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Guidelines for the Use of Antiretroviral Agents in HIV-1-Infected Adults and Adolescents

Considerations for Antiretroviral Use in Special Patient Populations

Acute and Recent (Early) HIV Infection

(Last updated: April 8, 2015; last reviewed: April 8, 2015)

Panel's Recommendations

Panel's Recommendations

  • Antiretroviral therapy (ART) is recommended for all individuals with HIV-1 infection and should be offered to those with earlya HIV-1 infection (BII), although definitive data to confirm whether this approach will result in long-term virologic, immunologic, or clinical benefits are lacking.
  • All pregnant women with early HIV-1 infection should start ART as soon as possible to prevent perinatal transmission of HIV-1 (AI).
  • If treatment is initiated in a patient with early HIV-1 infection, the goal is to suppress plasma HIV-1 RNA to undetectable levels (AIII).
  • In patients with early HIV-1 infection in whom therapy is initiated, testing for plasma HIV-1 RNA levels, CD4 T lymphocyte counts, and toxicity monitoring should be performed as described for patients with chronic HIV-1 infection (AII). 
  • Genotypic drug resistance testing should be performed before initiation of ART to guide the selection of the regimen (AII). If therapy is deferred, genotypic resistance testing should still be performed because the results will be useful in selecting a regimen with the greatest potential for achieving optimal virologic response once therapy is initiated (AII).
  • In patients without transmitted drug resistant virus, therapy should be initiated with one of the combination regimens that is recommended for patients with chronic HIV-1 infection (see What to Start) (AIII).
  • ART can be initiated before drug resistance test results are available. Because resistance to pharmacokinetically enhanced protease inhibitors emerges slowly and clinically significant transmitted resistance to protease inhibitors is uncommon, these drugs and 2 nucleoside reverse transcriptase inhibitors should be used in this setting (AIII).
  • Patients starting ART should be willing and able to commit to treatment and should understand the possible benefits and risks of therapy and the importance of adherence (AIII). Patients may choose to postpone therapy, and providers, on a case-by-case basis, may elect to defer therapy because of clinical and/or psychosocial factors.
Rating of Recommendations:  A = Strong; B = Moderate; C = Optional
Rating of Evidence:  I = Data from randomized controlled trials; II = Data from well-designed nonrandomized trials or observational cohort studies with long-term clinical outcomes; III = Expert opinion

a Early infection represents either acute or recent infection.

Definitions: Acute HIV-1 infection is the phase of HIV-1 disease immediately after infection that is characterized by an initial burst of viremia; although, anti-HIV-1 antibodies are undetectable, HIV-1 RNA or p24 antigen are present. Recent infection generally is considered the phase up to 6 months after infection during which anti-HIV-1 antibodies are detectable. Throughout this section, the term “early HIV-1 infection” is used to refer to either acute or recent HIV-1 infection.

An estimated 40% to 90% of patients with acute HIV-1 infection will experience symptoms of acute retroviral syndrome, such as fever, lymphadenopathy, pharyngitis, skin rash, myalgias/arthralgias, and other symptoms.1-6 However, because the self-limiting symptoms are similar to those of many other viral infections, such as influenza and infectious mononucleosis, primary care clinicians often do not recognize acute HIV-1 infection. Acute infection can also be asymptomatic. Table 11 provides practitioners with guidance to recognize, diagnose, and manage acute HIV-1 infection.

Diagnosing Acute HIV Infection

Health care providers should maintain a high level of suspicion of acute HIV-1 infection in patients who have a compatible clinical syndrome—especially in those who report recent high-risk behavior (see Table 11).7 Patients may not always disclose or admit to high-risk behaviors or perceive that their behaviors put them at risk for HIV-1 acquisition. Thus, even in the absence of reported high-risk behaviors, signs and symptoms consistent with acute retroviral syndrome should motivate consideration of a diagnosis of acute HIV-1 infection.

