AIDS was originally defined empirically by the Centers for Disease Control and Prevention (CDC) as “the presence of a reliably diagnosed disease that is at least moderately indicative of an underlying defect in cell-mediated immunity in the absence of any known cause for such a defect.” Following the recognition of the causative virus, HIV, and the development of sensitive and specific tests for HIV infection, the definition of AIDS has undergone substantial revision. The current surveillance definition categorizes HIV-infected persons on the basis of clinical conditions associated with HIV infection and CD4+ T lymphocyte counts (Tables 197-1, and 197-2, in HPIM-20). From a practical standpoint, the clinician should view HIV disease as a spectrum of disorders ranging from primary infection, with or without the acute HIV syndrome, to the asymptomatic infected state, to advanced disease characterized by opportunistic infections and neoplasms.
AIDS is caused by infection with the human retroviruses HIV-1 or 2. HIV-1 is the most common cause worldwide. These viruses are passed through sexual contact; through transfusion of contaminated blood or blood products; through sharing of contaminated needles and syringes among injection drug users (IDUs); intrapartum or perinatally from mother to infant; or via breast milk. There is a definite, though small, occupational risk of infection for health care workers and laboratory personnel who work with HIV-infected specimens, usually through injury from contaminated sharp instruments. The risk of transmission of HIV from an infected health care worker to his or her pts through invasive procedures is extremely low.
As of November 1, 2017, an estimated 1.8 million people have been infected with HIV and 1.1 million people are currently living with HIV in the United States; approximately 13% of these individuals are unaware that they are infected. Approximately 693,000 people with an AIDS diagnosis have died. However, the death rate from AIDS has decreased substantially over the past two decades, primarily due to the increased use of effective antiretroviral drugs. An estimated 40,000 individuals are newly infected each year in the United States; this figure has remained stable for at least 15 years. Among adults and adolescents newly diagnosed with HIV infection in 2017, ∼80% were men and ∼20% were women. Of new HIV/AIDS diagnoses, 68% were due to male-to-male sexual contact, 23% to heterosexual contact, and 6% to IDUs. HIV infection/AIDS is a global pandemic, especially in developing countries. At the end of 2017, the estimated number of cases of HIV infection worldwide was ∼36.9 million, more than two-thirds of which were in sub-Saharan Africa; ∼47% of cases were in women and 2.6 million were in children. In 2017, there were 1.8 million new HIV infections worldwide and 940,000 deaths.
The hallmark of HIV disease is a profound immunodeficiency resulting from a progressive quantitative and qualitative deficiency of the subset of T lymphocytes referred to as helper T cells that are defined phenotypically by the expression on the cell surface of the CD4 molecule, which serves as the primary cellular receptor for HIV. A co-receptor must be present with CD4 for efficient entry of HIV-1 into target cells. The two major co-receptors for HIV-1 are the chemokine receptors CCR5 and CXCR4. The CD4+ T lymphocyte and less so cells of monocyte lineage are the principal cellular targets of HIV.
Following initial transmission, the virus infects CD4+ cells, predominantly T lymphocytes, but also monocytes, or bone marrow–derived dendritic cells. Both during this initial stage and later in infection, the lymphoid system is a major site for the establishment and propagation of HIV infection. The gut-associated lymphoid tissue (GALT) plays a role in the establishment of infection and in the early depletion of memory CD4+ T cells.
Essentially all pts undergo a viremic stage during primary infection; in some pts this is associated with the “acute retroviral syndrome,” a mononucleosis-like illness (see below). This phase is important in disseminating virus to lymphoid and other organs throughout the body, and viral replication is ultimately contained only partially by the development of an HIV-specific immune response.
Despite the robust immune response that is mounted following primary infection, the virus is not cleared from the body. Instead, a chronic infection develops that persists for a median time of 10 years before the untreated pt becomes clinically ill. During this period of clinical latency, the number of CD4+ T cells gradually declines, and few if any clinical signs and symptoms may be evident. However, active viral replication can almost always be detected as plasma viremia and in lymphoid tissue. The level of steady-state viremia (referred to as the viral set point) at ∼6 months to 1 year post-infection has important prognostic implications for the progression of HIV disease; individuals with a low viral set point at 6 months to 1 year after infection progress to AIDS more slowly than do those whose set point is very high at this time (Fig. 197-22, in HPIM-20).
