HIV Prevention and Treatment: Latest Guidelines, ART, PrEP, and More (2025 Update)

HIV Prevention and Treatment

 

A. Primary Prevention

Until vaccination is a reality, prevention of HIV infection will depend on HIV testing and counseling, including precautions regarding sexual practices and injection drug use, initiation of ART as a prevention tool, pre-exposure and post-exposure use of ART, perinatal management including ART therapy for the mother, screening of blood products, and infection control practices in the health care setting.

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HIV testing and counseling

Primary care clinicians should routinely obtain a sexual history and provide risk factor assessment of their patients. Because approximately one-fifth of the HIV infected persons in the United States do not know they are infected, the USPSTF recommends that clinicians screen for HIV infection in adolescents and adults aged 15 to 65 years. Younger adolescents and older adults who are at increased risk should also be screened. Clinicians should review the risk factors for HIV infection with the patient and discuss safer sex and safer For persons whose test results are positive, although the CDC recommends "opt-out" testing in medical settings, some states require specific written consent. it is critically important that they be connected to ongoing medical care: Referrals for partner notification services, social services, mental health services, and HIV prevention services should also be provided. Prevention interventions focused on the importance of HIV-infected persons not putting others at risk have been successful.

For patients whose test results are negative, clinicians should review safer sex and needle use practices, including counseling not to exchange bodily fluids unless they are in a long-term mutually monogamous relationship with someone who has tested HIV antibody-negative and has not engaged in unsafe sex, injection drug use, or other HIV risk behaviors for at least 6 months before or at any time since the negative test.

To prevent sexual transmission of HIV, only latex condoms should be used, along with a water-soluble lubricant. Although nonoxynol-9, a spermicide, kills HIV, it is contraindicated because in some patients it may cause genital ulcers that could facilitate HIV transmission. Patients should be counseled that condoms are not 100% effective. They should be made familiar with the use of condoms, including, specifically, the advice that condoms must be used every time, that space should be left at the tip of the condom as a receptacle for semen, that intercourse with a condom should not be attempted if the penis is only partially erect, that men should hold on to the base of the condom when withdrawing the penis to prevent slippage, and that condoms should not be reused. Although anal intercourse remains the sexual practice at highest risk for transmitting HIV, seroconversions have been documented with vaginal and oral inter-course as well. Therefore, condoms should be used when engaging in these activities. Women, as well as men who have sex with men, should understand how to use condoms to be sure that their partners are using them correctly. Partners of HIV-infected women should use latex barriers such as dental dams (available at dental supply stores) to prevent direct oral contact with vaginal secretions. Several randomized trials in Africa demonstrated that male circumcision significantly reduced HIV incidence in men, but there are several barriers to performing widespread circumcisions among men in Africa.

 

Persons using injection drugs should be cautioned never to share needles or other drug paraphernalia. When sterile needles are not available, bleach does appear to inactivate HIV and should be used to clean needles.

 

2. ART for decreasing transmission of HIV to others

Besides preventing progression of HIV disease, effective ART likely decreases the risk of HIV transmission between sexual partners. An international study showed that among serodiscordant couples, early ART almost completely eliminated the risk of HIV transmission to the uninfected partner. Although HIV-negative persons in stable long-term partnerships with HIV-infected persons represent only one group of at-risk persons, theoretically increasing the use of ART among the population of HIV infected persons could decrease community-wide transmission of HIV. However, even patients who have been treated with antiretrovirals and have undetectable viral loads must practice safer sex and not share needles to avoid the possibility of transmitting HIV.

 

3. Preexposure ART prophylaxis

Several large randomized double-blind placebo-controlled trials demonstrated that administering emtricitabine/Tenofovir (Truvada) can reduce the risk of sexual transmission of HIV among uninfected individuals at high risk for infection: one study was of HIV-negative men and transgender women who have sex with men, two studies were of heterosexual HIV-discordant couples. However, two studies of African women showed no reduced risk of transmission-primarily related to non-adherence to study medications. Preexposure Tenofovir has also been shown to reduce HIV infection among injection drug users from Thailand. The combination of emtricitabine/Tenofovir is recommended for preexposure prophylaxis (PrEP) by the CDC for use in HIV-negative persons at risk for infection.

