#74714: HIV/AIDS: Update for Behavioral Health Professionals

As of 2021, an estimated 1.9 million individuals were living with HIV/AIDS in North America and western and central Europe, including approximately 1.2 million in the United States [8]. The CDC estimates that approximately 15% to 20% of these individuals are unaware of their infection [8,9]. To compound the problem, only 28% of individuals aware of their infection receive ongoing care. A majority of all individuals infected with HIV remain untested, without treatment, or both [8]. Unfortunately, this poses a risk both for those who are infected and for others.

Many changes in the progression of the HIV/AIDS epidemic should be considered. Since the first reported cases of HIV in 1981 in the United States, the epidemic continues to vary a great deal between regions, states, and even communities. Populations that are affected by HIV are also shifting. In addition to individuals traditionally considered to be high-risk (e.g., men who have sex with men [MSM] or injection drug users [IDUs]), new groups have been identified as being at greater risk. For example, in the beginning stages of the HIV/AIDS epidemic in the United States, white people were chiefly impacted. However, the epidemic now greatly affects racial and ethnic minorities, particularly black Americans, who represent approximately 42% of all new diagnoses in the United States [10]. Men continue to be heavily affected by HIV, accounting for 80% of new HIV diagnoses in 2020 [10].

One should keep in mind when reviewing HIV/AIDS trends that the widespread use of combination antiretroviral therapy (cART) has resulted in fewer deaths and longer survival [8]. As of 2020, the Centers for Disease Control and Prevention (CDC) report several trends in the HIV/AIDS epidemic [10]:

The CDC has published guidelines for medical professionals to integrate HIV prevention into the regular medical care of those living with HIV. The three major components of the recommendation are [11]:

The National HIV/AIDS Strategy for the United States 2022–2025 was developed by the White House Office of National AIDS Policy (ONAP) in collaboration with federal partners and with input from the HIV community across the country [12]. The Strategy is the nation's third national HIV strategy and updates the HIV National Strategic Plan of 2021. The Strategy sets targets for ending the HIV epidemic in the United States by 2030, including a 75% reduction in new HIV infections by 2025 and a 90% reduction by 2030 [12].

The CDC developed a method to better measure the rate of HIV infections in the United States. The Serologic Testing Algorithm for Recent HIV Seroconversion (STARHS) allows the CDC to more accurately monitor the number of new HIV infections in the United States, which in turn should facilitate targeted prevention in those populations most in need [13,14]. STARHS consists of two tests to determine both seropositivity and how recently the infection was contracted [15].

HIV has been isolated from blood, seminal fluid, pre-ejaculate, vaginal secretions, urine, cerebrospinal fluid, saliva, tears, and breast milk of infected individuals. Whether HIV infects spermatozoa is controversial. Reports of the removal of infected cells from semen, allowing artificial insemination without seroconversion, support the idea that spermatozoa are not infected. No cases of HIV infection have been traced to saliva or tears [19].

The virus is found in greater concentration in semen than in vaginal fluids, leading to a hypothesis that male-to-female transmission could occur more easily than female-to-male. Sexual behavior that involves exposure to blood is likely to increase transmission risks. Transmission could occur through contact with infected bowel epithelial cells in anal intercourse in addition to access to the bloodstream through breaks in the rectal mucosa.

Although all HIV-seropositive people are potentially infectious, there is widespread variation in the seropositivity and seroconversion of their sexual partners. Factors that could explain this variability include differences in sexual practices and numbers of sexual contacts, susceptibility of the partner, differences in viral strains, changing degrees of infectiousness of the person with HIV over time, co-factors that enhance or limit transmission, genetic resistance, or a combination of these factors.

Posing the highest risk of infection is unprotected receptive anal intercourse, followed by unprotected vaginal intercourse. Risk is reduced through the use of latex condoms. For the wearer, latex condoms provide a mechanical barrier limiting penile exposure to infectious cervical, vaginal, vulvar, or rectal secretions or lesions. Likewise, the partner is protected from infectious pre-ejaculate, semen, and penile lesions. Oil-based lubricants may make latex condoms ineffective and should not be used. Water-soluble lubricants are considered safe. Natural membrane condoms (made from lamb cecum) contain small pores and do not block HIV passage.

Latex condoms are considered highly effective at preventing HIV transmission, resulting in a 70% to 80% reduction compared to never users [20]. Although abstinence from sexual contact is the sole way to absolutely prevent transmission, using a latex condom to prevent transmission of HIV is more than 10,000 times safer than engaging in unprotected sex [21]. Sexual activity in a mutually monogamous relationship in which neither partner is HIV-infected and no other risk factors are present is considered safe [4].

