Management of HIV-Infected Women and Mother-to-Child HIV Transmission

Alexandra M. Levine, M.D.
Originally published by Medscape, July 2001

Women constitute the fastest growing population at risk for HIV infection in the United States and approximately 42% of all persons infected worldwide. Despite significant advances in our recent understanding of HIV disease in women, a great deal still remains to be learned. Many of the presentations made at the 1st IAS Conference on HIV Pathogenesis and Treatment in Buenos Aires, Argentina, concerned various characteristics of HIV disease in women.

Access to Care

Do women have access to highly active antiretroviral therapy (HAART) equal to that of men? Numerous studies over the years have demonstrated that women have not had the same access to antiretroviral therapy as men, even with the same indications. For example, in the early 1990s Stein and colleagues¹ found that HIV-infected women with AIDS were 3 times less likely to receive zidovudine than were men, while Hellinger² reported that women with HIV were statistically less likely to receive medical services than were men, including medications, hospital admissions, and outpatient visits. Likewise, evaluating Medicaid data from Florida from the years 1992-1997, Anderson and colleagues³ found a consistent disparity among women and men in terms of receipt of antiretroviral agents. Of interest, Mocroft and colleagues⁴ examined the management of HIV disease among a population in Alberta, Ontario, Canada, where all healthcare, including physician visits, medications, and hospitalization, is provided by the state. Even in this study, conducted among 1403 patients (9% of whom were female), women were significantly less likely to start HAART (defined as at least 3 antiretrovirals taken consecutively), and were significantly less likely to start a protease inhibitor (PI)-containing HAART regimen. These data would imply that the gender differences in receipt of antiretroviral agents extend from the beginning of the epidemic, when women were specifically excluded from entering trials of antiretroviral therapy, to the present time. Furthermore, the disparity in receipt of effective antiretroviral therapy seems to occur both in the United States and in other countries,⁴ and appears to be independent of financial considerations.^3,4

This disparity in receipt of HAART between the genders apparently is continuing, despite recent publicity concerning the issue. Carten and colleagues⁵ from Cook County Hospital in Chicago, Illinois, reported gender differences in HIV-infected patients who were admitted to the inpatient HIV ward between January 1999 and September 2000. In this study of 640 patients, including 175 women, 33% of women were receiving HAART at the time of admission vs 43% of the men (P = .002). Other characteristics of the men and women are summarized in Table 1.

Table 1. Selected Characteristics of HIV-Infected Patients at Cook County Hospital, Chicago, Illinois

Factor	Women	Men	P Value
Mean age (years)	39	41	.003
Injection-drug use	67%	56%	.046
Coinfection with hepatitis C virus	49%	38%	.026
Mean CD4+ cell count (cells/mm3)	230	181	.027
Mean viral load (copies/mL)	90,000	119,000	.10
At least 1 clinic visit within the past 6 months	62%	65%	NS

Thus, despite the fact that men and women were equally likely to have attended clinic within the past 6 months, and despite the fact that the mean viral load was equivalent (and high) in both groups, women were statistically less likely to have received HAART from the same group of providers. Details of the hospital admissions among this patient group are shown in Table 2.

Table 2. Hospital Admissions Among HIV-Infected Patients at Cook County Hospital, Chicago, Illinois

Factor	Women	Men
Average length of stay (days)	5.76	.9
Genitourinary infection	12%	4%
Skin condition	17%	24% (including 38 cases of Kaposi's sarcoma)
Congestive heart failure	4%	2.5%
Diabetes mellitus	8%	5%
Aspergillosis, histoplasmosis, or cryptococcosis	2%	4.5%

With regard to cancers, 4% of women were admitted for this reason, including 4 with invasive cervical cancer, 2 with lung cancer, 1 with Kaposi's sarcoma (KS), 1 with lymphoma, and 1 with oropharyngeal cancer. A total of 10% of the men were admitted with a diagnosis of cancer, including KS in 38; lymphoma in 18; lung cancer in 8; oropharyngeal cancer in 4; and 1 each of testicular cancer, anal cancer, liver cancer, and bladder cancer.

Although approximately 50% of both women and men were admitted due to opportunistic infections, the statistically significant disparity in receipt of HAART might have played a role in their development among the women. It is clear from these data, then, that in the HAART era, women are still less likely to receive HAART, even when they have the same healthcare providers and similar HIV characteristics. We still have a long way to go in this area.

