Human Immunodeficiency Virus (HIV) Infection

Global HIV statistics

The following HIV statistics were estimated by the World Health Organization (WHO) in 2024 (1):

• Global prevalence of HIV infection: 40.8 million people

• Children (0 to 14 years of age) with HIV infection: 1.4 million people

• People newly diagnosed with HIV infection: 1.3 million people newly infected with HIV compared to 3.4 million people in 1996 (2)

• Mortality from HIV-related causes: 630,000 people compared to 2.1 million people in 2004 and 1.4 million people in 2010

• People with HIV infection receiving antiretroviral therapy: 31.6 million

• People with HIV infection who know their status: 87% (77% of those who know their status are receiving treatment and 73% have suppressed viral loads)

HIV statistics in Africa

HIV infection is most prevalent in Africa, particularly in sub-Saharan Africa. WHO estimated 2024 statistics in Africa include the following (1):

• Prevalence: 26.3 million people (90% knew their status, 83% were receiving treatment, and 78% had suppressed viral loads)

• People with newly diagnosed with HIV infection: 650,000 (a decrease to 0.53/1000 uninfected population from 1.7/1000 in 2010)

• Mortality from HIV-related causes: 380,000 people (a decrease of 59% from 2010)

HIV statistics in the United States

The most recent estimates for HIV infection in people ≥ 13 years old in the United States from 2022 include the following (2):

• Prevalence: 1.2 million people (13% were not aware of their status)

• People who acquired HIV: 31,800 (estimated new HIV infections decreased 12% from 36,300 in 2018)

• People who acquired HIV by subpopulation: Men who have sex with men (21,400 [67%]); people who reported heterosexual contact (7,000 [22%]); people who inject drugs (2,300 [7%])

Epidemiologic factors affecting HIV transmission

HIV spreads through epidemiologically distinct routes:

• Heterosexual intercourse (affecting men and women about equally)

• Men who have sex with men

• Contact with infected blood (eg, through sharing of needles and via blood transfusions in the absence of effective donor-screening measures)

• Mother-to-child (vertical transmission)

• Direct physical contact of nonintact skin or mucous membrane to infectious body fluid (semen, cervicovaginal secretions, human milk, or any visibly bloody secretions) (3)

Most HIV infections are transmitted through heterosexual contact, but risk factors vary according to geographic region, socioeconomic status, and social dynamics. For instance, in high-resource countries, transmission through heterosexual intercourse is usually the most common way infection occurs. In some regions, such as Eastern Europe and Central Asia, heterosexual transmission is also the most common, but injection drug use remains a significant risk factor for HIV transmission.

In areas where heterosexual transmission is dominant, HIV infection follows routes of trade, transportation, and economic migration to cities and spreads secondarily to rural areas. In Africa, particularly southern Africa, tens of millions of adults have died because of the HIV epidemic. Factors associated with increased rates of spread include:

• Poverty and sexual violence

• Limited sexual education and awareness about HIV

• Health care systems that do not provide access to HIV testing and antiretroviral medications

• Stigmatization, criminalization, and discrimination against people with HIV infection

Many opportunistic infections that complicate HIV infection are reactivations of latent infections. Thus, epidemiologic factors that determine the prevalence of latent infections also influence the risk of specific opportunistic infections. In many countries with high rates of HIV infection, prevalence of latent tuberculosis and toxoplasmosis in the general population is higher than in other countries. Dramatic increases in reactivated tuberculosis and toxoplasmic encephalitis have followed the epidemic of HIV-induced immunosuppression in these countries. Similarly, in the United States, the incidence of coccidioidomycosis, common in the Southwest, and histoplasmosis, common in the Midwest, has increased because of HIV infection.

Human herpesvirus 8 infection, which causes Kaposi sarcoma, is common among men who have sex with men but is uncommon among other patients with HIV infection in the United States and Europe. Thus, in the United States, 89% of people with HIV infection who have developed Kaposi sarcoma are men who have sex with men (4).

Epidemiology references

1. 1. World Health Organization (WHO). Global HIV Programme: HIV data and statistics. UNAIDS/WHO estimates, 2025. Accessed February 1, 2026.

2. 2. UNAIDS. Global HIV & AIDS statistics — Fact sheet 2025. Accessed February 1, 2026.

3. 3. Tanner MR, O'Shea JG, Byrd KM, et al. Antiretroviral Postexposure Prophylaxis After Sexual, Injection Drug Use, or Other Nonoccupational Exposure to HIV - CDC Recommendations, United States, 2025. MMWR Recomm Rep. 2025;74(1):1-56. Published 2025 May 8. doi:10.15585/mmwr.rr7401a1

4. 4. Peprah S, Engels EA, Horner MJ, et al. Kaposi Sarcoma Incidence, Burden, and Prevalence in United States People with HIV, 2000-2015. Cancer Epidemiol Biomarkers Prev. 2021;30(9):1627-1633. doi:10.1158/1055-9965.EPI-21-0008

Sexual transmission of HIV

The sexual practices with the highest risks are those that cause mucosal trauma (see table HIV Transmission Risk of Several Sexual Activities. A systematic review reported the following risk of transmission per sex act (3):

• Receptive anal intercourse: 1 per 72 sex acts

• Insertive anal intercourse: 1 per 909

• Receptive penile–vaginal intercourse: 1 per 1250

• Insertive penile–vaginal intercourse: 1 per 2500

• Receptive or insertive oral sex: 0 to 4 per 10,000 exposures

The risk of transmission during oral sex does not increase significantly if semen or vaginal secretions are swallowed. However, open sores in the mouth, bleeding gums, or oral contact with genital sores may increase the risk (1). Other practices that cause mucosal trauma include fisting (inserting most or all of the hand into the rectum or vagina) and using sex toys. When used during intercourse with a partner with HIV infection, these practices increase the risk of HIV transmission. However, the risk is still lower than with vaginal or anal sex.

Mucous membrane inflammation facilitates HIV transmission (4). Sores on the mouth, vagina, penis, or rectum increase risk of transmission. Sexually transmitted infections, such as gonorrhea, chlamydia, trichomoniasis, and especially those that cause ulceration (eg, chancroid, herpes, syphilis), increase the risk several-fold. In endemic regions, female genital schistosomiasis can also cause mucosal lesions and inflammation that increases susceptibility to HIV infection, acting as an additional cofactor, similar to ulcerative sexually transmitted infections (5).

Risk of transmission is increased in the early and advanced stages of HIV infection when HIV concentrations in plasma and genital fluids are higher. Evidence shows that people with HIV infection treated with antiretroviral therapy (ART) who have low (plasma HIV RNA < 200 copies/mL) or undetectable viral loads (virally suppressed) do not sexually transmit the virus to their partners (6–8). This concept is known as "Undetectable = Untransmittable" (U=U) and may be explained to patients to help reinforce the importance of ART and the maintenance of low or undetectable viral loads (9).

Medical circumcision reduces the risk of heterosexual men acquiring HIV infection by 38 to 66% over 24 months (10). This reduction is attributed to the removal of the penile mucosa (underside of the foreskin), which is more susceptible to HIV infection than the keratinized, stratified squamous epithelium that covers the rest of the penis.

Needle- and instrument-related transmission

The risk of HIV transmission after skin penetration with a medical instrument contaminated with infected blood is approximately 1/400 without postexposure antiretroviral prophylaxis (3). Postexposure antiretroviral prophylaxis is recommended as soon as possible after exposure (11). The risk appears to be higher if the wound is deep or if blood is inoculated (eg, with a contaminated hollow-bore needle). Risk is also increased with hollow-bore needles and with punctures of arteries or veins compared with solid needles or other penetrating objects coated with blood because larger volumes of blood may be transferred. Thus, sharing needles that have entered the veins of other people is considered a very high-risk activity.

The risk of transmission from clinicians with HIV infection who take appropriate precautions is unclear but appears minimal. However, extensive investigations of patients cared for by physicians with HIV infection, including surgeons, have revealed zero transmission cases since 2010 (12).

Vertical (mother-to-child) transmission

HIV can be transmitted from a mother to her fetus or newborn:

• During pregnancy, transplacentally

• During childbirth

• Via breast (human) milk

The overall cumulative risk of vertical transmission to an infant born to a mother who did not take ART (and depending on whether or not the infant is breastfed) is 15 to approximately 45% (13–15).

Vertical transmission rates for at-risk infants can be reduced significantly by treating pregnant patients with HIV infection with antiretroviral medications during pregnancy, labor, and breastfeeding. Testing and prophylactic treatment of the infant also reduce the risk.

Cesarean delivery reduces the risk and is preferred for pregnant patients with HIV infection whose viral loads are > 1000 copies/mL at or near delivery, independent of antepartum ART, or whose levels are unknown (16).

HIV is excreted in human milk. The overall risk of transmission through breastfeeding is approximately 15 to 25%, reflecting varying durations of breastfeeding and plasma viral RNA concentrations (eg, risk is high in women who become infected during pregnancy or during the period of breastfeeding) (15, 17).