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4. Postexposure prophylaxis for sexual and drug use exposures to HIV

The goal of postexposure prophylaxis is to reduce or prevent local viral replication before dissemination such that the infection can be aborted. Although there is no proof that administration of antiretroviral medications following a sexual or parenteral drug use exposure reduces the likelihood of infection, there is suggestive data from animal models, perinatal experience. and a case-control study of health care workers who experienced a needle stick.

 

The choice of antiretroviral agents and the duration of treatment are the same as those for exposures that occur through the occupational route; the preferred regimen is Tenofovir 300 mg with emtricitabine 200 mg daily with raltegravir 400 mg twice a day.

Some clinicians prescribe a two-drug regimen of Tenofovir 300 mg and emtricitabine 200 mg (Truvada) because it is simpler for patients to take (single pill once a day), and more affordable for individuals and for public entities that provide this service to uninsured persons. In contrast to those with occupational exposures, some individuals may present very late after exposure. Because the likelihood of success declines with length of time from HIV exposure, treatment should be provided as soon as possible, and it is not recommended that treatment be offered more than 72 hours after exposure. In addition, because the psychosocial issues involved with postexposure prophylaxis for sexual and drug use exposures are complex, it should be offered only in the context of prevention counseling. Counseling should focus on how to prevent future exposures. Clinicians needing more information on postexposure prophylaxis for occupational or nonoccupational exposures should contact the National Clinicians' Post-exposure Hotline (1-888-448-1911: http://nccc.ucsf.edu/clinician-consultation/pep-post-exposure-prophylaxis/).

 

5. Prevention of perinatal transmission of HIV

Prevention of perinatal transmission of HIV begins by offering HIV counseling and testing to all women who are pregnant or considering pregnancy. HIV-infected women who are pregnant should start ART with at least three medications. Recommended regimens are zidovudine and lamivudine with either ritonavir-boosted lopinavir or ritonavir-boosted atazanavir, Cesarean delivery should be planned if HIV viral load is greater than 1000 copies near the time of delivery. Zidovudine should be given to the infant after birth for 6 weeks. When possible, breastfeeding should be avoided

 

6. Prevention of HIV transmission in health care settings

In health care settings, universal body fluid precautions should be used, including use of gloves when handling body fluids and the addition of gown, mask, and goggles for procedures that may result in splash or droplet spread, and use of specially designed needles with sheath devices to decrease the risk of needle sticks. Because transmission of tuberculosis may occur in health care settings, all patients with cough should be encouraged to wear masks. Hospitalized HIV-infected patients with cough should be placed in respiratory isolation until tuberculosis can be excluded by chest radiograph and sputum smear examination.

 

Epidemiologic studies show that needle sticks occur commonly among health care professionals, especially among surgeons performing invasive procedures, inexperienced hospital house staff, and medical students. Efforts to reduce needle sticks should focus on avoiding recapping needles and use of safety needles whenever doing invasive procedures under controlled circumstances. The risk of HIV transmission from a needle stick with blood from an HIV-infected patient is about 1:300. The risk is higher with deep punctures, large inoculum, and source patients with high viral loads. The risk from mucous membrane contact is too low to quantitate.

Health care professionals who sustain needle sticks should be counseled and offered HIV testing as soon as possible. HIV testing is done to establish a negative base-line for worker's compensation claims in case there is a subsequent conversion. Follow-up testing is usually per-formed at 6 weeks, 3 months, and 6 months.