Effect of HAART on Bacterial Pneumonia

Does receipt of HAART alter the likelihood of bacterial pneumonia in HIV-infected women? In a group of 885 women followed for an average of 4.5 years, 336 episodes of bacterial pneumonia were diagnosed among 204 women,⁶ giving a crude rate of 9.4 cases per 100 person-years. Of interest, receipt of trimethoprim-sulfamethoxazole as prophylaxis against Pneumocystis carinii had no effect on preventing bacterial pneumonia. However, receipt of HAART decreased the risk of pneumonia by 50% after controlling for smoking, viral load, CD4+ cell count, and receipt of less than a high school education, each of which was independently associated with an increased risk of pneumonia.

Toxicity of Antiretroviral Agents in Women

Gender Differences in Morphologic Alterations

Galli and colleagues⁷ from Milan, Italy, studied the correlation between gender and morphologic alterations (MAs) in a group of 2258 patients, of whom approximately 30% were women. A total of 750 patients (33.2%) developed at least 1 MA. Of interest, female gender was the strongest independent factor associated with an increased risk of MA (adjusted odds ratio [OR] = 2.019, P = .001) in a multivariate analysis that included duration of antiretroviral therapy, age, viral load, and use of combination antiretroviral therapy prior to study enrollment. The prevalence of various morphologic abnormalities is presented in Table 3.

Table 3. Gender Differences in Morphologic Alterations in HIV-Infected Patients

Specific Morphologic Alteration	Women	Men	P Value
Fat loss only	9.3%	12.2%	NS
Fat accumulation only	10.1%	7.7%	.0008
Both fat loss and fat accumulation	22.4%	9.7%	.0001

The timing of the development of lipodystrophy among HIV-infected women was addressed by Carpenter and colleagues⁸ in a 2.5-year follow-up study of a group of 21 women who reported morphologic changes after institution of HAART. These women were compared with 21 controls who were also receiving HAART but reported no such morphologic alterations. The mean duration of HAART at baseline in the cases was 12 months vs 15 months in the comparators. Of interest, the morphologic changes remained stable in cases over time in 10 of 14 cases, while 3 experienced modest improvement and 1 developed a dorsal fat pad. In the comparators, who had no morphologic changes at baseline, only 2 of 21 developed such changes. Serum lipid values were elevated at baseline in both cases and comparators, and did not change over time. This study would indicate that the morphologic and/or lipid changes that occur with HAART are likely to occur within the first 12-18 months of therapy, with very few additional cases over time. In this regard, these data are similar to those from the Multicenter AIDS Cohort Study presented at the 8th Conference on Retroviruses and Opportunistic Infections in February 2001, in which the prevalence of lipodystrophy among HIV-infected men rose steadily during the first 2 years of potent antiretroviral therapy use but appeared to stabilize thereafter.⁹

In a subsequent plenary session, David Cooper, MD,¹⁰ from Sydney, Australia, summarized the current state of knowledge of the lipodystrophy syndrome, including morphologic alterations. He acknowledged that there is no currently validated definition of lipodystrophy syndrome, leading to confusion and some lack of comparability of data; a multinational prospective case definition study is currently underway which should serve to clarify this issue. Summarizing data from 7 cohort studies that evaluated HIV-associated lipodystrophy, he concluded that the use and duration of therapy with PIs or NRTIs were associated with development of the syndrome. However, there does not appear to be an association between CD4+ cell counts and the development of the syndrome. Data regarding viral load and the likelihood of lipodystrophy have been disparate, with 3 of the 7 studies showing that lower plasma HIV-1 RNA levels were associated with lipodystrophy, while the other 4 showed no relationship. While concluding that antiretroviral therapy is the most likely etiology of this complication, he acknowledged that other factors may also play a role. These include increasing age, weight loss prior to HAART, and female gender. In explaining the possible role of gender in the development of lipodystrophy, however, his explanation was simply that women have more body fat than men, and that fat loss was thus more noticeable in men, while fat gain would be more noticeable in women. Clearly, further work will be required to ascertain the precise role of hormones and other factors in the development of lipodystrophy in women.