In untreated pts or in pts in whom therapy has not controlled viral replication (see next), after some period of time (often years), CD4+ T cell counts will fall below a critical level (∼200/µL) and pts become highly susceptible to opportunistic diseases. The presence of a CD4+ T cell count <200/µL or an AIDS-defining opportunistic disease establishes a diagnosis of AIDS. Control of plasma viremia by effective antiretroviral therapy, particularly maintaining the plasma viral load consistently at <50 copies of RNA per mL, even in individuals with low CD4+ T cell counts, has dramatically increased survival in these pts, including those whose CD4+ T cell counts may not increase significantly as a result of therapy.
A broad range of immune abnormalities has been documented in HIV-infected pts, resulting in varying degrees of immunodeficiency. These include both quantitative and qualitative defects in lymphocytes, and qualitative defects in monocyte/macrophage and natural killer (NK) cell function. Autoimmune phenomena also have been observed.
Both humoral and cellular immune responses to HIV develop soon after primary infection (see summary in Table 197-7 and Fig. 197-27, in HPIM-20). Humoral responses include antibodies with HIV binding and neutralizing activity, as well as antibodies participating in antibody-dependent cellular cytotoxicity (ADCC). Cellular immune responses include the generation of HIV-specific CD4+ and CD8+ T lymphocytes, as well as NK cells and mononuclear cells mediating ADCC. CD8+ T lymphocytes may also suppress HIV replication in a noncytolytic, non-MHC-restricted manner. This effect is mediated by soluble factors such as the CC-chemokines RANTES (CCL5), MIP-1α (CCL3), and MIP-1β (CCL4). For the most part, the natural immune response to HIV is not adequate. Broadly reacting neutralizing antibodies against HIV are not easily generated in infected individuals, and eradication of the virus from infected individuals by naturally occurring immune responses has not been reported.
Laboratory diagnosis of HIV infection depends on the demonstration of anti-HIV antibodies and/or the detection of HIV or one of its components.
The standard screening test for HIV infection is the detection of anti-HIV antibodies using an enzyme immunoassay (EIA). This test is highly sensitive (>99.5%) and is quite specific. Most commercial EIA kits are able to detect antibodies to both HIV-1 and 2 and many also detect the HIV core antigen p24. The Western blot detects antibodies to HIV antigens of specific molecular weights. Antibodies to HIV begin to appear within 2 weeks of infection, and the period of time between initial infection and the development of detectable antibodies is rarely >3 months. Plasma p24 antigen levels rise during the first few weeks following infection, prior to the appearance of anti-HIV antibodies. A guideline for the use of these serologic tests in the diagnosis of HIV infection is depicted in Fig. 107-1.
HIV can be cultured directly from peripheral blood cells, plasma, or tissue, but this is most commonly done in a research setting. HIV genetic material can be detected using reverse transcriptase PCR (RT-PCR), branched DNA (bDNA), or nucleic acid sequence–based assay (NASBA). These tests are useful in pts with a positive or indeterminate EIA and an indeterminate Western blot. Such tests turn positive early in infection and will usually be positive in pts in whom serologic testing may be unreliable (such as those with hypogammaglobulinemia).
Measurement of the CD4+ T cell count and level of plasma HIV RNA are important components of the routine evaluation and monitoring of HIV-infected individuals. The CD4+ T cell count is a generally accepted indicator of the immunologic competence of the pt with HIV infection, and there is a close relationship between the CD4+ T cell count and the clinical manifestations of AIDS (Fig. 197-32, in HPIM-20). Pts with CD4+ T cell counts <200/µL are at higher risk of infection with Pneumocystis jiroveci. Once the count declines to <50/µL, pts are also at higher risk for developing cytomegalovirus (CMV) disease and infection with Mycobacterium avium intracellulare. Pts should have their CD4+ T cell count measured at the time of diagnosis and every 3–6 months thereafter. (Measurements may be done more frequently with declining counts.) While the CD4+ T cell count provides information on the current immunologic status, the HIV RNA level predicts what will happen to the CD4+ T cell count in the near future. Measurements of plasma HIV RNA levels should be made at the time of HIV diagnosis and every 3–4 months thereafter in the untreated pt. Measurement of plasma HIV RNA is also useful in making therapeutic decisions about antiretroviral therapy (see next). Following the initiation of therapy or any change in therapy, HIV RNA levels should be monitored approximately every 4 weeks until the effectiveness of the therapeutic regimen is determined, ideally by achieving an undetectable plasma viral load. During therapy, levels of HIV RNA should be monitored every 3–6 months to evaluate the continuing effectiveness of therapy.
