Special Considerations for the Treatment of HIV in Women

Release Date: September 1, 2012

Expiration Date: September 30, 2014

FACULTY:

Allana J. Sucher, PharmD, BCPS
Associate Professor of Pharmacy Practice
Regis University School of Pharmacy
Denver, Colorado

Peter Clapp, PhD
Assistant Professor of Pharmaceutical Sciences
Regis University School of Pharmacy
Denver, Colorado

FACULTY DISCLOSURE STATEMENTS:

Drs. Sucher and Clapp have no actual or potential conflicts of interest in relation to this activity.

Postgraduate Healthcare Education, LLC does not view the existence of relationships as an implication of bias or that the value of the material is decreased. The content of the activity was planned to be balanced, objective, and scientifically rigorous. Occasionally, authors may express opinions that represent their own viewpoint. Conclusions drawn by participants should be derived from objective analysis of scientific data.

ACCREDITATION STATEMENT:

Pharmacy acpe
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UAN: 0430-0000-12-019-H02-P
Credits: 2.0 hours (0.20 ceu)
Type of Activity: Knowledge

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TARGET AUDIENCE:

This accredited activity is targeted to pharmacists. Estimated time to complete this activity is 120 minutes.

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DISCLAIMER:

Participants have an implied responsibility to use the newly acquired information to enhance patient outcomes and their own professional development. The information presented in this activity is not meant to serve as a guideline for patient management. Any procedures, medications, or other courses of diagnosis or treatment discussed or suggested in this activity should not be used by clinicians without evaluation of their patients' conditions and possible contraindications or dangers in use, review of any applicable manufacturer's product information, and comparison with recommendations of other authorities.

GOAL:

To provide participants with the knowledge necessary to appropriately manage female patients infected with HIV.

OBJECTIVES:

After completing this activity, the participant should be able to:

  1. Describe the impact of HIV on women and identify risk factors for HIV transmission in women.
  2. Recommend appropriate antiretroviral regimens for the treatment of HIV in pregnant and nonpregnant women.
  3. Recognize which antiretroviral agents are recommended and which should be avoided in pregnant women.
  4. Counsel a female patient who is receiving antiretroviral therapy for HIV and discuss strategies to prevent perinatal transmission of HIV.

In the United States, 1 in 139 women will be diagnosed with HIV during her lifetime, with black and Latina/Hispanic women representing a disproportionate number of cases.1 Although treatment goals and indications for initiation of antiretroviral therapy (ART) for HIV infection are the same for males and females, there are gender differences in ART-related adverse effects (AEs).2 In addition, ART plays an integral role in preventing perinatal transmission of HIV from a pregnant female to her infant.3 This article reviews guidelines for the use of antiretroviral agents in nonpregnant and pregnant women with HIV, with a focus on special considerations in females.

Epidemiology

In 2011, the CDC released modified estimates of HIV infection incidence for 2006 through 2009. According to these data, 24% of U.S. adults and adolescents with HIV in 2009 were female. Ethnic and racial minorities were represented disproportionately, such that the rate of new HIV infections in black women was 15 times that in white women and more than three times that in Latina/Hispanic women.4

From 2006 through 2009, the composite number of new HIV infections diagnosed in women decreased. It is unclear whether this decline is due to a lower rate of incidence or reflects trends in HIV testing and treatment. As treatment becomes more readily available, first-time diagnoses may inaccurately represent the number of new HIV infections, since the CDC data include persons who were tested late in the course of infection, had limited access to care, or experienced treatment failure. Despite advances in testing and treatment, AIDS remains one of the leading causes of death for black and Latina/Hispanic females in some age groups.4

Risk Factors in Women

In women diagnosed with HIV infection, the two most common methods of transmission are high-risk heterosexual contact and injection drug use (IDU). High-risk sexual contact includes nonconsensual sex, sex without using a condom, and sex with partners with high-risk behavior or undisclosed sexual history.1,5

There are several identified risk factors that contribute to the prevalence of HIV in women. Lack of education about the risk of acquiring HIV from unprotected vaginal or anal sex and reluctance to ask a partner to use a condom contribute to heterosexual transmission. Women with a history of sexual abuse are more likely to engage in high-risk behaviors or sexual activities (such as unprotected sex) and may have difficulty refusing unwanted sex. IDU increases infection risk in that the individual may share injection equipment contaminated with HIV or engage in high-risk behaviors while under the influence of drugs. The presence of other sexually transmitted diseases (STDs) increases the likelihood of acquiring or transmitting HIV, and certain ethnic groups are disproportionately affected by certain STDs; therefore, there is a disproportionate incidence of infection among certain ethnic groups. Finally, socioeconomic issues such as limited access to health care, the practice of exchanging sex to meet financial or other needs, and higher levels of substance use in areas of greater economic need influence risk factors for HIV transmission.1,5

