/mm³.
Cervical Cancer
Joel Palefsky, MD, of the University of California at San Francisco, published new findings on cervical cancer in HIV positive women in the Journal of the National Cancer Institute. The study screened nearly 1,200 HIV positive women and 500 HIV negative women who engaged in behaviors that put them at high risk for contracting sexually transmitted diseases (STDs), and analyzed risk for HPV, a major cause of cervical cancer.
Women with the greatest amount of immune system damage were most likely to have HPV. Women with HIV therefore were found to be at greater risk for HPV infection than their HIV negative counterparts. Other groups at elevated risk were African-American women, young women, and women who smoke, relative to white women, women over 40, and nonsmokers, respectively.
According to Palefsky, the impact of HIV on the women's immune systems "means they are on average twice as likely to have HPV." HIV positive women who smoke have a 50% greater risk for HPV than HIV positive women who do not smoke.
In HIV positive women, most cases of HPV infection were considered to be the reactivation of old, rather than new, infections. Immune system damage permits such reactivation. Palefsky comments that "[cervical cancer] may take many years to develop, [but] women who also have HPV infections unfortunately may face a greater likelihood than before of developing this cancer if they do not regularly undergo the currently recommended screening procedures such as Pap smears."
CDC Study Validates Heterosexual Transmission of HIV
Results of a Centers for Disease Control and Prevention (CDC) study published in the January 1999 issue of the American Journal of Epidemiology by J. Feinberg and others conclude that a majority of people with HIV who report a heterosexual risk or no risk most likely acquired HIV through heterosexual contact. Heterosexual risk was validated in 82% of almost 2,000 people 13 years of age or older with such initial risk responses. Among those in the study who at first reported no risk factors for HIV, approximately 20% of the men and over one-half of the women were later determined to have most likely contracted HIV heterosexually.
In many parts of the world, HIV/AIDS is a heterosexual epidemic. The study supports suspicions that a heterosexual HIV/AIDS epidemic is on the rise in the U.S. Heterosexual contact with intravenous drug users, transfusion recipients, hemophiliacs, or bisexual males were cited as factors "particularly relevant among HIV-infected white women." Investigators suggest that heath-care workers redouble efforts to identify risk factors and behaviors among persons in their care.
Elsewhere, previous studies have shown that women are at vastly increased risk for acquiring HIV through vaginal intercourse with male partners than vice versa. At the 6th CROI, Judith Feinberg reported one of the first known cases of heterosexual transmission of non-nucleoside reverse transcriptase inhibitor (NNRTI)-resistant HIV. A 19-year-old woman was infected by her male partner one month after giving birth. This partner was known to have been poorly adherent to an antiretroviral regimen consisting of AZT, ddI, and delavirdine (Rescriptor); poor adherence is well known to contribute to the development of resistance.
Resistance testing of both revealed the K130N mutation that confers NNRTI cross-resistance, and further tests confirmed that both the man and newly infected woman had HIV strains that were resistant to both delavirdine and nevirapine. The woman is reported now to be responding to treatment with combination indinavir, d4T, and 3TC.
The Menstrual Cycle and Viral Load
A new report presented by R. Reichelderfer as a poster at CROI indicates that different stages of the menstrual cycle are associated with fluctuations in the amount of HIV present in genital fluids. The analysis involved 33 women, all of whom had fewer than 350 CD4 cells/mm3, and all of whom were enrolled in either WIHS or the HIV Epidemiology Research Study (HERS). The women were followed for two full menstrual cycles, during which samples of cervical fluid were taken and analyzed by three different methods to evaluate the presence of HIV RNA.
The overall conclusion was that the amount of HIV viral load in cervical fluid, i.e., viral shedding, was variable over the course of the menstrual cycle. HIV RNA levels in cervical fluid were greatest during active menstruation, then fell to the lowest levels immediately thereafter, in the follicular phase (one week afterward). After that, levels began to rise, until peaking, again, with menses. Cell-free virus was highest "mid-cycle," or during the luteal phase two to three weeks after menses as well as again at menses. At those times, HIV RNA levels were higher than blood plasma viral load.
