#58904: HIV/AIDS: An Update

HIV has been isolated from blood, seminal fluid, spermatozoa, pre-ejaculate, vaginal secretions, urine, cerebrospinal fluid, saliva, tears, and breast milk of infected individuals. No cases of HIV infection have been traced to saliva or tears (though traces of the virus are present in these fluids). The virus is found in greater concentration in semen than in vaginal fluids, leading to a hypothesis that male-to-female transmission could occur more easily than female-to-male. Sexual behavior that involves exposure to blood is likely to increase transmission risks. Transmission could also occur through contact with infected bowel epithelial cells in anal intercourse, in addition to access to the bloodstream through breaks in the rectal mucosa [9,10].

Posing the highest risk of infection is unprotected anal receptive intercourse, followed by unprotected vaginal intercourse and unprotected insertive anal intercourse (particularly for uncircumcised men) [9]. Risk is reduced through the use of latex condoms. For the wearer, latex condoms provide a mechanical barrier limiting penile exposure to infectious cervical, vaginal, vulvar, or rectal secretions or lesions. Likewise, the partner is protected from infectious pre-ejaculate, semen, and penile lesions. Oil-based lubricants may make latex condoms ineffective and should not be used; water-soluble lubricants are considered safe. Natural membrane condoms (made from lamb cecum) contain small pores and do not block HIV passage. It is estimated that consistent use of latex condoms reduces the risk of HIV transmission by approximately 80% [16].

Although abstinence from sexual contact is the sole way to absolutely prevent transmission, sexual activity in a mutually monogamous relationship in which neither partner is HIV-infected and no other risk factors are present is considered safe. A study of serodifferent heterosexual and MSM couples in which the HIV-positive partner was on ART found no documented cases of within-couple transmission of HIV, despite engaging in condomless sex, after an average of 1.3 years [68]. However, men who identify publicly as heterosexual and generally have committed relationships with women, but who also engage in sexual activity with other men, may be a transmission bridge to heterosexual women [10,18]. To better understand the actual extent of this behavior and its impact on HIV transmission, more research is necessary.

Numerous studies have demonstrated that oral sex can result in the transmission of HIV and other STIs. While the risk of HIV transmission through oral sex is much smaller than the risk from anal or vaginal sex, there are several co-factors that can increase this risk, including oral ulcers, bleeding gums, genital sores, and the presence of other STIs. Prevention includes the use of latex condoms, a natural rubber latex sheet, plastic food wrap, a cut open condom, or a dental dam, all of which serve as a physical barrier to transmission [10,18].

It has been estimated that a milliliter of HIV-infected human blood contains up to 10,000 copies of the virus. In comparison, a milliliter of blood infected with hepatitis B virus has 100 million to 1 billion infective organisms [19]. Even so, HIV is transmitted via blood, primarily through sharing of contaminated needles among IDUs and, rarely, through blood transfusion. Transmission of HIV-1 has occurred after transfusion of the following components: whole blood, packed red blood cells (including washed and buffy coat poor), fresh frozen plasma, cryoprecipitate, platelets, and plasma-derived products, depending on the production process. With the implementation of a donor screening program of the nation's blood supply in 1985 and advances in the treatment of donated blood products, blood transfusion is now even safer; the current risk of transmission of HIV through this route is conservatively estimated to be less than 1 per 1 million [20]. It is possible that before blood screening implementation, more than 12,000 people were infected [21]. A large percentage of persons with hemophilia acquired HIV in this manner. Donor screening, HIV testing, and heat treatment of the clotting factor have greatly reduced the risks.