Acute HIV-1 infection is usually defined as detectable HIV-1 RNA or p24 antigen in serum or plasma in the setting of a negative or indeterminate HIV-1 antibody test result.7,8 Combination immunoassays that detect HIV-1 and HIV-2 antibodies and HIV-1 p24 antigen are now approved by the Food and Drug Administration (FDA), and the most recent Centers for Disease Control and Prevention testing algorithm recommends them as the preferred assay to use for HIV screening, including for possible acute HIV-1 infection. Specimens that are reactive on this initial assay should be tested with an immunoassay that differentiates HIV-1 and HIV-2 antibodies.9 Specimens that are reactive on the initial assay and have either negative or indeterminate antibody differentiation test results should undergo testing using an FDA-approved quantitative or qualitative HIV-1 RNA test; a negative HIV-1 RNA test result indicates that the original Ag/Ab test result was a false positive. Detection of HIV-1 RNA indicates that acute HIV-1 infection is highly likely,9 and that antiretroviral therapy (ART) may be warranted (see Treatment for Early HIV-1 Infection). HIV-1 infection should be confirmed by subsequent testing to document HIV antibody seroconversion.

Some health care facilities may still be following HIV testing algorithms that recommend initial testing with an assay that only tests for the presence of HIV antibody. In such settings, when acute HIV-1 infection is suspected in a patient with a negative or indeterminate HIV antibody result, a quantitative or qualitative FDA-approved HIV-1 RNA test should be performed (AII). A presumptive diagnosis of acute HIV-1 infection can be made on the basis of a negative or indeterminate HIV antibody test result and a positive HIV-1 RNA test result, in which case, ART may be warranted (see Treatment for Early HIV-1 Infection). Providers should be aware that a low-positive quantitative HIV-1 RNA level (e.g., <10,000 copies/mL) may represent a false-positive result because HIV-1 RNA levels in acute infection are generally very high (e.g., >100,000 copies/mL).5,6 Therefore, when a low-positive quantitative HIV-1 RNA result is obtained, the HIV-1 RNA test should be repeated using a different specimen from the same patient.6 In this setting, the diagnosis of HIV-1 infection should be confirmed by subsequent documentation of HIV antibody seroconversion (see Table 11).

Treating Early HIV-1 Infection

Clinical trial data regarding the treatment of early HIV-1 infection is limited. Many patients who enrolled in studies to assess the role of ART in early HIV-1 infection (outlined below) were identified as trial participants because they presented with signs or symptoms of acute infection. With the introduction of HIV screening tests that include assays for HIV-1 RNA or p24 antigen and wider HIV screening in healthcare systems, the number of asymptomatic patients identified with early infection may increase. The natural history of HIV-1 disease in these patients may differ from that in individuals with symptomatic infections, thus further studies on the impact of ART on the natural history of asymptomatic acute HIV-1 infection are needed. The initial burst of high level viremia in infected individuals usually declines shortly after acute infection (e.g., within 2 months); however, a rationale for treatment during recent infection (e.g., 2–6 months after infection) remains, because during this transition period the immune system may not yet have maximally contained viral replication in the lymphoid tissue.10 Several trials have addressed the question of the long-term benefit of potent treatment regimens initiated during early HIV-1 infection. The potential benefits and risks of treating HIV-1 during this stage of disease are discussed below.

Potential Benefits of Treatment During Early HIV-1 Infection

Preliminary data indicate that treatment of early HIV-1 infection with combination ART improves laboratory markers of disease progression.11-15 The data, though limited, indicate that treatment of early HIV-1 infection may also reduce the severity of acute disease; lower the viral set point,16-18 which can affect the rate of disease progression if therapy is stopped; reduce the size of the viral reservoir;19 and decrease the rate of viral mutation by suppressing viral replication and preserving immune function.20 Because early HIV-1 infection is often associated with high viral loads and increased infectiousness,21 and ART use by HIV-1-infected individuals reduces transmission to serodiscordant sexual partners,22 treatment during early HIV-1 infection is expected to substantially reduce the risk of HIV-1 transmission. In addition, although data are limited and the clinical relevance unclear, the profound loss of gastrointestinal lymphoid tissue that occurs during the first weeks of infection may be mitigated by initiating ART during early HIV-1 infection.23,24 Many of the potential benefits described above may be more likely to occur with treatment of acute infection, but they also may occur if treatment is initiated during recent HIV-1 infection. 