To prevent vertical transmission in high-resource countries, mothers with HIV infection are advised to discuss infant feeding options with a health care professional (18). Although avoiding breastfeeding eliminates HIV transmission risk, maternal ART with sustained viral suppression can reduce the risk to < 1% with breastfeeding.

To prevent vertical transmission in resource-limited settings, the benefits versus the risks of breastfeeding must be considered (19). Breastfeeding is associated with reduced infant morbidity and mortality due to malnutrition and infectious diseases. For mothers with HIV infection in resource-limited settings where safe, affordable infant formula or pasteurized donor milk from a milk bank is not available, the World Health Organization (WHO) recommends lifelong maternal ART and adherence support combined with breastfeeding exclusively for 6 months and with complementary feeding for at least 12 months and up to 24 months or longer.

Because many women with HIV infection take prophylactic antiretroviral medications during pregnancy and their infants are treated, the incidence of HIV in children has decreased significantly in many countries (see Human Immunodeficiency Virus (HIV) Infection in Infants and Children).

Transfusion- and transplant-related transmission

Screening of blood donors with tests for both antibodies to HIV and HIV RNA has minimized the risk of transmission via blood transfusion (20, 21). Current risk of transmitting HIV via blood transfusion is estimated to be approximately 1/2,300,000 per unit transfused in the United States (21). However, in many countries with a high prevalence of HIV infection, where blood and blood products are not screened for HIV, the risk of transfusion-transmitted HIV infection remains high.

Rarely, HIV has been transmitted via transplantation of organs from HIV-seropositive donors (22). Infection has been reported in recipients of kidney, liver, heart, pancreas, bone, and skin—all of which contain blood; however, screening for HIV greatly reduces the risk of transmission (23). HIV transmission is even more unlikely from transplantation of cornea, ethanol-treated and lyophilized bone, fresh-frozen bone without marrow, lyophilized tendon or fascia, or lyophilized and irradiated dura mater. Notably, transplantation of organs from donors who are HIV positive to recipients who are HIV positive is increasingly performed in select settings in the United States (24).

HIV transmission is possible via artificial insemination if the sperm donor is HIV positive. In the United States, sperm washing is considered an effective method of reducing the risk of transmission to a person via insemination if that person's partner is known to be HIV positive.

Transmission references

1. 1. Centers for Disease Control and Prevention (CDC). How HIV Spreads. November 25, 2024. Accessed April 8, 2026.

2. 2. HIV.gov. How Is HIV Transmitted? February 25, 2026. Accessed April 8, 2026.

3. 3. Patel P, Borkowf CB, Brooks JT, et al: Estimating per-act HIV transmission risk: A systematic review. AIDS 28(10):1509-1519, 2014. doi: 10.1097/QAD.0000000000000298

4. 4. Gonzalez SM, Aguilar-Jimenez W, Su RC, Rugeles MT. Mucosa: Key Interactions Determining Sexual Transmission of the HIV Infection. Front Immunol. 2019;10:144. Published 2019 Feb 6. doi:10.3389/fimmu.2019.00144

5. 5. Sturt AS, Webb EL, Francis SC, Hayes RJ, Bustinduy AL. Beyond the barrier: Female Genital Schistosomiasis as a potential risk factor for HIV-1 acquisition. Acta Trop. 2020;209:105524. doi:10.1016/j.actatropica.2020.105524

6. 6. Rodger AJ, Cambiano V, Bruun T, et al. Risk of HIV transmission through condomless sex in serodifferent gay couples with the HIV-positive partner taking suppressive antiretroviral therapy (PARTNER): Final results of a multicentre, prospective, observational study. Lancet. 20119;393(10189):2428-2438. doi:10.1016/S0140-6736(19)30418-0

7. 7. Rodger AJ, Cambiano V, Bruun T, et al. Sexual activity without condoms and risk of HIV transmission in serodifferent couples when the HIV-positive partner is using suppressive antiretroviral therapy [published correction appears in JAMA. 2016;316(2):171-181. doi:10.1001/jama.2016.5148

8. 8. Broyles LN, Luo R, Boeras D, Vojnov L. The risk of sexual transmission of HIV in individuals with low-level HIV viraemia: a systematic review. Lancet. 2023;402(10400):464-471. doi:10.1016/S0140-6736(23)00877-2

9. 9. ClinicalInfo.HIV.gov. Guidelines for the Use of Antiretroviral Agents in Adults and Adolescents With HIV. Baseline Evaluation. September 21, 2022. Accessed April 8, 2026.

10. 10. Siegfried N, Muller M, Deeks JJ, Volmink J. Male circumcision for prevention of heterosexual acquisition of HIV in men. Cochrane Database Syst Rev. 2009;2009(2):CD003362. Published 2009 Apr 15. doi:10.1002/14651858.CD003362.pub2

11. 11. Kofman AD, Struble KA, Heneine W, et al. 2025 US Public Health Service Guidelines for the Management of Occupational Exposures to Human Immunodeficiency Virus and Recommendations for Post-exposure Prophylaxis in Healthcare Settings. Infect Control Hosp Epidemiol. 2025;46(9):863-873. doi:10.1017/ice.2025.10254

12. 12. Henderson DK, Dembry LM, Sifri CD, et al. Management of healthcare personnel living with hepatitis B, hepatitis C, or human immunodeficiency virus in US healthcare institutions. Infect Control Hosp Epidemiol. 2022;43(2):147-155. doi:10.1017/ice.2020.458

13. 13. Newell ML, Coovadia H, Cortina-Borja M, et al: Mortality of infected and uninfected infants born to HIV-infected mothers in Africa: A pooled analysis. Lancet 364(9441):1236-1243, 2004. doi:10.1016/S0140-6736(04)17140-7

14. 14. Dude AM, Jones M, Wilson T. Human Immunodeficiency Virus in Pregnancy. Obstet Gynecol Clin North Am. 2023;50(2):389-399. doi:10.1016/j.ogc.2023.02.010

15. 15. Luzuriaga K, Mofenson LM. Challenges in the Elimination of Pediatric HIV-1 Infection. N Engl J Med. 2016;374(8):761-770. doi:10.1056/NEJMra1505256

16. 16. ACOG Committee Opinion No. 751 Summary: Labor and delivery management of women with human immunodeficiency virus infection. Obstet Gynecol. 2018;32(3):803-804. doi:10.1097/AOG.0000000000002821.

17. 17. Dunn DT, Newell ML, Ades AE, Peckham CS. Risk of human immunodeficiency virus type 1 transmission through breastfeeding. Lancet. 1992;340(8819):585-588. doi:10.1016/0140-6736(92)92115-v

18. 18. CDC. Breastfeeding special circumstances: HIV and Breastfeeding. December 8, 2025. Accessed April 8, 2026.

19. 19. World Health Organization (WHO). Guideline: updates on HIV and infant feeding. January 1, 2026. Accessed April 8, 2026.

20. 20. Steele WR, Dodd RY, Notari EP, et al. HIV, HCV, and HBV incidence and residual risk in US blood donors before and after implementation of the 12-month deferral policy for men who have sex with men. Transfusion. 2021;61(3):839-850. doi:10.1111/trf.16250

21. 21. Dodd RY, Crowder LA, Haynes JM, Notari EP, Stramer SL, Steele WR. Screening Blood Donors for HIV, HCV, and HBV at the American Red Cross: 10-Year Trends in Prevalence, Incidence, and Residual Risk, 2007 to 2016. Transfus Med Rev. 2020;34(2):81-93. doi:10.1016/j.tmrv.2020.02.001

22. 22. CDC. HIV transmitted from a living organ donor--New York City, 2009. MMWR Morb Mortal Wkly Rep. 2011;60(10):297-301.

23. 23. Simonds RJ. HIV transmission by organ and tissue transplantation. AIDS. 1993;7 Suppl 2:S35-S38. doi:10.1097/00002030-199311002-00008

24. 24. Health Resources and Services Administration (HRSA). HOPE Act. May 2026. Accessed June 2, 2026.

Immune system

The 2 main consequences of HIV infection are:

• Damage to the immune system, specifically depletion of CD4+ lymphocytes

• Immune activation

CD4+ lymphocytes are directly involved in cell-mediated immunity and indirectly involved in humoral immunity. CD4+ depletion may result from the following:

• Direct cytotoxic effects of HIV replication

• Cell-mediated immune cytotoxicity

• Thymic damage that impairs lymphocyte production

Infected CD4+ lymphocytes have a half-life of approximately 2 days, which is much shorter than that of uninfected CD4+ cells (3). Rates of CD4+ lymphocyte destruction correlate with plasma HIV level. Typically, during the initial or primary infection, HIV levels are highest (> 10⁶ copies/mL), and the CD4 count drops rapidly.

The normal CD4 count in healthy adolescents and adults is approximately 500 to 1500 cells/mcL (4). Cell-mediated immunity is minimally affected if the count is > 350 cells/mcL. If the count drops below approximately 200 cells/mcL, loss of cell-mediated immunity allows a variety of opportunistic pathogens to reactivate from latent states and cause clinical disease.

