Dr. Leila Alijani

Etiopathogenesis and Epidemiology

Causative agents of acquired immunodeficiencysyndrome (AIDS) are RNA retroviruses termed humanimmunodeficiency viruses, HIV-1 and HIV-2.

Most cases worldwide are caused by HIV-1 infection.Sexual intercourse is the major mode of transmission.The virus also is passed by blood, and infectedmothers may infect their fetuses during labor anddelivery or by breast milk. The primary determinant oftransmission is the plasma HIV-1viral load.

Clinical Manifestations

The incubation period from exposure to clinical diseaseaverages 3 to 6 weeks. Acute HIV infection is similar tomany other viral syndromes and usually lasts less than10 days. Common symptoms, if any, include fever,fatigue, rash, headache, lymphadenopathy,pharyngitis, myalgias, nausea, and diarrhea. Aftersymptoms abate, the level of viremia usually decreasesto a set point, and patients with the highest viralburden at this time progress more rapidly to AIDS anddeath.

According to the CDC, AIDS is defined by a CD4 T-cellcount <200 cells/μL, by CD4 T-cells comprising <14percent of all lymphocytes, or one of several AIDS-defining illnesses Route of infection, the pathogenicityof the infecting viral strain, the initial viral inoculum,and the immunological status of the host all affect therapidity of progression.

Prenatal HIV Screening

The CDC (2006b) and the American College ofObstetricians andGynecologists (2016e) recommendprenatal HIV screening using an opt-outapproach.This means that a woman is notified that HIV testingis included in a comprehensive set of antenatal tests,but that testing may be declined.

Women are given information regarding HIV but are notrequired to sign aspecific consent.

Repeat testing during the third trimester, preferablybefore 36 weeks’ gestation, is considered for allpregnant women. Retesting is recommended for thoseat risk for acquiring HIV or for women in high-riskareas, namely, those with rates of HIV infection of 1per 1000 pregnant women screened. At-risk factorsinclude injection drug use, prostitution, a suspected orknown HIV-infected sexual partner, multiple sexualpartners, or a diagnosis of another STD (AmericanCollege of Obstetricians and Gynecologists, 2016e.

Vertical Transmission

Viral burden and neonatal infection rates are directlyrelated. In one cohort, neonatal infection was 1 percentwith <400 copies/mL, and it was 23 percent whenmaternal viral RNA levels were >30,000 copies/mL

Transplacental HIV transmission can occur early, and thevirus has even been identified in specimens from electiveabortion . Kourtis and colleagues (2001) estimated that 20percent of vertical transmission occurs before 36 weeks’gestation, 50 percent in the days before delivery, and 30percent intrapartum. Transmission rates for breastfeedingmay be as high as 30 to 40 percent and are associated withincreasing HIV viral burden. In nonpregnant individuals,concomitant STDs and horizontal HIV transmission arelinked. Evidence also supports that vertical transmissionrates may be increased by comorbid STDs

Antepartum Care

At Parkland Hospital, an HIV-infected pregnant woman is initiallyassessed with the following:

Standard prenatal laboratory surveys that include serumcreatinine,complete blood count, and bacteriuria screening.

Plasma HIV RNA quantification—“viral load”—CD4 T-cell count, andSerum hepatic aminotransferase levels.

HSV-1 and 2, cytomegalovirus, toxoplasmosis, and hepatitis B and Cserological screening.

Baseline chest radiograph.

Tuberculosis testing with purified protein derivative (PPD) skin testing,or interferon-gamma release assay.

Evaluation of need for pneumococcal, hepatitis A, hepatitis B, Tdap,and influenza vaccines.

Sonographic evaluation to establish gestational age.

Antiretroviral Therapy

In overview, the ideal strategy to suppress viral load and minimizevertical HIV transmission includes:

(1) preconceptional ART,(2) antepartum ART,(3) intrapartum continuation of the antepartum oral ART regimen

plus IV zidovudine, and(4) newborn ART prophylaxis.ART is recommended for all HIV-infected pregnant women, and it

should be initiated as early in pregnancy as possible. Treatmentreduces the risk of perinatal transmission regardless of CD4 T-cell count or HIV RNA level. Adherence is essential because therisk of viral drug resistance is lessened. As for nonpregnantadults, pregnant women are treated with at least three antiviralagents.

First, women already taking ART at pregnancy onset areencouraged to continue the regimen if viralsuppression is adequate. Didanosine, stavudine, andfull-dose ritonavir, which differs from ritonavir-boosted agents, are exceptions due to pregnancytoxicity but not teratogenicity

Second, women who have never received antiretroviraltherapy —antiretroviral naïve—are given ARTregardless of trimester. In general, the starting egimencomprises two nucleoside reverse ranscriptaseinhibitorsplus either a ritonavir-boosted proteaseinhibitor or an integrase inhibitor.

