Help HIV-positive women reach reproductive goals

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As primary care providers for a significant proportion of women in their practices, ob/gyns need to be holistic in their approach to patient care. This includes a comprehensive assessment of risk factors for different diseases, including HIV. This article underscores the importance of keeping up to date on the latest evidence and recommendations on HIV prevention. The focus is on the Undetectable=Untransmittable (U=U) advocacy campaign, which has been essential in disseminating key science to both the healthcare community and the general public.

Ob/gyns must provide the highest quality, most effective care for patients who may be at risk for acquiring HIV, and for women living with HIV (WLHIV). Prevention has always been a cornerstone of high-quality and cost-effective medical care, but the growing understanding of how to effectively prevent HIV transmission makes this even more imperative. Ob/gyns also must consider how best to help women achieve their reproductive heath goals while preventing HIV acquisition or transmission to their partner.

Current guidelines and HIV prevention
The most recent American College of Obstetricians and Gynecologists (ACOG) guidelines to address gynecologic care for WLHIV are Practice Bulletin (PB) 167 and Committee Opinion 595.^1,2 PB 167 includes treatment considerations and recommendations for prevention of transmission to uninfected partners,¹ while the Committee Opinion specifically describes use of pre-exposure prophylaxis, or PrEP, for women at high risk of exposure to HIV. Screening and recommendations for prevention of mother-to-child transmission of HIV are detailed in other PBs and clinical guidelines, and are not the focus on this article.^2,3 PB 167 integrates the 2016 Department of Health and Human Services (DHHS) recommendation that antiretroviral therapy with a triple drug regimen be initiated in all adults and adolescents diagnosed with HIV, regardless of their current clinical symptoms or CD4+ count.^{1, 3} This update replaced previous recommendations for therapy based on a threshold CD4+ count, pregnancy or clinical signs of immunosuppression. In addition, the DHHS guidelines suggest that male partners of WLHIV may take a daily antiretroviral pill (tenofovir/emtricitabine or PrEP) to reduce risk of HIV acquisition. 

Consistent use of antiretroviral therapy reduces risk of short and long-term complications of HIV, including risks related to immunosuppression and development of drug resistance. Use of effective antiretroviral therapy that induces HIV viral suppression, which is the reduction of HIV viral load in the blood to undetectable levels, is a powerful HIV prevention mechanism, also known as Treatment as Prevention (TasP). In addition to several smaller studies, three large, randomized studies that
included over 3300 couples in which the infected partner was virally suppressed on anti-retroviral therapy for at least 6 months showed no HIV transmissions to the HIV-negative partner.^4-8 That protection has been shown to be durable for over 10 years in Switzerland, which has seen an overall decrease in HIV incidence despite an increase in condomless sex over the past decade, and reports no documented HIV transmission in the setting of suppression.⁹ Since these studies were published, researchers, advocates and patients have sought clarity on the practical implications for serodiscordant couples. What about condoms? PrEP? A combination of TasP + PrEP? These nuanced questions are especially relevant for serodiscordant couples seeking pregnancy, who for a long time have been treated as a high-risk group, and still have recommendations that fall outside of this list of evidence-based options. 

U=U Campaign
Despite strong evidence from clinical trials, the value of TasP had not reached people living with HIV (PLWH). To remedy inadequate dissemination of research findings and recommendations, Prevention Access Campaign spearheaded the Undetectable=Untransmittable, or U=U, campaign. In the past 3 years, the U=U campaign has become a popular global movement endorsed by over 400 organizations from 60 countries. Although the evidence for treatment as prevention has been around for almost 20 years, U=U has played a key role in simplifying and amplifying the message. Ob/gyns should understand the implications of the message, and how the science and tools for HIV prevention translate to their patients. The strong, consistent evidence that virally-suppressed individuals on antiretroviral therapy do not transmit HIV has the potential to transform the lives of people and couples living with HIV, removing barriers of stigma and allowing PLWH to imagine lives in which they are not risking their intimate partners with infection. The U=U movement scored major victories in 2017 when the director of the National Institute of Allergy and Infectious Diseases (NIAID), Dr. Anthony Fauci, declared that the evidence now shows that no HIV transmission has been documented when viral suppression treatment has been implemented. In October 2017, the Centers for Disease Control and Prevention (CDC) made a definitive statement supporting U=U, specifically affirming that “when ART results in viral suppression, defined as less than 200 copies/mL or undetectable levels, it prevents transmission.”¹⁰

