According to the World Health Organization (WHO), an estimated 39.9 million individuals worldwide were living with HIV at the end of 2023, 65% of whom are in the WHO African Region [5]. One study using HIV prevalence data from 68 countries noted that, in 2022, among the 37 million individuals infected with HIV, 53% were located in Southern/East Africa in one of 14 high-prevalence countries (defined as an HIV-prevalence rate of >3.5%); the remaining 47% of HIV-infections were spread across the globe. This study highlights that in 2022, although the overall rate of new infections were lower, for the first time there were more new HIV infections (770,000 vs. 468,000), more HIV-related deaths (383,000 vs. 225,000), higher rates of mother-to-child transmission (16% vs. 9%), and lower antiretroviral therapy (ART) coverage (67% vs. 83%) in low-prevalence countries versus high-prevalence countries. The annual epidemic growth rate in 2022 was 2.41% for high-prevalence countries, compared with 4.41% for low-prevalence countries; the highest epidemic growth rates (>5.2%) were found in Central and South America, Central Africa, and Central and East Asia [4,7]. Allocation of funding for treatment and prevention is noted as a potential cause for the shift in epidemic growth rates, as the majority of global efforts are concentrated in Southern and East Africa.

At year-end 2022, an estimated 1.238 million individuals 13 years of age or older were living with HIV/AIDS in the United States. The CDC estimates that approximately 11% of these individuals were unaware of their infection [9]. In 2022, the Centers for Disease Control and Prevention (CDC) report several statistics and trends in the prevalence of HIV/AIDS in the United States [9]:

Once the virus enters the cell, it may replicate, induce cell fusion and propagation of infection, or lead to cell death [12]. HIV targets the immune system, and the defining characteristic of HIV disease is progressive immunodeficiency caused by ongoing viral replication and cell-to-cell transmission within lymphoid tissue. With chronicity there is a progressive depletion of CD4 (helper-inducer) lymphocytes, the very T lymphocyte cohort whose function it is to direct other cells in the immune system, and to orchestrate the inactivation of virus antigen. The result is a depressed T lymphocyte functional capacity, characterized by depletion of helper T cells (T4), impaired killer T cell activity, and increased suppressor T cells (T8). Eventually, impaired immunity renders the individual vulnerable to opportunistic infection and certain malignancies. The common laboratory measure of immune function is the CD4 cell count. In persons with intact lymphocyte immune systems, the normal number of CD4 T cells ranges from 600–1,200 cells/mcL, depending on the stage and duration of infection.

Acute primary HIV infection may be asymptomatic, but most often it is manifest by a subacute viral syndrome of malaise and fatigue, fever, sore throat, rash, myalgia, headache, and lymphadenopathy—clinical features similar in many respects to that seen with Epstein-Barr virus mononucleosis, cytomegalovirus (CMV), and certain types of herpes simplex infections [12]. A variety of atypical symptoms and signs may be seen, including aseptic meningitis syndrome, genital ulcers, and ulcerations involving the gingiva, palate, or buccal mucosa. Acute primary HIV illness usually resolves in less than 14 days but may follow a protracted course over many weeks [12].

Advanced HIV disease is defined by the WHO as a CD4 count <200 cells/mcL in adults and adolescents, or HIV infection regardless of count in any child younger than 5 years of age. The median survival of adult and adolescent patients with advanced HIV is approximately 12 to 18 months. Patients succumb to complications of uncontrolled infection, malignancy, or critical organ failure (such as uremia or adrenal insufficiency) [5].

On the basis of newly reported cases, the transmission categories are [8,10]:

Posing the highest risk of infection is unprotected anal receptive intercourse, followed by unprotected vaginal intercourse and unprotected insertive anal intercourse (particularly for uncircumcised men) [9]. 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. It is estimated that consistent use of latex condoms reduces the risk of HIV transmission by approximately 80% [16].

Transmission of HIV among IDUs 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 [30]. Behavior such as needle sharing, "booting" the injection with blood, and performing frequent injections increases the risk. Crack 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, and some studies have linked higher levels of psychologic distress (e.g., anxiety and depressive symptoms) with an increased risk for needle sharing [22]. Secondary transmission occurs to children and sexual partners. Preventative strategies include medication-assisted 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.