A recent prospective study conducted in Africa investigated the association between hormonal contraceptive use and the risk of HIV acquisition and transmission. A twofold increased risk of HIV acquisition by women and of transmission from women to men occurred with the use of hormonal contraceptives, with long-acting injectable depot medroxyprogesterone acetate the most commonly used method among study participants. The investigators recommended that clinicians counsel women about the potential for an increased risk of acquiring and transmitting HIV with this contraceptive method and stress the importance of consistent condom use.6 However, because not all studies have found hormonal contraception to be a risk factor for HIV acquisition or transmission, further studies are needed to determine whether there is a definitive link.7

Goals of Therapy

As it is not possible to eradicate the HIV virus, the primary goals of ART initiation in both men and women are to reduce HIV-associated morbidity and mortality, restore and preserve immunologic function, suppress HIV viral load, and prevent behavior-associated HIV transmission.2,8 An additional goal in pregnant women is to prevent perinatal transmission.3

Initiating HIV Treatment

The Department of Health and Human Services guidelines for the use of antiretroviral agents in HIV-1 infected adults and adolescents were revised in March 2012. The updated guidelines recommend ART for all treatment-naïve HIV-infected individuals, with the strength of the recommendation based on the patient's pretreatment CD4+ T-cell count (TABLE 1).2


Regardless of an individual's CD4+ count, ART is strongly recommended for patients with certain conditions: pregnancy, history of an AIDS-defining illness, HIV-associated nephropathy, or coinfection with HIV and hepatitis B. The updated guidelines also state that, in order to prevent secondary transmission, ART should be offered to patients who are at risk for transmitting HIV to sexual partners. This recommendation is based on a study that showed reduced rates of sexual transmission of HIV in serodiscordant couples with early ART initiation (discussed in further detail later in this article). The strength of the recommendation varies based on the type of sexual transmission, with an AI recommendation for heterosexual transmission and an AIII recommendation for male-to-male and other types of transmission.2,9 In July 2012, the in HIV-uninfected men who have sex with men, HIV-uninfected partners in serodiscordant couples, and individuals who are at risk for acquiring HIV through sexual transmission.10

Prior to ART initiation, a number of laboratory tests should be performed. These include CD4+ count; plasma HIV RNA viral load; basic chemistry profile, including serum creatinine; CBC; liver-function tests; serology for hepatitis A, B, and C viruses; fasting blood glucose and lipid levels; and genotypic resistance testing. In addition, a pregnancy test should be administered prior to efavirenz use.2

Preferred Treatment Regimens:The guidelines recommend specific regimens as preferred treatments in both male and nonpregnant female antiretroviral-naïve patients (TABLE 2).11 However, a patient's antiretroviral regimen must be individualized according to virologic efficacy, AEs, drug-drug interaction potential, adherence, convenience, comorbid conditions, pregnancy and potential for pregnancy, and results of resistance testing. Based on all of these factors, an alternative regimen may be preferred for a specific patient.2


Special Considerations in Women

Disease-Related Effects:Authors of a recent study that found an increased risk of anal cancer in HIV-infected women recommend that clinicians consider measures to increase routine anal cancer screening. They also recommend that a high-resolution anoscopy be performed in patients who have abnormal findings upon anal cytology.12

Medication-Related Effects: Efavirenz should not be used in the first trimester of pregnancy because of the potential for birth defects (discussed later in this article). Since no contraceptive method is completely effective, the guidelines recommend that an additional or alternative method be considered in women of childbearing age. Before a woman begins taking efavirenz, a pregnancy test must be performed and the patient must have access to effective contraception. If efavirenz is used, women of childbearing age should be counseled about its teratogenic potential and the importance of avoiding pregnancy while taking it.3,11

Use of the nonnucleoside reverse transcriptase inhibitor (NNRTI) nevirapine in women with CD4+ counts >250 cells/mm3 or elevated baseline transaminase levels confers an increased risk of potentially fatal liver toxicity. This agent is not recommended in this population unless the benefit outweighs the risk.2,11