A casecontrol study by the CDC indicates that administration of zidovudine following a needle stick decreases the rate of HIV seroconversion by 79%. Therefore, providers should be offered ART as soon as possible after exposure and continued for 4 weeks. The preferred regimen is Tenofovir 300 mg with emtricitabine 200 mg (Truvada) daily with raltegravir 400 mg twice a day. Providers who have exposures to persons who are likely to have antiretroviral medication resistance (eg, persons receiving therapy who have detectable viral loads) should have their therapy individualized, using at least two medications to which the source is unlikely to be resistant. Because reports have noted hepatotoxicity due to nevirapine in this setting, this agent should be avoided.

Unfortunately, there have been documented cases of seroconversion following potential parenteral exposure to HIV despite prompt use of zidovudine prophylaxis. Counseling of the provider should include "safer sex" guidelines.

 

7. Prevention of transmission of HIV through blood or blood products

Current efforts in the United States to screen blood and blood products have lowered the risk of HIV transmission with transfusion of a unit of blood to 1:1,000,000. Use of blood and blood products should be judicious, with patients receiving the least amount necessary, and patients should be encouraged to donate their own blood prior to elective procedures.

 

8. HIV vaccine

Primate model data have suggested that the development of a protective vaccine may be possible, but clinical trials in humans have been disappointing. Only one vaccine trial has shown any degree of efficacy. In this randomized, double-blind, placebo-controlled trial, a recombinant canarypox vector vaccine plus two booster injections of a recombinant gp120 vaccine was moderately efficacious (26-31%) in reducing the risk of HIV among a primarily heterosexual population in Thailand. Vaccine development efforts are aimed at identifying broadly neutralizing antibodies to the highly conserved regions of the HIV envelope.

 

 

B. Secondary Prevention

 

In the era before the development of effective ART, cohort studies of individuals with documented dates of seroconversion demonstrate that AIDS developed within 10 years in approximately 50% of untreated seropositive persons. With the currently available treatment, the progression of disease has been markedly decreased. In addition to antiretroviral treatment, prophylactic regimens can prevent opportunistic infections and improve survival. Prophylaxis and early intervention prevent several infectious diseases, including tuberculosis and syphilis, which are transmissible to others. Recommendations for screening tests,

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Tuberculosis

Because of the increased occurrence of tuberculosis among HIV-infected patients, all such individuals should undergo annual PPD testing. Although anergy is common among AIDS patients, the likelihood of a false negative result is much lower when the test is done early in the infection. Those with positive tests (defined for HIV infected patients as greater than 5 mm of induration) need a chest radiograph. Patients with an infiltrate in any location, especially if accompanied by mediastinal adenopathy, should have sputum sent for acid-fast staining. Patients with a positive PPD but negative evaluations for active disease should receive isoniazid (300 mg orally daily) with pyridoxine (50 mg orally daily) for 9 months to a year. Blood tests can also be used to assess prior tuberculosis exposure. Blood samples are mixed with synthetic antigens representing M tuberculosis. Patients infected with M. tuberculosis produce interferon gamma in response to contact with the antigens. Unlike the PPI, the patient does not have to return for a second visit. The test is less likely to result in false positive results than a PPD HIV-infected person with a CD4 count less than 100 cells may not respond to the Mitogen positive control, their results will be reported as indeterminate by QuantiFERON.

 