Risk of Nevirapine-Induced Rash in HIV-Infected Women

Any toxicity of nevirapine that is specific to or elevated in women would be of particular interest, since the drug has been shown to be an easy, inexpensive, and feasible option for reducing mother-to-child transmission of HIV in resource-poor regions of the world. Mazhude and colleagues¹¹ from King's College Hospital in London, United Kingdom, reported on the prevalence of skin rash after exposure to nevirapine among 285 HIV-infected individuals. Rash occurred in 7.4% of the cohort overall, and led to cessation of nevirapine in 67%. Nevirapine rash was more likely to occur in women, 15% of whom were affected, with no statistical difference between blacks and whites. In a multivariate analysis, the relative risk of rash was increased 11.7-fold in women compared with men (P = .006). The median time to onset of rash was 17 days. Three patients developed Stevens-Johnson syndrome, including 2 women. Of 9 patients who switched to efavirenz, none had a recurrence of rash. Further information on the likelihood of developing a rash when nevirapine is taken solely during labor and delivery would be of interest.

Role of HAART in Development of Hypertension Among HIV-Infected Women

Khalsa and colleagues¹² from the Women's Interagency HIV Study (WIHS) in the United States investigated the prevalence and incidence of hypertension among a cohort of 2057 HIV-infected women and 569 demographically similar HIV-negative women at risk. All participants are seen every 6 months, during which a careful history, physical examination, and extensive laboratory evaluation are performed. The study began in 1994, and data were presented through 1999. Hypertension at baseline was defined as a systolic blood pressure of 140 or greater, and/or a diastolic blood pressure of 90 or above, or receipt of antihypertensive medications. Over time, hypertension was defined as elevated blood pressure (as defined above) occurring at 2 or more 6-monthly visits, and/or receipt of antihypertensive medications. At baseline, the prevalence of hypertension in HIV-infected women (25.8%) was identical to that in the HIV-negative group (25.8%). In analyzing those factors associated with hypertension in the HIV-infected women, 4 factors were found to be statistically significant on multivariate analysis: African American ethnicity (OR = 2.14, P < .001); increasing age (OR = 4.53, P < .001); body mass index over 25 (OR = 1.55, P < .01); and receipt of HAART for at least 4 intervals (ie, 2 years or more; OR = 1.79, P < .01). Future analyses will seek to determine whether hypertension is associated with the occurrence of lipodystrophy.

This study is of interest for several reasons. First, approximately one third of all women in the study had hypertension at baseline. Second, the prevalence of hypertension in women who had been on HAART for 2 or more years approached 41.3%. These data will be especially important in terms of the potential for coronary artery disease over time, as the women grow older, as they continue to smoke, and as HAART leads to prolonged elevation of cholesterol and triglycerides. Clearly this will be an area of importance for future investigations.

Mother-to-Child Transmission

Mechanisms and Timing of Mother-to-Child Transmission

John Sullivan, MD,¹³ from the University of Massachusetts gave an excellent overview of the current state of knowledge concerning mother-to-child HIV transmission (MTCT), which can occur in utero, during birth and delivery (intrapartum), or postpartum as a consequence of breastfeeding. The profile of in utero vs intrapartum infection is represented in Table 4.

Table 4. First Detection of HIV in Infants: Characteristics of In Utero vs Intrapartum Transmission

Timing of Infection	Cord Blood	First 48 Hours	1 Week	4-8 Weeks
In utero	+	+	++	+++
Intrapartum	-	-	+/-	+++

Intrapartum transmission occurs by the transmission of maternal HIV present in the vaginal secretions or blood via the fetal conjunctiva, gastrointestinal tract, or a break in fetal skin. In non-breastfeeding populations, approximately 65% of transmission is thought to occur in the intrapartum period. With regard to the precise timing of in utero HIV transmission, most recent evidence would suggest that the most vulnerable time is at the end of the second trimester and the beginning of the third trimester.