Menses and Duration of Cycles
Another study of HIV and menstruation reported by S. D. Harlow at CROI evaluated the nature and duration of cycles in women with HIV. Although anecdotal reports of alterations in the menstrual cycle are abundant, the CROI report concurs with the findings of many other scientific studies that HIV has little if any influence on these changes. In more than 800 HIV positive women, no significant effect of HIV was found on the duration of cycles except in women with advanced HIV.
Women with fewer than 200 CD4 cells/mm³ appeared to have slightly longer cycles (defined as greater than 40 days). The same researchers noted that the factors of age, ethnicity, and body mass index play bigger roles than HIV in terms of influencing the duration and nature of menstrual cycles.
Syphilis
Another study presented by A. M. Rompalo at CROI evaluated syphilis in women with HIV by comparing rates in HIV positive and HIV negative women. The HIV Epidemiology Study (HERS) screened for syphilis using the rapid plasma reagin test (RPR) in approximately 850 HIV positive and 435 HIV negative women in the U.S. Every six months, all women received detailed physical exams and laboratory tests including HIV viral load and CD4 cell count.
Overall syphilis prevalence was low. Over a two-year period, 4,000 syphilis tests were given, with the following results: 91% negative, 7% positive, and 2% false positive (determined by a confirmatory test). The proportions of test results were the same in both groups, HIV positive and HIV negative. Having high titers on a positive syphilis test result was not correlated with CD4 count in HIV positive women, nor was HIV found to influence the likelihood of a false-positive test result.
Women Answer Questions about STDs and Microbicides
Researchers have been urging the rapid development of female-controlled methods to prevent acquisition of HIV and others STDs as a necessary tool for stopping the spread of HIV among women and children. Now a survey of 1,000 U.S. women aged 18 to 40 that assessed attitudes about STDs, published in the February 1999 Family Planning Perspectives, reports that the women who would use them are equally enthusiastic about the concept.
According to the survey, 30% of women reported that they worry about STDs but only about 10% reported condom use. Women indicated that the fact that male partners tend to control condom use was a significant factor. Most, particularly single women, were very interested in a microbicide that could be used intravaginally to prevent STDs. Other qualities they would like to see in such a product would be widespread access, i.e., in a drugstore, and low cost.
U.S. health officials estimate that 15.3 million new cases of STDs occur each year.
Intravaginal Microbicidal Gel to be Tested
The National Institutes of Health (NIH) will begin late-stage laboratory tests of an experimental microbicide described as a "slimy green gel." The gel, called Geda, is designed to be inserted by plunger in the vagina, up to four hours before intercourse. Key ingredients are octoxynol-9, which is used to help coat the vaginal lining, and benzalkonium chloride, which inactivates bacteria and viruses including HIV.
Preliminary tests indicate that Geda kills HIV, E. coli, and hepatitis B virus. After "use," the gel can be removed by douching. (Elsewhere, douching has been shown to cause irritation of the vaginal tissue that is associated with the possiblity of increased risk for acquiring HIV and other STDs.) Another product using the same active ingredients, PrevenTx, is already being sold as a hand wash, and the manufacturer, Empyrean Bioscience of Phoenix, Arizona, is developing disinfectant and mouthwash versions.
Candidate Microbicide Highly Promising in Test-Tube Studies
An article published by M. Howatt and others in the February issue of Antimicrobial Agents and Chemotherapy suggests that a compound commonly found in shampoo and toothpaste, sodium dodecyl sulfate (SDS), may be useful as a microbicide. Researchers at Pennsylvania State University who studied the compound in the laboratory report that it has powerful antiviral potential against HIV, herpes simplex virus, and HPV, the cause of cervical cancer. It is the first experimental microbicide identified to combat HPV thus far. SDS also is effective against other STDs including chlamydia. SDS is considered safe and inexpensive.