 Syphilis

Because of the increased number of cases of syphilis among MSM, including those who are HIV infected, all such men should be screened for syphilis by rapid plasma reagin (RPR) or Venereal Disease Research Laboratories (VDRL) test every 6 months. Increases of syphilis cases among HIV-infected persons are of particular concern because these individuals are at increased risk for reactivation of syphilis and progression to tertiary syphilis despite standard treatment. Because the only widely available tests for syphilis are serologic and because HIV-infected individuals are known to have disordered antibody production, there is concern about the interpretation of these titers. This concern has been fueled by a report of an HIV-infected patient with secondary syphilis and negative syphilis serologic testing. Furthermore, HIV-infected individuals may lose fluorescent treponemal antibody absorption (FTA-ABS) reactivity after treatment for syphilis, particularly if they have low CD4 counts. Thus, in this population, a nonreactive treponemal test does not rule out a past history of syphilis. In addition, persistence of treponemes in the spinal fluid after one dose of benzathine penicillin has been demonstrated in HIV-infected patients with primary and secondary syphilis. Therefore, the CDC has recommended an aggressive diagnostic approach to HIV-infected patients with reactive RPR or VDRL tests of longer than 1 year or unknown duration. All such patients should have a lumbar puncture with cerebrospinal fluid cell count and cerebrospinal fluid VDRL. Those with a normal cerebrospinal fluid evaluation are treated as having late latent syphilis (benzathine penicillin G, 24 million units intramuscularly weekly for 3 weeks) with follow-up titers. Those with a pleocytosis or a positive cerebrospinal fluid VDRL test are treated as having neurosyphilis (aqueous penicillin G, 2-4 million units intravenously every 4 hours, or procaine penicillin G. 2.4 million units intramuscularly daily, with probenecid, 500 mg four times daily, for 10 days) followed by weekly benzanthine penicillin G 2.4 million units intramuscularly for 3 weeks. Some clinicians take a less aggressive approach to patients who have low titers fless than 1:8), a history of having been treated for syphilis, and a normal neurologic examination. Close follow-up of titers is mandatory if such a course is taken. For a more detailed discussion of this topic, see Chapter 34.

 

Immunizations

HIV-infected individuals should receive immunizations as outlined in Table 31-3. Patients without evidence of hepatitis B surface antigen or surface antibody should receive hepatitis B vaccination, using the 40 meg formulation, the higher dose is to increase the chance of developing protective immunity. If the patient does not have immunity 1 month after the three-shot series, then the series should be repeated. HIV-infected persons should also receive the standard inactivated vaccines, such as tetanus and diphtheria boosters, that would be given to uninfected persons. Most live vaccines, such as the yellow fever vaccine, should be avoided. Measles vaccination, while a live virus vaccine, appears relatively safe when administered to HIV-infected individuals and should be given to the patient if they have never had measles or been adequately vaccinated. The herpes zoster vaccine, two doses 6 weeks apart, is reasonably safe for HIV-infected persons with CD4 counts greater than 200 cells/ml. and undetectable viral loads, even though it is a live vaccine and is likely to be added as a treatment recommendation for persons 50 years of age or older.

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 Other measures

A randomized study found that multi-vitamin supplementation decreased HIV disease progression and mortality in HIV-infected women in Africa. However, supplementation is unlikely to be as effective in well-nourished populations,

HIV infected individuals should be counseled with regard to the importance of practicing safer sex even with other HIV-infected persons because of the possibility of contracting a sexually transmitted disease, such as gonorrhea or syphilis. There is also the possibility of transmission of a particularly virulent or drug-resistant strain between HIV infected persons. Substance abuse treatment should be recommended for persons who are using recreational drugs. They should be warned to avoid consuming Taw meat, eggs, or shellfish to avoid infections with Taxo plasma, Campylobacter, and Salmonella. HIV-infected patients should wash their hands thoroughly after cleaning cat litter or should forgo this household chore to avoid pos sible exposure to toxoplasmosis. To reduce the likelihood of infection with Hartonella species, patients should avoid activities that might result in cat scratches or bites. Although the data are not conclusive, many clinicians recommend that HIV-infected persons-especially those with low CD4 counts, drink bottled water instead of tap water to prevent cryptosporidia infection. Because of the emotional impact of HIV infection and subsequent illness, many patients will benefit from supportive counseling.

 

Treatment

 

Treatment for HIV infection can be broadly divided into the following categories (1) prophylaxis for opportunistic infections, malignancies, and other complications of HIV infection,

(2) Treatment of opportunistic infections, malignancies, and other complications of HIV infection; and

 (3) Treatment of the HIV infection itself with combination ART.