There is an increased risk of symptomatic and potentially fatal lactic acidosis with prolonged exposure to the nucleoside reverse transcriptase inhibitor (NRTI) class of drugs. Although this AE has been reported most frequently with stavudine, didanosine, and zidovudine, it can occur with any agent in the NRTI class.2,13

An increased prevalence of bone disease has been described in HIV-infected individuals, most commonly low bone mineral density (BMD) and osteoporosis. In addition to general risk factors, viral infection and ART may be involved in the pathogenesis of osteoporosis in older women. ART initiation, especially with regimens containing tenofovir, is associated with reduced BMD and recently was linked to a greater risk of bone fracture.14,15

Finally, HIV-infected women receiving ART have a higher incidence of central fat distribution and a lower incidence of elevated triglycerides compared with HIV-infected men.2,16,17

Drug Interactions With Contraceptives: It is important for pharmacists to be aware of the potential for drug interactions between hormonal contraceptives and agents in the protease inhibitor (PI) and NNRTI classes of antiretrovirals (TABLE 3). Women taking an antiretroviral agent that may significantly lower oral contraceptive (OC) efficacy should use an additional or alternative method (e.g., intrauterine device) in order to prevent unintended pregnancy. In cases where an interaction would result in higher levels of the OC, certain OC dosages should not be exceeded, so that AEs are minimized. Efavirenz reduces levels of levonorgestrel, which may reduce the efficacy of this emergency contraceptive. Consistent use of condoms is recommended for all HIV-infected women and their partners, regardless of the use of other contraceptives, to protect against transmission of HIV and other STDs.2


Serodiscordant Couples

Expert consultation regarding reproductive options is recommended for serodiscordant couples (i.e., one person is HIV infected and the other is not). Both partners should be screened and treated for genital-tract infections, and maximal viral suppression should be achieved prior to any attempts to conceive. For an HIV-infected female whose male partner is not infected, artificial insemination is considered the safest conception method. In cases when the male is infected and the female partner is not, the use of sperm-preparation techniques in combination with intrauterine insemination, invitro fertilization, or sperm injection is recommended. Couples must be counseled about the potential risk of transmission to the uninfected partner and the fetus with these techniques, since no method has been shown to protect fully against HIV transmission.3

HPTN 052 was a clinical trial that evaluated the effects of immediate versus delayed initiation of ART in patients with CD4+ counts between 350 and 550 cells/mm3 on sexual transmission of HIV to uninfected partners. It was the first randomized trial to show that use of ART in HIV-infected individuals reduced the risk of viral transmission to an uninfected sexual partner. Based on trial results, if a serodiscordant couple is trying to conceive, ART should be started in the infected partner if his or her CD4+ count is ≤550 cells/mm3. ART initiation may be considered in patients with higher CD4+ counts, but therapy has not been proven to reduce sexual HIV transmission in this population. Again, it is important to counsel patients that this method does not fully protect against transmission of HIV.3,9

HIV Treatment in Pregnancy

Prior to Treatment: It is important for clinicians to be aware of the National Perinatal HIV Hotline (1-888-448-8765), a federally funded service that provides free clinical advice to health care providers (HCPs) caring for HIV-infected women and their infants.3

Perinatal infection has occurred in women with undetectable viral loads. Therefore, to prevent perinatal transmission, ART should be considered and offered regardless of the mother's HIV RNA level or CD4+ count. HCPs should discuss ART's benefits for maternal health and reductions in perinatal transmission, as well as the risk of medication AEs for the mother, fetus, and newborn infant. A woman's informed choice on whether or not to take medication should be respected, since coercive or punitive actions may discourage her from seeking appropriate prenatal care.3

The clinician should monitor for symptoms of acute retroviral syndrome (ARS), including fever, swollen lymph nodes, sore throat, skin rash, and myalgias or arthralgias. If ARS is suspected at any time during pregnancy or breastfeeding, HIV antibody and HIV RNA tests should be performed. All pregnant women with acute or recently acquired HIV should have baseline resistance testing and begin ART as soon as possible in order to prevent perinatal transmission. Repeat HIV antibody testing is recommended in the third trimester in women known to be at risk for HIV infection, including those who are incarcerated or live in areas with a higher incidence of HIV.3

Treatment Regimens: A combination regimen of at least three antiretroviral medications is recommended in pregnancy, regardless of the woman's CD4+ count. Although studies have suggested that an increased risk of preterm birth is possible with the use of ART, combination therapy is still recommended during pregnancy because of its benefits for maternal health and reduction in perinatal HIV transmission.3