The phenomenon of men who identify publicly as heterosexual and generally have committed relationships with women, but who also engage in sexual activity with other men, termed being on the "down low" or DL, may be a transmission bridge to heterosexual women. In a 2005 study, researchers surveyed 328 MSM in 12 cities and found that 43% of black men, 26% of Hispanic men, and 7% of white men reported being on the down low [22]. However, it is important to note that men on the "down low" are not the only MSM who report having sexual contact with women. In a larger study of 5,000 HIV-positive MSM, 22% of gay-identified black MSM and 61% of bisexual-identified black MSM reported having had sex with a woman in the past five years [23]. Also, a 2009 study of 1,151 black MSM found that men who identified as "down low" were not more likely to engage in unprotected vaginal or anal sex with women or men [24]. Research has also shown that men who have sex with both men and women are less likely to have ever been tested for HIV or to have received information about HIV prevention than men who have sex with men only [25]. To better understand the actual extent of this behavior and its impact on HIV transmission, more research and studies must be undertaken.

It has been estimated that a milliliter of HIV-infected human blood contains up to 10,000 copies of the virus. In comparison, a milliliter of blood infected with hepatitis B virus has 100 million to 1 billion infective organisms. Even so, HIV is transmitted via blood, primarily through sharing of contaminated needles among IDUs and, rarely, through blood transfusion. Transmission of HIV-1 has occurred after transfusion of the following components: whole blood, packed red blood cells (including washed and buffy coat poor), fresh frozen plasma, cryoprecipitate, platelets, and plasma-derived products, depending on the production process. With the implementation of a donor screening program of the nation's blood supply in 1985 and advances in the treatment of donated blood products, blood transfusion is now even safer; the current risk of transmission of HIV through this route is conservatively estimated to be 1 in 1.5 million [27]. It is possible that before blood screening implementation, more than 12,000 people were infected. A large percentage of hemophiliacs acquired HIV in this manner. Donor screening, HIV testing, and heat treatment of the clotting factor have greatly reduced the risks.

More than 3,100 new HIV infections occurred in 2020 among IDUs [10]. Transmission of HIV among injecting drug users occurs primarily through contamination of injection paraphernalia with infected blood. The risk of sustaining HIV infection from a needle stick with infected blood is approximately 1 in 300. Behavior such as needle sharing, "booting" the injection with blood, and performing frequent injections increases the risk. Cocaine use (by injection or smoking) is associated with a higher prevalence of HIV infection. This may in part be attributed to the exchange of cocaine for sex. Sharing of equipment is common due to legal and financial restrictions and cultural norms. Geographically, the rate of infection varies; 80% of New York City addict needle-sharers are infected, as opposed to lower rates in other metropolitan area clusters. Secondary transmission occurs to children and sexual partners. Preventive strategies include drug treatment, onsite medical care in a drug treatment program, recruitment of "street" outreach workers for intensive drug and sex "risk reduction" educational campaigns, teaching addicts to sterilize their equipment between use, the free provision or exchange of sterile injection equipment (as allowed by law), distribution of condoms and bleach to clean drug use equipment, or a combination of these interventions [4].

Syringe services programs (SSPs) are community-based prevention programs that provide a range of services, including access to and disposal of sterile syringes and injection equipment. SSPs can reduce needlestick injuries and overdose deaths. Studies show that SSPs protect first responders and the public by providing safe needle disposal. They can also serve as a bridge to other health services, including HCV and HIV diagnosis and treatment [28].

Health professionals should stress the following messages when they counsel IDUs [29]:

It is important to note that a disinfected syringe is not a sterile syringe. The best option is always to use a new, sterile syringe with every injection.

In the absence of prophylactic treatment, approximately 30% to 50% of children born to mothers with HIV will contract HIV infection. HIV is transmitted to infants by transplacental spread from mother to fetus in utero, during parturition, or through breastfeeding after birth [30]. Because infants have underdeveloped natural resistance systems, they are highly susceptible to many infections, including HIV. Both uninfected and infected infants have been born to mothers who have previously borne an infected infant. Studies have dramatically shown the beneficial effect of treating pregnant women and newborns with zidovudine (ZDV) to prevent transmission to the child, resulting in dramatic declines in the incidence of perinatally acquired AIDS [30]. Standard screening of all pregnant women is necessary to reduce transmission of HIV to infants.

Worldwide, perinatal transmission accounts for most HIV infections among children. In the United States in 2019, an estimated 84 infants were born with HIV infection, a 41% decrease from 2015 [30]. This dramatic decrease is mainly attributed to the use of cART [31]. Other strategies for reducing perinatally acquired HIV infection have included preventing HIV infection among women and, for women with HIV, avoiding pregnancy or refraining from breastfeeding.

On February 21, 1994, the National Institutes of Health's National Institute of Allergy and Infectious Diseases (NIAID) and National Institute of Child Health and Human Development (NICHD) announced preliminary results from a randomized, multicenter, double-blind clinical trial of ZDV to prevent HIV transmission from mothers to their infants. This report summarizes the interim results of that trial, which indicate effectiveness of ZDV for prevention of perinatal transmission. Based on these interim findings, NIAID accepted the recommendation of an independent data and safety monitoring board to terminate enrollment into the trial and to offer ZDV to women in the group who had received the placebo but had not yet delivered and to their infants younger than 6 weeks of age [32].