Potential Risks of Treatment During Early HIV-1 Infection

The potential disadvantages of initiating therapy during early HIV-1 infection include more prolonged exposure to ART without a known long-term clinical benefit. This prolonged exposure to ART could result in drug toxicities, development of drug resistance if the patient is non-adherent to the regimen, and adverse effects on the patient’s quality of life due to earlier initiation of lifelong therapy that requires strict adherence.

Clinical Trial Data on Treatment During Early Infection 

Several randomized controlled trials have studied the effect of ART during acute and recent infection to assess whether initiating early therapy would allow patients to stop treatment and still maintain lower viral loads and higher CD4 T lymphocyte (CD4) counts while off ART for prolonged periods of time. This objective was of interest when these studies were initiated but is now less relevant because treatment is recommended for virtually all HIV-1-infected patients and treatment interruptions are not recommended (see Initiating Antiretroviral Therapy in Treatment-Naive Patients).

The Setpoint Study (ACTG A5217 Study) randomized patients with recent but not acute HIV-1 infection to either defer therapy or immediately initiate ART for 36 weeks and then stop treatment.16 The primary study end point was a composite of meeting criteria for ART or re-initiation of ART and viral load results at week 72 in both groups and at week 36 in the deferred treatment group. The study was stopped prematurely by the Data and Safety Monitoring Board because of an apparent benefit associated with early therapy that was driven mostly by the greater proportion of participants meeting the criteria for ART initiation in the deferred treatment group (50%) than in the immediate treatment group (10%). Nearly half of the patients in the deferred treatment group needed to start therapy during the first year of study enrollment. 

The Randomized Primo-SHM Trial randomized patients with acute (~70%) or recent (~30%) infection to either defer ART or undergo treatment for 24 or 60 weeks and then stop.17 Significantly lower viral loads were observed 36 weeks after treatment interruption in the patients who had been treated early. These patients also took longer to reach a CD4 count threshold of <350 cells/mm3 for restarting ART. The median time to starting treatment was 0.7 years for the deferred therapy group and 3.0 and 1.8 years for the 24- and 60-week treatment arms, respectively. The time to reaching a CD4 count of <500 cells/mm3 was only 0.5 years in the deferred group. 

The SPARTAC Trial included patients with acute and recent infection randomized to either defer therapy or received ART for 12 or 48 weeks and then stop.18 In this trial, the time to reach CD4 <350 cells/mm3 or initiate therapy was significantly longer in the group treated for 48 weeks than in the deferred treatment group or the group treated for 12 weeks. However, no difference was observed between the participants who received 12 weeks of ART and those who deferred treatment during early infection.

The strategies tested in these studies are of limited relevance today given that treatment interruption is not recommended. The study results may not fully reflect the natural history of HIV-1 disease in persons with asymptomatic acute infection because most patients in these trials were enrolled on the basis of identified early symptomatic HIV-1 infections. Nevertheless, the results do demonstrate that some immunologic and virologic benefits may be associated with the treatment of early HIV-1 infection. Moreover, all the findings suggest, at least in the population recruited for these studies, that the time to initiating ART after identification of early infection is quite short when the threshold for ART initiation is 350 CD4 cells/mm3, and nonexistent when therapy is advised for all individuals regardless of CD4 cell count as currently recommended in these guidelines. These observations must be balanced with the risks of early treatment, risks that are largely the same as those when therapy is initiated in chronically infected asymptomatic patients with high CD4 counts. Consequently, the health care provider and the patient should be fully aware that the rationale for initiating therapy during early HIV-1 infection is based on theoretical benefits and the extrapolation of data from the strategy trials outlined above. These potential benefits must be weighed against the risks. For these reasons, and because ART is currently recommended for all HIV-1-infected patients (see Initiating Antiretroviral Therapy in Treatment Naive Patients), ART should be offered to all patients with early HIV-1 infection (BII). However, patients must be willing and able to commit to treatment, and providers, on a case-by-case basis, may elect to defer therapy for clinical and/or psychosocial reasons. Providers also should consider enrolling patients with early HIV-1 infection in clinical studies to further evaluate the natural history of this stage of HIV-1 infection and to further define the role of ART in this setting. Providers can obtain information regarding such trials at www.clinicaltrials.gov or from local HIV treatment experts.