In general, women who become pregnant while already on a fully suppressive HIV regimen should continue their treatment so as to suppress viral load, preserve immune status, prevent disease progression, and minimize risk of viral transmission to the fetus. A key exception to this recommendation is that an alternative agent should be substituted for efavirenz in the first trimester, if possible. This is because significant birth defects (anencephaly, microphthalmia, cleft palate) have occurred in primates and cases of neural tube defects have been reported in humans with first-trimester exposure. Although the use of efavirenz may be considered after the first trimester if it is determined to be the best choice over alternative agents, the drug is classified as Pregnancy Category D, and safety data are limited on its use in later stages of pregnancy.3,18

For women who were not already receiving ART when they presented for obstetric care and are now starting treatment, certain agents are preferred. For ART-naïve pregnant women, a combination regimen containing two NRTIs plus either an NNRTI or a PI is preferred (TABLE 4). Because resistance to NNRTIs is more common than resistance to PIs in ART-naïve patients, a PI-based regimen should be initiated in most cases. In women with HIV RNA viral loads >500 to 1,000 copies/mL, drug-resistance studies should be performed prior to ART initiation. If HIV is not diagnosed in the mother until late in pregnancy, it is recommended to initiate ART pending results of resistance testing so as not to delay therapy.3


Based on safety data for pregnancy and efficacy data for prevention of perinatal transmission, the preferred NRTI backbone for most patients is a combination of zidovudine and lamivudine. Zidovudine should be included in a pregnant woman's ART regimen unless she experiences toxicity (such as severe anemia), has documented resistance to the agent, is receiving stavudine (because of the potential for antagonism), or is already on a fully suppressive regimen. In these cases, alternative regimens should be used. However, the regimen should not contain didanosine in combination with stavudine because of the potential for fatal lactic acidosis and hepatic failure with their combined use during pregnancy.2,3

In terms of the NNRTIs, the use of efavirenz should be avoided during the first trimester, and safety data on its use in other trimesters are limited.3,11,18 Although nevirapine should not be started in treatment-naïve women with a CD4+ count >250 cells/mm3, it may be continued in treatment-experienced women already receiving and tolerating a nevirapine-based regimen, regardless of CD4+ count.19 Finally, the use of etravirine or rilpivirine is not recommended in ART-naïve patients because insufficient safety and pharmacokinetic data exist regarding these drugs' use in pregnancy.3

Lopinavir/ritonavir is the preferred PI in pregnant antiretroviral-naïve patients based on efficacy and safety data. Because of limited experience with their use in pregnancy, atazanavir and saquinavir boosted with low-dose ritonavir are considered to be alternative PIs. Indinavir (because of its higher pill burden and potential for kidney stones) and nelfinavir (because of its lower rate of viral response versus lopinavir/ritonavir) should be considered only in special circumstances. Safety and pharmacokinetic data are insufficient to recommend the routine use of other PIs (darunavir, fosamprenavir, tipranavir), entry inhibitors (enfuvirtide, maraviroc), or the integrase inhibitor raltegravir during pregnancy.3

The use of any antiretroviral agent during pregnancy should be reported to the Antiretroviral Pregnancy Registry (APR). This registry assesses the potential teratogenicity of agents in order to assist HCPs in weighing potential risks versus benefits of using medications during pregnancy. Information may be reported to the APR at www.APRegistry.com or 1-800-258-4263. In addition, long-term monitoring is recommended for any child who was exposed to ART in utero.3

Monitoring Parameters: All pregnant women receiving ART should take a glucose screening test at 24 to 48 weeks' gestation to assess for hyperglycemia and/or diabetes mellitus. Some experts recommend earlier screening in patients who were started on a PI-based regimen prior to pregnancy.3

Plasma HIV RNA levels should be monitored at baseline and 2 to 4 weeks after initiation of or changes to an antiretroviral regimen. Subsequently, levels should be assessed monthly until they are undetectable and reassessed at least every 3 months during pregnancy and at 34 to 36 weeks' gestation to determine whether cesarean section is indicated. For women with a baseline HIV RNA level >500 to 1,000 copies/mL, drug-resistance testing should be performed prior to ART initiation. In addition, women who have an increased viral load after prior suppression should undergo resistance testing. CD4+ counts should be monitored at baseline and reassessed at least every 3 months during pregnancy. For patients who have been on therapy for at least 2 years and are clinically stable with sustained suppression of HIV RNA levels, CD4+ counts may be reassessed less frequently (every 6 months).3