Because these procedures are less common than other transmission-related activities, there have been very few case reports of HIV acquisition by this route. HIV has been transmitted via transplanted kidneys, liver, heart, pancreas, bone, and, possibly, skin grafts and through artificial insemination. HIV testing is used in these circumstances to rule out infection. Most cases of transmission through transplants of organs, bone, or tissue occurred before HIV screening was available. However, in 2007, four organ transplant recipients contracted HIV and hepatitis C from a single deceased organ donor [33]. This was the first case of HIV infection resulting from transplantation since 1985. Since then, a living kidney donor who tested negative for HIV 12 days prior to donation was found to have transmitted HIV to the donor recipient, the first case of transmission from a living donor since 1989 [34]. As with blood transfusions, donors testing antibody seronegative may pass HIV infection on to recipients [4]. The use of nucleic acid testing and reconsideration of the use of high-risk donors have both been recommended to ensure the safety of donor recipients [33].

In 2013, Congress passed the HIV Organ Policy Equity (HOPE) Act, which called for the use of organs from HIV-positive donors for transplantation into HIV-positive candidates under approved research protocols. The provisions of the Act took effect In November 2015. The protocol initially only authorized kidney and liver transplants, but as a result of a 2020 update, organs of any type may now be transplanted under HOPE Act protocols [35,36]. As of 2020, 324 hospitals have performed a total of 223 transplants (170 kidney, 53 liver), and a total of 30 transplant hospitals are enrolled with the Organ Procurement and Transplantation Network to participate in HOPE Act research [36].

Transmission due to occupational exposure of healthcare workers has occurred in needlestick accidents and blood splashes to the mucous membranes. Needlestick is the most common route. Thousands of healthcare personnel who were so exposed have been studied, and only 57 cases of well-documented infection have been reported in the United States (24 of which were nurses) [37]. The risk of infection through this route is low, and every effort should be made to decrease the exposure rate. Educational efforts, implementation of engineering controls in needled and sharp-edged medical devices, the use of hard plastic needle disposal units where these devices are most frequently used, and the development of procedural details to avoid blood and body fluid contact have greatly reduced the exposure rate. Healthcare personnel should apply Universal Precautions, as discussed in the Occupational Safety and Health Administration (OSHA) Bloodborne Pathogens standard regulations, to all activities to avoid contact with human fluids [4].

All body fluids should be considered potentially infectious. Contaminated needles or other sharps should not be bent, recapped or removed, unless specifically required by a particular medical or dental procedure. All healthcare professionals should have access to and use personal protective equipment, such as gloves, gowns, face shields, masks, eye protection, and ventilation devices, to limit exposure to potentially infectious fluids. OSHA standards require that single-use gloves be worn when contact with blood or other potentially infectious substance, including mucous membranes, can be reasonably anticipated [38].

Strategies for the treatment of HIV infection are based on an understanding of the molecular biology of HIV and the life cycle of the virus within the host cell. Antiviral agents have been developed that act predominately on processes specific to the virus particle in order to preserve the integrity of the host cell. Several potential strategies specifically aimed at interruption of the viral life cycle have been defined, including:

More than 30 antiretrovial drugs in several mechanistic classes are FDA-approved for treatment of HIV infection. These classes are: nucleoside reverse transcriptase inhibitors (NRTIs), non-nucleoside reverse transcriptase inhibitors (NNRTIs), protease inhibitors (PIs), fusion inhibitors, integrase strand transfer inhibitors (INSTIs), chemokine (C-C motif) receptor 5 (CCR5) antagonists, CD4 T lymphocyte (CD4) post-attachment inhibitors, gp120 attachment inhibitors, and capsid inhibitors. In addition, two drugs, ritonavir and cobicistat, are used as pharmacokinetic enhancers (or boosters) to improve the pharmacokinetic profiles of PIs [44]. Initiated in 1995 in the United States, cART regimens have been effective in dramatically decreasing HIV-related morbidity and mortality and should be considered for all persons with HIV who qualify for such therapy. In addition to combination therapy, the sequencing of drugs and the preservation of future treatment options are also important.

An initial regimen generally consists of two NRTIs administered in combination with a third active antiretroviral drug from one of three drug classes: an INSTI, a NNRTI, or a PI with a pharmacokinetic enhancer booster. Data also support the use of the two-drug regimen dolutegravir plus lamivudine for initial treatment [44]. The goal of these regimens is to effectively reduce HIV-associated morbidity, prolong the duration and quality of survival, restore and preserve immunologic function, and prevent HIV transmission while also avoiding drug resistance [44]. A significant proportion of patients starting cART are infected with drug-resistant strains of HIV, which may lead to suboptimal virologic responses. Therefore, pretreatment genotypic resistance testing should be used to guide selection of the most optimal initial regimen [44].

Multidisciplinary approaches to find solutions to compliance with cART and appointment adherence problems are often necessary, including collaboration with social work and case management.

(https://clinicalinfo.hiv.gov/sites/default/files/guidelines/documents/adult-adolescent-arv/guidelines-adult-adolescent-arv.pdf Last Accessed: February 23, 2023)

Strength of Recommendation: Expert Opinion/Consensus Statement

The decision to initiate antiretroviral therapy is one that requires careful discussion with the patient, usually in consultation with an infectious disease specialist or other physician well versed in the use of cART. Physicians and patients alike should be aware of the advantages, potential toxicities, and complexity of monitoring therapy. At the present time, the most active triple-drug regimen in a previously untreated patient can be expected to reduce the viral load below detectable levels, increase CD4 counts by an average of 100–150 cells/mcL, reduce the risk of HIV-associated complications, and prolong survival. However, the ability to achieve this advantage depends on the patient's willingness to accept a complex medical regimen that requires "many pills," rigorous compliance, frequent follow-up, and moderate risk for drug toxicity.