Transmission of HIV among IDUs occurs primarily through contamination of injection paraphernalia with infected blood. The risk of sustaining HIV infection from a needle stick with infected blood is approximately 1 in 300 [30]. Behavior such as needle sharing, "booting" the injection with blood, and performing frequent injections increases the risk. Crack cocaine use (by injection or smoking) is associated with a higher prevalence of HIV infection. This may in part be attributed to the exchange of cocaine for sex. Sharing of equipment is common due to legal and financial restrictions and cultural norms, and some studies have linked higher levels of psychologic distress (e.g., anxiety and depressive symptoms) with an increased risk for needle sharing [22]. Secondary transmission occurs to children and sexual partners. Preventative strategies include medication-assisted drug treatment, onsite medical care in a drug treatment program, recruitment of "street" outreach workers for intensive drug and sex risk-reduction educational campaigns, teaching addicts to sterilize their equipment between use, the free provision or exchange of sterile injection equipment (as allowed by law), distribution of condoms and bleach to clean drug use equipment, or a combination of these interventions.

In the absence of prophylactic treatment, approximately 15% to 45% of children born to HIV-infected mothers will contract HIV infection; this increases to 50% with prolonged breastfeeding [32]. HIV is transmitted to infants by transplacental spread from mother to fetus in utero, during parturition, or through breastfeeding after birth. Because infants have underdeveloped natural resistance systems, they are highly susceptible to many infections, including HIV. Transmission usually occurs during labor and delivery and the early breastfeeding stage [33].

Worldwide, perinatal transmission accounts for most HIV infections among children. In the United States, perinatal transmission has been markedly decreased, by more than 95%, since the mid-1990s; in 2019, there were 3,540 hospital-based live births among persons with an HIV diagnosis, of which 32 infants were diagnosed with perinatally acquired HIV [33]. Studies have shown that treating pregnant and breastfeeding women with antiretroviral therapy (ART) to achieve viral suppression results in a <1% infection rate of HIV transmitted mother-to-infant [32,34]. The American Academy of Pediatrics recommends that for people with HIV in the United States, avoidance of breastfeeding is the only infant feeding option with 0% risk of HIV transmission; however, if an individual with HIV expresses an interest to breastfeed, a family-centered, nonjudgmental, harm-reduction approach to support the individual, including ensuring ART with sustained viral suppression less than 50 copies/mL, should be employed. Patients with HIV who are considering breastfeeding and are not on ART, or are on ART without viral suppression, should be advised not to breastfeed [41]. Standard screening of all pregnant women is necessary to reduce transmission of HIV to infants.

Because these procedures are less common than other transmission-related activities, there have been very few case reports of HIV acquisition by this route. HIV has been transmitted via transplanted kidneys, liver, heart, pancreas, bone, and, possibly, skin grafts and through artificial insemination. HIV testing is used in these circumstances to rule out infection. Most cases of transmission through transplants of organs, bone, or tissue occurred before HIV screening was available. However, in 2007, four organ transplant recipients contracted HIV and hepatitis C from a single organ donor, and in 2009, HIV was transmitted by a living kidney donor [36,37]. These were the first cases of HIV infection resulting from transplantation since 1985. Though the donors were tested for HIV and hepatitis, the tests resulted in false negatives. As with blood transfusions, donors testing antibody seronegative may pass HIV infection on to recipients. The use of nucleic acid testing and reconsideration of the use of high-risk donors have both been recommended to ensure the safety of donor recipients [36].

In 2018, the CDC began investigating a spa in New Mexico, after a woman was diagnosed positive for HIV in connection to a micro-needling facial treatment. The woman received a "platelet-rich plasma" (PRP) with microneedling procedure (i.e., vampire facial) that involves drawing blood from the client, separating the blood into its components of plasma and cells, and using single-use disposable or multiuse sterile equipment (microneedles) to inject PRP in specific areas of the face, with the goal of skin rejuvenation and reduced appearance of scars [31]. Within months of the treatment, the woman received a positive HIV diagnosis, marking the first case of transmission by a nonsterile cosmetic injection procedure. As of 2023, five people were found to have been diagnosed positive with HIV in relation to the PRP facial at the spa; four women who directly received the procedure at least once, and one male who was a sexual partner of one of the directly infected women. In the investigation, the CDC found several violations and examples of unsafe infection control practices in the spa, highlighting the need for adherence to established infection control practices and public education for consumers of these services to be aware of the risks [27,31].