Discontinuing Therapy: An HIV regimen may need to be stopped because of severe or life-threatening toxicity, illness that prohibits oral intake (e.g., severe pregnancy-induced hyperemesis that is unresponsive to treatment), or lack of available medication; it also may be stopped at the patient's request. In acute situations, all ART agents should be stopped simultaneously and reintroduced simultaneously. In nonacute situations in which an NNRTI-containing regimen is being stopped electively, there are specific timing recommendations. Since this drug class has a long half-life, if an NNRTI is stopped at the same time as other agents, drug levels of only the NNRTI will remain in the body, potentially resulting in resistance to the class. The clinician may choose to stop the NNRTI first and continue the other agents for a period of time, or to switch from an NNRTI to a PI for a period of time and then stop all agents. Although the optimal time period between stopping an NNRTI and stopping other agents is not known, at least 7 days should be allowed (some experts recommend up to 30 days). The guidelines acknowledge that further research is needed to determine optimal timing strategies.3

If nevirapine is stopped for 2 or more weeks and then restarted, it must be reinitiated at a starting dose of 200 mg of the immediate-release formulation orally once daily for 2 weeks. This dose titration is necessary because nevirapine induces its own metabolism. Restarting the patient on a therapeutic dose will result in elevated drug levels and the increased potential for rash until enzyme induction has occurred.3

Prevention of Perinatal Transmission: The hallmark Pediatric AIDS Clinical Trials Group 076 trial showed a 68% reduction in perinatal transmission of HIV with the administration of zidovudine to the mother both antepartum and intrapartum and to the neonate for 6 weeks.20 Since that time, improvements in HIV counseling, HIV testing, and the use of triple drug regimens in pregnant women have resulted in perinatal transmission rates of less than 2% in the U.S. With the use of combined antepartum, intrapartum, and infant prophylaxis, it is currently estimated that fewer than 200 HIV-infected infants are born each year in the U.S.3,21

In general, women previously receiving ART should continue on the same regimen during pregnancy, with the avoidance of certain agents (as discussed earlier). Since ART prophylaxis is more effective when it is given for a longer time period, HIV treatment according to the preferred regimens (as described in the previous section) should be started as soon as possible during pregnancy in women not previously receiving treatment. If HIV RNA levels are >1,000 copies/mL near the time of delivery, cesarean delivery should be performed at 38 weeks' gestation. During the intrapartum period, oral ART should be continued and zidovudine should be given as a continuous infusion at a dosing regimen of 2 mg/kg IV over 1 hour, followed by 1 mg/kg/h until delivery. If a cesarean delivery is scheduled, IV zidovudine should be started 3 hours prior to the time of surgery. Oral zidovudine should be administered to the infant as soon as possible after birth and continued for 6 weeks.3

In women who did not receive ART during pregnancy, a continuous infusion of zidovudine should be given to the mother during labor and a combination ART regimen should be started in the infant as soon as possible after birth to reduce the risk of perinatal transmission. A typical infant ART regimen includes oral zidovudine for 6 weeks in combination with three doses of oral nevirapine given at birth, 48 hours later, and 96 hours after the second dose. If the mother did not receive antepartum or intrapartum ART, infant prophylaxis with a combination regimen of zidovudine and nevirapine (started as soon as possible after birth) should be given. In all cases, the mother should be evaluated to determine the need for therapy postpartum.3

Feeding of Infants and Children: Since affordable, safe, and sustainable replacement feeding options are available in the U.S., breastfeeding is not recommended for women infected with HIV. Although combination ART reduces the risk of perinatal transmission, it does not entirely eliminate the presence of intracellular virus in breast milk, thereby placing the infant at risk for infection and the resultant development of drug resistance. In addition, HIV-infected women should avoid premasticating food, since this practice has resulted in mother-to-child transmission of HIV.3,22

Psychosocial Issues Psychosocial issues, including abuse, discrimination, stigma, and poverty, lead to increased vulnerability in HIV-infected women and their families. In addition, the emotional impact of receiving an HIV-positive diagnosis can be profound. Access to primary care and therapy is affected by a woman's level of social support and her ability to afford treatment. Feelings of helplessness and skepticism about the efficacy of treatment may influence a woman's decision about beginning ART and the likelihood of her medication adherence. Effective medical management for women should include appropriate psychosocial care to mitigate the impact of HIV infection on self-esteem, relationships, reproductive choices, and family care.23