The sensitivity of an individual’s HIV virus(es) to different antiretroviral agents can be tested by either genotypic or phenotypic assays. In the hands of experts, the use of resistance testing to select a new antiretroviral regimen in pts failing their current regimen leads to a ∼0.5-log greater decline in viral load compared with the efficacy of regimens selected solely on the basis of drug history. HIV resistance testing may also be of value in selecting an initial treatment regimen in geographic areas with a high prevalence of baseline resistance.
A complete discussion is beyond the scope of this short chapter; however, the major clinical features of the various stages of HIV infection are summarized next (see also Chap. 197, HPIM-20).
Approximately 50–70% of infected individuals experience an acute syndrome following primary infection. The acute syndrome follows infection by 3–6 weeks. It can have multiple clinical features (Table 107-1), lasts 1–2 weeks, and resolves spontaneously as an immune response to HIV develops and the viral load diminishes from its peak levels. Most pts will then enter a phase of clinical latency, although occasionally rapidly progressive immunologic and clinical deterioration occurs.
Erythematous maculopapular rash
The length of time between HIV infection and development of disease in untreated individuals varies greatly; however, the median is estimated to be 10 years. HIV disease with active viral replication usually progresses during this asymptomatic period, and, in the absence of combination antiretroviral therapy (cART) CD4+ T cell counts invariably fall. The rate of disease progression is directly correlated with plasma HIV RNA levels. Pts with high levels of HIV RNA progress to symptomatic disease faster than do those with low levels of HIV RNA.
Symptoms of HIV disease can develop at any time during the course of HIV infection. In general, the spectrum of illness changes as the CD4+ T cell count declines. The more severe and life-threatening complications of HIV infection occur in pts with CD4+ T cell counts <200/µL. Overall, the clinical spectrum of HIV disease is constantly changing as individuals live longer and new and better approaches to treatment and prophylaxis of opportunistic infections are developed. In addition, a variety of neurologic, cardiovascular, renal, metabolic, and hepatic problems are increasingly seen associated with HIV infection and may be a direct consequence of HIV infection. The key element to treating symptomatic complications of HIV disease, whether primary or secondary, is achieving good control of HIV replication through the use of cART and instituting primary and secondary prophylaxis as indicated. Major clinical syndromes seen in the symptomatic stage of HIV infection are summarized below.
General principles of pt management include counseling, psychosocial support, and screening for infections and other conditions and require comprehensive knowledge of the disease processes associated with HIV infection (see also Chap. 197, HPIM-20).
The cornerstone of medical management of HIV infection is combination antiretroviral therapy, or cART. Suppression of HIV replication is an important component in prolonging life as well as in improving the quality of life of pts with HIV infection (see Table 107-2). Data from observational studies and randomized controlled trials have demonstrated that with few exceptions cART should be administered to everyone who is HIV infected and that it is also associated with a profoundly decreased risk of transmitting infection to an uninfected partner. However, several important questions related to the treatment of HIV disease lack definitive answers. Among them are what is the best initial cART regimen, when should a given regimen be changed, and which drugs in a regimen should be changed when a change is made. Currently available treatment guidelines facilitate these choices (see below). The drugs that are currently licensed for the treatment of HIV infection are listed in Table 107-2. These drugs fall into four main categories: those that inhibit the viral reverse transcriptase enzyme, those that inhibit the viral protease enzyme, those that inhibit viral entry, and those that inhibit the viral integrase enzyme. In addition, more than a dozen combination drugs that combine two or more agents have been licensed (Table 107-2A). There are numerous drug–drug interactions that must be taken into consideration when using antiretroviral medications.
These agents act by causing premature DNA-chain termination during the reverse transcription of viral RNA to proviral DNA and should be used in combination with other antiretroviral agents. The most common usage is together with another nucleoside/nucleotide analogue and a nonnucleoside reverse transcriptase inhibitor or a protease inhibitor (see below).
These agents interfere with the function of HIV-1 reverse transcriptase by binding to regions outside the active site and causing conformational changes in the enzyme that render it inactive. Five members of this class, nevirapine, delavirdine, efavirenz, etravirine, and rilpivirine are currently available for clinical use. These drugs are licensed for use in combination with other antiretrovirals.