The humoral immune system is also affected. Plasma cells are a subset of B cells that secrete antibodies. Thus, hyperplasia of B cells in lymph nodes causes lymphadenopathy, and secretion of antibodies to previously encountered antigens increases, often leading to hyperglobulinemia. Total antibody levels (especially IgG and IgA) and titers against previously encountered antigens may be unusually high. However, because CD4+ T cells are important for the maturation of B cells (and thereby plasma cells), antibody responses to new antigens (eg, in vaccines) may decrease as the CD4 count decreases.

The immune activation is primarily a consequence of HIV-induced damage to gut mucosal immunity, rather than CD4 depletion alone (5). Early depletion of gut-resident CD4+ T cells leads to microbial translocation, which drives chronic immune activation. This immune activation in turn contributes to progressive CD4+ T-cell loss, creating a pathogenic feedback loop.

Other tissues

HIV also infects nonlymphoid monocytic cells (eg, dendritic cells in the skin, macrophages, brain microglia) and cells of the brain, genital tract, heart, and kidneys, causing disease in the corresponding organ systems.

HIV strains in several compartments, such as the nervous system (brain and cerebrospinal fluid) and genital tract (semen, cervico-vaginal fluid), can acquire mutations and become genetically distinct from those in plasma, suggesting that they have been selected by or have adapted to these anatomic compartments (6–8). Thus, HIV levels and resistance patterns in these compartments may diverge from those in plasma.

Disease progression

During the first few weeks of primary infection, both humoral and cellular immune responses occur:

• Humoral: Antibodies to HIV are usually measurable within a few weeks after primary infection; however, antibodies cannot fully control HIV infection because mutated forms of HIV that are not controlled by the patient’s current anti-HIV antibodies are generated.

• Cellular: Cell-mediated immunity is a more important means of controlling the high levels of viremia (usually over 10⁶ copies/mL) at first. However, rapid mutation of viral antigens that are targeted by lymphocyte-mediated cytotoxicity subvert control of HIV in most patients.

Plasma HIV virion levels, expressed as number of HIV RNA copies/mL, stabilize after about 6 months at a level (set point) that varies widely among patients but averages 30,000 to 100,000 copies/mL (4.2 to 5 log₁₀/mL). This variability depends on how host factors interact and impact HIV viral genetic diversity (9). The higher this set point, the more quickly the CD4 count decreases to a level that seriously impairs immunity (< 200/mcL) and results in the opportunistic infections and cancers that define advanced HIV infection (10–12).

Risk and severity of opportunistic infections, advanced HIV infection, and cancer associated with advanced HIV-related illness (formerly called acquired immune deficiency syndrome [AIDS]) are determined by 2 factors:

• CD4 count

• Exposure to opportunistic pathogens

Risk of specific opportunistic infections increases below threshold CD4 counts of about 200 cells/mcL for some infections and 50 cells/mcL for others, as in the following:

• CD4 count < 200 cells/mcL: Increased risk of Pneumocystis jirovecii pneumonia, toxoplasmic encephalitis, and cryptococcal meningitis

• CD4 count < 50 cells/mcL: Increased risk of cytomegalovirus (CMV) and Mycobacterium avium complex (MAC) infections

For every 3-fold (0.5 log₁₀) increase in plasma HIV RNA in untreated patients, the risk of progression to advanced HIV-related illness or death over the next 2 to 3 years increases approximately 50% (10).

The progression rate of HIV infection after initial infection is not uniform. Without treatment, the median time to advanced HIV-related illness is approximately 10 years (13), with progression risk varying substantially based on patient age, viral load set point, and CD4 trajectory. Eventually, advanced HIV infection invariably develops in untreated patients.

Pathophysiology references

1. 1. HIVinfo.NIH.gov. HIV Overview: The HIV Life Cycle. April 9, 2025. Accessed April 8, 2026.

2. 2. Ho DD, Neumann AU, Perelson AS, et al: Rapid turnover of plasma virions and CD4 lymphocytes in HIV-1 infection. Nature 373(6510):123-126, 1995. doi:10.1038/373123a0

3. 3. Perelson AS, Neumann AU, Markowitz M, Leonard JM, Ho DD. HIV-1 dynamics in vivo: virion clearance rate, infected cell life-span, and viral generation time. Science. 1996;271(5255):1582-1586. doi:10.1126/science.271.5255.1582

4. 4. Valiathan R, Deeb K, Diamante M, Ashman M, Sachdeva N, Asthana D. Reference ranges of lymphocyte subsets in healthy adults and adolescents with special mention of T cell maturation subsets in adults of South Florida. Immunobiology. 2014;219(7):487-496. doi:10.1016/j.imbio.2014.02.010

5. 5. Brenchley JM, Price DA, Schacker TW, et al. Microbial translocation is a cause of systemic immune activation in chronic HIV infection. Nat Med. 2006;12(12):1365-1371. doi:10.1038/nm1511

6. 6. Bednar MM, Sturdevant CB, Tompkins LA, et al: Compartmentalization, viral evolution, and viral latency of HIV in the CNS. Curr HIV/AIDS Rep 12(2):262-271, 2015. doi:10.1007/s11904-015-0265-9

7. 7. Mabvakure BM, Lambson BE, Ramdayal K, et al: Evidence for both intermittent and persistent compartmentalization of HIV-1 in the female genital tract. J Virol 93(10):e00311-e00319, 2019. doi:10.1128/JVI.00311-19

8. 8. Ghosn J, Viard JP, Katlama C, et al: Evidence of genotypic resistance diversity of archived and circulating viral strains in blood and semen of pre-treated HIV-infected men. AIDS (London, England). 18(3):447-457, 2004. doi:10.1097/00002030-200402200-00011

9. 9. Bartha I, McLaren PJ, Brumme C, et al: Estimating the respective contributions of human and viral genetic variation to HIV control. PLoS Comput Biol 13(2):e1005339, 2017. Published 2017 Feb 9. doi:10.1371/journal.pcbi.1005339

10. 10. Mellors JW, Muñoz A, Giorgi JV, et al. Plasma viral load and CD4+ lymphocytes as prognostic markers of HIV-1 infection. Ann Intern Med. 1997;126(12):946-954. doi:10.7326/0003-4819-126-12-199706150-00003

11. 11. Lavreys L, Baeten JM, Chohan V, et al: Higher set point plasma viral load and more-severe acute HIV type 1 (HIV-1) illness predict mortality among high-risk HIV-1-infected African women. Clin Infect Dis 42(9):1333-9, 2006. doi:10.1086/503258

12. 12. Lyles RH, Muñoz A, Yamashita TE, et al: Natural history of human immunodeficiency virus type 1 viremia after seroconversion and proximal to AIDS in a large cohort of homosexual men. Multicenter AIDS cohort study. J Infect Dis 181(3):872-80, 2000. doi:10.1086/315339

13. 13. Glaubius R, Kothegal N, Birhanu S, et al. Disease progression and mortality with untreated HIV infection: evidence synthesis of HIV seroconverter cohorts, antiretroviral treatment clinical cohorts and population-based survey data. J Int AIDS Soc. 2021;24 Suppl 5(Suppl 5):e25784. doi:10.1002/jia2.25784

Initial HIV infection

Initially, primary HIV infection may be asymptomatic or cause transient nonspecific symptoms (acute retroviral syndrome).

Oral Candidiasis (Labial Mucosa)

Image

This photo shows oral candidiasis manifesting as a white exudate overlying a beefy, red, and raw mucosal surface of the labial mucosa.

© Springer Science+Business Media

Oral Candidiasis Due to HIV

Image

This photo shows fluffy white exudate (thrush) on the tongue of a child with HIV infection.

© Springer Science+Business Media

Acute retroviral syndrome usually begins within 2 to 4 weeks of infection and usually lasts for a few days to several weeks (1). Symptoms and signs are often mistaken for infectious mononucleosis or benign, nonspecific viral syndromes and may include fever, malaise, fatigue, several types of dermatitis, sore throat, arthralgias, generalized lymphadenopathy, and septic meningitis.

After the first symptoms disappear, most patients, even without treatment, have no symptoms or only a few mild, intermittent, nonspecific symptoms for a highly variable time period (typically 10 to 11 years) (2, 3).

Symptoms during this relatively asymptomatic period may result from HIV infection directly or from opportunistic infections. The following are most common:

• Lymphadenopathy

• White plaques due to oral candidiasis

• Herpes zoster

• Diarrhea

• Fatigue

• Fever with intermittent sweats

Asymptomatic, mild-to-moderate cytopenias (eg, leukopenia, anemia, thrombocytopenia) are also common. Some patients have progressive muscle wasting (which may be related to anorexia and increased catabolism due to chronic inflammation and opportunistic infections) and low-grade fevers or diarrhea.

Worsening HIV infection

When the CD4 count drops to < 200 cells/mcL, nonspecific symptoms may worsen, and conditions associated with advanced HIV-related illness may emerge.

