HTB

HIV-positive women, pregnancy and newborns

14 April 2000. Related: Conference reports, Pregnancy, Drug resistance, .

Karen Beckerman, MD for hivandhepatitis.com

Karen Beckerman, MD, is Assistant Professor of Obstetrics, Gynecology and Reproductive Sciences, University of California at San Francisco, and Director of the Bay Area Perinatal AIDS Center (BAPAC).

‘Deworming (treating intestinal parasites) is a low-cost and effective treatment that may have a significant effect on progression [and transmission] of HIV infection, especially in developing countries where the vast majority of the population is infested with helminths (worms) and HAART (highly active antiretroviral therapy) is not available.’ Ñ D. Wolday, MD, from Armauer Hansen Research Institute in Ethiopia

The 7TH CROI has provided significant emphasis on clinical and scientific study of maternal-child health in the context of the HIV pandemic. Beginning with the Bernard Fields Memorial Lecture, Our Retroviral Heritage [ref 28], the eminent Robin Weiss, MD, delivered his opening salvo that, ‘The pandemic of HIV has more to do with SEX’ than with the virus’ direct attack on CD4 T-helper cells. This set the stage for a fresh appraisal of those other consequences of that three-letter word of the hour, namely mothers, fathers and babies. Dr. Weiss is from the Windeyer Institute of Medical Science in London, United Kingdom.

Orphans and HIV

In his Keynote Lecture, The State of HIV Vaccine Research [19], Gary Nabel, MD, PhD, was careful to describe the obvious, but all too frequently neglected, analysis of the HIV pandemic as a global epidemic of orphans. Dr. Nabel reminded attendees that due to HIV/AIDS, the number of orphans worldwide will soon reach 40 million, with 11 million orphans in Sub-Saharan Africa alone. While Dr. Nabel cited cause to be optimistic, many in the audience would have been grateful for more direct evidence of the arrival of an effective vaccine in the near future. Dr. Nabel is the Director of the Vaccine Research Center at the NIH (US National Institutes of Health).

Drug side effect differences in women

Throughout the Conference, there was an impressive emphasis on sex and age differences in HIV disease, and how that relates to pathogenesis, therapy and complications of therapy received. On the first day, one entire poster session was devoted to ‘Gender (Sex) Differences in Body Habitus Changes/Fat Redistribution.’ It was clear that much of our knowledge in this area is limited by the lack of definitions of these various syndromes (groups of symptoms, body changes and abnormal laboratory tests). Posters revealed a wide range in the reported frequency and type of body shape changes that researchers find in women. The disparities in data further emphasizes the need for ongoing research in this area.

Drug side effects in infants and children

In another poster session, ‘Complications of Antiretroviral Therapies in Children,’ there was both disturbing and reassuring news. Body habitus and blood lipid level changes in HIV-infected children (both with and without protease inhibitor drug therapy) were reported by groups from New York City and Seattle [1, 17]. One study reported abnormal levels of ‘lactic acid’ in the blood of 6 out of 11 newborns who were exposed to HIV in the womb and to anti-HIV drugs during pregnancy. (Note lactic acidosis is a rare, but life-threatening complication of the NRTI [nucleoside reverse transcriptase inhibitor] anti-HIV drugs associated with liver steatosis (fatty liver.) None had signs or symptoms of lactic acidosis or mitochondrial dysfunction (the NRTI drugs can cause damage to mitochondria). The ‘lactic acidosis’ appeared to resolve by 3 months of age.

Most reassuring was the report by Dr. Pat M. Garcia from the US Antiretroviral Pregnancy Registry [10]. Dr. Garcia said that from among almost 1,000 cases of infants exposed to zidovudine (ZDV) during the first three months of pregnancy, there has been no detectable increase in the rate of birth defects.