 

A. Prophylactic Treatment of Complications of HIV Infection

In general, decisions about prophylaxis of opportunistic infections are based on the CD4 count, recent HIV viral load, and a history of having had the infection in the past. In the era before ART, patients who started taking prophylactic regimens were maintained on them indefinitely. However, studies have shown that in patients with robust improvements in immune function measured by increases in CD4 counts above the levels that are used to initiate treatment-prophylactic regimens can safely be discontinued. Because individuals with advanced HIV infection are susceptible to several opportunistic pathogens, the use of agents with activity against more than one pathogen is preferable.

 

1. Prophylaxis against Pneumocystis pneumonia

Patients with CD4 counts below 200 cells/mcl., a CD4 lymphocyte percentage below 14%, or weight loss or oral candidiasis should be offered primary prophylaxis for Pneumocystis pneumonia. Patients with a history of Pneumocystis pneumonia should receive secondary prophylaxis until their viral load is undetectable and they have maintained a CD4 count of 200 cells/mcl. or more while receiving ART for longer than 3 months.

 

2. Prophylaxis against M avium complex infection

Patients whose CD4 counts fall to below 75-100 cells/mcl. should be given prophylaxis against M avium complex infection. Clarithromycin (500 mg orally twice daily) and azithromycin (1200 mg orally weekly) have both been shown to decrease the incidence of disseminated Mycobacterium complex infection by approximately 75%, with a low rate of breakthrough of resistant disease. The azithromycin regimen is generally preferred based on high compliance and low cost. Prophylaxis against M avium complex infection may be discontinued in patients whose CD4 counts rise above 100 cells/mcl. In response to ART for longer than 3 months.

 

3. Prophylaxis against M tuberculosis infection

Isoniazid, 300 mg orally daily, plus pyridoxine, 50 mg orally daily, for 9-12 months, should be given to all HIV-infected patients with positive PPD reactions (defined as greater than 5 mm of induration for HIV-infected patients) without evidence of active disease..

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4. Prophylaxis against toxoplasmosis

Toxoplasmosis prophylaxis is desirable in patients with a positive IgG toxoplasma serology and CD4 counts below 100 cells/mcl., Trimethoprim-sulfamethoxazole (one double-strength tablet daily) offers good protection against toxoplasmosis, as does a combination of pyrimethamine. 25 mg orally once a week, plus dapsone, 50 mg orally daily, plus leucovorin, 25 mg orally once a week. A glucose-6-phosphate dehydrogenase (G6PD) level should be checked before dapsone therapy, and a methemoglobin level should be checked at 1 month. Prophylaxis can be discontinued when the CD4 cells have increased to greater than 200 cells/mcL for more than 3 months.

 

B. Treatment of Complications of HIV Infection

 

Treatment of common AIDS-related complications is detailed above and in Table 31-5. In the era before the use of ART, patients required lifelong treatment for many infections, including CMV retinitis, toxoplasmosis, and cryptococcal meningitis. However, among patients who have a good response to ART, maintenance therapy for some opportunistic infections can be terminated. For example, in consultation with an ophthalmologist, maintenance treatment for CMV infection can be discontinued when persons receiving ART have had a sustained increase in CD4 count to greater than 100 cells/mcL for at least months. Similar results have been observed in patients with M avium complex bacteremia, who have completed a year or more of therapy for M avium complex and have an increase in their CD4 count for greater than 6 months while receiving ART. Cessation of secondary prophylaxis for Pneumocystis pneumonia is described above.

 

Treating patients with repeated episodes of the same opportunistic infection can pose difficult therapeutic challenges. For example, patients with second or third episodes of Pneumocystis pneumonia may have developed allergic reactions to standard treatments after a prior episode. Fortunately, there are several alternatives available for the treatment of Pneumocystis infection. Trimethoprim with dapsone and primaquine with clindamycin are two combinations that are often tolerated in patients with a prior allergic reaction to trimethoprim-sulfamethoxazole and intravenous pentamidine. Patients in whom second episodes of Pneumocystis pneumonia develop while taking prophylaxis tend to have milder courses.