How does this now widely accepted understanding of the lack of HIV-transmission risk among virally suppressed individuals align with the 2016 ACOG PB?¹ ACOG does not directly address U=U, and it recommends that women with HIV use condoms to prevent transmission of HIV, citing level A evidence. Published before the NIH and CDC statements of 2017, the ACOG PB states that “women infected with HIV with undetectable plasma loads should be counseled that they can still transmit HIV.”¹ While the recommendation for universal treatment is important, ob/gyns should rely on DHHS and CDC recommendations when counseling serodiscordant couples.

Preconception counseling
Another key area where guidance from an ob/gyn may impact decision-making and health behaviors is preconception counseling. While ACOG recognizes that WLHIV and HIV-uninfected women have similar reproductive health desires, the PB states that the safest way for serodiscordant couples to conceive is through artificial insemination.¹ Unfortunately, a CDC update on conception among serodiscordant couples released in August 2017 echoed this recommendation, which was not reflective of the strong evidence on TasP. Many experts in the field would argue that the evidence for TasP does not support the continued need for assisted reproductive technology in women who are virally suppressed.^{11, 12} I support the opinion expressed in the consensus statement that  recommendations to use assisted reproductive technology in spite of evidence supporting TasP and PrEP as options for safe conception do a disservice to women and couples. These recommendations continue to “other” and stigmatize serodiscordant couples, and putting the achievement of a desired pregnancy out of financial reach for many of them. This is compounded by continued evidence that many laboratories that provide assisted reproductive technology discriminate against and do not provide services for serodiscordant couples.¹³ In the face of strong and consistent evidence supporting the effectiveness of both TasP and PrEP, WLHIV should know that they have the option to achieve pregnancy safely and effectively without assisted reproductive technology. ACOG and the Society and Maternal and Fetal Medicine are the bodies that most ob/gyns look to for guidance in practicing evidence-based and patient-centered decisions, so they should ensure that their guidelines reflect the latest evidence in this key area of reproductive health for WLWH and women in HIV-serodiscordant relationships.

HIV prevention
Finally, ob/gyns can play a key role in assessing risk for HIV exposure, and counseling their patients about use of PrEP. The Committee Opinion provides guidelines for identifying who, beyond women in serodiscordant relationships, would benefit from PrEP.² In alignment with CDC guidelines, risk factors include sexual activity within a high HIV-prevalence area or high-risk sexual network along with one or more of the following: inconsistent or no condom use; diagnosis of sexually transmitted infections (STIs); exchange of sex for commodities (such as money, shelter, food, or drugs); use of intravenous drugs or alcohol dependence or both; or incarceration. Importantly, providers should ask patients about potential partner(s) whose HIV status may be unknown and who may share any of the characteristics listed above.¹⁴ Counseling around family planning, STI and abortion services may be an ideal time to identify and discuss risks and benefits of PrEP with patients, although ob/gyns should do a risk and pregnancy desires assessment at each well-woman visit.

Beyond HIV risk reduction and preconception counseling, the increased number of women living longer, healthier lives on antiretroviral therapy means that ob/gyns should become familiar with gynecologic care of WLHIV, including cytology screening guidelines,¹⁵ potential complications of antiretroviral therapy, and factors that may change their transmission risk and medication adherence. Most importantly, ob/gyns should reinforce the importance of adherence to antiretroviral therapy, both for women’s own health and to reduce the risk for HIV and partner with a primary HIV-care provider or seek expert advice when complex issues arise. The National Clinician Consultation Center through the University of California, San Francisco, is an excellent source of up-to-date guidelines for  care of WLHIV and HIV-exposed women and free real-time clinician support for HIV-related questions (http://nccc.ucsf.edu/clinical-resources/hiv-aids-resources/womens-health/).