In studies in mice, SDS inactivated HPV in infected cells while allowing the cells to continue to grow normally. Currently, researchers are working to formulate SDS in a microbicidal form that can be used in humans. Clinical trials are likely to begin in six to twelve months.
New Microbicide Enters Clinical Testing
The University of Pennsylvania Medical School has begun enrolling participants in a phase I clinical trial of Savvy, a new microbicide manufactured by Biosyn, Inc. Savvy, or glyminox gel, is a vaginal gel that will be tested for its ability to prevent pregnancy and the transmission of STDs, including HIV. This study will gather safety and contraceptive efficacy data for Savvy and compare it to the data on nonoxynol-9. For information on the Savvy trial, call 215-387-5338.
Development of an effective vaginal microbicide to prevent HIV transmission was proposed years ago, but thus far the endeavor has proved to be a formidable challenge. The ideal microbicide could be used by a woman without the express consent or knowledge of a male sexual partner.
Promising Findings from the PETRA Study of Perinatal Transmission
Preliminary results of the UNAIDS-sponsored PErinatal TRAnsmission (PETRA) trial prompted researchers at the 6th CROI to pronounce the prophylactic regimen studied "the shortest effective regimen ever." An evaluation of nearly 2,000 women and their infants, the PETRA trial is the largest yet to evaluate a prophylactic regimen. The study is being conducted in South Africa, Uganda, and Tanzania, and specifically seeks a short-course regimen that would be of value for resource-poor developing countries.
Researchers evaluated three combinations, or regimens, of AZT and 3TC in 1,792 participants. Women were randomized to receive AZT/3TC or placebo. Mothers and babies were evaluated at six weeks postpartum. Data are still being collected and evaluated, since breast-feeding is a significant route of HIV transmission and perinatal transmission is not ruled out until 18 months of age.
Women who received AZT/3TC took it either intrapartum only (during labor and delivery) or beginning in the 36th week of pregnancy, during labor and delivery, and one week postpartum. Infants received AZT/3TC during the first week of life only.
Results indicate that the postpartum phase of the regimen is crucial. There was no reduction in perinatal HIV transmission for women who received the regimen intrapartum only. The women in the third, or longest arm, experienced a 50% decrease in perinatal HIV transmission. Results also indicated a significant reduction in perinatal transmission with only one or two doses of AZT/3TC for the mother during labor and one week of AZT/3TC for the newborn.
Awa Col-Seck, Director of Policy, Strategy, and Research for UNAIDS, has said that it is "vital to develop a range of prevention options so that countries can cater to women living in different real-life situations."
HIV Negative Children Exposed to AZT in the Womb Doing Well
A study for the NIH published by M. Culnane and others in the January 13, 1999 issue of the Journal of the American Medical Association (JAMA) reports that HIV negative children born to women who took prophylactic AZT during pregnancy appear thus far to have suffered no adverse effects. The study, called Pediatric AIDS Clinical Trials Group (PACTG) 219, enrolled more than 2,000 children who have been involved in HIV-related scientific studies. Their ages range from 3.2 to 5.6 years.
While National Institute of Allergy and Infectious Diseases (NIAID) Director Anthony S. Fauci, MD, cautioned that the children would continue to need to be followed closely in the future, he called the findings "reassuring [since] the current recommendation is to treat HIV-infected pregnant women with regimens that include AZT to prevent perinatal HIV transmission." Investigators plan to follow the children until they are 21.
Of the 2,000-plus children in PACTG 219, 234 HIV negative children were born to women who participated in the landmark study ACTG 076. That study found that women who took a regimen of AZT after the fourteenth week of pregnancy and labor could reduce the chances of transmitting HIV to their babies by two-thirds. Infants also took AZT for six weeks after birth.
Of these 234, 122 had mothers who took AZT in utero; the other 112 received placebo. The researchers compared the health status of these children, whose median age was now 4.2 years. Specifically, researchers looked at various measures including developmental milestones, physical growth, cognitive development, immunologic status, and malignancies.