Transmission due to occupational exposure of healthcare workers has occurred in needlestick accidents and blood splashes to the mucous membranes. Needlestick is the most common route. Thousands of healthcare personnel who were so exposed have been studied, and only 58 cases of well-documented infection have been reported in the United States (24 of which were nurses), and only one case has been reported since 2008 [38]. The risk of infection through this route is low, and every effort should be made to decrease the exposure rate. Educational efforts, implementation of engineering controls in needled and sharp-edged medical devices, the use of hard plastic needle disposal units where these devices are most frequently used, and the development of procedural details to avoid blood and body fluid contact have greatly reduced the exposure rate. Healthcare personnel should apply Universal Precautions, as discussed in the Occupational Safety and Health Administration (OSHA) Bloodborne Pathogens standard regulations, to all activities to avoid contact with human fluids [27].

Postexposure Prophylaxis

The U.S. Public Health Service (PHS) provides guidance for managing healthcare personnel who have occupational exposure to blood and/or other bodily fluids from a person suspected or known to have HIV infection [39]. Because most occupational HIV exposures do not result in transmission of HIV, potential toxicity should be carefully considered when prescribing postexposure prophylaxis (PEP). The 2013 updated guidelines for occupational PEP focused on tolerability, side effects, toxicity, safety in pregnancy and lactation, pill burden, and frequency of dosing to maximize adherence to a PEP regimen. Although the principles of exposure management remain unchanged, recommended PEP regimens and the duration of follow-up HIV testing for exposed personnel were updated in 2018 [39]. When possible, these recommendations should be implemented in consultation with persons having expertise in antiretroviral therapy and HIV transmission, due to the complexity of selecting appropriate treatment.

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

Healthcare professionals with occupational exposure to HIV should receive close follow-up to assure counseling, baseline and follow-up HIV testing, and medical evaluation regardless of whether they receive PEP. The 2018 PHS guideline highlights the importance of follow-up within 72 hours of an HIV exposure to allow the initial shock to fade and to provide greater opportunity for full understanding of the risks and benefits of PEP; confirmation testing to ensure the necessity of PEP; increase adherence to PEP; monitoring for adverse reactions and side effects; and treating comorbidities and altering the regimen [39]. This window provides an opportunity to discuss the importance of preventing secondary transmission of HIV in the 6 to 12 weeks following initial infection. If a newer fourth-generation HIV p24 antigen-HIV antibody test is utilized for follow-up, then HIV-antibody testing may be concluded at four months after exposure. If a newer testing platform is not available, follow-up HIV testing should be performed for a six-month postexposure period (e.g., at 6 weeks, 12 weeks, and 6 months) [39]. It is unclear whether an extended follow-up period (e.g., 12 months) is indicated for individuals not coinfected with hepatitis C and HIV. If PEP is used, drug-toxicity monitoring should be performed at baseline and again two weeks after starting PEP. Clinical judgment, based on medical conditions that may exist in pre-exposure and/or as a result of the regimen, should determine the scope of testing. If the source patient is found to be HIV negative, PEP should be discontinued immediately [39].

In 2016, the CDC published updated guidelines for the recommendation of PEP for nonoccupational exposures. This section is taken from Updated Guidelines for Antiretroviral Postexposure Prophylaxis After Sexual, Injection Drug Use, or Other Nonoccupational Exposure to HIV—United States, 2016 [40].

