SUMMARY The availability of an increasing number of antiretroviral agents and the rapid evolution of new information has introduced extraordinary complexity into the treatment of HIV-infected persons. In 1996, the Department of Health and Human Services and the Henry J. Kaiser Family Foundation convened the Panel on Clinical Practices for the Treatment of HIV to develop guidelines for the clinical management of HIV-infected adults and adolescents. This report recommends that care should be supervised by an expert, and makes recommendations for laboratory monitoring including plasma HIV RNA, CD4 cell counts and HIV drug resistance testing. The report also provides guidelines for antiretroviral therapy, including when to start treatment, what drugs to initiate, when to change therapy, and therapeutic options when changing therapy. Special considerations are provided for adolescents and pregnant women. As with treatment of other chronic conditions, therapeutic decisions require a mutual understanding between the patient and the health care provider regarding the benefits and risks of treatment. Antiretroviral regimens are complex, have major side effects, pose difficulty with adherence, and carry serious potential consequences from the development of viral resistance due to non-adherence to the drug regimen or suboptimal levels of antiretroviral agents. Patient education and involvement in therapeutic

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Guidelines for the use of antiretroviral agents in HIV-infected adults and adolescents

These recommendations update the February 4,2002, guidelines developed by the Public Health Service for the use of zidovudine (ZDV) to reduce the risk for perinatal human immunodeficiency virus type 1 (HIV-1) transmission. This report provides healthcare providers with information for discussion with HIV-1-infected pregnant women to enable such women to make an informed decision regarding the use of antiretroviral drugs during pregnancy and use of elective cesarean delivery to reduce perinatal HIV-1 transmission. Various circumstances that commonly occur in clinical practice are presented, and the factors influencing treatment considerations are highlighted in this report. The Perinatal HIV Guidelines Working Group recognizes that strategies to prevent perinatal transmission and concepts related to management of HIV disease in pregnant women are rapidly evolving and will continually review new data and provide regular updates to the guidelines. The most recent information is available from the HIV/AIDS Treatment Information Service (available at http.//www.hivatis.org). In February 1994, the results of Pediatric AIDS Clinical Trials Group (PACTG) Protocol 076 documented that ZDV chemoprophylaxis could reduce perinatal HIV-1 transmission by nearly 70%. Epidemiologic data have since confirmed the efficacy of ZDV for reduction of perinatal transmission and have extended this efficacy to children of women with advanced disease, low CD4+ T-lymphocyte counts, and prior ZDV therapy. Additionally, substantial advances have been made in the understanding of the pathogenesis of HIV-1 infection and in the treatment and monitoring of persons with HIV-1 disease. These advances have resulted in changes in standard antiretroviral therapy for HIV-1-infected adults. More aggressive combination drug regimens that maximally suppress viral replication are now recommended. Although considerations associated with pregnancy may affect decisions regarding timing and choice of therapy pregnancy is not a reason to defer standard therapy. Use of antiretroviral drugs in pregnancy requires unique considerations, including the possible need to alter dosage as a result of physiologic changes associated with pregnancy the potential for adverse short- or long-term effects on the fetus and newborn, and the effectiveness of the drugs in reducing the risk for perinatal transmission. Data to address many of these considerations are not yet available. Therefore, offering antiretroviral therapy to HIV-1-infected women during pregnancy, whether primarily for HIV-1 infection, for reduction of perinatal transmission, or for both purposes, should be accompanied by a discussion of the known and unknown short- and long-term benefits and risks of such therapy to infected women and their infants. Standard antiretroviral therapy should be discussed with and offered to HIV-1-infected pregnant women. Additionally, to prevent perinatal transmission, ZDV chemoprophylaxis should be incorporated into the antiretroviral regimen.

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U.S. Public Health Service Task Force recommendations for use of antiretroviral drugs in pregnant HIV-1-infected women for maternal health and interventions to reduce perinatal HIV-1 transmission in the United States.

Aim: In the United Kingdom (UK) and Ireland, avoidance of breastfeeding and alternative combinations of antiretroviral therapy regimen and mode of delivery are recommended according to maternal clinical status. The aim of this analysis was to explore the impact of different strategies to prevent mother-to-child transmission at a population level. Design: Comprehensive national surveillance study. Methods: Pregnancies in diagnosed HIV-infected women in the UK and Ireland are notified to the National Study of HIV in Pregnancy and Childhood; infant infection status is subsequently reported. Factors associated with transmission in this observational study were explored for singleton births between 2000 and 2006. Results: The overall mother-to-child transmission rate was 1.2% (61/5151, 95% confidence interval: 0.9‐1.5%), and 0.8% (40/4864) for women who received at least 14 days of antiretroviral therapy. Transmission rates following combinations recommended in British guidelines were 0.7% (17/2286) for highly active antiretroviral therapy with planned Caesarean section, 0.7% (4/559) for highly active antiretroviral therapy with planned vaginal delivery, and 0% (0/464) for zidovudine monotherapy with planned Caesarean section (P ¼0.150). Longer duration of highly active antiretroviral therapy was associated with reduced transmission after adjusting for viral load, mode of delivery and sex (adjusted odds ratio ¼0.90 per week of highly active antiretroviral therapy, P ¼0.007). Among 2117 infants born to women on highly active antiretroviral therapy with viral load less than 50copies/ml, only three (0.1%) were infected, two with evidence of in-utero transmission. Conclusion: Sustained low HIV transmission rates following different combinations of interventions in this large unselected population are encouraging. Current options for treatment and delivery offered to pregnant women according to British guidelines appear to be effective. 2008 Wolters Kluwer Health | Lippincott Williams & Wilkins AIDS 2008, 22:973‐981