Breastfeeding is clearly a risk factor for MTCT and remains a major obstacle in reducing vertical transmission in resource-poor regions, where breastfeeding is very much the norm, and alternatives such as formula-feeding are expensive and serve to mark the woman as "different" and possibly HIV-infected. Approximately 75% of transmission due to HIV-infected breast milk occurs within the first 6 months. Risk factors for transmission through breast milk include younger maternal age, seroconversion during breastfeeding, prolonged duration of breastfeeding, and presence of mastitis or breast abscesses. Formula-fed infants have a 44% reduction in rates of HIV infection.¹⁴

Eradication of MTCT in Resource-Rich Regions

Importance of maternal viral load and use of antiretroviral therapy. The seminal Pediatric AIDS Clinical Trials Group (PACTG) study 076¹⁵ was exceedingly important, demonstrating a decrease in the transmission rate from 25.5% in the placebo group to 8.3% in those who received zidovudine. This regimen required a rather intensive zidovudine exposure, beginning at week 14 in the mothers, who received 300 mg twice daily or 100 mg 5 times per day. An intravenous loading dose of zidovudine was given at the onset of labor, with a continuous infusion of the drug (2 mg/kg) throughout the entire time of labor and delivery, followed by oral zidovudine (2 mg/kg per dose every 6 hours) to the infant for the first 6 weeks of life. The study was also important in that it provided the data to prove that maternal viral load was the most critical factor in predicting MTCT. However, as shown by Sperling and colleagues,¹⁶ even among women with the lowest viral loads, those who received zidovudine were statistically less likely to transmit HIV to their infants than were those who received placebo, as shown in Table 5.

Table 5. Effects of Maternal Viral Load and Receipt of Zidovudine in PACTG 076

Viral Load Transmission Rate	Zidovudine Recipients	Placebo Recipients
< 1730 copies/mL	2.5%	7.1%
> 15,700 copies/mL	13.3%	41.7%

The importance of antiretroviral therapy, even in women with very low viral loads, was also demonstrated by Ioannidis and colleagues,¹⁷ reporting from a collaborative study of 1202 women with plasma HIV-1 RNA levels less than 1000 copies/mL who were enrolled in 7 European and US prospective studies. MTCT occurred in a total of 44 women (3.6%), with statistically less likelihood of transmission if antiretroviral therapy had been given during pregnancy and/or delivery. Thus, of the 834 women who received antiretroviral therapy, the transmission rate was 1% (8 women), while transmission occurred in 36 (9.8%) of 368 women who did not receive antiretroviral therapy, even though their viral loads were less than 1000 copies/mL. This difference was highly significant (P < .001).

Subsequent to the initial PACTG 076 report, abbreviated regimens of zidovudine were also evaluated, and have been proven efficacious in preventing MTCT. In a study conducted in New York State, Wade and coworkers¹⁸ found that the transmission rate among mothers who did not take zidovudine was 26.6%. However, in mothers who began zidovudine for the first time during delivery, the transmission rate was 10%, and in infants who first received zidovudine during the first 48 hours of life, without prior maternal exposure, the infection rate was 9.3%—both of which were statistically less than the transmission rate among mother-child pairs who remained untreated. Other abbreviated regimens of zidovudine have also been studied, with proven efficacy.¹⁹

The use of nevirapine in preventing MTCT has led to a practically feasible and affordable (US$5) method that might be applicable to resource-poor regions. Nevirapine has a long half-life (25-30 hours) and is lipophilic, and therefore is present in breast milk. An oral suspension is available, making administration to the newborn possible. The drug is potent, resulting in a 1.3 log10 copies/mL decrease in viral load 7 days after a single dose. PACTG study 316 evaluated the addition of placebo or nevirapine (200 mg administered to the mother during labor and 2 mg/kg to the infant at birth) to the antiretroviral regimen of pregnant women who were nevirapine-naive.²⁰ After 1503 mother-child pairs had been enrolled, the study was stopped prematurely because the overall rate of MTCT was only 1% to 2%, making it impossible to show any incremental effect of nevirapine. Of importance, however, 104 women enrolled in PACTG 316 had plasma HIV-1 RNA levels > 400 copies/mL and were studied for the development of nevirapine resistance. A total of 5 (11%) of 46 women developed nevirapine resistance mutations after the single dose. These women have been followed for over 1 year, by which time the mutations can no longer be detected. Certainly, the development of resistance after single-dose exposure to nevirapine is of concern, although the long-term clinical consequences of these resistance mutations are not yet understood.

Mary Louise Newell, MD,²¹ discussed the recent finding of premature delivery (50% delivered by week 37) in HIV-infected pregnant women who had been given PI-containing antiretroviral regimens. The use of PIs may thus have a wider effect on the mother and infant than previously understood, mandating thorough additional study of HAART-treated pregnant women in the years ahead.