Healthcare providers should evaluate persons rapidly for nPEP when care is sought within 72 hours after a potential nonoccupational exposure that presents a substantial risk for HIV acquisition. All persons considered for nPEP should have determination of their HIV infection status by HIV testing, preferably by using rapid combined Ag/Ab, or antibody blood tests. If rapid HIV blood test results are unavailable, and nPEP is otherwise indicated, it should be initiated without delay and can be discontinued if the patient is later determined to have HIV infection already or the source is determined not to have HIV infection. nPEP is recommended when the source of the body fluids is known to be HIV-positive and the reported exposure presents a substantial risk for transmission. nPEP is not recommended when the reported exposure presents no substantial risk of HIV transmission or when care is sought more than 72 hours after potential exposure. A case-by-case determination about the nPEP is recommended when the HIV infection status of the source of the body fluids is unknown and the reported exposure presents a substantial risk for transmission if the source did have HIV infection.

Healthcare providers should evaluate persons rapidly for nPEP when care is sought within 72 hours after a potential nonoccupational exposure that presents a substantial risk for HIV acquisition. All persons considered for nPEP should have determination of their HIV infection status by HIV testing, preferably by using rapid combined Ag/Ab, or antibody blood tests. If rapid HIV blood test results are unavailable, and nPEP is otherwise indicated, it should be initiated without delay and can be discontinued if the patient is later determined to have HIV infection already or the source is determined not to have HIV infection. nPEP is recommended when the source of the body fluids is known to be HIV-positive and the reported exposure presents a substantial risk for transmission. nPEP is not recommended when the reported exposure presents no substantial risk of HIV transmission or when care is sought more than 72 hours after potential exposure. A case-by-case determination about the nPEP is recommended when the HIV infection status of the source of the body fluids is unknown, and the reported exposure presents a substantial risk for transmission if the source did have HIV infection.

All persons offered nPEP should be prescribed a 28-day course of a three-drug antiretroviral regimen. The preferred regimen for otherwise healthy adults and adolescents is tenofovir disoproxil fumarate (300 mg) with emtricitabine (200 mg) once daily plus raltegravir 400 mg twice daily or dolutegravir 50 mg daily.

All persons evaluated for possible nPEP should be provided any indicated prevention, treatment, or supportive care for other exposure-associated health risks and conditions (e.g., bacterial sexually transmitted infections, traumatic injuries, hepatitis B virus and hepatitis C virus infection, or pregnancy). All persons who report behaviors or situations that place them at risk for frequently recurring HIV exposures (e.g., injection drug use, sex without condoms) or who report receipt of a course of nPEP in the past year should be provided risk-reduction counseling and intervention services, including consideration of pre-exposure prophylaxis.

NRTIs, used singularly or in combination, can increase CD4 count, decrease viral load, and prolong survival. Sequential monotherapy is followed eventually by clinical failure based on the emergence of drug resistance in HIV. Combinations of two NRTIs result in better viral suppression, more sustained CD4 counts and decreased emergence of resistance. Available NRTI agents include: abacavir (Ziagen, ABC); zidovudine (Retrovir, ZDV, AZT); lamivudine (Epivir, 3TC); and emtricitabine (Emtriva, FTC) [43]. Tenofovir (Viread, TDF) is often categorized as an NRTI but is actually a nucleotide reverse transcriptase inhibitor [43].

NNRTIs have a high affinity for the active site of HIV-RT. When used as a single agent, this class is associated with rapid emergence of resistance in as little as six weeks. Thus, these drugs should not be used as single agents but are best employed in combination regimens for patients who have not received prior antiretroviral therapy. Available agents include: efavirenz (Sustiva, EFV); doravirine (Pifeltro, DOR); nevirapine (Viramune, NVP; viramune XR); etravirine (Intelence, ETR); and rilpivirine (Edurant, RPV, Endurant PED) [43].

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

Enfuvirtide (Fuzeon, T-20), a fusion inhibitor, works by blocking the ability of HIV to infect healthy CD4 cells [43]. When used in combination with other anti-HIV medications, enfuvirtide can reduce the amount of HIV in the blood and increase the number of CD4 cells, slowing the progression of HIV in patients who have developed resistance to currently available medications.