 

Well-established alternative regimens also exist for most AIDS-related opportunistic infections: amphotericin B or fluconazole for cryptococcal meningitis; valganciclovir, ganciclovir, cidofovir, or foscarnet for CMV infection; and sulfadiazine or clindamycin with pyrimethamine for toxoplasmosis.

 

Adjunctive Treatments

Although conceptually, it would seem that corticosteroids should be avoided in HIV. For infected patients, corticosteroid therapy has been shown to improve the course of patients with moderate to severe P. jirovecii pneumonia (oxygen saturation less than 90%, PO, 2 less than 65 mm Hg) when administered within 72 hours after diagnosis. Either intravenous methylprednisolone (Solumedrol) or oral prednisone (40-80 mg daily tapering over 21 days) can be used. The mechanism of action is presumed to be a decrease in alveolar inflammation.

 

Corticosteroids have also been used to treat IRIS that can sometimes complicate the early treatment course when ART is initiated in patients with advanced AIDS (see section Inflammatory reactions [immune reconstitution inflammatory syndromes] above).

 

Epoetin alfa (erythropoietin) is approved for use in HIV-infected patients with anemia, including those with anemia secondary to zidovudine use. As zidovudine is rarely used now, especially at high doses, the use of epoetin alfa has also decreased. An erythropoietin level greater than 500 milli-units/mL should be demonstrated before starting therapy. The starting dose of epoetin alfa is 8000 units subcutaneously three times a week. Hypertension is the most common side effect.

Human G-CSF (filgrastim) and granulocyte-macro-phage colony-stimulating factor (GM-CSF [sargramostim]) have been shown to increase the neutrophil counts of HIV-infected patients. Because of the high cost of this therapy, the dosage should be closely monitored and minimized, aiming for a neutrophil count of 1000/mcl.. When the medication is used for indications other than cytotoxic chemotherapy, one or two doses at 5 mcg/kg per week subcutaneously are usually sufficient.

 

References

1.     Baeten JM et al: Partners PrEP Study Team. Antiretroviral pro-phylaxis for HIV prevention in heterosexual men and women. N Engl J Med. 2012 Aug 2:367(5):399-410 [PMID: 22784037)

2.     Choopanya K et al. Antiretroviral prophylaxis for HIV infection in injecting drug users in Bangkok, Thailand (the Bangkok Tenofovir Study): a randomised, double-blind, placebo-controlled phase 3 trial. Lancet. 2013 Jun 15:381(9883):2083-90. [PMID: 23769234)

3.     Kuhar DT et al. Updated US Public Health Service guidelines for the management of occupational exposures to human immu-nodeficiency virus and recommendations for postexposure prophylaxis. Infect Control Hosp Epidemiol. 2013 Sep:34(9): 875-92. PMID: 23917901|

4.     Marrazzo JM et al. HIV prevention in clinical care settings 2014 recommendations of the International Antiviral Society-USA Panel. JAMA. 2014 Jul 23-30:312(4):390-409. Erratum in: JAMA. 2014 Aug 13:312(6):652. PMID: 25038358]

5.     New York State Department of Health AIDS Institute. HIV pro-phylaxis following non-occupational exposure. October 2014 update. http://www.hivguidelines.org/wp-content/uploads/2014/12/hiv-prophylaxis-following-non-occupational-exposure.pdf

6.     Saunders KO. The design and evaluation of HIV-1 vaccines, AIDS. 2012 Jun 19:26(10):1293-302. [PMID: 22706011] U.S. Preventive Services Task Force. Screening for HIV: US. Preventive Services Task Force Recommendation Statement. April 2013. http://www.uspreventiveservicestaskforce.org/ uspstf13/hiv/hivfinalrs.htm

 

7.     U.S. Public Health Service. Preexposure prophylaxis for the prevention of HIV infection in the United States-2014: a clinical practice guideline. http://www.cdc.gov/hiv/pdf/PrEPguide-lines2014.pdf