Patient compliance may be improved with therapies that combine more than one drug into a single pill, making it easier for patients to comply with their medication regimen. As of 2023, there were 23 combination medications available [45]. In addition to those medications that have been FDA-approved for the treatment of HIV, there is a long list of investigational, or "pipeline," drugs being tested in clinical trials. For more information on those agents and the trials, please visit the National Institutes of Health information website at https://hivinfo.nih.gov/understanding-hiv/fact-sheets/what-investigational-hiv-drug.

In 2021, the FDA approved the first monthly injectable cART—Cabenuva (cabotegravir/rilpivirine) [46]. This monthly injectable is intended to improve compliance and quality of life in patients with controlled HIV. Prior to initiating injectable therapy, oral therapy with cabotegravir/rilpivirine is started to ensure the agents are well-tolerated [46]. In 2022, the FDA approved lenacapavir for adult patients living with HIV-1 whose infections cannot be successfully treated with other available treatments due to resistance, intolerance, or safety considerations [47]. Lenacapavir is the first of a new class of drugs called capsid inhibitors to be FDA-approved for treating HIV-1. It works by blocking the protein shell (the capsid) of the HIV virus, thereby interfering with essential steps in the viral lifecycle. The two recommended dosage regimens include oral tablets and subcutaneous injections [47].

Depending on the CD4 count and other risk factors, asymptomatic patients may benefit from treatment to prevent opportunistic infections. In many cases, cART is useful in the prevention and treatment of these infections. Guidelines for antimicrobial prophylaxis of opportunistic infections are provided by the CDC, National Institutes of Health, HIV Medicine Association, and Infectious Diseases Society of America [48]. Prophylactic therapy for these conditions is strongly recommended because these infections are relatively common in patients with HIV, preventive therapy is simple and cost effective, and efficacy has been established in clinical studies. In addition, all patients should be vaccinated with pneumococcal vaccine. Hepatitis B vaccination should be considered in patients whose serologic testing indicates susceptibility.

The CDC, the National Institutes of Health, the HIV Medicine Association, and the Infectious Diseases Society of America have developed guidelines for the prevention of opportunistic infections among individuals with HIV. The report offers guidelines specific to each type of opportunistic infection [48]. Initiation of cART within two weeks of starting treatment of a concurrent opportunistic infection is recommended, except in instances when delaying cART is warranted due to increased risk of morbidity or mortality [47]. For persons with active tuberculosis (TB), cART should be initiated within two weeks after initiation of treatment for TB, particularly if the CD4 cell count is <50 [47].

It is well-established that the COVID-19 pandemic disrupted access to and delivery of a wide range of healthcare services, including HIV care and services [49,50]. While evidence indicates that people with HIV are not at increased risk of acquisition of SARS-CoV-2 compared with people without HIV, preventative interventions have been recommended, including [41]:

A global surge in monkeypox virus infections, with up to 50% occurring among people with HIV, was first identified in 2022 [41]. People with HIV and low CD4 cell counts or with no viral suppression may experience more severe disease [51]. Because co-infection with other STIs is frequent, people with HIV should be screened when monkeypox is first recognized or suspected [41].

Because HIV is spread predominantly through sexual transmission, the development of chemical and physical barriers that can be used intravaginally or intrarectally to inactivate HIV and other STI pathogens is critically important for controlling HIV infection.

Researchers are developing and testing new chemical compounds that women could apply before intercourse to protect themselves against HIV and other sexually transmitted organisms, especially in situations in which a woman is at risk of sexual violence or her sexual partner is unwilling to use latex condoms [60]. These include creams or gels, known as topical microbicides, which ideally would be non-irritating and inexpensive. Vaginal microbicides may also come in the form of an intravaginal ring, which can release the microbicide over time (up to 28 days) in order to provide more protection and to ensure adherence to the treatment [60]. Microbicides in the form of a small and quick-dissolving vaginal film are also in clinical trials. Vaginal films are considered to be more discrete and easier to carry and apply than gels [60]. Ideally, microbicides should be available in both spermicidal and non-spermicidal formulations so women do not have to put themselves at risk for acquiring HIV and other STIs in order to conceive a child. The research effort for developing topical microbicides includes basic research, preclinical product development, and clinical evaluation. Vaginal microbicides in clinical trials have shown to be between 27% and 54% effective in reducing HIV infection, with adherence to treatment being an important factor in their success [60].

Research is being conducted to determine whether the clinical manifestations of HIV, other than those related to the reproductive tract, are different for women than for men. It appears that many symptoms and signs of acute HIV infection and non-specific manifestations, such as fevers, weight loss, and fatigue, are the same. Because past research has either excluded women altogether or included only small cohorts of women, it has been difficult to determine gender differences in the clinical course of HIV disease.