Maraviroc (Selzentry, MVC) is a CCR5 antagonist; it blocks replication of the virus by preventing it from entering noninfected CD4 cells via the predominant route of entry, the CCR5 co-receptor. This medication is intended for use in combination with other antiretroviral agents in treatment-experienced patients with evidence of viral replication and HIV-1 strains resistant to multiple agents [43]. Because both fusion inhibitors and CCR5 antagonists block HIV from entering CD4 cells, they are sometimes grouped together under the category of entry inhibitors.

Integrase strand transfer inhibitors act by preventing the viral DNA from inserting into the host DNA, effectively limiting infection of additional cells and decreasing viral load. INSTIs are approved for use in combination with other antiretrovirals in treatment-experienced and treatment-naïve patients with evidence of HIV replication. Available agents include raltegravir (Isentress, RAL, Isentress HD), dolutegravir (Tivicay, DTG, Tivicay PD), and cabotegravir (Vocabria, CAB) [43].

In 2020, the FDA approved the first gp120 attachment inhibitor, fostemsavir (Rukobia, FTR), for the treatment of HIV in patients whose infection cannot be successfully treated with other therapies because of resistance, intolerance, or safety considerations. Fostemsavir acts by binding to the gp120 protein on the outer surface of the HIV virus, preventing it from entering CD4 cells [58].

In 2022, the FDA approved lenacapavir (Sunlenca, GS-6207, GS-HIV, GS-CA2, GS-CA1), the first capsid inhibitor, for the treatment of HIV-1 infection in adults for whom other available treatments have failed or are inappropriate due to resistance, intolerance, or safety considerations. These agents directly target virus' protein shell (the capsid), interfering with multiple essential steps of the viral lifecycle [43].

Post-attachment inhibitors block CD4 receptors on the surface of certain immune cells that HIV needs to enter the cells. In 2018, the FDA approved ibalizumab (Trogarzo, IBA), the first of its class [43].

In an effort to improve the efficacy of other antiretroviral medications in an ART regimen, a pharmacokinetic enhancer may also be included. The agents most commonly used for this purpose are cobicistat and ritonavir (a PI). Both of these agents inhibit cytochrome P450 (CYP) 3A enzymes, prolonging the effects of other medications [43,47]. However, they are not interchangeable; cobicistat is a more potent inhibitor of CYP [47]. The use of pharmacokinetic enhancers increases systemic exposure of effective antiretroviral medications, allowing for less frequent dosing and a lower pill burden.

Patient compliance may be improved with therapies that combine more than one drug into a single pill, making it easier for patients to comply with their medication regimen. Available oral combination medications include [43]:

In addition to oral medications, in 2021 the FDA approved the first monthly injectable ART—Cabenuva (cabotegravir/rilpivirine). This monthly injectable is an optional regimen to replace a current ART regimen in patients who are virologically suppressed on a stable regimen with no history of treatment failure and with no known HIV resistance to either cabotegravir or rilpivirine. This regimen is intended to improve compliance and quality of life for patients who have achieved control of HIV on daily oral therapy. Prior to initiating injectable therapy, oral therapy with cabotegravir/rilpivirine is started to ensure the agents are well-tolerated [43,59].

The decision to initiate antiretroviral therapy is one that requires careful discussion with the patient, usually in consultation with an infectious disease specialist or other physician well versed in the use of ART. Physicians and patients alike should be aware of the advantages, potential toxicities, and complexity of monitoring therapy. Clinicians should consult the appropriate HHS guideline for antiretroviral agents; separate guidelines have been developed for adults and adolescents, pediatrics, and pregnant women with HIV infection [23,24,42]. For adults and adolescents, a typical initial regimen consists of three HIV medications from two drug classes. At the present time, the most active triple-drug regimen in a previously untreated patient can be expected to reduce the viral load below detectable levels, increase CD4 counts by an average of 100–150 cells/mcL, reduce the risk of HIV-associated complications, and prolong survival. However, the ability to achieve this advantage depends on the patient's willingness to accept a complex medical regimen that requires multiple medications, rigorous compliance, frequent follow-up, and moderate risk for drug toxicity. In reaching a decision it is helpful to bear in mind that prognosis is determined by viral load and the CD4 count. Patients having a viral load in excess of 100,000 copies/mL are considered to have a high HIV viral load and a relatively rapid course of disease, significantly lowering the average survival rate to little more than a few years. In contrast, those with a viral load <20 copies/mL have reached viral suppression and have a life expectancy similar to that of the general population. The CD4 count is also a prognostic factor, as counts less than 350 cells/mcL indicate damage to immune function and corresponding risk for opportunistic infection [19].