HIV infection has long been associated with an increased lifetime prevalence of depression and anxiety. Evidence that psychosocial factors can produce changes in cellular immunity—including increased susceptibility to infection and reactivation of latent virus—led investigators to examine how these factors may influence disease progression in immune-based disorders such as AIDS. Prior to the advent of highly active ART, depression in women living with HIV infection had been linked to clinical disease progression and increased AIDS-based mortality. Although the increased availability of antiretroviral medications has reduced the prevalence of opportunistic infections, the effects of psychosocial stressors on HIV-related health outcomes persist.23

Psychosocial issues also affect a woman's vulnerability to contracting HIV. Cultural pressure to have children, sexual coercion, and lack of access to or knowledge about safe practices, in combination with elevated biological vulnerability, contribute to disproportionate risk among women. Higher levels of depression associated with symptoms of HIV infection may lead to increased self-blame and distress among women, further promoting high-risk IDU and sexual behaviors. Psychosocial care that encourages self-efficacy in women may reduce the distress associated with living with chronic disease and coping with the social stigma attached to HIV infection.24

Conclusion

HIV remains a major public health challenge, particularly in women. Pharmacists play an important role in educating HCPs and patients about the appropriate use of ART for HIV treatment in both pregnant and nonpregnant females and for the prevention of HIV transmission. Pharmacists should work with clinicians to select the most suitable regimen for a particular patient. In addition, pharmacists can monitor and counsel patients regarding their drug therapy in order to achieve optimal outcomes, avoid drug interactions, and minimize unnecessary toxicity. Pharmacists must actively work with patients and other HCPs to ensure the proper treatment of HIV infection in women.

REFERENCES

  1. CDC. HIV among women. www.cdc.gov/hiv/topics/ women. Accessed May 11, 2012.
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  3. Panel on Treatment of HIV-Infected Pregnant Women and Prevention of Perinatal Transmission. Recommendations for use of antiretroviral drugs in pregnant HIV-1-infected women for maternal health and interventions to reduce perinatal HIV transmission in the United States;1-207. www.aidsinfo.nih.gov/contentfiles/lvguidelines/perinatalgl.pdf. Accessed August 16, 2012.
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  9. Cohen MS, Chen YQ, McCauley M. Prevention of HIV-1 infection with early antiretroviral therapy. N Engl J Med. 2011;365:493-505.
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  11. Lexi-Drugs [online database]. Hudson, OH: Lexi-Comp, Inc; 2012.
  12. Hou JY, Smotkin D, Grossberg R, et al. High prevalence of high grade anal intraepithelial neoplasia in HIV-infected women screened for anal cancer. J Acquir Immune Defic Syndr. 2012;60:169-172.
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  15. Yin MT, Zhang CA, McMahon DJ, et al. Higher rates of bone loss in postmenopausal HIV-infected women: a longitudinal study. J Clin Endocrinol Metab. 2012;97:554-562.
  16. Thiébaut R, Dequae-Merchadou L, Ekouevi D, et al. Incidence and risk factors of severe hypertriglyceridaemia in the era of highly active antiretroviral therapy: the Aquitaine Cohort, France, 1996-99. HIV Med. 2001;2:84-88.
  17. Galli M, Veglia F, Angarano G, et al. Gender differences in antiretroviral drug-related adipose tissue alterations. Women are at higher risk than men and develop particular lipodystrophy patterns. J Acquir Immune Defic Syndr. 2003;34:58-61.
  18. Sustiva (efavirenz) product information. Princeton, NJ: Bristol-Myers Squibb Co; June 2012.
  19. Kesselring AM, Wit FW, Sabin CA, et al. Risk factors for treatment-limiting toxicities in patients starting nevirapine-containing antiretroviral therapy. AIDS. 2009;23:1689-1699.
  20. Connor EM, Sperling RS, Gelber R, et al. Reduction of maternal-infant transmission of human immunodeficiency virus type 1 with zidovudine treatment. New Engl J Med. 1994;331:1173-1180.
  21. Achievements in public health: reduction in perinatal transmission of HIV infection—United States, 1985-2005. MMWR Morb Mortal Wkly Rep. 2006;55:592-597.
  22. Gaur AH, Freimanis-Hance L, Dominguez K, et al. Knowledge and practice of prechewing/prewarming food by HIV-infected women. Pediatrics. 2011;127:e1206-e1211.
  23. Leserman J. Role of depression, stress, and trauma in HIV disease progression. Psychosom Med. 2008;70:539-545.
  24. Vosvick M, Martin LA, Smith NG, Jenkins SR. Gender differences in HIV-related coping and depression. AIDS Behav. 2010;14:390-400.

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