In a large, multicenter cohort study comparing mortality and disease progression between women and men, women were more likely than men to develop bacterial pneumonia, especially if they were injection drug users. In addition, women were more likely to have mycobacterial infections, whereas men had higher rates of oral hairy leukoplakia and Kaposi sarcoma [59,61].

It is noteworthy that many healthcare providers fail to recognize recurrent vaginal candidiasis as a potential indicator of HIV [61]. This failure to diagnose results in delays in treatment. As many as 60% of women with HIV also test positive for some type of human papillomavirus (HPV). HIV infection is a risk factor for higher prevalence of HPV in the cervix and increased likelihood of infection by multiple HPV types. HIV infection is associated with a high rate of cervical cancer and cervical intra-epithelial neoplasia (CIN) or squamous intra-epithelial lesions (SIL). Menstrual irregularities are also frequently reported by women with HIV [62].

Biologically, women and persons with vaginas are more vulnerable than men (and persons without vaginas) to HIV infection from heterosexual intercourse because of their substantial mucosal exposure to seminal fluids. Women's risk is increased by other factors, such as non-consensual sex, sex without condoms, and the unknown or high-risk behaviors of their partners. Once infected with HIV, women can face obstacles in seeking and getting treatment and accessing health care. They often lack social support and face challenges (e.g., caring for children, caring for other family members) that may impede their ability to adhere to treatment. If they do follow through with treatment, studies have shown that women differ from men in the way they metabolize drugs, which could result in unexpected responses to cART and an increase in adverse reactions to the drugs [61].

The U.S. Preventive Services Task Force recommends that clinicians screen for HIV infection in all pregnant persons, including those who present in labor or at delivery whose HIV status is unknown.

(https://www.uspreventiveservicestaskforce.org/uspstf/recommendation/human-immunodeficiency-virus-hiv-infection-screening Last Accessed: February 23, 2023)

Strength of Recommendation: A (The USPSTF recommends the service based on high certainty that the net benefit is substantial.)

HIV counseling and the offer of HIV testing to pregnant patients have been universally recommended in the United States and are now mandatory in some states. Care of the pregnant patient with HIV should involve a collaboration between the HIV specialist caring for the patient when they are not pregnant, an obstetrician, and the patient. Treatment recommendations for pregnant patient with HIV are based on the belief that therapies of known benefit should not be withheld during pregnancy unless there are known adverse effects on the patient, fetus, or infant that outweigh the potential benefit to the patient [63,64]. All patients with HIV who are pregnant should receive cART both for their own health and to prevent perinatal transmission [41]. Regardless of the stage of pregnancy or childbirth, if a patient is found to be HIV-positive, there are treatment options that should be explored.

Patients should be registered with the Antiretroviral Pregnancy Registry, which collects observational, nonexperimental data. The registry is sponsored by GlaxoSmithKline, in affiliation with the CDC and Kendle International Inc. Patient who have been treated with cART at any time during their pregnancies are eligible for registry enrollment. The telephone number for registration is (800) 258-4263, and the website is http://www.apregistry.com.

There is evidence that the utilization of healthcare services is different for women with HIV disease than for men. Women are less likely than men to receive cART and generally have poorer access to services than men. Additionally, uptake of PrEP has been slow among women in the United States [31]. Overall, women received fewer services even after they had been diagnosed and had accessed healthcare services. Women with HIV are more likely to utilize emergency services and to be hospitalized than men with HIV [31,65].

There are several factors that affect HIV-positive women's ability to utilize available services. Studies have shown that women are almost twice as likely as men to postpone necessary care due to lack of available transportation or being too sick to visit their physician [31]. Other factors identified as barriers to equal access to care for women with HIV are stigma and isolation, lack of empowerment, competing concerns (e.g., food, housing, care for other family members), child care, insurance, and domestic or partner violence [65]. Predictors for poor access to care include racial or ethnic minority status and lack of insurance [65].

Healthcare professionals should assume a greater role in advocating for women with HIV, shaping public policy, and increasing knowledge about HIV infection through research. Behavioral health professionals are in an ideal position to participate in the early identification of women with HIV and to facilitate their entry into the healthcare system. Clinicians with a holistic perspective are ideally suited to provide a comprehensive family-oriented approach to healthcare that incorporates multiple services in one setting for women with HIV.

Lending their experience and expertise, healthcare professionals can influence the development of appropriate institutional and public policies that affect women with HIV. For example, in substance abuse programs, behavioral health professionals can advocate for policies that support gender-appropriate and culturally sensitive services and incorporate the use of the harm reduction model into the program. On a local government level, professionals can be active in the support of community-based efforts established to meet the needs of women with HIV. On a national level, it is imperative that the protection of women's reproductive rights, confidentiality regarding HIV status, and other critical issues that women with HIV face are advocated [59].

The epidemiology, clinical manifestations, and social factors that affect women with HIV have been reviewed. Many of these issues have been only briefly touched on because they are too lengthy to cover in this course. Readers are encouraged to seek more information about these issues from the recently growing body of literature on women and HIV. Finally, it is important for healthcare professionals to respond to the need for quality healthcare for the growing number of women infected with HIV and their families, to serve as advocates by influencing public policy, and to pursue research that increases our understanding of the problems faced by women living with HIV [59].