In patients with HIV infection, certain syndromes are common and may require different considerations (see table Common Manifestations of HIV Infection by Organ System). Some patients present with cancers (eg, Kaposi sarcoma, B-cell lymphomas) that occur more frequently, are unusually severe, or have unique features in patients with HIV infection (see Cancers Common in Patients With HIV Infection). In other patients, neurologic dysfunction may occur.

Evaluation may detect infections that do not typically occur in the general population, such as:

• Disseminated mycobacterial infections

• P. jirovecii infection

• Cryptococcus neoformans infection

• Other fungal infections

Infections that also occur in the general population but suggest advanced HIV infection if they are unusually severe or frequently recur include:

• Herpes zoster

• Herpes simplex

• Vaginal candidiasis

• Invasive pneumococcal infections

• Salmonella septicemia

Additional Manifestations of HIV Infection

Disseminated Bartonellosis in HIV Infection

This patient with HIV infection has disseminated cutaneous papules on the face as well as exophytic nodules on the eyelids.

This patient with HIV infection has disseminated cutaneous papules on the face as well as exophytic nodules on the eyel

... read more

© Springer Science+Business Media

Crusted (Norwegian) Scabies

This photo shows diffuse scaling and hyperkeratotic plaques in a patient with HIV infection and crusted scabies.

This photo shows diffuse scaling and hyperkeratotic plaques in a patient with HIV infection and crusted scabies.

© Springer Science+Business Media

Kaposi Sarcoma

Kaposi sarcoma is an aggressive, multicentric tumor that may involve the face, trunk, mucosal surfaces, lymphatics, or gastrointestinal tract in patients with advanced HIV infection. Lesions appear as bluish to violaceous macules, plaques, or tumors.

Kaposi sarcoma is an aggressive, multicentric tumor that may involve the face, trunk, mucosal surfaces, lymphatics, or

... read more

CDC/Sol Silverman, Jr., DDS

Kaposi Sarcoma (Early Stage)

This photo shows purplish red nodules consistent with Kaposi sarcoma over the lower eyelid skin in a patient with HIV infection.

This photo shows purplish red nodules consistent with Kaposi sarcoma over the lower eyelid skin in a patient with HIV i

... read more

© Springer Science+Business Media

Kaposi Sarcoma (Face)

This photo shows Kaposi sarcoma on the face, ear, and neck.

This photo shows Kaposi sarcoma on the face, ear, and neck.

© Springer Science+Business Media

Kaposi Sarcoma (Shoulder)

This photo shows disseminated oval plaques of Kaposi sarcoma on the shoulder of a patient with HIV infection.

This photo shows disseminated oval plaques of Kaposi sarcoma on the shoulder of a patient with HIV infection.

© Springer Science+Business Media

Kaposi Sarcoma (Forearm)

This photo shows violaceous plaques on the forearm in a patient with HIV infection.

This photo shows violaceous plaques on the forearm in a patient with HIV infection.

© Springer Science+Business Media

Oral Hairy Leukoplakia

Oral hairy leukoplakia appears as verrucous white outgrowths on the lateral margins of the tongue.

Oral hairy leukoplakia appears as verrucous white outgrowths on the lateral margins of the tongue.

CDC/Sol Silverman, Jr., DDS

Anal Carcinoma

This photo shows condylomata (1) and squamous cell invasive cancer (2) caused by persistent human papillomavirus (HPV) infection in a person with HIV infection.

This photo shows condylomata (1) and squamous cell invasive cancer (2) caused by persistent human papillomavirus (HPV)

... read more

Edward R. Cachay, MD, MAS

Disseminated Bartonellosis in HIV Infection

This patient with HIV infection has disseminated cutaneous papules on the face as well as exophytic nodules on the eyelids.

This patient with HIV infection has disseminated cutaneous papules on the face as well as exophytic nodules on the eyel

... read more

© Springer Science+Business Media

Crusted (Norwegian) Scabies

This photo shows diffuse scaling and hyperkeratotic plaques in a patient with HIV infection and crusted scabies.

This photo shows diffuse scaling and hyperkeratotic plaques in a patient with HIV infection and crusted scabies.

© Springer Science+Business Media

Kaposi Sarcoma

Kaposi sarcoma is an aggressive, multicentric tumor that may involve the face, trunk, mucosal surfaces, lymphatics, or gastrointestinal tract in patients with advanced HIV infection. Lesions appear as bluish to violaceous macules, plaques, or tumors.

Kaposi sarcoma is an aggressive, multicentric tumor that may involve the face, trunk, mucosal surfaces, lymphatics, or

... read more

CDC/Sol Silverman, Jr., DDS

Kaposi Sarcoma (Early Stage)

This photo shows purplish red nodules consistent with Kaposi sarcoma over the lower eyelid skin in a patient with HIV infection.

This photo shows purplish red nodules consistent with Kaposi sarcoma over the lower eyelid skin in a patient with HIV i

... read more

© Springer Science+Business Media

Kaposi Sarcoma (Face)

This photo shows Kaposi sarcoma on the face, ear, and neck.

This photo shows Kaposi sarcoma on the face, ear, and neck.

© Springer Science+Business Media

Kaposi Sarcoma (Shoulder)

This photo shows disseminated oval plaques of Kaposi sarcoma on the shoulder of a patient with HIV infection.

This photo shows disseminated oval plaques of Kaposi sarcoma on the shoulder of a patient with HIV infection.

© Springer Science+Business Media

Kaposi Sarcoma (Forearm)

This photo shows violaceous plaques on the forearm in a patient with HIV infection.

This photo shows violaceous plaques on the forearm in a patient with HIV infection.

© Springer Science+Business Media

Oral Hairy Leukoplakia

Oral hairy leukoplakia appears as verrucous white outgrowths on the lateral margins of the tongue.

Oral hairy leukoplakia appears as verrucous white outgrowths on the lateral margins of the tongue.

CDC/Sol Silverman, Jr., DDS

Anal Carcinoma

This photo shows condylomata (1) and squamous cell invasive cancer (2) caused by persistent human papillomavirus (HPV) infection in a person with HIV infection.

This photo shows condylomata (1) and squamous cell invasive cancer (2) caused by persistent human papillomavirus (HPV)

... read more

Edward R. Cachay, MD, MAS

Advanced HIV-related illness

Advanced HIV-related illness (formerly called acquired immune deficiency syndrome [AIDS]) is defined as HIV infection with one or more of the following:

• One or more advanced HIV-related illnesses (4)

• A CD4+ T lymphocyte (helper cell) count of < 200 cells/mcL

• A CD4+ lymphocyte percentage of ≤ 14% of the total lymphocyte count

Advanced HIV-related illnesses include:

• Serious opportunistic infections

• Certain cancers (eg, Kaposi sarcoma, non-Hodgkin lymphoma) to which defective cell-mediated immunity predisposes

• Neurologic dysfunction

• Wasting syndrome

Advanced HIV-Related Illness: Coccidioidomycosis

Image

This coronal view of a chest CT shows multiple micronodular opacities throughout both lung parenchyma in a patient in Southern California, a known endemic region where Coccidioides immitis, a soil fungus that causes coccidioidomycosis, is commonly found. The lesions resemble miliary tuberculosis. In endemic areas, disseminated coccidioidomycosis produces similar lesions.

Edward R. Cachay, MD, MAS

Symptoms and signs references

1. 1. Centers for Disease Control and Prevention (CDC). About HIV. November 25, 2024. Accessed April 8, 2026.

2. 2. Glaubius R, Kothegal N, Birhanu S, et al. Disease progression and mortality with untreated HIV infection: evidence synthesis of HIV seroconverter cohorts, antiretroviral treatment clinical cohorts and population-based survey data. J Int AIDS Soc. 2021;24 Suppl 5(Suppl 5):e25784. doi:10.1002/jia2.25784

3. 3. Pantaleo G, Graziosi C, Fauci AS. The immunopathogenesis of human immunodeficiency virus infection. N Engl J Med. 1993;328(5):327-335. doi:10.1056/NEJM199302043280508

4. 4. Selik RM, Mokotoff ED, Branson, B, et al. Revised Surveillance Case Definition for HIV Infection—United States, 2014. MMWR. 2014;63(RR03):1–10.

Diagnostic principles and window period (acute HIV infection)

In clinical practice, the stage of HIV infection (ie, acute infection or established infection) is usually unknown at the time of testing; therefore, diagnostic strategies are based on assay performance across the spectrum of disease course rather than timing of exposure to HIV (4).

After exposure to HIV, laboratory markers become detectable in a predictable sequence. HIV RNA is the first detectable marker in plasma (approximately 10 to 12 days), followed by p24 antigen (15 to 17 days) and HIV-specific antibodies (approximately 21 days, depending on assay sensitivity). This interval corresponds to the “window period” of acute HIV infection.

During early infection, although serologic test results may be negative, they are still obtained. HIV RNA testing is the most sensitive method for diagnosis when acute infection is suspected.