In his oral presentation, Kenneth McIntosh, MD, from Children’s Hospital in Boston, Massachusetts presented a review of five large databases about newborns exposed to ZDV [16]. Dr. McIntosh examined the records of over 20,000 infants who had been exposed to maternal antiretroviral therapy. By investigating infant deaths in this group, he was unable to attribute any infant deaths due to ‘mitochondrial toxicity,’ or to identify any deaths that were even ‘consistent with mitochondrial toxicity.’ A recent report in the medical literature had documented two cases of fatal neurologic disease due to mitochondrial toxicity that was associated with anti-HIV drug exposure. Even though their mothers were HIV positive, both offspring were HIV negative and had been exposed to ZDV and lamivudine (3TC) [3]. Dr. McIntosh indicated that a review of living, HIV-uninfected children who were exposed to ZDV is underway.

Dr. McIntosh’s analysis of more limited information about exposure to the NNRTI (non-nucleoside reverse transcriptase inhibitor) and/or PI (protease inhibitor) drugs was reassuring. However, the analysis was by no means complete.

The importance of intensive follow-up of HIV-exposed, uninfected children was highlighted by M. Vigano, MD, and colleagues from the University of Milano in Rome, Italy [27]. Dr. Vigano reported what appeared to be abnormal development of the thymus gland in these babies. It was unclear whether this might have been due to ZDV exposure, or exposure to HIV itself.

Hope for resource-poor countries

Other presentations introduced exciting information with considerable potential impact on the global epidemic. D. Wolday, MD, and colleagues [30] reported the strong association of helminthic (worm) infestation in the intestines with high HIV viral loads among a group of patients in Addis Ababa, Ethiopia.

Dr. Wolday found that treating the worm infections (‘de-worming’) was associated with significant reductions in HIV viral burden. The authors concluded, ‘Deworming is a low-cost and effective treatment that may have a significant effect on progression of HIV infection.’ This was one of a very few conclusions having any possible relevance to treatment of HIV disease in resource-poor countries. Indeed, such treatment might also serve to decrease the risk of sexual transmission of the virus.

Heterosexual transmission

In two oral presentations, heterosexual transmission of HIV was reported to be highly correlated with HIV viral burden in blood in two African studies of discordant couples (meaning one partner is HIV positive, while the other is not) [9, 22]. The 915 heterosexual couples were from Uganda or Zambia. Previous studies have shown that a pregnant woman’s viral load in blood is directly correlated with risk of HIV transmission from mother-to-newborn [11, 23].

Pregnant HIV positive women and mother-to-newborn transmission and prevention

The relationship between mother-to-newborn transmission and variations in HIV’s envelope (surface) gene were studied by R. Dickover, MD, and colleagues from the University of California at Los Angeles [8]. Dr. Dickover reported that a high rate of variation in HIV’s surface protein was associated with a lack of protection from transmission to newborns. Dr. Dickover also found that a low rate of diversity in the surface protein carried an increased risk of transmission. Many in the audience were concerned that ‘low viral diversity’ might simply be a marker for high viral burden.

Mary Jo O’Sullivan, MD, from the University of Miami in Florida presented a State-of-the-Art Lecture, Management of the HIV-Infected Pregnant Woman [21]. Dr. O’Sullivan had the honour of being the first obstetrician to address a Conference on Retroviruses and Opportunistic Infections in a plenary session. She concisely described the goals of maternal anti-HIV therapy: to maintain maternal immune function, to prevent HIV disease progression, to prolong survival, to increase quality of life, and to decrease the risk of HIV transmission to her offspring. Her presentation stressed the importance of screening for HIV disease in pregnancy, but fell short of stressing the importance of screening all women who have had unsafe sex.

Dr. O’Sullivan gave helpful guidelines for the clinical care of HIV-infected pregnant women, stressing that a pregnant woman’s own health care came first, and that anti-HIV therapy had to be tailored to a pregnant woman’s own health needs. She presented important information about the risks to both mother and baby of using caesarean (‘C’) section to prevent HIV transmission to the unborn infant.