According to the Panel on Antiretroviral Guidelines for Adults and Adolescents, antiretroviral therapy is recommended for all individuals with HIV, including those with early HIV infection and should be initiated as soon as possible after diagnosis.

(https://clinicalinfo.hiv.gov/sites/default/files/guidelines/documents/adult-adolescent-arv/guidelines-adult-adolescent-arv.pdf Last Accessed: March 21, 2025)

Strength of Recommendation: AII (Strong recommendation based on well-designed nonrandomized trials or observational cohort studies with long-term clinical outcomes)

Antiretroviral therapy should be initiated immediately for all patients infected with HIV in order to reduce the risk of disease progression and limit transmission [42]. There is growing evidence that early initiation of ART is effective in preventing clinical events (e.g., non-AIDS malignancies, infection, AIDS-defining illness) regardless of pre-treatment CD4 count [42,48,49]. Advances in the development of antiretroviral medications, combination tablets, and injectable ART makes adherence to therapy more effective, more convenient, and better tolerated than regimens used in the past. Deferral of therapy should only be considered in patients with high CD4 counts (e.g., more than 500 cells/mcL) if adherence will be very difficult or impossible, comorbidities complicate or prohibit antiviral therapy, or a patient is considered a long-term non-progressor [42].

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

Tuberculosis is the leading cause of morbidity and mortality among people living with HIV worldwide, with an estimated 10.8 million reported cases and 1.25 million deaths in 2023, of which 161,000 deaths were related to HIV-associated TB. Individuals with HIV are at an approximate 16 times greater risk of developing tuberculosis compared with people not infected with HIV. While ART significantly decreases the risk of conversion from latent to active disease, only 56% of patients with TB living with HIV were on ART in 2023. Although the majority of cases of TB are among low- and middle-income countries, the United States accounted for nearly 9,500 cases in 2023, 410 of which were among individuals coinfected with HIV. There were 545 TB-related deaths in 2022 in the United States [52].

In addition to the recommended prophylaxis to prevent a first episode of opportunistic tuberculosis, guidelines for the treatment of HIV-related active tuberculosis were updated in 2024 [50]. In individuals with HIV infection, the ART regimen should be assessed with attention to potential interactions between ARTs and TB drugs, including rifamycin antibiotics (e.g., rifabutin, rifampin, rifapentine) and isoniazid, which have considerable potential for drug-drug interactions.

For drug-susceptible TB, or if drug resistance is currently unknown, preferred therapy consists of an intensive phase of eight weeks with an initial four-drug combination of isoniazid, rifampin or rifabutin, ethambutol, and pyrazinamide daily until susceptibility to isoniazid and rifampin has been confirmed [52]. If rapid drug sensitivity testing indicates resistance to isoniazid and rifampin, ethambutol may be immediately discontinued; if resistance is not indicated, ethambutol should be discontinued until the end of the eight-week intensive phase. Continuation of therapy with the remaining three drugs may continue for 6 to 12 months, depending on clinical and/or bacteriologic response to therapy. Alternative preferred therapy used for patients receiving an efavirenz-based ART regimen that do not have extrapulmonary TB is isoniazid plus rifapentine plus moxifloxacin plus pyrazinamide plus pyridoxine. The continuation of therapy is nine weeks of isoniazid plus rifapentine plus moxifloxacin plus pyridoxine daily [50].