These drugs are potent and selective inhibitors of the HIV-1 protease enzyme and are active in the nanomolar range. As with other classes of antiretroviral drugs, the protease inhibitors should be used only in combination with other antiretroviral drugs.
These agents act by interfering with the binding of HIV to its receptor or co-receptor or by interfering with the process of fusion. A variety of small molecules that bind to HIV-1 co-receptors are currently in clinical trials. The first drugs in this class to be licensed are the fusion inhibitor enfuvirtide and the entry inhibitor maraviroc.
These drugs interfere with the integration of proviral DNA into the host cell genome. The first agent in this class, raltegravir, was approved in 2007 for use in treatment-experienced pts. Three other integrase inhibitors, dolutegravir, elvitegravir, and bictegravir are also licensed.
The large number of available antiretroviral agents make the subject of antiretroviral therapy one of the more complicated in the management of HIV-infected pts.
The principles of therapy for HIV infection have been articulated by a panel sponsored by the U.S. Department of Health and Human Services (Table 107-3). At present, most guidelines recommend cART for anyone with a diagnosis of HIV infection. In addition, one may wish to administer a 4-week course of therapy to uninfected individuals immediately following a high-risk exposure to HIV (see next).
When the decision to initiate therapy is made, the physician must decide which drugs to use in the initial regimen. The options for initial therapy most commonly in use today are listed in Table 107-4. There are no clear data at present on which to base a distinction between these approaches.
Following the initiation of therapy, one should expect a 1-log (tenfold) reduction in plasma HIV RNA within 1–2 months; eventually a decline in plasma HIV RNA to <50 copies/mL; and a rise in CD4+ T cell count of 100–150/µL during the first year. Failure to achieve and maintain an HIV RNA level <50 copies/mL is an indication to consider a change in therapy. Other reasons for changing therapy are listed in Table 107-5. When changing therapy because of treatment failure, it is important to attempt to provide a regimen with at least two new drugs. In the pt in whom a change is made for reasons of drug toxicity, a simple replacement of one drug is reasonable.
Specific for each infection and neoplasm (see Chap. 197, in HPIM-20).
|DRUG||STATUS||INDICATION||DOSE IN COMBINATION||SUPPORTING DATA||TOXICITY|
|Nucleoside or nucleotide reverse transcriptase inhibitors|
|Zidovudine (AZT, azidothymidine, *Retrovir, 3′azido-3′-deoxythymidine)||Licensed||Treatment of HIV infection in combination with other antiretroviral agents||200 mg q8h or 300 mg bid||19 vs 1 death in original placebo-controlled trial in 281 pts with AIDS or ARC||Anemia, granulocytopenia, myopathy, lactic acidosis, hepatomegaly with steatosis, headache, nausea, nail pigmentation, lipid abnormalities, lipoatrophy, hyperglycemia|
|Prevention of maternal-fetal HIV transmission||In pregnant women with CD4+ T cell count ≥200/µL, AZT PO beginning at weeks 14–34 of gestation plus IV drug during labor and delivery plus PO AZT to infant for 6 weeks decreased transmission of HIV by 67.5% (from 25.5% to 8.3%); n = 363|
|Lamivudine (Epivir, 2′3′-dideoxy-3′-thiacytidine, 3TC)||Licensed||In combination with other antiretroviral agents for the treatment of HIV infection|
150 mg bid
300 mg qd
|In combination with AZT superior to AZT alone with respect to changes in CD4+ T cell counts in 495 pts who were zidovudine-naïve and 477 pts who were zidovudine-experienced; overall CD4+ T cell counts for the zidovudine group were at baseline by 24 weeks, while in the group treated with zidovudine plus lamivudine, they were 10–50 cells/µL above baseline; 54% decrease in progression to AIDS/death compared with AZT alone||Flare of hepatitis in HBV-co-infected pts who discontinue drug|
|Emtricitabine (FTC, Emtriva)||Licensed||In combination with other antiretroviral agents for the treatment of HIV infection||200 mg qd||Comparable to lamivudine in combination with stavudine and nevirapine/efavirenz||Hepatotoxicity in HBV-co-infected pts who discontinue drug, skin discoloration|