Conclusion
The U=U movement has helped to inform the greater public that PLWH who are virally suppressed cannot transmit the virus through sexual activity. Their message, which has been instrumental in reducing stigma and discrimination among PLWH, is built on a strong foundation of scientific evidence. As ob/gyns, we owe it to our patients to understand the evidence and provide the information and potentially life-saving HIV-prevention strategies to our patients. 

Disclosures:

The author reports no potential conflicts of interest with regard to this article.

References:

• Gynecologic care for women and adolescents with human immunodeficiency virus. Practice Bulletin No. 167. American College of Obstetricians and Gynecologists. Obstet Gynecol 2016;128:e89–110.

• Prenatal and perinatal human immunodeficiency virus testing. ACOG Committee Opinion No. 752. American College of Obstetricians and Gynecologists. Obstet Gynecol 2018;132:e138–42.

• Panel on Antiretroviral Guidelines for Adults and Adolescents. Guidelines for the Use of Antiretroviral Agents in Adults and Adolescents Living with HIV. Department of Health and Human Services. Available at http://aidsinfo.nih.gov/contentfiles/lvguidelines/AdultandAdolescentGL.pdf. Section accessed October 1, 2018.

• Baeten J, Donnell D, Ndase P, Mugo N, Campbell J, Wangisi J, et al. Antiretroviral prophylaxis for HIV prevention in heterosexual men and women. . N Engl J Med 2012; 367:399–410.

• Cohen M, Chen Y, McCauley M, Gamble T, Hosseinipour M, Kumarasamy N ea, et al. Prevention of HIV-1 infection with early antiretroviral therapy. . N Engl J Med 2011; 365:493-505.

• Rodger AJ, Cambiano V, Bruun T, Vernazza P, Collins S, van Lunzen J, et al. Sexual Activity Without Condoms and Risk of HIV Transmission in Serodifferent Couples When the HIV-Positive Partner Is Using Suppressive Antiretroviral Therapy. JAMA 2016; 316(2):171-181.

• Jia Z, Mao Y, Zhang F, Ruan Y, Ma Y, Li J, et al. Antiretroviral therapy to prevent HIV transmission in serodiscordant couples in China (2003-11): a national observational cohort study. Lancet 2013; 382(9899):1195-1203.

• Tang Z, Lan G, Chen YQ, Zhu Q, Yang X, Shen Z, et al. HIV-1 Treatment-as-Prevention: A Cohort Study Analysis of Serodiscordant Couples in Rural Southwest China. Medicine (Baltimore) 2015; 94(24):e902.

• Vernazza P, Bernard EJ. HIV is not transmitted under fully suppressive therapy: The Swiss Statement--eight years later. Swiss Med Wkly 2016; 146:w14246.

• Dear Colleague. Centers for Disease Control and Prevention Report, September 2017. https://www.cdc.gov/hiv/library/dcl/dcl/092717.html Accessed October 1, 2018.

• Brooks JT, Kawwass JF, Smith DK, Kissin DM, Lampe M, Haddad LB, et al. Effects of Antiretroviral Therapy to Prevent HIV Transmission to Women in Couples Attempting Conception When the Man Has HIV Infection - United States, 2017. MMWR Morb Mortal Wkly Rep 2017; 66(32):859-860.

• Matthews LT, Beyeza-Kashesya J, Cooke I, Davies N, Heffron R, Kaida A, et al. Consensus statement: Supporting Safer Conception and Pregnancy For Men And Women Living with and Affected by HIV. AIDS Behav 2018; 22(6):1713-1724.

• Leech AA, Bortoletto P, Christiansen C, Drainoni ML, Linas BP, Roeca C, et al. Assessing access to assisted reproductive services for serodiscordant couples with human immunodeficiency virus infection. Fertil Steril 2018; 109(3):473-477.

• ACOG Committee Opinion no 595: Committee on Gynecologic Practice: Preexposure prophylaxis for the prevention of human immunodeficiency virus. Obstet Gynecol 2014; 123(5):1133-1136.

• Guidelines for Prevention and Treatment of Opportunistic Infections in HIV-Infected Adults and Adolescents. In; 2018.