Using a human in vitro placental perfusion model, Peytavin and colleagues²² from France studied the perfusion of nelfinavir, noting that only 5.0% +/- 2.4% of the parent drug actually reached the fetal side of the circulation, with no evidence of placental metabolism of the drug. While not a major study in itself, the model is an interesting one that should prove useful in future studies of antiretroviral drugs used in an attempt to prevent MTCT.

Mode of delivery. The European Collaborative Study, based on 721 children born to 701 mothers, demonstrated that elective cesarean section (C-section) was associated with a decreased risk of MTCT (relative risk [RR] = 0.56), although these results were not statistically significant.²³ A subsequent meta-analysis of North American and European studies, each one of which included at least 100 mother-child pairs, analyzed data from a total of 8533 mother-child pairs.²⁴ After adjusting for the use of antiretroviral therapy, maternal stage of HIV infection, and infant birth weight, the risk of perinatal transmission was decreased by approximately 50% in those women who underwent elective C-section (OR, 0.43; 95% confidence interval [CI], 0.33-0.56). Similar results were found when the control population was limited only to those women with rupture of the membranes immediately prior to delivery. As presented by Newell,²¹ use of antiretroviral therapy during pregnancy and delivery, use of elective C-section, and avoidance of breastfeeding have all resulted in a decrease in the rate of MTCT in Europe to approximately 2%. According to Dr. Newell, up to 85% of HIV-infected pregnant women now undergo elective C-section in Europe, which is considerably different from the experience in the United States. It is important to mention, however, that elective C-section has been associated with complications in HIV-infected women, as published by Watts and colleagues²⁵ and summarized in Table 6.

Table 6. Rate of Complications of Elective C-Section in HIV-Infected Women

Complication	Planned C-Section (n=37)	Other C-Section (n=95)	Vaginal Delivery (n=365)
Amnionitis or endometritis	16%	27%	7%
Wound infection	5%	8%	< 1%
Transfusion required	8%	6%	3%

In a multivariate analysis, factors associated with amnionitis or endometritis were C-section and African American race. In the question-and-answer period, when these issues were raised, Dr. Newell commented that the severity of these problems was relatively mild, thus not serving to negate the value of the procedure in preventing MTCT. Nonetheless, when Dr. Sullivan was asked if he would consider elective C-section in women who had undetectable viral loads, he replied that he would not, although he clearly stated that the issue of elective C-section remains an area of controversy, especially in women with low viral loads.

In concluding this discussion, Dr. Sullivan was asked for his recommendation regarding optimal antiretroviral therapy for HIV-infected pregnant women in resource-rich areas of the world. He replied that he would use zidovudine, lamivudine, and nevirapine, and would probably start therapy during the second trimester, since a substantial proportion of in utero transmission occurs at the end of the second trimester. With regard to this 3-drug antiretroviral combination, Coll and colleagues²⁶ from Buenos Aires studied its safety and efficacy in a group of 36 HIV-infected pregnant women, accrued between May 1998 and February 2001. Their median age was 28 years, and 23 women were antiretroviral-naive. The median duration of pregnancy when therapy was initiated was 20 weeks (range, 12-36 weeks), and the median gestational age at delivery was 38 weeks (range, 24-40 weeks). After the 36 children had been monitored for a median of 24 weeks, all 29 babies who underwent 2 polymerase chain reaction tests during this period were uninfected. No mother discontinued therapy during pregnancy, and the median baseline viral load of 35,446 copies/mL fell to a median of 67 copies/mL by delivery. The only adverse event in the 36 infants was anemia, occurring in 5 (13.8%) and resolving spontaneously over time. This study, although small, confirms the short-term safety of this approach and its efficacy in preventing MTCT.

MTCT in Resource-Poor Regions of the World

A great deal has been written about the difficulties of preventing MTCT in the developing world, where adequate healthcare infrastructure is not available, where poverty does not allow the use or monitoring of expensive antiretroviral combinations, and where breastfeeding is the norm and the only currently feasible method by which HIV-infected mothers may nourish their children. With all of these factors in mind, several studies have sought to define abbreviated regimens of antiretroviral therapy, which might be financially possible in very poor areas.