No children have developed cancers or died. Children exposed to AZT were no different from children not exposed in terms of physical or cognitive growth. Researchers conclude that AZT exposure in the womb causes no adverse effects in children at least up to preschool age. They also said that birth registry data from the Antiretroviral Pregnancy Registry found no increased risk of congenital birth defects among infants exposed in utero to AZT.
Children are frequently lost to follow-up for various reasons, including adoption or placement in foster care. Plans are underway for a more comprehensive registry that would track infants exposed to multiple antiretroviral drugs taken by the mother when in the womb. These systems will be more important as aggressive antiretroviral treatment becomes increasingly common among HIV-infected pregnant women.
Ritonavir for Preventing Perinatal HIV Transmission
At the 6th CROI, S. Limpongsanurak presented results of a Thai study using short-term ritonavir to interrupt perinatal HIV transmission. Investigators evaluated the safety, tolerability, and efficacy of ritonavir in a phase IV open-label study that involved 86 pregnant women. Women began taking ritonavir approximately two weeks before their due dates at the dose of 300 mg twice daily. Over the course of the next two weeks, the dose was gradually titrated upward to 600 mg twice daily until delivery. Breast-feeding was not permitted; infants were PCR-tested for HIV at birth and one and six weeks after birth.
Twelve women had to quit taking ritonavir because of elevated liver enzymes (10), excessive side effects including vomiting (1), and difficulty taking the capsules (1). So far, data have been analyzed for 74 mothers and their children. The mean time on ritonavir for mothers was 18.6 days. The median maternal HIV viral load at delivery was 2.8 logs, compared to 4.3 logs before ritonavir treatment. The rate of perinatal HIV transmission was 9.46%, compared to approximately 25% without treatment in the U.S. (Rates in developing nations including Thailand are generally found to be higher than U.S. or European rates.)
Researchers credit the ritonavir regimen with reducing maternal viral load and the rate of perinatal HIV transmission.
Maternal AZT Use Influences Gestational Age and Weight
Data gathered in the European Collaborative Study and reported by the CDC suggest that babies born to women who used AZT during pregnancy may be more likely to be carried to term and to be of normal birthweight. Researchers are following more than 2,300 women and their infants living in seven European countries. Among women and children who followed an antenatal (before birth) AZT regimen, the risk of premature birth was found to be decreased by one-fourth. The risk of low birthweight was reduced by one-half. This finding was an association and did not study or prove cause and effect.
Pregnant Women on HAART Report Adverse Events
A Swiss study reported in the December 1998 issue of AIDS indicates that women who take combination therapy during pregnancy are likely to experience some adverse effects. The study evaluated 37 women and 30 infants who received combination therapy. Of the women, 15 experienced anemia, four reported nausea and vomiting, and four had elevations of the liver enzyme transaminase. Other adverse events in the mothers included glucose intolerance, nephrolithiasis (kidney stones), and diarrhea.
As for the infants, ten were premature, eight had anemia, and two showed cutaneous angioma (blood vessel abnormality). Two infants had cryptorchidism (undescended testicles) and one had transient hepatitis (liver inflammation).
HAART Appears to Prevent Mother-to-Child HIV Transmission
Researchers at the Bronx-Lebanon Hospital Center in New York evaluated the safety and efficacy of combination antiretroviral therapy in 30 pregnant women. The study was presented at the 36th annual meeting of the Infectious Disease Society of America (IDSA) held in Denver, Colorado, in 1998.
Over one-third (39%) of the women had an AIDS diagnosis. About 50% of the women were initially on combination therapy (consisting of various combinations of nucleoside reverse transcriptase inhibitors with or without a non-nucleoside reverse transcriptase inhibitor, and/or a protease inhibitor). If a woman was not on therapy when she discovered she was pregnant, it was avoided in the first trimester; those already on therapy stayed on therapy. Viral load was suppressed to below detectable levels during pregnancy in 24 (80%) of the women. At the time of delivery, about one-third still had undetectable viral loads.