Initial diagnostic testing includes:

• Fourth-generation HIV antigen/antibody combination immunoassay (detecting HIV-1/2 antibodies and p24 antigen; preferred screening test in all settings)

Confirmatory testing includes:

• HIV-1/HIV-2 differentiation assay if screening is reactive

• HIV RNA nucleic acid amplification testing (NAAT) if the differentiation assay is negative or indeterminate, or if clinical suspicion persists despite negative serology

Testing in established infection (post-seroconversion)

After seroconversion, HIV-specific antibodies are reliably detectable, and fourth-generation assays demonstrate high sensitivity and specificity. Diagnostic algorithms at this stage are focused on confirmation and viral differentiation.

Initial diagnostic testing includes:

• Fourth-generation HIV antigen/antibody combination immunoassay (detecting HIV-1/2 antibodies and p24 antigen; preferred screening test in all settings)

• Rapid antibody-based tests (used primarily in low-resource and point-of-care settings)

Confirmatory testing includes:

• HIV-1/HIV-2 differentiation assay (standard confirmatory test in high-resource settings)

• HIV RNA nucleic acid amplification testing (NAAT) in cases of discordant, indeterminate, or unresolved results

• Serial algorithm of multiple rapid diagnostic tests based on different antigen platforms (in low-resource settings without routine access to differentiation assays or NAAT)

Staging

HIV infection can be staged based on the CD4 count. In patients ≥ 6 years old, stages are as follows:

• Stage 1: ≥ 500 cells/mcL

• Stage 2: 200 to 499 cells/mcL

• Stage 3: < 200 cells/mcL

The CD4 count after 1 to 2 years of treatment provides an indication of ultimate immune recovery. Clinicians should note CD4 counts may not return to the normal range despite prolonged suppression of HIV.

Monitoring

When HIV infection is diagnosed, the following should be determined:

• CD4 count

• Plasma HIV RNA level (also called viral load)

These markers are crucial for determining individual prognosis, assessing the risk of opportunistic infections, and monitoring the effectiveness of ART.

The CD4 count is calculated as the product of the following:

• White blood cell count (eg, 4000 cells/mcL)

• Percentage of white blood cells that are lymphocytes (eg, 30%)

• Percentage of lymphocytes that are CD4+ (eg, 20%)

As an example (using the numbers above), the CD4 count (4000 × 0.3 × 0.2) is 240 cells/mcL, or about 1/3 of the CD4 count in adults, which normally ranges between 500 and 1250 cells/mcL.

The plasma HIV RNA level (viral load) reflects HIV replication rates. The higher the set point (ie, the relatively stable virus levels that occur after primary infection), the more quickly the CD4 count decreases and the greater the risk of opportunistic infection, even in patients without symptoms.

Additional testing

• Genotyping resistance assay

• Co-receptor tropism assays

• HLA-B*5701 testing

Other types of testing may be required for certain patients who require the use of certain antiretroviral medications. A baseline HIV genotype (also called a genotyping resistance assay) using standard genotype sequencing (eg, Sanger) or next-generation sequencing can be ordered if the HIV viral load is > 500 copies/mL (5). The availability of this testing varies by location. HIV genotyping is used to identify mutations known to cause resistance to certain antiretroviral medications and to help select a medication regimen likely to be effective for a specific patient with HIV infection. In addition to genotyping, co-receptor tropism assays and HLA-B*5701 testing may be required (eg, for induction using a CCR5 co-receptor antagonist and/or abacavir) (6, 7).

Diagnosis of HIV-related conditions

The diagnosis of the various opportunistic infections, cancers, and other syndromes that occur in patients with HIV infection is directed at the underlying cause (see table Common Manifestations of HIV Infection by Organ System). Many of these conditions have aspects unique to HIV infection.

Hematologic disorders (eg, cytopenias, lymphomas, cancers) are common and may be evaluated with bone marrow aspiration and biopsy. This procedure can also help diagnose disseminated infections with M. avium complex (MAC), M. tuberculosis, Cryptococcus, Histoplasma, human parvovirus B19, P. jirovecii, and Leishmania. Most patients have normocellular or hypercellular marrow despite peripheral cytopenia, reflecting peripheral destruction. Iron stores are usually normal or increased, reflecting anemia of chronic disease (an iron-reutilization defect). Mild to moderate plasmacytosis, lymphoid aggregates, increased numbers of histiocytes, and dysplastic changes in hematopoietic cells are common.

HIV-associated neurologic syndromes can be differentiated via lumbar puncture with cerebrospinal fluid analysis and central nervous system contrast-enhanced CT or MRI.

Diagnosis references

1. 1. ClinicalInfo.HIV.gov. Guidelines for the Use of Antiretroviral Agents in Adults and Adolescents With HIV. Baseline Evaluation. September 21, 2022. Accessed April 8, 2026.

2. 2. ClinicalInfo.HIV.gov. Guidelines for the Use of Antiretroviral Agents in Adults and Adolescents With HIV. Laboratory Testing for Initial Assessment and Monitoring of People With HIV. September 25, 2025. Accessed April 9, 2026.

3. 3. Horberg M, Thompson M, Agwu A, et al. Primary Care Guidance for Providers of Care for Persons With Human Immunodeficiency Virus: 2024 Update by the HIV Medicine Association of the Infectious Diseases Society of America. Clin Infect Dis. Published online October 12, 2024. doi:10.1093/cid/ciae479

4. 4. Centers for Disease Control and Prevention (CDC) Stacks. Quick Reference Guide: Laboratory Testing for the Diagnosis of HIV Infection: Updated Recommendations. June 27, 2014. Accessed April 9, 2026.

5. 5. Fine SM, Vail RM, McGowan JP, et al. HIV Resistance Assays [Internet]. Baltimore (MD): Johns Hopkins University; 2023 Jun. Available from: https://www.ncbi.nlm.nih.gov/books/NBK558864/

6. 6. ClinicalInfo.HIV.gov. Guidelines for the Use of Antiretroviral Agents in Adults and Adolescents With HIV. Laboratory Testing for Initial Assessment and Monitoring of People With HIV. Co-Receptor Tropism Assays. October 25, 2018. Accessed April 9, 2026.

7. 7. ClinicalInfo.HIV.gov. Guidelines for the Use of Antiretroviral Agents in Adults and Adolescents With HIV. Laboratory Testing for Initial Assessment and Monitoring of People With HIV. HLA-B* 5701 Screening. January 10, 2011. Accessed April 9, 2026.

Screening references

1. 1. Centers for Disease Control and Prevention (CDC). Clinical Testing Guidance for HIV. February 10, 2025. Accessed April 9, 2026.

2. 2. World Health Organization (WHO). Consolidated guidelines on HIV testing services. December 1, 2019. Accessed April 9, 2026.

3. 3. WHO. Consolidated guidelines on differentiated HIV testing services. July 19, 2024. Accessed April 9, 2026.

4. 4. WHO. Consolidated guidelines on HIV prevention, testing, treatment, service delivery and monitoring: recommendations for a public health approach. July 16, 2021. Accessed April 9, 2026.

ART: General principles

The primary goals of ART are to:

• Reduce the plasma HIV RNA level to undetectable (ie, < 20 to 50 copies/mL).

• Restore the CD4 count to a normal level (immune restoration or reconstitution).

A poor CD4 count response is more likely if the CD4 count at initiation of treatment is low (especially if < 50/mcL) and/or the HIV RNA level is high. However, marked improvement is likely even in patients with advanced immunosuppression.

An increased CD4 count correlates with a markedly decreased risk of opportunistic infections, other complications, and death. With immune restoration, patients, even those with complications that have no specific treatment (eg, HIV-induced cognitive dysfunction) or that were previously considered untreatable (eg, progressive multifocal leukoencephalopathy), may improve. Outcomes are also improved for patients with cancers (eg, lymphoma, Kaposi sarcoma) and most opportunistic infections.

Patients with most acute opportunistic infections benefit from early ART (initiated during the management of the opportunistic infection). However, for some opportunistic infections, such as tuberculous meningitis or cryptococcal meningitis, evidence suggests that ART should be delayed (2 to 4 weeks in most cases) until the first phase of antimicrobial therapy for the infections is finished because of the increased frequency of adverse events and death.

Most patients who take ART as prescribed can reach the primary goals usually within 6 months of starting treatment (2). However, maintaining this degree of adherence may be difficult for some patients. Partial suppression (failure to lower plasma HIV RNA levels to undetectable levels) may select for single or multiple accumulated mutations in HIV that make viruses partially or completely resistant to a single medication or entire classes of medications. Unless subsequent treatment uses medications of other classes to which HIV remains sensitive, treatment is more likely to fail.