One complication is a 6-fold increase in maternal complications in the setting of immune compromise. Another is a 120-fold increase in the need for ventilatory support for infants delivered at 37-39 weeks, when compared to those delivered at 39-41 weeks of pregnancy. (Note: 37-39 weeks is the current timing recommendation for those mothers desiring delivery by caesarean section.) She also stressed the fact that all studies demonstrating a protective effect of caesarean section against mother-to-newborn transmission have come from cohorts who did not receive anti-HIV combination therapy for the treatment of maternal disease.

The unique problems of adherence during pregnancy and, in particular, the period after delivery were emphasized. Unfortunately, despite Dr. O’Sullivan’s concern for maternal health and well-being, no information regarding the dangers of even short courses of antiretroviral mono- and dual-therapy during pregnancy was presented (dangers of promoting drug resistant HIV). Also, she appeared to recommend such hazardous prophylactic interventions for women presenting late in pregnancy. Nonetheless, in terms of HIV transmission to her newborn, in most cases monotherapy would be better than no therapy.

Laura Guay, MD, from Johns Hopkins University in Baltimore, Maryland presented interim results of the already-published HIVNET 012 trial [13, 13a]. This study demonstrated a decrease in mother-to-newborn transmission of HIV from 26% to 13% when mothers received a single dose of nevirapine, followed by another dose for her baby within 72 hours after birth. (Nevirapine is a non-nucleoside reverse transcriptase inhibitor [NNRTI] drug.) Importantly, children in this study will be followed until they are five years of age. All members of the audience were anxious to hear of the next round of data analysis which will be presented at the XIII International Conference on AIDS that will take place during July in Durban, South Africa.

NNRTI resistance from administration of a single, monotherapy, dose

The same Ugandan/American team presented some disturbing new information about nevirapine resistance in a small sample of women from this study [2]. To address ongoing concerns about the impact of one dose of nevirapine on the mothers’ health, blood was sampled six weeks after delivery from 18 mothers who took one dose of nevirapine at the start of labour. That blood was analysed for the presence of NNRTI (non-nucleoside reverse transcriptase inhibitor) drug resistance mutations (K103N, Y181C and six others).

Results were obtained from 15 of the 18 women. Unfortunately, the K103N primary nNRTI resistance mutation was detected in three of these 15 (20%). Importantly, no other drug resistance mutations were detected. Two blood samples were available that had been drawn prior to the single nevirapine dosing from these three women. The results showed that both lacked the K103N mutation. In addition, it was absent in samples from 30 women in the study who did not take nevirapine. This suggested that the K103N mutation was not found at baseline in drug-na•ve HIV positive women from Uganda, and that 20% developed it after only one dose of nevirapine. The speaker took trouble to emphasize that these findings deserve careful follow-up, which will be done in the ongoing HIVNET 012 trial, and stated ‘The most urgent issue is the infection of infants.’ One wonders if that will be the case in the next decade if the most promising therapies in resource-poor countries, such as once or twice daily nNRTI-based combinations, are found to be ineffective in large numbers of mothers exposed to nevirapine. The lead author was G. Becker-Pergola, MD, from Johns Hopkins University.

Mothers health first?

Paediatrician John Sullivan, MD, from the University of Massachusetts in Worcester presented an overview report entitled, ‘Clinical Summary: Perinatal Transmission; Where Do We Go From Here?’ [26]. He highlighted a number of disturbing trends regarding issues in maternal-child health in the HIV/AIDS epidemic.

Dr. Sullivan discussed the fact that single-dose or short course prophylactic (prevention) drug interventions given to the mother around the time of birth or labour have been, and will continue to be, actively pursued at the international level. This will be the case despite the evidence (known since 1992) that resistance to the entire class of NNTRI drugs develops extremely rapidly following brief exposure to only one NNRTI drug.

Similarly, resistance to some NRTI drugs might develop following limited exposure to Retrovir monotherapy or to a lesser degree when combined with 3TC. Not only does maternal health seem to be overlooked, the development of anti-HIV drug resistance might limit her future therapeutic options significantly, and thereby compromise her future health.