The tragedy of MTCT is that women may be unaware of their risk. The CDC has adapted recommendations that advocate universal counseling and testing with informed consent for every pregnant woman regardless of geography, identified risk behavior, or self-identified risk. In its 2019 guideline, the U.S. Preventive Services Task Force (USPSTF) recommends screening all pregnant patients for HIV, including those who present in labor who are untested and whose HIV status is unknown. The benefits supporting this statement included a potential for decreased perinatal transmission of HIV resulting from maternal and neonatal cART treatment and the increased opportunity to provide counseling regarding risks associated with breastfeeding and elective cesarean delivery [66]. As stated, all patients with HIV who are pregnant should receive cART both for their own health and to prevent perinatal transmission [41].

Many pregnant patients do not have an identified care provider, lack insurance coverage, seek care only for acute illness, or lack access to ongoing care. Nonetheless, by making counseling and testing a component of routine prenatal care, these recommendations will improve the care given to pregnant women with HIV and identify infants at risk for HIV prior to their birth. The American Academy of Pediatrics recommends HIV testing of newborn infants if testing was not offered or accepted by the patient during the prenatal period or if the patient did not receive prenatal care [67]. Testing should be offered confidentially, with counseling and informed consent provided and available healthcare services that are readily accessible.

The major advances in diagnosis and treatment are profoundly influencing the care of women and children with HIV infection. The documented ability of ZDV to interrupt MTCT has had a tremendous impact on the field of maternal and pediatric HIV. A second major advance is in the diagnosis of HIV infection in infants, which may be completed as early as 14 to 21 days in nonbreastfed infants with the use of virologic assays [68].

In settings throughout the United States, healthcare professionals encounter women and children in their daily practice. Knowledge about and understanding of the nationwide spread of HIV and its implications are crucial. Every pregnant woman should be offered an opportunity to know her HIV status in order to receive the best prenatal care and to assure prompt assessment of her newborn. Although surveys provide a statistical picture, each woman is an individual. HIV testing should always be offered after information and counseling has been provided to the pregnant woman.

More critical than pretest counseling is post-test support. Negative results provide opportunity to reinforce risk. Positive results should always be given in person, never over the telephone. If the site is unable to provide continuing services, arrangements should be made for uninterrupted prenatal care that is acceptable to the woman. The diagnosis of HIV is devastating to a pregnant woman, and intense support through an identified friend or family member may be helpful. Depending on the length of gestation, the woman will have many questions regarding the pregnancy as well as her own health.

The full spectrum of HIV disease in children has become evident as children survive longer. Early in the epidemic, only the most symptomatic and ill children were diagnosed, and so death appeared to occur in infancy and early childhood for most children. It is now recognized that to understand the natural history (disease progression), the progress of infected children should be followed from birth. Several prospective studies in the United States and Europe are following the progress of infants born to women with HIV; these cohorts serve as the basis for our description and understanding of the disease in children. Recent reports from these groups show that the median survival for infected children is 8 years, with children with PCP and encephalopathy having the poorest prognosis and the highest mortality in the first year of life. The period from infection to onset of AIDS-defining symptoms is often referred to as the clinical latency period. However, ongoing, complex interaction occurs between the virus and the immune system. The absence of clinical symptoms does not mean that the child is truly "well." Except for age at diagnosis and type of clinical presentation, no demographic or clinical indicators have been related to prognosis. Low CD4 counts for age are the best indicators of immunodeficiency and indicators of the risk of developing opportunistic infections. Early identification of the infected infant, specific prophylactic regimens to prevent infections, and ongoing supportive care are important in improving survival.

cART is believed to play a major role in slowing progression of the disease process. Many of the antiretroviral medications approved for use in the treatment of HIV/AIDS in adults have multiple formulations and age and weight recommendations specifically intended for infants and children [68].

Children receiving cART should be monitored for side effects, adherence, efficacy, and toxicity. The U.S. Department of Health and Human Services recommends evaluating all pediatric patients within one to two weeks and again within one to two months to monitor compliance, side effects, and response to treatment. Subsequently, a visit should be scheduled every three to four months [68]. Strategies to improve adherence should focus on selecting an appropriate regimen, educating the family/caregiver, and consistent follow-up.

HIV infection is a chronic health condition meeting the classic definition as "a condition with a protracted course which can be progressive and fatal, or associated with a normal life span despite impaired physical and mental functioning" [69]. It is helpful to view HIV infection as developing along a continuum with little direct impact on the child on one end and profound impact on the child and family on the other. This continuum occurs within a framework of family illness and loss that should be acknowledged by counselors, social workers, nurses, physicians, and other healthcare and service providers. Continuum of family illness is one of the most significant differences between HIV and other chronic health conditions of childhood. Experience gained while working with other chronic childhood conditions can be used when dealing with healthcare concerns of the child with HIV. Healthcare providers have played a central role in building and staffing networks for children with HIV and continue to be key care providers in an era of changing healthcare delivery models.