The success of ART is assessed by measuring plasma HIV RNA levels every 8 to 12 weeks for the first 4 to 6 months or until HIV levels are undetectable and every 6 months thereafter. Treatment failure is defined as the inability of an antiviral regimen to adequately control HIV infection. Increasing HIV levels are the earliest evidence of treatment failure and may precede a decreasing CD4 count by months; this is often called virologic failure (3). In contrast, suboptimal immunologic response occurs when there is failure to achieve and maintain adequate CD4 counts despite adequate viral suppression (4). Both virologic failure and suboptimal immunologic response are types of treatment failure. Maintaining patients on treatment regimens that are failing selects for HIV mutants that are more drug-resistant. However, compared with wild-type HIV, these mutants appear less able to reduce the CD4 count, and unsuccessful medication regimens may often be continued when no fully suppressive regimen can be found.

If treatment failure occurs, drug susceptibility (resistance) assays can determine the susceptibility of the dominant HIV strain to all available medications. Genotypic and phenotypic assays are available and can help clinicians select a new regimen that should contain at least 2 and preferably 3 medications to which the HIV strain is more susceptible. The dominant HIV strain in the blood of patients who are taken off ART may revert over months to years to the wild-type (ie, susceptible) strain because the resistant mutants replicate more slowly and are replaced by the wild type. Thus, if patients have not been treated recently, the full extent of resistance may not be apparent through resistance testing, but when treatment resumes, strains with resistance mutations often reemerge from latency and again replace the wild-type HIV strain.

Many patients with HIV infection follow complex regimens involving multiple pills to control their HIV RNA level (viral load), but, often, no conventional HIV RNA resistance tests are done when viral treatment fails. With the availability of coformulated HIV medications, many patients could benefit from simplification of their ART regimen, guided by HIV DNA archive genotype testing (GenoSure Archive in the United States). The HIV DNA genotype archive provides HIV-1 antiretroviral drug resistance data when conventional HIV RNA resistance testing cannot be done because patients have a low plasma HIV RNA level (< 500 copies/mL). The HIV DNA archive genotype test analyzes integrated and unintegrated archived HIV-1 proviral DNA embedded in host cells. The test amplifies cell-associated HIV-1 DNA from infected cells in whole blood samples, then uses next-generation sequencing technology to analyze the HIV-1 polymerase region. The positive predictive value of the HIV DNA archive resistance test results may enable clinicians to identify HIV-resistance mutations that were previously unidentified and may assist in selecting a potentially simpler regimen with coformulated medications (≥ 2 medications in a single pill) (5).

Immune reconstitution inflammatory syndrome (IRIS)

Patients beginning ART sometimes deteriorate clinically, even though HIV levels in their blood are suppressed and their CD4 count increases, because of an immune reaction to subclinical opportunistic infections or to residual microbial antigens after successful treatment of opportunistic infections. IRIS usually occurs in the first months of HIV treatment but is occasionally delayed. IRIS can complicate virtually any opportunistic infection and even tumors (eg, Kaposi sarcoma) but is usually self-limited or responds to brief regimens of glucocorticoids (6).

IRIS has 2 forms:

• Paradoxical IRIS: Worsening symptoms due to a previously diagnosed infection

• Unmasked IRIS: First appearance of symptoms of an infection not previously diagnosed

Paradoxical IRIS typically occurs during the first few months of HIV treatment and usually resolves on its own. If it does not, glucocorticoids, given for a short time, are often effective. Paradoxical IRIS is more likely to cause symptoms and symptoms are more likely to be severe when ART is started soon after treatment of an opportunistic infection is started. Thus, for some opportunistic infections, ART should be delayed until treatment of the opportunistic infection has reduced or eliminated the infection.

In patients with unmasked IRIS, the newly identified opportunistic infection is treated with antimicrobial medications. Occasionally, when symptoms are severe, glucocorticoids are also used. Usually, when unmasked IRIS occurs, ART should be continued (with one exception being cryptococcal meningitis, for which ART may be temporarily interrupted until the infection is controlled).

Determining whether clinical deterioration is caused by treatment failure, IRIS, or both requires assessment of the persistence of active infections with cultures and can be difficult.

Interruption of ART

Interruption of ART is usually safe if all medications are stopped simultaneously, but levels of slowly metabolized medications (eg, nevirapine, efavirenz) may remain high and thus increase the risk of resistance. Interruption may be necessary if intervening illnesses require treatment or if medication toxicity is intolerable or needs to be evaluated. After interruption to determine which drug is responsible for toxicity, clinicians can safely restart most medications as monotherapy for up to a few days.

NOTE: The most important exception is abacavir. Patients who had fever or rash during previous exposure to abacavir may develop severe, potentially fatal hypersensitivity reactions with reexposure. Risk of an adverse reaction to abacavir is 100-fold higher in patients with HLA-B*5701, which can be detected by genetic testing (7).

Prevention of opportunistic infections

Effective chemoprophylaxis is available for many opportunistic infections and reduces rates of disease due to P. jirovecii, Candida species, Cryptococcus, and MAC. If therapy restores CD4 counts to above threshold values for > 3 months, chemoprophylaxis can be stopped (8).

Primary prophylaxis depends on the CD4 count:

• CD4 count < 200 cells/mcL or oropharyngeal candidiasis (active or previous): Prophylaxis against P. jirovecii pneumonia is recommended. Double-strength trimethoprim/sulfamethoxazole (TMP/SMX) tablets given once/day or 3 times/week are effective. Some adverse effects can be minimized with the 3 times/week dose or by gradual dose escalation. Some patients who cannot tolerate TMP/SMX can tolerate oral dapsone 100 mg once/day. Patients with glucose-6-phosphate dehydrogenase (G6PD) deficiency are at risk of developing severe hemolysis with dapsone use and, therefore, should be screened for G6PD deficiency before using dapsone. For the few patients who cannot tolerate either medication because of a troublesome adverse effect (eg, fever, neutropenia, rash), aerosolized pentamidine 300 mg once/month or oral atovaquone 1500 mg once/day can be used.

• CD4 count < 100 cells/mcL: Primary prophylaxis against Toxoplasma gondii is recommended in seropositive patients, typically using TMP/SMX.

• CD4 count < 50 cells/mcL: Primary prophylaxis against disseminated MAC disease is not recommended for adults and adolescents with HIV infection who immediately initiate ART. People with HIV infection who are not receiving ART or who remain viremic while receiving ART but have no current options for a fully suppressive ART regimen should receive chemoprophylaxis against disseminated MAC disease if they have a CD4 count < 50 cells/mcL as a CD4-based indication that is separate from P. jirovecii prophylaxis (9). Prophylaxis against disseminated MAC disease consists of azithromycin or clarithromycin; if neither of these medications is tolerated, rifabutin can be used. Azithromycin can be given weekly as 2 600-mg tablets; it provides protection (approximately 60%) similar to daily clarithromycin and does not interact with other medications (10).

If latent tuberculosis is suspected (based on tuberculin skin tests, interferon-gamma release assays, high-risk exposure, personal history of active tuberculosis, or residence in a region with high tuberculosis prevalence), regardless of CD4 count. Preferred regimens include isoniazid plus rifapentine weekly for 3 months (with pyridoxine supplementation) or rifampin-based regimens for 3 to 4 months; isoniazid for 6 to 9 months remains an alternative when rifamycin-based therapy is not suitable.

For primary prophylaxis against some fungal infections (eg, esophageal candidiasis), oral fluconazole 100 to 200 mg once/day is successful but is infrequently used because the cost per infection prevented is high and diagnosis and treatment of these infections are usually successful (11).

Secondary prophylaxis (after control of the initial infection) is indicated if patients have had the following (8):

• Recurrent oral, vaginal, or esophageal candidiasis; coccidioidomycosis; or cryptococcal infection: Oral fluconazole

• Histoplasmosis: Oral itraconazole

• Latent toxoplasmosis: Oral TMP/SMX

• P. jirovecii pneumonia: Oral TMP/SMX

• Herpes simplex infection: Oral acyclovir

Immunization

Guidance on vaccination schedules evolves over time, and various expert organizations issue differing recommendations. See the United States Immunizations for Preventable Diseases in Adults and Adolescents With HIV (ClinicalInfo.HIV.gov), American Academy of Pediatrics (AAP), American Academy of Family Physicians (AAFP), and the World Health Organization for specific recommendations and further information.

For adolescents and adults with HIV infection, immunizations generally include the following:

• Patients who have not received a conjugate pneumococcal vaccine or whose previous vaccination history is unknown should be given PCV15, PCV20, or PCV21; if PCV15 is given, follow with PPSV23 ≥ 8 weeks after the PCV15 dose.

• All patients should be given the influenza vaccine annually.

• All patients should be given the hepatitis B vaccine.

• Patients at risk of hepatitis A or desiring protection from it should be given the hepatitis A vaccine.

• At the appropriate age, males and females should be given the human papillomavirus (HPV) vaccine to prevent HPV-related cervical and anal cancers.

• Adults who have not been previously vaccinated with the meningococcal vaccine should be given a 2-dose primary series of MenACWY ≥ 8 weeks apart and be revaccinated every 5 years.

• Patients who did not receive tetanus-diphtheria-pertussis vaccine (Tdap) as part of their completed tetanus-diphtheria vaccine (Td) series should be given Tdap for their next Td booster. For patients who are beginning or continuing their Td series and have not yet been given Tdap, Tdap should be substituted for one of the Td boosters.