Breast not always best

Dr. Ruth N’duati, of Kenyetta National Hospital in Nairobi, Kenya, discussed her group’s courageous randomised trial of breast milk versus bottled milk feeding for HIV-exposed infants [20]. This study required access to safe water, the ability to boil water, and the commitment to feed infants freeze-dried milk formula by cup, in order to avoid contamination by latex nipples that were inadequately sterilized. Randomisation information reflected the realities of family life in Kenya. For example: (1) More than 90% of families shared a toilet with another family; (2) 50% of mothers were anaemic (low red cell count); (3) 9% of mothers had syphilis (sexually-transmitted infection); (4) 17% of infants were lost to follow-up before HIV or mortality endpoints were reached; and (5) 20% of all infants died before their second birthday, regardless of whether they were assigned to breast feedings or bottle feedings. Formula for the first six months of life costs the average Kenyan family more than US$1,000Ñan amount that is prohibitive for most of these women.

Using a strict ‘intent-to-treat’ (all enrollees included) analysis, the results were as follows. During the first 17 months of life, a significantly greater number of breast-fed infants were infected (61 of 212, or 29%), compared to only 31 of 213 (15%) formula-fed infants that were infected. Information about cumulative risk was compelling: 75% of all HIV transmission by breast milk had occurred by 6 months of age. Under ideal circumstances, Dr. N’Duati concluded that breast milk substitutes could reduce mother-to-child transmission by 44%.

The discussion period that followed was all too brief. However, Dr. N’Duati’s closing comments were, ‘Nevirapine and AZT (ZDV) should be a small part of prevention efforts and used only in the context of improved care for all mothers and all babies.’ This statement may well have been the most meaningful remark regarding mother-to-newborn transmission of HIV of the entire Conference.

Lastly, Dr. John Sullivan made predictions of a subcutaneous (under the skin) implant/controlled delivery system for nevirapine to protect against breast milk transmission. That seemed scarcely relevant to the picture of shared toilets, maternal syphilis rates of 9%, feeding newborns by cup and tens of millions of orphans that is a part of the epidemic. An AIDS activist in the audience politely inquired, ‘What about the mothers?’ Grimly, the answer came, ‘We’ve got to start somewhere.’

HAART during pregnancy

More information was presented that demonstrates the benefits and safety of HAART (highly active antiretroviral therapy) during pregnancy. In a preliminary report from Pediatric AIDS Clinical Trial Group (PACTG) 367 [24], early experience with protease inhibitor (PI)-based HAART during pregnancy added to the growing amount of reassuring information in this area. In the study, a retrospective review of prenatal records of HIV-infected women who gave birth between January 1998 and May 1999 was undertaken. A total of 164 mothers were identified who received PI-containing HAART during pregnancy. Major and minor birth defects were identified in their infants at rates identical to those in the general population. Premature birth rates (less than 37 weeks of pregnancy) were similar among those who were and were not exposed to PI combination therapy. However, very premature birth rates (less than 32 weeks of pregnancy) were lower in infants of mothers who received (PI) therapy in pregnancy than those who did not.

Transmission rates were quite impressive: in the entire study of 347 mothers, only 12 infants (3%) were infected. Ten of those 12 infants received either unknown therapy or ZDV alone. Only two of 119 (2%) infants of mothers on PI-based combination regimens were infected. Yet, HIV viral burden information in this study was limited. In another study by this group of researchers, they reported that the highest transmission rates to newborns (12%) occurred among mothers with unknown viral loads; the lowest rates (1%) were among mothers with undetectable viraemia [31]. There was no information presented about the impact of HAART on the health of the mothers in this study. The lead author was D. Shapiro, MD, from Harvard University.