The HIVNET 012 trial^27,28 compared nevirapine (200 mg orally during delivery to the mother and 2 mg/kg orally to the child within the first 48 hours following birth) with zidovudine (600 mg orally at the onset of labor, and 300 mg orally every 3 hours during delivery, plus 4 mg/kg orally twice daily to the child for the first 7 days of life). The results are presented in Table 7.

Table 7. Results of HIVNET 012

Regimen	% Infants Infected at Birth	% Infected 6-8 Weeks	% Infected 14-16 Weeks
Nevirapine (n = 310)	8.1	11.8	13.6
Zidovudine (n = 309)	10.3	20.0	22.1

Of importance, 98.8% of the babies were breastfed, and 95.6% were still breastfeeding at 14-16 weeks. Nonetheless, nevirapine administered during delivery and at birth remained statistically more effective than short-course zidovudine in decreasing MTCT at 2 months of life (P= .0027) and even out to 4 months of life (P= .00063).

Nevirapine was also studied, in comparison with zidovudine plus lamivudine, in the South African Intrapartum Nevirapine Trial (SAINT) study.^29,30 The results of this study indicated no significant difference in MTCT rates between these 2 regimens (Table 8). Additional vertical transmission occurred in each arm over time, secondary to transmission from breast milk.

Table 8. Regimens and Results of the SAINT Study

Treatment Groups	Dosing During Labor	Dosing Following Delivery	Rate of MTCT at Birth
Nevirapine (n = 652) 200-mg single dose	Mother: 200-mg single dose	Infant: 6-mg single dose	8.5%
Zidovudine +lamivudine 600 mg at onset, then (n = 654)	Zidovudine: 300 mg 3 times hourly	Mother: zidovudine 300 mg twice daily + lamivudine 150 mg twice daily for 1 week Lamivudine: 150 mg 12 times hourly Infant: zidovudine 12 mg twice daily + lamivudine 6 mg twice daily for 1 week	7.4%

The PETRA (PErinatal TRAnsmission) study evaluated several different antiretroviral regimens at 5 African sites.³¹ In one arm of the trial, women received no antiretroviral therapy during pregnancy, but received zidovudine (300 mg orally every 3 hours) and lamivudine (150 mg orally every 12 hours) during delivery. Both mother and infant were also treated with standard oral doses of zidovudine and lamivudine for 1 week postpartum. The rate of MTCT at 6 weeks was 9.6%, increasing to 25% at 24 months, in a population in whom 70% breastfed. Thus, very short-course zidovudine/lamivudine also appears effective in decreasing MTCT in resource-poor areas.

These studies, then, would suggest that short courses of antiretroviral therapy may be effective in preventing MTCT in resource-poor regions of the world. As pointed out by Dr. Newell, however, there have been no data so far on one of the most important end points—the mortality rate of antiretroviral-exposed, HIV-negative children beyond the current follow-up period of 18-24 months.

The cost of the zidovudine regimen studied as part of PACTG 076 is estimated to be approximately US$1000-$1500, while that of zidovudine/lamivudine as used in the PETRA study is approximately $50. The approximate cost of the single-dose nevirapine regimen is about US$5, and the manufacturer has offered free nevirapine to all pregnant HIV-infected women in Africa for the next 5 years. At the recent United Nations summit on HIV/AIDS in June 2001, a goal was established to ensure that 80% of all HIV-infected pregnant women worldwide have access to antiretroviral therapy by 2005, with a 20% reduction in MTCT by 2005 and a 50% reduction by 2010. The precise strategies to achieve these goals are currently under discussion. However, both Drs. Sullivan and Newell stated that their recommendation would be to ensure that women in resource-poor regions have access to therapy, thereby decreasing viral load and in so doing markedly decreasing the risk of MTCT, both in terms of in utero and delivery-related transmission. Furthermore, a reduction in viral load would also result in a decreased risk of transmission through mother's milk. Current World Health Organization guidelines for prevention of MTCT in HIV-infected women state that breastfeeding should be avoided where it is safe and affordable to do so. However, when breastfeeding is the only option, exclusive breastfeeding should proceed for the first 4-6 months and should then be stopped entirely.