• All patients should be given the recombinant zoster vaccine.

• The varicella vaccine and the measles, mumps, and rubella (MMR) vaccine may be given to patients with CD4 percentage ≥ 15% and CD4 count ≥ 200 cells/mcL, but these vaccines are contraindicated in patients with CD4 percentage < 15% or CD4 count < 200 cells/mcL.

• Patients with HIV infection should receive the full series of a COVID-19 vaccine and recommended booster doses. Additional vaccine doses are advised for patients with moderate to severe immunocompromise, including those with advanced or uncontrolled HIV infection.

• Mpox vaccination is recommended for people with HIV infection who are at risk of mpox. The main mpox vaccine recommended for people with HIV infection in the United States is the replication-limited vaccinia virus vaccine (also called modified vaccine Ankara, MVA), which, although a live-virus vaccine, has an excellent safety profile.

Generally, inactivated vaccines should be used. Inactivated vaccines are effective less often in patients who are HIV-positive than in those who are HIV-negative (12). The degree of impaired response varies by vaccine type and the patient's immune status.

Pregnant patients with HIV should receive the routine vaccinations recommended during pregnancy. Expert opinion should be sought for the care of patients at risk of primary varicella; recommendations vary (see vaccination information in Treatment of HIV Infection in Infants and Children: Routine vaccinations).

Treatment references

1. 1. INSIGHT START Study Group, Lundgren JD, Babiker AG, et al. Initiation of antiretroviral therapy in early asymptomatic HIV infection. N Engl J Med. 2015;373 (9):795–807. doi:10.1056/NEJMoa1506816

2. 2. HIV.gov. Viral Suppression and an Undetectable Viral Load. April 2, 2026. Accessed April 13, 2026.

3. 3. ClinicalInfo.HIV.gov. Guidelines for the Use of Antiretroviral Agents in Adults and Adolescents With HIV. Management of People With HIV and Antiretroviral Therapy Experience. Virologic Failure. September 14, 2024. Accessed April 13, 2026.

4. 4. ClinicalInfo.HIV.gov. Guidelines for the Use of Antiretroviral Agents in Adults and Adolescents With HIV. Management of People With HIV and Antiretroviral Therapy Experience. Suboptimal CD4 Cell Recovery Despite Viral Suppression. September 14, 2024. Accessed April 13, 2026.

5. 5. ClinicalInfo.HIV.gov. Guidelines for the Use of Antiretroviral Agents in Adults and Adolescents With HIV. Laboratory Testing: Drug-Resistance Testing. September 12, 2024. Accessed June 3, 2026.

6. 6. French MA. HIV/AIDS: immune reconstitution inflammatory syndrome: a reappraisal. Clin Infect Dis. 2009;48(1):101-107. doi:10.1086/595006

7. 7. ClinicalInfo.HIV.gov. Guidelines for the Use of Antiretroviral Agents in Adults and Adolescents With HIV. Laboratory Testing for Initial Assessment and Monitoring of People With HIV. HLA-B* 5701 Screening. January 10, 2011. Accessed April 9, 2026.

8. 8. ClinicalInfo.HIV.gov. Guidelines for the Prevention and Treatment of Opportunistic Infections in Adults and Adolescents With HIV. Introduction. December 16, 2024. Accessed April 13, 2026.

9. 9. ClinicalInfo.HIV.gov. Guidelines for the Prevention and Treatment of Opportunistic Infections in Adults and Adolescents With HIV. Disseminated Mycobacterium avium Complex Disease. August 15, 2024. Accessed April 13, 2026.

10. 10. Uthman MM, Uthman OA, Yahaya I. Interventions for the prevention of Mycobacterium avium complex in adults and children with HIV. Cochrane Database Syst Rev. 2013;2013(4):CD007191. Published 2013 Apr 30. doi:10.1002/14651858.CD007191.pub2

11. 11. ClinicalInfo.HIV.gov. Guidelines for the Prevention and Treatment of Opportunistic Infections in Adults and Adolescents with HIV. Cryptococcosis. March 16, 2026. Accessed April 21, 2026.

12. 12. Tortellini E, Fosso Ngangue YC, Dominelli F, et al. Immunogenicity and Efficacy of Vaccination in People Living with Human Immunodeficiency Virus. Viruses. 2023;15(9):1844. Published 2023 Aug 30. doi:10.3390/v15091844

End-of-life care

Although ART has dramatically increased life expectancy for patients with advanced HIV-related illness, many patients still deteriorate and die. Death may result from the following:

• Inability to take ART consistently, resulting in progressive immunosuppression

• Occurrence of untreatable opportunistic infections and cancers

• Liver failure due to hepatitis B or C

• Accelerated aging and age-related disorders

• Cancers unrelated to advanced HIV-related illness that may be more prevalent among patients with HIV infection

Death is rarely sudden; thus, patients usually have time to make plans. Nonetheless, patients should record their plans for health care early, with clear instructions for end-of-life care. Other legal documents, including powers of attorney and wills, should be in place.

As patients near the end of life, clinicians may need to prescribe medications to relieve pain, anorexia, agitation, and other distressing symptoms. The profound redistribution of weight and overall weight loss in many people during the last stages of HIV infection make good skin care difficult. The comprehensive support provided by hospice programs helps many patients because hospice providers are skilled at symptom management, and they support caregivers and patient autonomy.

Prevention of transmission

Vaginal microbicides (including antiretroviral medications) inserted before sexual contact have thus far proved ineffective in preventing HIV transmission in most clinical trials. Notably, randomized trials have shown the dapivirine vaginal ring has modest efficacy in reducing HIV transmission, with meta-analyses suggesting an approximately 30% relative risk reduction, particularly with higher adherence (5).

Effective prevention measures include the following:

• Public education: Education is effective and appears to have decreased rates of infection in some countries, notably Thailand and Uganda. Because sexual contact accounts for most cases, teaching people to avoid unsafe sex practices is the most relevant measure (see table HIV Transmission Risk of Several Sexual Activities).

• Safer sex practices: People with HIV infection who are not virally suppressed (ie, do not have an undetectable viral load) should practice safer sex behaviors that are essential to prevent the spread of the infection. People with HIV infection who maintain a sustained undetectable viral load do not sexually transmit HIV to their partners (6). Safer sex practices should be used by a patient with HIV infection whose infection is not virally suppressed regardless of who they have sex with. Safer sex practices are also advised when both partners are HIV-positive and one or both partners are not virally suppressed; unprotected sex between people with virally unsuppressed HIV infection may expose the sex partner to resistant or more virulent strains of HIV. In addition, safer sex practices help prevent transmission of other viruses (eg, cytomegalovirus, Epstein-Barr virus, herpes simplex virus, hepatitis B virus) that cause severe disease in patients with advanced HIV infection, as well as help prevent transmission of syphilis and other sexually transmitted infections (STIs), including concerning infections such as multi-drug–resistant gonorrhea and sexually transmitted Neisseria meningitidis. Condoms offer the best protection. Oil-based lubricants should not be used because they may dissolve latex, increasing the risk of condom failure.

• Counseling to prevent HIV transmission for people who inject drugs: Counseling about the risk of sharing needles is important but is probably more effective if combined with provision of sterile needles and syringes to reduce transmission of HIV and other bloodborne viruses that are acquired by sharing contaminated injecting equipment, treatment of drug dependence, and rehabilitation.

• Confidential testing for HIV infection: Testing should be offered routinely to sexually active adolescents and adults ages 13 to 75. To facilitate routine testing, some jurisdictions in high-resource countries (eg, states in the United States) do not require written consent or extensive pre-test counseling.

• Counseling for pregnant patients: Mother-to-child transmission has been virtually eliminated by HIV testing, treatment with ART, and, in high-resource countries, use of human milk substitutes. If pregnant patients are known to have HIV infection or test positive for HIV, they should be counseled about the risk of mother-to-child transmission. Pregnant patients with HIV infection should be encouraged to accept ART to prevent infection of the fetus or neonate, typically beginning at about 14 weeks gestation. Combination therapy is typically used because it is more effective than monotherapy and less likely to result in drug resistance. Some medications can be toxic to the fetus or pregnant patient and should be avoided. If pregnant patients meet criteria for ART, they should begin a regimen tailored to their history and stage of pregnancy and continue it throughout pregnancy. Cesarean delivery can also reduce risk of transmission. Regardless of the antepartum regimen used or mode of delivery, all pregnant patients with HIV infection should be given IV zidovudine during labor, and, postpartum, neonates should be given oral zidovudine, which is continued for 2 to 6 weeks depending on the risk status of the infant (see also Prevention of perinatal transmission). Some pregnant patients choose to terminate their pregnancy because HIV can be transmitted in utero to the fetus or for other reasons.