HAART benefits for women

There were several presentations that emphasized the benefits of HAART upon HIV disease activity in women. Howard Minkoff, MD and colleagues described a protective effect of HAART against precancerous changes (dysplasia) in the uterine cervix that are caused by HPV (human papilloma virus) [18]. In their study, women receiving HAART were two-thirds less likely to show progression of cervical dysplasia and 1.4 times as likely to show regression of dysplasia than those who were not receiving treatment. S. Massad, MD, and colleagues from Cook County Hospital in Chicago, Illinois reported that HPV and immune suppression by HIV promoted progression of cervical abnormalities [15]. Other abstracts in this session emphasized that suppression of HIV-1 viral RNA in the genital tract is accomplished by controlling plasma viraemia with HAART, treating Candida vaginitis and treating bacterial vaginosis [5, 6, 29].

Deaths in women with HIV are not always due to AIDS

Information about recent trends in the causes and rates of death among HIV-infected women in the US was presented by Dr. D.K. Smith and colleagues from the CDC (Centers for Disease Control and Prevention [25]. A total of 885 women from the HERS (HIV Epidemiology Research Study) were studied between April 1993 to December 1998. The HERS is a multicentre study of women with or at risk for HIV infection. The authors identified 196 deaths. Interestingly, 44% of deaths were due to causes not related to HIV/AIDS. They included drug overdose, hepatitis and endocarditis/sepsis.

Even after HAART became available in the US, AIDS mortality was essentially unchanged in this group when comparing 1995 and 1998, 6.1 and 6.5 deaths per 100 person-years respectively. This lack of improvement in AIDS-related women’s mortality was thought by the authors to be attributable to the low rate of utilizing HAART. Among women with CD4 counts less than 200 cells/mm3, HAART use rose from 0% in 1995 to only 24% in 1998. Other combination therapy rose from 7% to only 23% in the same years. The researchers concluded that deaths among HIV-infected women should be addressed by improving access to drug abuse treatment centres, hepatitis vaccination and early HIV-1 treatment. Their conclusions deserve considerable emphasis. In addition, those of us involved in women’s health care in this epidemic know all to well what this group has been able to demonstrate here with objective information: ‘Optimal reduction in HIV/AIDS attributable death will not occur for women until utilization of HAART is maximized for this population.’

Stopping PCP prophylaxis during pregnancy

The safety of stopping secondary prophylaxis for Pneumocystis carinii pneumonia (PCP) was presented by B. Ledergerber, MD, in a Late Breaker presentation [14)] As a result, some pregnant women will choose to stop prophylaxis. However, the risks of life-threatening opportunistic infections during pregnancy are considerable. Therefore, in the population of HIV positive pregnant women, stopping prophylaxis would best be done in the setting of a clinical trial, or at least as part of an observational database.

‘Drug Holidays’ may have additional risks in pregnant women

Steven Deeks, MD, from San Francisco General Hospital reported that a STI (Structured Treatment Interruption,drug holiday’) of HAART in patients with detectable viral loads led to increased viral loads and decreased CD4 counts [7]. The virus that returned was ‘wild-type’ (without mutations) and had increased replicative (growth) capacity. At best, these results suggest that STIs will have a very limited role in the management of pregnant, HIV positive women. This would be due to both the hazards to the mothers’ health and the increased risk of transmitting to their unborn infants HIV that might be more virulent. At best, any woman considering such risky interruptions should be carefully counselled about these findings.

Final thoughts

The 7th Conference on Retroviruses and Opportunistic Infections has provided a strong focus on maternal-child health in the context of the HIV pandemic. In the industrialized world, this focus reveals several issues. They include the following: (1) improvement in maternal health; (2) prevention of paediatric HIV infection; (3) the impact of exposure to HIV and anti-HIV drugs on uninfected infants; and (4) the insights into the causes of and treatment of paediatric HIV disease. In the developing world, progress has been limited to studies of preventing HIV transmission from mother-to-newborn and by breast milk. Sadly, the larger issues of poverty, illiteracy and uninfected orphans of the pandemic (11 million in Africa, 40 million worldwide at last count) remained beyond the scope of this Conference.

Source: hivandhepatitis.com

Comment

HIV becoming resistant to nevirapine after a single dose is sobering news indeed. As noted it has grave consequences for both the future antiretroviral treatment of the mother, and for subsequent prevention of vertical transmission in pregnancies which may follow.