Other factors that are particularly applicable to resource-poor regions may also play a role in the transmission of HIV from mother to infant. Mwanyumba and colleagues³² from Belgium studied the effect of placental inflammation on MTCT among 298 HIV-infected women in Mombasa, Kenya. After adjusting for maternal viral load, the presence of HIV-1 in genital secretions, and the presence of HIV-1 in oropharyngeal secretions of the newborns, acute chorioamnionitis (defined histologically) was statistically associated with increased HIV transmission (17.9% vs 6.7% in those without inflammation, P = .005). Other correlates of increased likelihood of MTCT were higher maternal viral load, presence of HIV-1 in genital secretions, and presence of HIV-1 in oropharyngeal secretions of the infant. This study would indicate that other interventions, such as antibiotic therapy of women with placental inflammation, may also help to decrease MTCT.

References

Stein MD, Piette J, Mor V, et al. Differences in access to zidovudine among symptomatic HIV infected persons. J Gen Intern Med. 1991;6:35-40.
Hellinger FJ. The use of health services by women with HIV infection. Health Serv Res. 1993;28:543-561.
Anderson KH, Mitchell JM. Access to antiretrovirals for HIV/AIDS treatment differs by gender, race/ethnicity. Arch Intern Med. 2000;160:3114-3120.
Mocroft A, Gill MJ, Davidson W, Phillips AN. Are there gender differences in starting PI's, HAART, and disease progression despite equal access to care? J Acquir Immune Defic Syndr. 2000;24:475-482.
Carten M, Puvirenti J, Sarazine J, et al. Gender differentials in hospitalized patients with HIV. Program and abstracts of The 1st IAS Conference on HIV Pathogenesis and Treatment; July 8-11, 2001; Buenos Aires, Argentina. Abstract 309.
Schoenbaum E, Home P, Romaplo A, et al. Does use of HAART and/or trimethoprim-sulfamethoxazole prophylaxis (TMP-SMS) affect the rate of bacterial pneumonia in HIV infected women? Program and abstracts of The 1st IAS Conference on HIV Pathogenesis and Treatment; July 8-11, 2001; Buenos Aires, Argentina. Abstract 479.
Galli M, Veglia F, Angarano G, et al. Correlation between gender and morphologic alterations in treated HIV patients. Program and abstracts of The 1st IAS Conference on HIV Pathogenesis and Treatment; July 8-11, 2001; Buenos Aires, Argentina. Abstract 505.
Carpenter C, Mahajan A, Dispigno M, et al. Changes in body habitus and serum lipid abnormalities in HIV infected women on highly active antiretroviral therapy: A 3.5 year study. Program and abstracts of The 1st IAS Conference on HIV Pathogenesis and Treatment; July 8-11, 2001; Buenos Aires, Argentina. Abstract 502.
Kingsley L, Smit E, Riddler S, et al. Prevalence of lipodystrophy and metabolic abnormalities in the Multicenter AIDS Cohort Study (MACS). Program and abstracts of the 8th Conference on Retroviruses and Opportunistic Infections; February 4-8, 2001; Chicago, Illinois. Abstract 538.
Cooper DA. Lipodystrophy syndrome. Program and abstracts of The 1st IAS Conference on HIV Pathogenesis and Treatment; July 8-11, 2001; Buenos Aires, Argentina. Abstract PL11.
Mazhude C, Jones S, Taylor C. Ethnic and gender differences in non-nucleoside reverse transcriptase inhibitor induced rash. Program and abstracts of The 1st IAS Conference on HIV Pathogenesis and Treatment; July 8-11, 2001; Buenos Aires, Argentina. Abstract 526.
Khalsa A, Minkoff H, Cohen M, et al. Hypertension in HIV infected women: Relationship to HAART in the Women's Interagency HIV Study (WIHS). Program and abstracts of The 1st IAS Conference on HIV Pathogenesis and Treatment; July 8-11, 2001; Buenos Aires, Argentina. Abstract 512.
Sullivan J. Mother-to-child transmission: What have we learned? Program and abstracts of The 1st IAS Conference on HIV Pathogenesis and Treatment; July 8-11, 2001; Buenos Aires, Argentina. Abstract IL5.
Nduati R, John G, Mbori-Ngacha D, et al. Effect of breastfeeding and formula feeding on transmission of HIV-1: a randomized clinical trial. JAMA. 2000;283:1167-1174.