Low rates of mother-to-child transmission of HIV following effective pregnancy interventions in the United Kingdom and Ireland, 2000-2006

Background. Very low rates of mother-to-child transmission (MTCT) of human immunodeficiency virus (HIV) are achievable with use of highly active antiretroviral therapy (HAART). We examine risk factors for MTCT in the HAART era and describe infants who were vertically infected, despite exposure to prophylactic MTCT interventions. Methods. Of the 4525 mother-child pairs in this prospective cohort study, 1983 were enrolled during the period of January 1997 through May 2004. Factors examined included use of antiretroviral therapy during pregnancy, maternal CD4 cell count and HIV RNA level, mode of delivery, and gestational age in logistic regression analysis. Results. Receipt of antenatal antiretroviral therapy increased from 5% at the start of the HAART era to 92% in 2001-2003. The overall MTCT rate in this period was 2.87% (95% confidence interval [CI], 2.11%-3.81%), but it was 0.99% (95% CI, 0.32%-2.30%) during 2001-2003. In logistic regression analysis that included 885 mother-child pairs, MTCT risk was associated with high maternal viral load (adjusted odds ratio [AOR], 12.1; P = .003) and elective Caesarean section (AOR, 0.33; P = .04). Detection of maternal HIV RNA was significantly associated with antenatal use of antiretroviral therapy, CD4 cell count, and mode of delivery. Among 560 women with undetectable HIV RNA levels, elective Caesarean section was associated with a 90% reduction in MTCT risk (odds ratio, 0.10; 95% CI, 0.03-0.33), compared with vaginal delivery or emergency Caesarean section. Conclusions. Our results suggest that offering an elective Caesarean section delivery to all HIV-infected women, even in areas where HAART is available, is appropriate clinical management, especially for persons with detectable viral loads. Our results also suggest that previously identified risk factors remain important.

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Mother to child transmission of HIV infection in the era of highly active antiretroviral therapy

In a collaboration of 7 European and United States prospective studies, 44 cases of vertical human immunodeficiency virus type 1 (HIV-1) transmission were identified among 1202 women with RNA virus loads 500 copies/mL. Perinatal HIV-1 transmission occurs in only 1% of treated women with RNA virus loads <1000 copies/mL and may be almost eliminated with antiretroviral prophylaxis accompanied by suppression of maternal viremia.

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Perinatal Transmission of Human Immunodeficiency Virus Type 1 by Pregnant Women with RNA Virus Loads <1000 Copies/mL

OBJECTIVES
To investigate the association between maternal RNA load, risk of vertical transmission of HIV-1, and other variables.


METHODS
Plasma or serum samples from mothers of 373 children, enrolled in the prospective European Collaborative Study, were collected around time of delivery, and HIV-RNA quantified using two types of commercial assay. Women and children were followed according to a standard protocol. Adjusted odds ratios (AOR) were calculated to estimate the effect of RNA load and other maternal factors on vertical transmission.


RESULTS
Maternal RNA levels, mode of delivery and gestational age were independently associated with transmission. Vertical transmission increased with increasing RNA levels, but there was no threshold below which transmission did not occur. The risk was more than double for women with RNA above the sample specific median [AOR 2.36 (1.23-4.52)]. Elective caesarean section was associated with a substantial and significant decrease in transmission [AOR 0.19 (0.06-0.55)], and delivery before 37 weeks gestation with an increased risk [AOR 2.67 (1.33-5.38)]. Elective caesarean section was effective in both subgroups defined by median RNA level [AORs 0.37 (0.08-1.71) and 0.15 (0.03-0.64) below and above median respectively]. The predicted rate of transmission in a woman with a low RNA load delivering by elective caesarean section or vaginally after 37 weeks is around 2%, and 11%, respectively.


INTERPRETATION
Mother-to-child transmission of HIV-1 is multi-factorial; high RNA load is an important determinant but clearly not the only one. Interventions that target risk factors other than maternal RNA load remain important.

A deRossi

Papers

Maternal viral load and vertical transmission of HIV-1 an important factor but not the only one