The 2018 updated PHS guidelines recommend initiating PEP medication as soon as possible after occupational exposure to HIV and continuation of the regimen for four weeks. PEP regimens should contain three (or more) antiretroviral drugs for all occupational exposures to HIV [39]. Examples of recommended PEP regimens include those consisting of a dual nucleoside reverse transcriptase inhibitor (NRTI) backbone plus an integrase strand transfer inhibitor (INSTI), protease inhibitor (PI) (boosted with ritonavir), or non-nucleoside reverse transcriptase inhibitor (NNRTI). The PHS preferred regimen for management of most healthcare professionals' exposures to HIV is raltegravir 400 mg twice daily plus Truvada (combination emtricitabine 200 mg and tenofovir 300 mg) once daily, [39]. This preparation is available as a starter packet that should be stocked at every healthcare facility where exposure to HIV is possible. As discussed, the regimen has been selected for its tolerability and safety profile. There are several alternative regimens that may be selected due to individual patient concerns. For example, tenofovir is associated with renal toxicity, and an alternative NRTI/NNRTI pair, such as zidovudine plus lamivudine (available as Combivir), would be selected for patients with renal disease [39].

HIV infection is a protracted illness that passes through several stages and, if untreated, is ultimately fatal, with a median survival time from seroconversion of 8 to 10 years [28,29]. Within 15 to 30 days after acquisition of HIV infection, the majority of patients (50% to 90% in reported series) develop an acute retroviral syndrome similar to infectious mononucleosis [12]. Symptoms include fever, sore throat, malaise, rash, diarrhea, lymphadenopathy, mucocutaneous ulcerations and weight loss averaging 10 pounds. A variety of neurologic syndromes including encephalitis may occur. The illness is self-limited, with an average duration of two to three weeks. Laboratory abnormalities include lymphopenia, atypical lymphocytosis, thrombocytopenia, and a decreased CD4 cell count. During this early phase of clinical illness, HIV antibody tests are often negative and the diagnosis rests on the demonstration of HIV P24 antigen or, preferably, quantitative plasma HIV RNA. Concentrations of HIV RNA in the blood (viral load) are high during the acute syndrome [11].

Following the host immune response, coincident with seroconversion and the rise in CD8 cytotoxic T cells, the viral load decreases steadily, reaching a relatively stable level at about six months. At this juncture, the degree of viral load correlates with the subsequent pace of disease progression. Patients having the highest viral load, exhibit the most rapid progression to AIDS. As a result of the ongoing, protracted infection of target lymphocytes, the CD4 count gradually declines over time in the absence of treatment, at an average annual rate of about 50 cells/mcL [11].

A variety of clinical syndromes may supervene at this juncture including dementia, peripheral neuropathy, wasting syndrome, and chronic diarrhea. In the United States, the most common AIDS-defining opportunistic diseases are: PCP, Kaposi sarcoma, candidiasis, cryptococcosis, cryptosporidiosis, CMV, atypical mycobacteriosis, systemic herpes, toxoplasmosis, and tuberculosis [50].

Development of mature infectious virus depends upon enzymatic cleavage of HIV transcribed polyprotein by HIV protease. In binding to the active site of the HIV protease, PIs interrupt the formation of mature infectious particles and reduce viral replication by as much as 99%. Resistance to PIs develops rapidly when these agents are used alone. However, in combination with nucleoside analogs the effect can last for years, often resulting in a reduction of viral load to undetectable levels. Available agents include: atazanavir (Reyataz, ATZ); tipranavir (Aptivus, TPV); darunavir (Prezista; DRV); fosamprenavir (Lexiva, FPV); and ritonavir (Norvir, RTV) [43]. Although ritonavir is a PI, it is generally used as a pharmacokinetic enhancer [42,43].

As noted, for treatment-naïve patients, initial recommended ART generally consists of an oral second-generation INSTI plus two NRTIs. If INSTI resistance is possible and/or if genotype results are not yet available, a boosted PI in combination with two NRTIs is recommended [42]. These regimens result in maximum reduction of viral load for the longest period of time. When used as initial therapy, these regimens will achieve the goal of no detectable virus in the majority of patients after four to six months [42].