• Screening of blood and organs: Transmission by blood transfusion is still remotely possible in the United States because antibody results may be false-negative during early infection (ie, before seroconversion in the window period). Currently, screening blood for antibody and p24 antigen is mandated in the United States and probably further reduces risk of transmission. Risk is reduced further by asking people with risk factors for HIV infection, even those with recent negative HIV antibody test results, not to donate blood or organs for transplantation. The American Red Cross has issued guidance for deferral of blood donation, including deferral for having had a new sex partner or more than one sex partner in the previous 3 months and having engaged in anal sex in the last 3 months (see American Red Cross Blood Donation Eligibility Criteria: Alphabetical ). However, use of sensitive HIV screening tests and deferral of donors of organs, blood, and blood products have not been implemented consistently in countries with high HIV burden.

• Circumcision of men: Data from young African men show that circumcision reduces the risk of acquiring HIV infection from female partners during vaginal sex to between 38% and 66% (7); male circumcision is probably similarly effective in other male-patient populations. Whether male circumcision reduces HIV transmission from men who are HIV positive to women or reduces the risk of acquiring HIV infection from an infected male partner is unknown.

• Universal precautions: Medical and dental clinicians should wear gloves in situations that may involve contact with any patient’s mucous membranes or body fluids and should be taught how to avoid needlestick accidents. Home caregivers of patients with HIV infection should wear gloves if their hands may be exposed to body fluids. Surfaces or instruments contaminated by blood or other body fluids should be cleaned and disinfected. Effective disinfectants include heat, peroxide, alcohols, phenolics, and hypochlorite (bleach). Isolation of patients with HIV infection is unnecessary unless indicated by an active opportunistic infection (eg, tuberculosis).

• Treatment of HIV infection: Treatment with ART lowers the risk of transmission.

Postexposure prophylaxis (PEP)

Potential consequences of exposure to HIV have prompted the development of policies and procedures, particularly preventive treatment, to decrease the risk of infection to health care professionals (10).

Preventive treatment is indicated after:

• Penetrating injuries involving HIV-infected blood (usually needlesticks)

• Heavy exposure of mucous membranes (eye or mouth) to infected body fluids such as semen, vaginal fluids, or other body fluids containing blood (eg, amniotic fluid)

Body fluids such as saliva, urine, tears, nasal secretions, vomitus, or sweat are not considered potentially infectious unless they are visibly bloody.

After initial exposure to blood, the exposed area is immediately cleaned with soap and water for skin exposures and with antiseptic for puncture wounds. If mucous membranes are exposed, the area is flushed with large amounts of water.

The following should be documented:

• Type of exposure

• Time elapsed since exposure

• Clinical information (including risk factors and serologic tests for HIV) about the individual who is the source of the exposure and about the individual exposed

Type of exposure is defined by:

• Which body fluid is involved

• Whether exposure involved a penetrating injury (eg, needlestick, cut with sharp object) and the depth of the injury

• Whether the fluid is in contact with nonintact skin (eg, abraded, chapped) or mucous membrane

Risk of infection depends on the type of exposure. It is about 0.3% (1:300) after a typical percutaneous exposure and about 0.09% (1:1100) after mucous membrane exposure. These risks vary, reflecting the amount of HIV transferred to the individual with the injury; the amount of HIV transferred is affected by multiple factors, including viral load of the source and type of needle (eg, hollow or solid). However, these factors are not taken into account in PEP recommendations.

Clinicians should note that the risk of HIV transmission via condomless sex is effectively zero when the viral load is suppressed for both same-sex as well as heterosexual encounters (11).

The source is qualified by whether it is known or unknown. If the source is unknown (eg, a needle on the street or in a sharps disposal container), risk should be assessed based on the circumstances of the exposure (eg, whether the exposure occurred in an area where injection drug use is prevalent, whether a needle discarded in a drug-treatment facility was used). If the source is known but HIV infection status is not, the source is assessed for HIV risk factors, and prophylaxis is considered.

The goal is to start PEP as soon after exposure as possible if prophylaxis is warranted. PEP should ideally be started within 24 to 36 hours after exposure; a longer interval after exposure requires additional expert consultation.

Use of PEP is determined by risk of acquisition; current guidelines recommend initiation of a 28-day course of ≥ 3 antiretroviral medications (12), ideally started within 24 to 36 hours and no later than 72 hours after exposure. The medications should be carefully selected to minimize adverse effects, support once-daily dosing, and optimize adherence and completion. Preferred regimens include a combination of 2 nucleoside reverse transcriptase inhibitors (NRTIs) and an integrase inhibitor:

Recommended 28-day PEP regimens include:

• Tenofovir disoproxil fumarate 300 mg once daily, plus

• Emtricitabine 200 mg once daily, plus

• Raltegravir 400 mg twice daily or dolutegravir 50 mg once daily

Or:

• Tenofovir disoproxil fumarate 300 mg once daily, plus

• Emtricitabine 200 mg once daily, plus

• Darunavir 800 mg or ritonavir 100 mg once daily

Although darunavir-based regimens remain an alternative option for PEP, they are used less frequently because of the preference for integrase inhibitor–based regimens, which are better tolerated and more convenient.

HIV testing of the exposed individual should be done at the initial visit (using point-of-care and/or laboratory-based antigen/antibody testing). Follow-up HIV testing is recommended at should be done at 4 to 6 weeks and again at 12 weeks after exposure using a fourth-generation antigen/antibody combination assay (12).

If the source’s virus is known or suspected to be resistant to ≥ 1 medication, an expert in ART and HIV transmission should be consulted. However, clinicians should not delay PEP pending expert consultation or drug susceptibility testing. Also, clinicians should provide immediate evaluation and face-to-face counseling and not delay follow-up care.

In people who may become or are pregnant, first-line PEP regimens are the same as those for nonpregnant people (10).

Prevention references

1. 1. Buchbinder SP, Spinosa Guzman S, Sanchez J, et al. Efficacy and safety of a mosaic HIV-1 vaccine regimen in men who have sex with men and transgender individuals (HVTN 706/HPX3002/Mosaico): a global, randomised, double-blind, placebo-controlled, phase 3 trial. Lancet HIV. 2025;12(12):e823-e835. doi:10.1016/S2352-3018(25)00195-X

2. 2. Gray GE, Mngadi K, Lavreys L, et al. Mosaic HIV-1 vaccine regimen in southern African women (Imbokodo/HVTN 705/HPX2008): a randomised, double-blind, placebo-controlled, phase 2b trial. Lancet Infect Dis. 2024;24(11):1201-1212. doi:10.1016/S1473-3099(24)00358-X

3. 3. Nkolola JP, Barouch DH. Prophylactic HIV-1 vaccine trials: past, present, and future. Lancet HIV. 2024;11(2):e117-e124. doi:10.1016/S2352-3018(23)00264-3

4. 4. Boomgarden AC, Upadhyay C. Progress and Challenges in HIV-1 Vaccine Research: A Comprehensive Overview. Vaccines (Basel). 2025;13(2):148. Published 2025 Jan 31. doi:10.3390/vaccines13020148

5. 5. Obiero J, Ogongo P, Mwethera PG, Wiysonge CS. Topical microbicides for preventing sexually transmitted infections. Cochrane Database Syst Rev. 2021;3(3):CD007961. Published 2021 Mar 13. doi:10.1002/14651858.CD007961.pub3

6. 6. Rodger AJ, Cambiano V, Bruun T, 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):171-81. doi:10.1001/jama.2016.5148

7. 7. Siegfried N, Muller M, Deeks JJ, Volmink J. Male circumcision for prevention of heterosexual acquisition of HIV in men. Cochrane Database Syst Rev. 2009;2009(2):CD003362. Published 2009 Apr 15. doi:10.1002/14651858.CD003362.pub2

8. 8. Centers for Disease Control and Prevention (CDC). Clinical Guidance for PrEP. April 30, 2026. Accessed May 7, 2026.

9. 9. Patel RR, Hoover KW, Lale A, Cabrales J, Byrd KM, Kourtis AP. Clinical Recommendation for the Use of Injectable Lenacapavir as HIV Preexposure Prophylaxis — United States, 2025. MMWR Morb Mortal Wkly Rep 2025;74:541–549. doi:10.15585/mmwr.mm7435a1

10. 10. Centers for Disease Control and Prevention (CDC). Clinical Guidance for PEP. February 10, 2025. Accessed May 7, 2026.

11. 11. Rodger AJ, Cambiano V, Bruun T, et al. Risk of HIV transmission through condomless sex in serodifferent gay couples with the HIV-positive partner taking suppressive antiretroviral therapy (PARTNER): final results of a multicentre, prospective, observational study. Lancet. 2019;393(10189):2428-2438. doi:10.1016/S0140-6736(19)30418-0

12. 12. Tanner MR, O'Shea JG, Byrd KM, et al. Antiretroviral Postexposure Prophylaxis After Sexual, Injection Drug Use, or Other Nonoccupational Exposure to HIV - CDC Recommendations, United States, 2025. MMWR Recomm Rep. 2025;74(1):1-56. Published 2025 May 8. doi:10.15585/mmwr.rr7401a1