Connor EM, Sperling RS, Gever R, et al. Reduction of maternal-infant transmission of HIV with zidovudine treatment. N Engl J Med. 1994;331:1173-1180.
Sperling RS, Shapiro DE, Coombs RW, et al. Maternal viral load, zidovudine treatment, and the risk of transmission of HIV-1 from mother to infant. N Engl J Med. 1996;335:1621-1629.
Ioannidis JPA, Abrams EJ, Ammann A, et al. Perinatal transmission of HIV virus type 1 by pregnant women with RNA virus loads <1000 copies/mL. J Infect Dis. 2001;183:539-545.
Wade NA, Birkhead GS, Warren BL, et al. Abbreviated regimens of zidovudine prophylaxis and perinatal transmission of the human immunodeficiency virus. N Engl J Med. 1998;339:1409-1414.
Lallemant M, Jourdain G, Le Couer S, et al. A trial of shortened zidovudine regimens to prevent mother-to-child transmission of HIV type 1. N Eng J Med. 2000;343:982-991.
Dorenbaum A for the PACTG 316 Study Team. Report of results of PACTG 316: an international phase III trial of the standard antiretroviral (ARV) prophylaxis plus nevirapine (nevirapine) for prevention of perinatal HIV transmission. Program and abstracts of the 8th Conference on Retroviruses and Opportunistic Infections; February 4-8, 2001; Chicago, Illinois. Abstract LB7.
Newell ML. Vertically acquired HIV infection: Where do we go from here? Program and abstracts of The 1st IAS Conference on HIV Pathogenesis and Treatment; July 8-11, 2001; Buenos Aires, Argentina. Abstract 130.
Peytavin G, Wrobel C, Camus M, et al. Placental transfer of nelfinavir studied in the human in vitro placental perfusion model. Program and abstracts of The 1st IAS Conference on HIV Pathogenesis and Treatment; July 8-11, 2001; Buenos Aires, Argentina. Abstract 769. 23.
European Collaborative Study: Risk factors for mother-to-child-transmission of HIV-1. Lancet. 1992;339:1007-1012.
The International Perinatal HIV Group: The mode of delivery and the risk of vertical transmission of HIV-1: A meta-analysis of 15 prospective cohort studies. N Eng J Med. 1999;340:977-987.
Watts HD, Lambert JS, Stiehm ER, et al, for the PACTG 185 Study Team: Complications according to mode of delivery among HIV infected women with CD4 lymphocyte counts of £ 500/µL. Am J Obstet Gynecol. 2000;183:100-107.
Coll P, Avila M, Ruda A, et al. Safety and efficacy of ZDV + 3TC+ nevirapine in HIV infected pregnant women. Program and abstracts of The 1st IAS Conference on HIV Pathogenesis and Treatment; July 8-11, 2001; Buenos Aires, Argentina. Abstract 761.
Guay LA, Musoke P, Fleming T, 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 randomized trial. Lancet. 1999; 354: 795-802.
Owar M, Deseyne M, Duefield C, et al. The one year safety and efficacy data of the HIVNET 012 trial. Program and abstracts of the XIII International AIDS Conference; July 9-14, 2000; Durban, South Africa. Abstract LbOr1.
McIntyre J, for SAINT Study Team: Evaluation of safety of two simple regimens for prevention of mother to child transmission of HIV infections: Nevirapine versus lamivudine + zidovudine used in a randomized clinical trial (The SAINT Study). Program and abstracts of the XIII International AIDS Conference; July 9-14, 2000; Durban, South Africa. Abstract TuOr B356.
Moodley D. The SAINT Trial: Nevirapine versus zidovudine + lamivudine in prevention of peripartum HIV transmission. Program and abstracts of the XIII International AIDS Conference; July 9-14, 2000; Durban, South Africa. Abstract LbOr2.
Grey G. The PETRA study: early and late efficacy of three short ZDV/3TC combination regimens to prevent mother-to-child transmission of HIV-1. Program and abstracts of the XIII International AIDS Conference; July 9-14, 2000; Durban, South Africa. Abstract LbOr5.
Mwanyumba F, Gaillard P, Inion I, et al. Placental inflammation and perinatal transmission of HIV-1. Program and abstracts of The 1st IAS Conference on HIV Pathogenesis and Treatment; July 8-11, 2001; Buenos Aires, Argentina. Abstract 753.