Third, women who have previously receivedantiretroviral therapy but are currently not takingmedications should undergo HIV resistance testingbecause prior ART use raises their risk of drugresistance. Typically, ART is initiated prior to receivingresults of these drug-resistance tests. In this case,initial ART selection should factor results of priorresistance testing, if available; prior ART regimen; andcurrent ART pregnancy guidelines, that is, those forART-naïve women. Drug-resistance testing may thenmodify the initial regimen.

Most patients with adequate viral response have at least a 1-log viral load decline within 1 to 4 weeks after

starting therapy. For those who fail to achieve thisdecline, options include review of drug resistancestudy results, confirmation of regimen compliance,

and ART modification

During labor and delivery, oral medications can be takenwith sips of water. Additionally, IV zidovudine is given towomen with an HIV RNA viral load >1000 copies/mL orwho have an unknown viral load near delivery. At ParklandHospital, we administer intrapartum IV zidovudine to allHIV-positive women, regardless of viral load. A 2 mg/kgload is infused over 1 hour followed by zidovudine 1mg/kg/hr until delivery. In this instance, for gravidasalready taking antepartum oral zidovudine, their oral dosecan be held, and IV drug is instead administered. HIV-infected women undergoing a scheduled cesarean deliveryare given IV zidovudine as a loading dose followed by 2more hours of continuous maintenance therapy—

a total of 3 hours of infused zidovudine.

The fourth group includes women who present in labor and who are taking no medications. These women are given IV zidovudine intrapartum as just described

Delivery Planning

During labor, artificial membrane rupture, fetal scalpelectrode placement,vepisiotomy, and operative vaginaldelivery are reserved for clear obstetrical indications. Laboraugmentation is used when needed to shorten the intervalto delivery to further lower the transmission risk. Delayedcord clamping in preterm neonates is acceptableNeuraxialanalgesia is suitable. Postpartum hemorrhage is bestmanaged with oxytocin and prostaglandin analogues.Methylergonovine (Methergine) and other ergot alkaloidsadversely interact with reverse transcriptase and proteaseinhibitors to cause severe vasoconstriction.

In some cases, cesarean delivery lowers HIV prenataltransmission (European Mode of DeliveryCollaboration, 1999; International Perinatal HIVGroup, 1999). The American College of Obstetriciansand Gynecologists (2017b) recommends thatscheduled cesarean delivery be discussed andrecommended for HIV-infected women with HIV-1RNA loads >1000 copies/mL. Scheduled delivery isrecommended at 38 weeks’ gestation in these womento avert spontaneous labor.

For women with HIV RNA levels ≤1000 copies/mL, data areinsufficient to predict similar benefits, and scheduledcesarean delivery is unlikely to confer additional riskreduction for women already taking ART and achievingviral suppressio.

Vaginal delivery in this group may be elected. However, ifcesarean delivery is instead chosen for a well-counseledwoman in this group, it should be performed at 39 weeks.Similarly, cesarean delivery performed for obstetrical

indications in this lower-viral-load group should be done at39 weeks when possible.

Postpartum Care

Vertical transmission is increased by breastfeeding, andit generally is not recommended for HIV-positivewomen in the United States, where formula is readilyavailable (Read, 2003). In nutritionally deprivedcountries, where infectious disease and malnutritionare primary causes of infant death, the World HealthOrganization (2016) recommends exclusivebreastfeeding during the first 6 to 12 month.

The Panel on Treatment of HIV-Infected PregnantWomen and Prevention of Perinatal Transmission(2016) strongly recommends that ART regimens

not be discontinued postpartum but continued lifelongfor the advantages of viral suppression.

For women who do not have HIV infection, but whosepartner is seropositive, current guidance supports theuse of highly active antiretroviral therapy with viralsuppression in the infected partner (treatment asprevention), and consideration of antiretroviralpreexposure prophylaxis (PreP) for the HIV-negativepartner. The well-counseled couple can considerperiovulatory condomless intercourse, or uterineinsemination or in vitro fertilization after spermwashing for assisted conception.

If, instead, pregnancy is undesired, effectivecontraception is discussed (Chap. 38, p. 680).Counseling also includes education for decreasinghighrisk sexual behaviors to prevent transmission andto decrease other STD acquisition. Similarly, womenwith HIV have unique gynecological issues, such asgenital neoplasia, which require special attention(American College of Obstetricians and Gynecologists,2016a; Werner, 2016).