According to the World Health Organization (WHO), an estimated 37.7 million individuals worldwide were living with HIV by the end of 2020, of whom more than two-thirds (25.4 million) were in the WHO African Region [5]. Northern Africa, the Middle East, and eastern Europe and central Asia (particularly the Russian Federation) have had the fastest growing epidemics—new HIV infections in these regions have approximately doubled in the past 20 years. In 2020, an estimated 680,000 people died from HIV-related causes and 1.5 million people acquired HIV infection [5]. It is important to note that despite increases in certain geographic areas and demographic groups, overall, the rate of new infections was declining prior to the COVID-19 pandemic. Service disruptions during COVID-19 have slowed the pace of public health response to HIV, raising concern that increasing HIV infections and excess HIV-related deaths may erode the progress made in sub-Saharan Africa [5].

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 infections 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.

Without satisfactory antiretroviral therapy, the usual patient with HIV/AIDS experiences a slow, inexorable wasting illness punctuated by periods of feverishness and diarrhea, becoming increasingly anorectic, malnourished, and lethargic. Late clinical signs include muscle wasting and weakness, anemia and thrombocytopenia, lymphadenopathy, pulmonary infiltrates, and neurologic abnormalities (such as dementia, peripheral neuropathy, and tremors). The median survival of patients with advanced HIV/AIDS (i.e., CD4 count <50 cells/mcL) is 12 to 18 months. Patients succumb to complications of uncontrolled infection, malignancy, or critical organ failure (such as uremia or adrenal insufficiency).

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

As discussed, HIV infection is a protracted illness that passes through several stages and, if untreated, carries an 80% mortality rate at 10 years. 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.

Chronic, asymptomatic HIV infection with ongoing low-level viral activity may last for many years before eventual progression to AIDS. Symptomatic illness can be expected to supervene as the CD4 count declines to a level less than 200 cells/mcL, as this correlates with severe immunodeficiency. The CDC defines late-stage HIV infection as AIDS on the basis of two criteria: CD4 count less than 200 cells/mcL or a characteristic AIDS-defining illness such as PJP, central nervous system (CNS) toxoplasmosis, or other opportunistic infections or tumors (Kaposi sarcoma). 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: PJP, Kaposi sarcoma, candidiasis, cryptococcosis, cryptosporidiosis, CMV, atypical mycobacteriosis, systemic herpes, toxoplasmosis, and tuberculosis [41].

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: ritonavir (Norvir, RTV); saquinavir (Invirase, Fortovase, SQV); atazanavir (Reyataz, ATZ); tipranavir (Aptivus, TPV); darunavir (Prezista; DRV); and fosamprenavir (Lexiva, FPV) [43].

AIDS is no longer a leading cause of death in women overall in the United States, but it remains the fifth leading cause of death in African American women 35 to 44 years of age [55]. Women of color have been disproportionately affected by HIV/AIDS, with black women accounting for 64% of new HIV diagnoses among women in the United States while representing only 13% of the female population [53]. Women of color also tend to contract HIV at a younger age than their white counterparts.

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 [59]. 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 [59]. Research indicates that cART 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 [60].

Approximately 17% of newly diagnosed cases of HIV/AIDS in 2018 occurred in individuals 50 years of age or older; 51% of all persons living with HIV/AIDS are 50 years of age or older [68]. Until recently, there had been little attention given to this group. HIV/AIDS has traditionally been thought to be the disease of the young; therefore, in the past, prevention and education campaigns had not been targeted toward older adults. However, evidence points to the increasing number of infected older people and a need for change in prevention and education campaigns. Some older persons may have less knowledge about HIV and risk reduction strategies. Due to divorce or being widowed and the availability of medications to treat erectile dysfunction, increasing numbers of older people are becoming sexually active with multiple partners [68]. For postmenopausal women, contraception is no longer a concern, and they are less likely to use a condom. Furthermore, vaginal drying and thinning associated with aging can result in small tears or cuts during sexual activity, which also raises the risk for infection with HIV/AIDS [68]. Studies indicate that at-risk individuals in this age group are significantly less likely than younger at-risk adults to use condoms during sex [69]. In addition, healthcare professionals are less likely to discuss sexual activity or take a sexual history if the patient is older than 50 years of age [69]. The combination of these factors increases the risk for unprotected sex with new or multiple partners in this age group, thereby increasing their risk for AIDS. This increase should be considered when evaluating older patients.