For drug-resistant TB, empiric therapy for suspected resistance to rifamycin with or without resistance to other drugs is isoniazid plus pyrazinamide plus ethambutol plus moxifloxacin or levofloxacin, plus linezolid or amikacin. For suspected or confirmed resistance to isoniazid, the recommended treatment is moxifloxacin or levofloxacin plus rifampin or rifabutin plus ethambutol plus pyrazinamide daily for six months. In patients resistant to rifamycins with or without other antimycobacterial agents, the preferred therapy is 14 days of pretomanid plus linezolid plus moxifloxacin plus bedaquiline daily, followed by 24 weeks of pretomanid plus linezolid plus moxifloxacin daily, and bedaquiline three times per week; moxifloxacin should be omitted if resistant to fluoroquinolones. Alternative therapy for drug-resistant TB consists of an individualized regimen based on drug susceptibility test results and clinical and microbiological responses, and includes at least five active drugs, with close consultation with experienced specialists. Duration of treatment is 6 to 24 months depending on clinical and/or bacteriologic response to therapy [50].

Optimal management of HIV-related tuberculosis is complex, involving decisions around duration of therapy, timing of ART, and support services to assure adherence to observed therapy and regular follow-up care. Healthcare professionals should consult the guidelines to ensure use of the most effective management strategies for patients with tuberculosis and HIV, while concurrently promoting optimal ART for these patients. Special considerations apply to children and pregnant women with HIV-related tuberculosis.

Many symptoms and signs of acute HIV infection and non-specific manifestations, such as fevers, weight loss, and fatigue, are the same for women and men. Because past research has either excluded women altogether or included only small cohorts of women, it has been difficult to determine gender differences in the clinical course of HIV disease. In general, studies have not shown significant differences in response to ART based on sex. However, limited data show that pharmacokinetics for some ART drugs may differ between men and women, possibly due to variations in factors such as body weight, plasma volume, gastric emptying time, plasma protein levels, cytochrome P450 activity, drug transporter function, and excretion activity [35].

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

Studies have shown that women with HIV have a poorer prognosis than men, with poorer access to or use of healthcare resources (later diagnosis), domestic violence, homelessness, and lack of community support all potential factors that may contribute to the seemingly higher mortality rate for HIV-infected women [64].

There are some unique clinical and therapeutic issues to consider when caring for women with HIV, and care providers should consult the updated guidelines. Considerations for ART in women living with HIV include [35]:

Considerations for Antiretroviral Therapy in HIV-Infected Pregnant Individuals

HIV counseling and the offer of HIV testing to pregnant persons have been universally recommended in the United States and are now mandatory in some states. A pregnancy test should be performed for those with childbearing potential before initiating ART. Care of the HIV-infected pregnant individuals should involve collaboration between the HIV specialist caring for the patient when they are not pregnant, an obstetrician, and the patient. Treatment recommendations for HIV-infected pregnant patients are based on the belief that therapies of known benefit should not be withheld during pregnancy unless there are known adverse effects on the mother, fetus, or infant that outweigh the potential benefit. When selecting ART for a pregnant individual, clinicians should consider available safety and efficacy data on the use of each agent during pregnancy. The risks and benefits of ART during pregnancy should be discussed with all individuals of child-bearing potential, and clinicians should consult the most recent perinatal guidelines when designing a regimen [24,35].

Initiation of ART is recommended for pregnant patients with HIV in all stages of pregnancy. Regardless of the stage of pregnancy or childbirth, if a patient is found to be HIV-positive, there are treatment options that should be explored [24].

Patients should be registered with the Antiretroviral Pregnancy Registry, which collects observational, nonexperimental data. The registry is sponsored by GlaxoSmithKline, in affiliation with the CDC and Kendle International, Inc. Those who have been treated with ART at any time during their pregnancies are eligible for registry enrollment. Additional information and registration are available at https://www.apregistry.com [24,56].

Children with HIV/AIDS may have more than one infection at the same time or in succession (multiple opportunistic infections). Conditions associated with HIV infection in children are [25]:

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