Treating Early HIV-1 Infection During Pregnancy

Because early HIV-1 infection is associated with a high risk of perinatal transmission, all HIV-1-infected pregnant women should start combination ART as soon as possible to prevent perinatal transmission of HIV-1 (AI).25 

Treatment Regimen for Early HIV-1 Infection

Data from the United States and Europe demonstrate that transmitted virus may be resistant to at least 1 antiretroviral drug in 6% to 16% of patients.26-28 In one study, 21% of isolates from patients with acute HIV-1 infection demonstrated resistance to at least 1 drug.29 Therefore, before initiating ART in a person with early HIV-1 infection, genotypic antiretroviral (ARV) drug resistance testing should be performed to guide selection of a regimen (AII). If the decision is made to initiate therapy during early infection, especially in the setting of acute infection, treatment initiation should not be delayed pending resistance testing results. Once results are available, the treatment regimen can be modified if warranted. If therapy is deferred, resistance testing still should be performed because the results will help guide selection of a regimen that has the greatest potential to optimize virologic response once therapy is initiated (AII).

The goal of therapy during early HIV-1 infection is to suppress plasma HIV-1 RNA to undetectable levels (AIII). Because data are insufficient to draw firm conclusions regarding specific drug combinations to use in this stage of HIV-1 infection, ART should be initiated with one of the combination regimens recommended for patients with chronic infection (AIII) (see What to Start). If therapy is started before the results of drug resistance testing are available, a pharmacologically boosted protease inhibitor (PI) should be used because resistance to these agents emerges slowly and clinically significant transmitted resistance is uncommon (AIII). If available, the results of ARV drug resistance testing or the ARV resistance pattern of the source person’s virus should be used to guide selection of the ARV regimen. Given the increasing use of daily tenofovir disoproxil fumarate/emtricitabine (TDF/FTC) for pre-exposure prophylaxis (PrEP) in HIV-negative individuals,30-32 early infection may be diagnosed in some patients while they are taking TDF/FTC as PrEP. In this setting, resistance testing should be performed; however, because PI resistance is unlikely, use of a pharmacologically boosted PI and TDF/FTC remains a reasonable option pending resistance testing results (see What to Start).

Patient Follow-Up

Testing for plasma HIV-1 RNA levels, CD4 cell counts, and toxicity monitoring should be performed as described in Laboratory Testing for Initial Assessment and Monitoring While on Antiretroviral Therapy (i.e., HIV-1 RNA at initiation of therapy, after 2 to 8 weeks, then every 4 to 8 weeks until viral suppression, and thereafter, every 3 to 4 months) (AII).

Duration of Therapy for Early HIV-1 Infection

The optimal duration of therapy for patients with early HIV-1 infection is unknown. Recent studies of early HIV-1 infection have evaluated starting and then stopping treatment as a potential strategy.16-18 Although these studies showed some benefits associated with this strategy, a large randomized controlled trial of patients with chronic HIV-1 infection found that treatment interruption was harmful in terms of increased risk of AIDS and non-AIDS events,33 and that the strategy was associated with increased markers of inflammation, immune activation, and coagulation.34 For these reasons and the potential benefit of ART in reducing the risk of HIV-1 transmission, the Panel does not recommend discontinuation of ART in patients treated for early HIV-1 infection (AIII).