|Abacavir (Ziagen)||Licensed||For treatment of HIV infection in combination with other antiretroviral agents||300 mg bid||Abacavir + AZT + 3TC equivalent to indinavir + AZT + 3TC with regard to viral load suppression (∼60% in each group with <400 HIV RNA copies/mL plasma) and CD4+ T cell increase (∼100/µL in each group) at 24 weeks||Hypersensitivity reaction in HLA-B5701+ individuals (can be fatal); fever, rash, nausea, vomiting, malaise or fatigue, and loss of appetite|
|Tenofovir disoproxil fumarate (Viread)||Licensed||For use in combination with other antiretroviral agents when treatment is indicated||300 mg qd||Reduction of ∼0.6 log in HIV-1 RNA levels when added to background regimen in treatment-experienced pts||Renal, osteomalacia, flare of hepatitis in HBV-co-infected pts who discontinue drug|
|Tenofovir alafenamide (Vemlidy)||Licensed||In combination with emtricitabine and other antiretroviral agents for treatment of HIV-1 infection||25 mg qd||92% of pts treated in combination with emtricitabine, elvitegravir, and cobicistat had HIV-1 RNA levels <50 copies/mL||Nausea, less renal toxicity than tenofovir disoproxil fumarate|
|Non-nucleoside reverse transcriptase inhibitors|
|Nevirapine (Viramune)||Licensed||In combination with other antiretroviral agents for treatment of progressive HIV infection|
200 mg/d × 14 days then 200 mg bid
400 mg extended release qd
|Increase in CD4+ T cell count, decrease in HIV RNA when used in combination with nucleosides||Skin rash, hepatotoxicity|
|Efavirenz (Sustiva)||Licensed||For treatment of HIV infection in combination with other antiretroviral agents||600 mg qhs||Efavirenz + AZT + 3TC comparable to indinavir + AZT + 3TC with regard to viral load suppression (a higher percentage of the efavirenz group achieved viral load <50 copies/mL, but the discontinuation rate in the indinavir group was unexpectedly high, accounting for most treatment “failures”); CD4 cell increase (∼140/µL in each group) at 24 weeks||Rash, dysphoria, elevated liver function tests, drowsiness, abnormal dreams, depression, lipid abnormalities, potentially teratogenic|
|Etravirine (Intelence)||Licensed||In combination with other antiretroviral agents in treatment-experienced pts whose HIV is resistant to nonnucleoside reverse transcriptase inhibitors and other antiretroviral medications||200 mg bid||Higher rates of HIV RNA suppression to <50 copies/mL (56% vs 39%); greater increases in CD4+ T cell count (89 vs 64 cells) compared to placebo when given in combination with an optimized background regimen||Rash, nausea, hypersensitivity reactions|
|Rilpivirine (Edurant)||Licensed||In combination with other drugs in previously untreated pts when treatment is indicated||25 mg qd||Noninferior to efavirenz with respect to suppression at week 48 in 1368 treatment-naive individuals, except in pts with pretherapy HIV RNA levels >100,000 where it was inferior||Nausea, dizziness, somnolence, vertigo, less CNS toxicity, and rash than efavirenz|
|Ritonavir (Norvir)||Licensed||In combination with other antiretroviral agents for treatment of HIV infection when treatment is warranted||600 mg bid (also used in lower doses as pharmacokinetic booster)||Reduction in the cumulative incidence of clinical progression or death from 34% to 17% in pts with CD4+ T cell count <100/µL treated for a median of 6 months||Nausea, abdominal pain, hyperglycemia, fat redistribution, lipid abnormalities, may alter levels of many other drugs, paresthesias, hepatitis|
|Atazanavir (Reyataz)||Licensed||For treatment of HIV infection in combination with other antiretroviral agents||400 mg qd or 300 mg qd + ritonavir 100 mg qd when given with efavirenz||Comparable to efavirenz when given in combination with AZT + 3TC in a study of 810 treatment-naïve pts; comparable to nelfinavir when given in combination with stavudine + 3TC in a study of 467 treatment-naïve pts||Hyperbilirubinemia, PR prolongation, nausea, vomiting, hyperglycemia, fat maldistribution, rash transaminase elevations, renal stones|
|Darunavir (Prezista)||Licensed||In combination with 100 mg ritonavir for combination therapy in treatment-experienced adults||600 mg + 100 mg ritonavir twice daily with food||At 24 weeks, pts with prior extensive exposure to antiretrovirals treated with a new combination including darunavir showed a –1.89-log change in HIV RNA levels and a 92-cell increase in CD4+ T cells compared with –0.48 log and 17 cells in the control arm||Diarrhea, nausea, headache, skin rash, hepatotoxicity, hyperlipidemia, hyperglycemia|