One of the most challenging aspects of caring for children and adolescents with HIV is engaging the patient in his or her own care and ensuring adherence to prescribed medications. In particular, adolescents face difficulties accessing services and have worse outcomes than other age groups [70]. Experts recommend offering individual and group education and counseling, increasing clinic accessibility, and providing specific adolescent-tailored services in order to best help these patients.

The advanced stage of HIV disease in children is manifested by multiple complications. Usually, several organ systems are affected, producing many symptoms, and the progression of disease can be slow or rapid. This uncertainty makes planning and decision making difficult for patients, families, and providers. Quality of life issues come into conflict with treatment decisions. Symptoms that are caused either by the disease itself or its treatment are extremely complicated to manage. Multiple services are required in the community to allow a child to remain at home for as long as possible.

In 2008, the CDC published a revised case definition for pediatric HIV. This definition was revised again in 2014 [71,72]. The 2014 revision combined the surveillance case definitions for HIV infection into a single case definition for persons of all ages, including adults, adolescents 13 years of age and older, and children younger than 13 years of age [72]. The revisions were made primarily to adapt to changes in diagnostic criteria that differentiate between HIV-1 and HIV-2 infection and recognize early HIV infection. Clinical symptoms are classified into five HIV infection stages: 0, 1, 2, 3, and unknown. Early infection is classified as stage 0; AIDS is classified as stage 3. The 2014 revised case definition extends the use of CD4 counts and percentages for determining the stage of HIV infection to children as well as adults and adolescents, and now determines the stage in children aged 6 to 12 years the same way as in adults and adolescents. (In the 2008 case definition, only the presence or absence of opportunistic illnesses was used as criteria for staging cases among children younger than 13 years of age [72].) The revised surveillance case definition is intended primarily for monitoring HIV infection burden and planning for prevention and care on a population level, not as a basis for clinical decisions for individual patients.

If HIV disease progresses and the child becomes increasingly ill, it is still in the child's best interest to remain at home and to engage in as many normal activities as possible. In order for this to happen, a great deal of coordination and planning is required by various healthcare providers, including nurses, social workers, physicians, psychologists, nutritionists, and community outreach workers. A system such as case management can assure good planning and implementation of services and avoid duplication. Using community-based home care services including visiting nurses, home health aides, pharmacies, infusion therapy, and respiratory therapy services can assist the family in caring for a child at home for a long period of time. Good communication with these agencies is essential. Social workers play a critical role in assisting families to find resources and entitlement programs that provide payment for these services. Developing a relationship with the child's school can result in a child continuing to attend school for a few hours a day.

For children to remain in their homes, their families should be able to care for them safely and comfortably. This care can present a big challenge to the family and healthcare providers. Children with HIV live in many kinds of family situations. Many live with biologic parents who also may have HIV. Drug and alcohol abuse may be present in the home. Many children live in homes with low incomes in high-crime areas. Others live with extended family members, often grandparents, who may be elderly with health problems of their own. Some live in foster homes in which there are more than one sick child who needs care. All of these situations can make the provision of safe home care a challenge.

Caregiver education about the child's problems, treatments, and medications is essential. Frequently, this information should be repeated numerous times. Tools such as medication schedules, calendars, and diaries are helpful. Assessing the home before implementing a complex treatment such as oxygen or parenteral therapy is mandatory because the environment may need to be altered to accommodate the equipment. Some environments may be deemed unsafe, and alternate living arrangements may be required. Infrequently, the child's family, even with home care services, cannot carry out a treatment plan. The options are limited to forgoing the treatment or placing the child in another situation, possibly a foster home or group or nursing home. This should always be the last option considered, when all other means of maintaining the child at home have been exhausted. With the appropriate community-based services, most children with advanced HIV can remain at home throughout the course of the disease. This should always be the goal. Only when the child's safety is clearly at risk should other options be considered [73].

Employment can pose a problem for individuals with HIV/AIDS. Possible issues that may be raised include difficulty maintaining employment or resuming employment after health has been restored or stabilized, stigma associated with the disease, future disability risk, confidentiality concerns, and the resulting financial burden for the employer.

Although individuals diagnosed with HIV/AIDS are living much longer as a result of available treatments, they may be forced into extended "HIV retirement," whereby employment is no longer possible due to the effects of the disease. Data collected on the employment status of these individuals are scarce, but level of employment appears to be related to advanced disease, number of complications, and level of support/use of resources [80,81]. The U.S. Department of Labor Office of Disability studies issues of employment among persons living with HIV/AIDS and provides several toolkits and resources for employees and employers [82].

At the beginning of the AIDS epidemic, insurance companies would generally approve AIDS-related disability claims quickly, as the prognosis for infected individuals was so poor. As prognosis for individuals with HIV has improved, it has become more difficult to obtain insurance approval for treatments and/or disability services [81].

Practitioners should take extreme care in not violating the patient's confidence and should obtain the patient's consent before sharing information about their health status. Ethical judgment may be enhanced by knowing the specific state law and regulations pertaining to persons with HIV and the release of confidential information [79].