It is also a warning relevant to stopping long half-life NNRTI drugs (such as nevirapine and efavirenz) in ongoing combination therapy. As the blood plasma levels of these NNRTIs continues to decay long after the antiviral cover of the other agents has gone, the potential for rapid resistance is similar to that observed in the HIVNET 012 trial.

What should we do when either stopping or interrupting combination regimens containing these drugs? With a planned stop expert advice at present is to take the last dose of the NNRTI two days before the last dose of the other agents in the combination.

References:

  1. Arpadi S et al. Changes in regional fat distribution in HIV-1 infected children. Abstract and poster presentation 65 at the 7th CROI; January 30-February 2, 2000; San Francisco, CA.
  2. Becker-Pergola G et al. Selection of the K103N nevirapine (NVP) resistance mutation in Ugandan women receiving NVP prophylaxisto prevent HIV-1 vertical transmission (HIVNET-066). Abstract and oral presentation 658 at the 7th CROI; January 30-February 2, 2000; San Francisco, CA.
  3. Blanche S et al. Persistent mitochondrial dysfunction and perinatal exposure to antiretroviral nucleoside analogues. Lancet. 1999 Sep 25;354(9184):1084-9.
  4. Chuachoowong R et al. Short-course antenatal zidovudine reduces both cervicovaginal human immunodeficiency virus type 1 RNA levels and risk of perinatal transmission. Journal of Infectious Diseases. 2000 January;181(1):99-106.
  5. Cu-Uvin S et al. Bacterial vaginosis decreases suppression of female genital tract HIV-1 RNA levels. Abstract and poster presentation 678 at the 7th CROI; January 30-February 2, 2000; San Francisco, CA.
  6. Cu-Uvin S et al. HIV-1 RNA in the female genital tract: durability of response to highly active antiretroviral therapy. Abstract and poster presentation 680 at the 7th CROI; January 30-February 2, 2000; San Francisco, CA.
  7. Deeks S et al. Virologic and immunologic evaluation of structured treatment interruptions (STI) in patients experiencing long-term virologic failure. Abstract and poster presentation LB-10 at the 7th CROI; January 30-February 2, 2000; San Francisco, CA.
  8. Dickover R et al. Perinatal transmission of major, minor, and multiple HIV-1 strains in utero and intrapartum. Abstract and oral presentation 181 at the 7th CROI; January 30-February 2, 2000; San Francisco, CA.
  9. Fideli U et al. Virologic determinants of heterosexual transmission in Africa. Abstract and oral presentation 194 at the 7th CROI; January 30-February 2, 2000; San Francisco, CA.
  10. Garcia PM et al. Assessing the teratogenic potential of antiretroviral drugs: data from the antiretroviral pregnancy registry (APR). Abstract and poster presentation 68 at the 7th CROI; January 30-February 2, 2000; San Francisco, CA.
  11. Garcia PM et al. Maternal levels of plasma human immunodeficiency virus type 1 RNA and the risk of perinatal transmission. Women and Infants Transmission Study Group. New England Journal of Medicine. 1999 August 5;341(6):394-402.
  12. Giaquinto C et al. Is lactic acid a predictor of mitochondrial dysfunction in ARV (antiretroviral) exposed noninfected infants? Abstract and poster presentation 67 at the 7th CROI; January 30-February 2, 2000; San Francisco, CA.
  13. Guay L et al. A randomised trial of single-dose nevirapine to mother and infant vs. azidothymidine in Kampala, Uganda for prevention of mother-to-infant transmission of HIV-1 (HIVNET 012). Abstract and oral presentation S12 at the 7th CROI; January 30-February 2, 2000; San Francisco, CA
    13a. Guay L et al. Intrapartum and neonatal single-dose nevirapine compared with zidovudine for prevention of mother-to-child transmission of HIV-1 in Kampala, Uganda: HIVNET 012 randomised trial. Lancet 1999 September 4:354(9191):795 -802.