|Enfuvirtide (Fuzeon)||Licensed||In combination with other agents in treatment-experienced pts with evidence of HIV-1 replication despite ongoing anti-retroviral therapy||90 mg SC bid||In treatment of experienced pts, superior to placebo when added to new optimized background (37% vs 16% with <400 HIV RNA copies/mL at 24 weeks; + 71 vs + 35 CD4+ T cells at 24 weeks)||Local injection reactions, hypersensitivity reactions, increased rate of bacterial pneumonia|
|Maraviroc (Selzentry)||Licensed||In combination with other antiretroviral agents in adults infected with only CCR5-tropic HIV-1||150–600 mg bid depending on concomitant medications (see text)||At 24 weeks, among 635 pts with CCR5-tropic virus and HIV-1 RNA >5000 copies/mL despite at least 6 months of prior therapy with at least 1 agent from 3 of the 4 antiretroviral drug classes, 61% of pts randomized to maraviroc achieved HIV RNA levels <400 copies/mL compared with 28% of pts randomized to placebo||Hepatotoxicity, nasopharyngitis, fever, cough, rash, abdominal pain, dizziness, musculoskeletal symptoms|
|Ibalizumab (Trogarzo)||Licensed||In combination with other antiretroviral agents in pts with multidrug-resistant HIV-1||Single loading dose of 2000 mg followed by a maintenance dose of 800 mg every 2 weeks||At 25 weeks, 50% of pts with multi-drug resistant HIV-1 with HIV-1 RNA >1000 copies/mL treated with an optimized background of 1 active drug and ibalizumab achieved HIV RNA levels <200 copies/mL||Rash, diarrhea, nausea|
|Raltegravir (Isentress)||Licensed||In combination with other antiretroviral agents||400 mg bid||At 24 weeks, among 436 pts with 3-class drug resistance, 76% of pts randomized to receive raltegravir achieved HIV RNA levels <400 copies/mL compared with 41% of pts randomized to receive placebo||Nausea, headache, diarrhea, CPK elevation, muscle weakness, rhabdomyolysis|
(Available only in combination with cobicistat, tenofovir, and emtricitabine [Stribild])
|Licensed||Fixed-dose combination||1 tablet daily||Noninferior to raltegravir or atazanavir/ritonavir in treatment-experienced pts||Diarrhea, nausea, upper respiratory infections, headache|
|Dolutegravir (Tivicay)||Licensed||In combination with other antiretroviral agents|
50 mg daily for treatment-naïve pts
50 mg twice daily for treatment-experienced pts or those also receiving efavirenz or rifampin
|Noninferior to raltegravir, superior to efavirenz or darunavir/ritonavir||Insomnia, headache, hypersensitivity reactions, hepatotoxicity|
(Available only in combination with tenofovir alafenamide and emtricitabine [Biktarvy])
|Licensed||For treatment of HIV infection in adults||50 mg bictegravir/25 mg tenofovir alafenamide/200 mg emtricitabine qd||Noninferior to dolutegravir/tenofovir/emtricitabine and noninferior to dolutegravir/abacavir/lamivudine||Nausea, diarrhea, headache|
|Atriplaa||Tenofovir disoproxil fumarate + emtricitabine + efavirenz|
|Biktarvya||Tenofovir alafenamide + emtricitabine + bictegravir|
|Cimduo||Tenofovir disoproxil fumarate + lamivudine|
|Combivir||Zidovudine + lamivudine|
|Compleraa||Tenofovir disoproxil fumarate+ emtricitabine + rilpivirine|
|Descovy||Tenofovir alafenamide + emtricitabine|
|Dutrebis||Raltegravir + lamivudine|
|Epzicom||Abacavir + lamivudine|
|Evotaz||Atazanavir + cobicistat|
|Genvoyaa||Tenofovir alafenamide + emtricitabine + elvitegravir + cobicistat|
|Juluca||Dolutegravir + rilpivirine|
|Kaletra||Lopinavir + ritonavir|
|Odefseya||Tenofovir alafenamide + emtricitabine + rilpivirine|
|Prezcobix||Darunavir + cobicistat|
|Stribilda||Tenofovir disoproxil fumarate + emtricitabine + elvitegravir + cobicistat|
|Symfia||Tenofovir disoproxil fumarate + lamivudine + efavirenz (600 mg)|
|Symfi Loa||Tenofovir disoproxil fumarate + lamivudine + efavirenz (400 mg)|
|Triumeqa||Abacavir + lamivudine + dolutegravir|
|Truvada||Tenofovir disoproxil fumarate + emtricitabine|
|Trizivir||Zidovudine + lamivudine + abacavir|
Dolutegravir + tenofovir* + emtricitabine**
Raltegravir + tenofovir* + emtricitabine**
Bictegravir + tenofovir* + emtricitabine**
Elvitegravir + cobicistat + tenofovir* + emtricitabine**
Dolutegravir + abacavir + lamivudine** (only for those HLA-B*5701 negative)
Less than a 1-log drop in plasma HIV RNA by 4 weeks following the initiation of therapy
A reproducible significant increase (defined as threefold or greater) from the nadir of plasma HIV RNA level not attributable to intercurrent infection, vaccination, or test methodology
Persistently declining CD4+ T cell numbers
(See also Table 197-11, in HPIM-20.)