HIV/AIDS is no longer a leading cause of death in women overall in the United States, but it remains the ninth leading cause of death in Black women 25 to 34 years of age. Women of color have been disproportionately affected by HIV/AIDS, with Black women accounting for 50% of new HIV diagnoses among women in the United States while representing only 13% of the female population. In comparison, White women accounted for 24% and Hispanic/Latina women accounted for 20% of HIV diagnoses. Black women also have the highest rates of HIV-related deaths among women with HIV, accounting for 57% in 2022, compared with 20% for White women and 15% for Hispanic/Latina women [53].

Gender-specific manifestations of HIV disease include irregular menstruation, recurrent vulvovaginal candidiasis, human papillomavirus (HPV)-related cervical dysplasia (abnormal, precancerous cell growth), and cervical cancer. HIV-infected women have a higher prevalence of HPV infection, a higher risk of progression from infection to disease, and an increased risk of invasive cervical cancer and other HPV-related cancers than non-infected women [54]. Research indicates that ART does not significantly decrease the incidence of HPV-related cancers. As such, the American College of Obstetricians and Gynecologists recommends that women with HIV should have cervical cytology screening twice in the first year after diagnosis and annually thereafter [55].

As with adults, ART is believed to play a major role in slowing progression of HIV in children and adolescents. Children receiving ART should be monitored for side effects, adherence, efficacy and toxicity. Recommendations for initial antiretroviral therapy of HIV infection in children have been updated based on FDA approvals and new data; clinicians should consult HHS Guidelines for the Use of Antiretroviral Agents in Pediatric HIV Infection when making management decisions for pediatric HIV care [23]. Following initiation of ART, all pediatric patients should be evaluated within one to two weeks to monitor compliance, side effects, and response to treatment. Subsequent visits should be scheduled every three to four months [23]. Strategies to improve adherence should focus on selecting an appropriate regimen, educating the family/caregiver, and consistent follow-up.

In 2024, approximately 41% of individuals living with HIV were 55 years of age or older [26]. In the early years of the AIDS epidemic, little attention was given to older people with HIV, and HIV/AIDS was thought to be the disease of the young. As a result, prevention and education campaigns were traditionally not targeted toward older adults. However, effective ART and an emphasis on HIV research in older adults now allows individuals to live long, healthy lives, increasing the number of older people living with HIV. Due to the large proportion of older people with HIV, evidence points to the increasing need for change in prevention and education campaigns [26].

In 2021, the CDC updated their clinical practice guideline on PrEP used for the prevention of HIV infection [62]. Previously, candidates for PrEP were primarily individuals at high risk for HIV (e.g., MSM, IDU). In the updated guidelines, the CDC recommends informing all sexually active and/or injecting drug using patients about PrEP, regardless of HIV risk factors. In addition, any patient requesting PrEP should be considered for treatment. These updates are intended to increase the number of patients who know about PrEP and prevent stigma or embarrassment that may prevent an individual from disclosing HIV risk factors [62].

Those identified as being at a substantially increased risk of acquiring HIV infection include sexually active individuals that have had anal or vaginal sexual contact in the past six months, in addition to having an HIV-positive sexual partner; a bacterial STI in the past six months; and/or a history of inconsistent or no condom use with sexual partners. Persons who inject drugs and have a HIV-positive injecting partner or share injection equipment are also at a high risk of HIV infection [62].

Patients should have a documented negative HIV test result within seven days prior to initiating treatment, and hepatitis B, kidney function, and a lipid profile should be reviewed to ensure appropriate PrEP selection.

Many adolescents engage in behaviors that put them at risk for HIV infection. According to the CDC, in 2023, 48.1% of sexually active high school students had not used a condom during last sexual intercourse and 1.2% had injected an illegal drug [66]. In an analysis of the Youth Risk Behavior Survey, researchers found that 84% of adolescents report having received education on HIV prevention in school. Among those students, it was found that HIV education was associated with increased rates of abstaining from substance use during intercourse. Further, for boys, receiving HIV education was associated with increased condom use at last sexual encounter, as well as increased rate of testing for HIV [67]. This evidence highlights HIV education as a promising intervention for risk behavior reduction. While the availability of HIV prevention education is important, the quality and content may not provide adequate information on the subject or may not provide necessary opportunities for confidential discussions or targeted counseling. Healthcare professionals have a unique opportunity to intervene in this population to provide accurate and complete information on HIV transmission and risk reduction.