Of 27 infants available for follow-up, none became infected with HIV. Two babies were born prematurely and five were low birthweight (less than 2,500 grams), but all were reported to be doing well. One baby was born with an abnormally small head (microencephaly) but his mother also had multiple substance abuse problems. Another infant was stillborn.
The oldest baby is now about 1.5 years old. Most continue to be followed in the clinic.
Glaxo Wellcome Will Provide AZT/3TC to Pregnant Women
In an effort to address the needs of pregnant women in impoverished regions, Glaxo Wellcome has pledged to provide AZT free-of-charge to 23,000 pregnant women through their Prevention of Mother-to-Child Transmission (MCTC) pilot project. A presentation at the 6th CROI described the efficacy of a short course of AZT and lamivudine (3TC) (both manufactured by Glaxo) beginning at labor onset and for the child during the first week of life to help prevent perinatal transmission.
While the short-course method is less expensive than the standard 076 regimen, its cost is still too high for many who would benefit from the treatment. Glaxo spokespersons have said that the company is committed to continued assistance, through providing the drugs at a 75% cost reduction at the end of the project. They also have said that they will extend the price reductions to the AZT/3TC regimen. Under the MCTC program, one course of the drugs will cost $50 U.S.
An editorial in the February 13, 1999 issue of the Lancet praised both the new, less expensive method for reducing perinatal HIV transmission and the efforts of Glaxo Wellcome to ensure that the cost of the drug does not prevent access to it by many of those in need. "Glaxo Wellcome has set a quiet example of good corporate citizenship. In so doing, it has issued a challenge not only to its pharmaceutical colleagues but also to itself," said the Lancet.
Leslie Hanna is Editor of BETA.
Anastos, K. and others. "Gender specific differences in quantitative HIV-1 RNA levels", 6th Conference on Retroviruses and Opportunistic Infections. Chicago. January 31-February 4, 1999. Abstract 274.
Andieh, L. and others. "Cervical neoplasia and the persistence of HPV infection in HIV+ women". 6th CROI. Abstract 463.
Conley, L.J. and others. "Incidence of HPV-associated vulvovaginal lesions in HIV-infected and uninfected women". 6th CROI. Abstract 462.
Culnane, M. and others. "Lack of long-term effects of in utero exposure to zidovudine among uninfected children born to HIV-infected women". JAMA 1999 Jan 13;281(2):151-7.
Feinberg, J. and others. "Heterosexual transmission of NNRTI-resistant HIV-1". 6th CROI. Abstract 219.
French, A.L. and others. "Association of retinol deficiency with cervical squamous intraepithelial lesions (SIL) in the HIV-infected woman", 6th CROI. Abstract 464.
Harlow, S.D. and others. "Menstrual function and HIV serostatus", 6th CROI. Abstract 461.
Hoesly, C.J. and others. "Molecular epidemiology of HPV infection in the genital tract of HIV seropositive women", 6th CROI. Abstract 465.
Justman, J. and others. "Association of diabetes and protease inhibitor use in a large natural history cohort of HIV+ women", 6th CROI. Abstract 661.
Limpongsanurak, S. and others. "Safety, tolerability and efficacy of ritonavir in the prevention of vertical transmission", 6th CROI. Abstract 241.
Maiman, M. and others. "A phase III randomized trial of topical vaginal 5-fluorouracil maintenance therapy versus observation after standard treatment for high-grade cervical dysplasia in HIV-infected women: ACTG 200", 6th CROI. Abstract 466.
Reichelderfer, P. and others. "Variation in genital tract shedding of HIV RNA with menstrual cycle", 6th CROI. Abstract 223.
Rompalo, A.M. and others. "Syphilis serologic patterns among women with or at risk for HIV", 6th CROI. Abstract 468.
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