  14. Ledergerber B et al. It is safe to discontinue secondary prophylaxis for PCP in HIV-infected patients treated with HAART: results from eight prospective European cohorts. Abstract and oral presentation LB-5 (Late Breaker) at the 7th CROI; January 30-February 2, 2000; San Francisco, CA.
  15. Massad S et al. Incidence and progression of cervical squamous lesions among women with HIV: insights from the first 13,038 PAP smears of the Women’s Interagency HIV Study. Abstract and poster presentation 675 at the 7th CROI; January 30-February 2, 2000; San Francisco, CA.
  16. McIntosh K. Mitochondrial toxicity of perinatally administered zidovudine. Abstract and oral presentation S14 at the 7th CROI; January 30-February 2, 2000; San Francisco, CA.
  17. Melvin A et al. Blood lipid levels and body composition in HIV-infected children treated with protease inhibitors. Abstract and presentation 66 at the 7th CROI; January 30-February 2, 2000; San Francisco, CA.
  18. Minkoff H et al. Effect of highly active antiretroviral therapy (HAART) on cervical cytologic changes associated with oncogenic HPV among HIV and women. Abstract and poster presentation 674 at the 7th CROI; January 30-February 2, 2000; San Francisco, CA.
  19. Nabel G. The state of HIV vaccine research. Abstract and oral presentation (Keynote Lecture) L2 at the 7th CROI; January 30-February 2, 2000; San Francisco, CA.
  20. Nduati R et al. Breastmilk transmission of HIV-1. Abstract and oral presentation S13 at the 7th CROI; January 30-February 2, 2000; San Francisco, CA.
  21. O’Sullivan MJ. Management of the HIV-infected woman. Abstract and State-of-the Art oral presentation L3 at the 7th CROI; January 30-February 2, 2000; San Francisco, CA.
  22. Quinn TC et al. Viral load and risk of heterosexual transmission of HIV-1 among sexual partners. Abstract and oral presentation 193 at the 7th CROI; January 30-February 2, 2000; San Francisco, CA.
  23. Shaffer N et al. Maternal virus load and perinatal human immunodeficiency virus type 1 subtype E transmission, Thailand. Bangkok Collaborative Perinatal HIV Transmission Study Group. Journal of Infectious Diseases. 1999 March;179(3):590-9.
  24. Shapiro D et al. Antepartum antiretroviral therapy and pregnancy outcomes in 462 HIV-infected women in 1998-1999 (PACTG 367). Abstract and oral presentation 664 at the 7th CROI; January 30-February 2, 2000; San Francisco, CA.
  25. Smith DK et al. Causes and rates of death among HIV-infected women 1993-1998: the contribution of illicit drug use and suboptimal HAART use. Abstract and poster presentation 682 at the 7th CROI; January 30-February 2, 2000; San Francisco, CA.
  26. Sullivan J. Clinical summary: perinatal transmission; where do we go from here? Oral presentation S15 at the 7th CROI; January 30-February 2, 2000; San Francisco, CA.
  27. Vigano A et al. T-lymphocyte maturation abnormalities in vertically HIV-exposed uninfected children. Abstract and oral presentation 182 at the 7th CROI; January 30-February 2, 2000; San Francisco.
  28. Weiss RA. Our retroviral heritage. Abstract and oral presentation (Bernard Fields Memorial Lecture) L1 at the 7th CROI; January 30-February 2, 2000; San Francisco, CA.
  29. Williams A et al. Weekly treatment for prophylaxis of Candida vaginitis. Abstract and poster presentation 677 at the 7th CROI; January 30-February 2, 2000; San Francisco, CA.
  30. Wolday D et al. Eradication of helminthic infection decreases HIV plasma viral load in dually infected people. Abstract and poster presentation 157 at the 7th CROI; January 30-February 2, 2000; San Francisco, CA.
  31. Society for Maternal Fetal Medicine, Miami, Florida; 2000, abs. 276.

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