Some professionals, reluctant to care for patients with HIV/AIDS, may find that the law enforces the duty to care for all patients [79]. Many states have passed laws requiring specific consent from the patient before an HIV test may be performed [83]. Nurses, for example, may refuse to compromise their own safety and ethical standards, but they have a professional responsibility to ensure that the nursing needs of patients are met on an emergency basis. Whether the nurse has a duty to care for all patients combines the nurse's ability, the requirements of the patient, and the degree of risk. Nurses may consider the risk of nursing some patients in the light of whether there is risk to themselves, their families, and their personal ethics.

Informed consent should be obtained from each person being tested. Each individual should be fully aware of the limitations of the HIV-antibody test regarding HIV infection and the development of AIDS. The test and its meaning, the reason for ordering the test, and its potential adverse consequences should be understood. The consent also includes information about how the test information will be used.

In 2012, the FDA approved the first medication for the prevention of sexually transmitted HIV infection, the combination drug Truvada (emtricitabine/tenofovir DF) [90]. In 2019, another combination drug—Descovy (emtricitabine/tenofovir)—was approved to prevent HIV infection [91]. In 2021, the FDA approved the first injectable agent for the prevention of HIV infection; cabotegravir is given first as two initiation injections administered one month apart, and then every two months thereafter [92]. In conjunction with safer sex practices, these agents have been found to be partially effective as pre-exposure prophylaxis in high-risk patients [93]. Also in 2021, the CDC and the U.S. Department of Health and Human Services updated their clinical practice guidelines for pre-exposure prophylaxis for the prevention of HIV infection [94]. In 2022, the International Antiviral Society, published recommendations for the treatment and prevention of HIV infection in adults [41]. These guidelines outline indications for prophylaxis as one prevention option for HIV transmission, in particular for high-risk, IDUs, MSM, and heterosexually active men, women, and adolescents. The most important first step in determining if an individual is a candidate for PrEP is a thorough history, including sexual and injection drug activities. PrEP should be offered to all sexually active adults and adolescents at substantial risk of acquiring HIV [41,94]. The optimal PrEP regimen is the one most acceptable to an individual and congruent with their sexual behavior, ability to reliably take prescribed medications, anticipated sexual activity, and adverse effect profile. Delaying PrEP is not recommended for individuals at risk [41]. Recommendations on the frequency and type of laboratory testing for people receiving PrEP vary according to the chosen regimen and patient risk profile [41]. All patients prescribed pre-exposure prophylaxis must have a negative HIV test prior to initiating treatment and every three months thereafter. In addition, patients should be advised regarding possible side effects and the continued necessity for safe sex practices. Eligible patients should also be screened for hepatitis B and possible kidney problems [94].

Achieving an end to the AIDS epidemic will require the development of an effective vaccine. Both preventive and therapeutic vaccines are being studied for use in the fight against HIV. Preventive vaccines are developed to protect individuals from contracting HIV, while the goal of therapeutic vaccines is to boost immune response to and better control existing HIV infection [95]. Of course, the ultimate goal in vaccine research is a vaccine that will prevent infection; however, despite several trials, no vaccine effective in preventing HIV has been discovered. In 2014, a study of a new approach involving injection of known neutralizing antibodies (rather than an antigen to stimulate the body to produce antibodies) was initiated [96]. While much progress has been made in understanding the HIV pathogen, it has provided many challenges in vaccine development, and as of 2023, there is no vaccine to prevent HIV [95,97,98].

The International AIDS Vaccine Initiative (IAVI) is working to speed the development and distribution of preventive AIDS vaccines, focusing on four areas: mobilizing support through advocacy and education; accelerating scientific progress; encouraging industrial participation in AIDS vaccine development; and assuring global access.

Many adolescents engage in behaviors that put them at risk for HIV infection. According to the CDC, 37.4% of high school students reported being sexually active [99]. Approximately 54.3% of sexually active high school students had not used a condom at last sexual intercourse; 1.2% had ever injected an illegal drug [99]. The CDC asserts that renewed educational efforts that reach all students before risk behaviors are initiated and that seek to delay the onset of sexual activity, increase condom use among students who are sexually active, and decrease injection drug use are warranted [100]. Education and interventions are considered vital to the reduction of high-risk behaviors in this population.

Although more than 85.3% of adolescents report having received education on HIV prevention in school, the content of these discussions may not provide adequate information on the subject. Furthermore, the American Academy of Pediatrics determined that school-based education and intervention programs do not provide the necessary opportunities of confidential discussions or targeted counseling [101]. Healthcare professionals have a unique opportunity to intervene in this population to provide accurate and complete information on HIV transmission and risk reduction.

The CDC HIV/AIDS Prevention Research Synthesis Project collects and analyzes systematic reviews and identifies evidence-based interventions that have been proven effective in eliminating or reducing sex- or drug-related risk behaviors, reducing the rate of new HIV infections, or increasing HIV-protective behaviors [102]. As of 2023, 78 best-evidence interventions and 58 best practices had been identified, many of which target specific populations. Intervention packages and more information on these interventions are available at https://www.cdc.gov/hiv/research/interventionresearch/prs.