Primary prophylaxis is clearly indicated for P. jiroveci pneumonia (especially when CD4+ T cell counts fall to <200 cells/µL), for M. avium complex infections in pts with CD4+ T cell counts <50 cells/µL, and for M. tuberculosis infections in pts with a positive PPD or anergy if at high risk of TB. Vaccination with influenza and pneumococcal polysaccharide vaccines is generally recommended for all pts and may need to be repeated in those with CD4+ T cell counts <200/µL when their counts increase to >200/µL. Secondary prophylaxis, when available, is indicated for virtually every infection experienced by HIV-infected pts until they have significant immunologic recovery.
There is a small but definite risk to health care workers of acquiring HIV infection via needle stick exposures, large mucosal surface exposures, or exposure of open wounds to HIV-infected secretions or blood products. The risk of HIV transmission after a skin puncture by an object contaminated with blood from a person with documented HIV infection is ∼0.3%, compared with a 20–30% risk for hepatitis B infection from a similar incident. Postexposure prophylaxis may be effective in decreasing the likelihood of acquisition of infection through accidental exposure in the health care setting. In this regard, a U.S. Public Health Service working group has recommended that chemoprophylaxis be given as soon as possible after occupational exposure. While the precise regimen remains a subject of debate, the U.S. Public Health Service guidelines recommend a combination of two nucleoside analogue reverse transcriptase inhibitors plus a third drug given for 4 weeks for high-risk or otherwise complicated exposures. Regardless of which regimen is used, treatment should be initiated as soon as possible after exposure and take into count any available resistance data on the infecting virus.
Prevention of exposure is the best strategy and includes following universal precautions and proper handling of needles and other potentially contaminated objects.
Transmission of TB is another potential risk for all health care workers, including those dealing with HIV-infected pts. All workers should know their PPD status, which should be checked yearly.
A clinical trial conducted in Thailand demonstrated moderate (31% effective) protection against acquisition of HIV infection. However, this modest degree of efficacy does not justify deployment of the vaccine; active investigation continues in the pursuit of a safe and effective vaccine against HIV, including focusing on the induction of broadly neutralizing antibodies to HIV.
Education, counseling, and behavior modification along with the consistent and correct use of condoms in risk situations remain the cornerstones of HIV prevention efforts. Avoidance of shared needle use by IDUs is critical. If possible, breast-feeding should be avoided by HIV-positive women, as the virus can be transmitted to infants via this route. In societies where withholding of breast-feeding is not feasible, treatment of the mother, if possible, greatly decreases the chances of transmission. Recent studies have demonstrated the important role of medically supervised adult male circumcision in the prevention of acquisition of heterosexually transmitted HIV infection in men. In addition, pre-exposure prophylaxis (PrEP) with Truvada, a single pill formulation containing emtricitabine and tenofovir that has been approved for PrEP in men who have sex with men and in heterosexual men and women engaging in risk behaviors, has proven to be an effective means of prevention of HIV acquisition. Finally, treatment of the HIV-infected partner in heterosexual discordant couples has proved highly effective in preventing transmission of HIV to the uninfected partner.
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