Table 11. Identifying, Diagnosing, and Managing Acute and Recent HIV-1 Infection
 
Suspicion of Acute HIV-1 Infection:
  • Acute HIV-1 infection should be considered in individuals with signs or symptoms of acute HIV-1 infection and recent (within 2 to 6 weeks) high risk of exposure to HIV-1.a
  • Signs, symptoms, or laboratory findings may include but are not limited to one or more of the following: fever, lymphadenopathy, skin rash, myalgia/arthralgia, headache, diarrhea, oral ulcers, leucopenia, thrombocytopenia, transaminase elevation.
  • High-risk exposures include sexual contact with an HIV-1-infected person or a person at risk of HIV-1 infection, sharing injection drug use paraphernalia, or contact of mucous membranes or breaks in skin with potentially infectious fluids.
  • Differential diagnosis: The differential diagnosis of patients presenting with HIV-1 infection may include but is not limited to viral illnesses such as Epstein-Barr virus (EBV) and non-EBV (e.g., cytomegalovirus) infectious mononucleosis syndromes, influenza, viral hepatitis, streptococcal infection, or syphilis.
Evaluation/Diagnosis of Acute HIV-1 Infection:
  • Acute HIV-1 infection is defined as detectable HIV-1 RNA or p24 antigen (the antigen used in currently available HIV antigen/antibody [Ag/Ab] combination assays) in the setting of a negative or indeterminate HIV-1 antibody test result.
    • A reactive HIV antibody test result or Ag/Ab combination test result must be followed by supplemental confirmatory testing.
    • A negative or indeterminate HIV-1 antibody test result in a person with a reactive Ag/Ab test result or in whom acute HIV-1 infection is suspected requires assessment of plasma HIV-1 RNA to diagnose acute HIV-1 infection.
    • A positive result on an FDA-approved quantitative or qualitative plasma HIV-1 RNA test in the setting of a negative or indeterminate antibody test result is consistent with acute HIV-1 infection.
Considerations for ART During Early HIV-1 Infection:
  • All pregnant women with early HIV-1 infection should begin taking combination ART as soon as possible to prevent perinatal transmission of HIV-1 (AI).
  • Treatment for early HIV-1 infection should be offered to all non-pregnant individuals (BII).
  • The risks of ART during early HIV-1 infection are largely the same as those when ART is initiated in chronically infected asymptomatic patients with high CD4 counts.
  • If therapy is initiated, the goal should be sustained plasma virologic suppression (AIII).
 a In some settings, behaviors that increase the risk of HIV-1 infection may not be recognized or perceived as risky by the health care provider or the patient or both. Thus, even in the absence of reported high-risk behaviors, symptoms and signs consistent with acute retroviral syndrome should motivate consideration of a diagnosis of acute HIV-1 infection.

References

  1. Tindall B, Cooper DA. Primary HIV infection: host responses and intervention strategies. AIDS. 1991;5(1):1-14. Available at http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=1812848.
  2. Niu MT, Stein DS, Schnittman SM. Primary human immunodeficiency virus type 1 infection: review of pathogenesis and early treatment intervention in humans and animal retrovirus infections. J Infect Dis. 1993;168(6):1490-1501. Available at http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=8245534.
  3. Kinloch-de Loes S, de Saussure P, Saurat JH, Stalder H, Hirschel B, Perrin LH. Symptomatic primary infection due to human immunodeficiency virus type 1: review of 31 cases. Clin Infect Dis. 1993;17(1):59-65. Available at http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=8353247.
  4. Schacker T, Collier AC, Hughes J, Shea T, Corey L. Clinical and epidemiologic features of primary HIV infection. Ann Intern Med. 1996;125(4):257-264. Available at http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=8678387.
  5. Daar ES, Little S, Pitt J, et al. Diagnosis of primary HIV-1 infection. Los Angeles County Primary HIV Infection Recruitment Network. Ann Intern Med. 2001;134(1):25-29. Available at http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=11187417.
  6. Hecht FM, Busch MP, Rawal B, et al. Use of laboratory tests and clinical symptoms for identification of primary HIV infection. AIDS. 2002;16(8):1119-1129. Available at http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=12004270.
  7. Branson BM, Handsfield HH, Lampe MA, et al. Revised recommendations for HIV testing of adults, adolescents, and pregnant women in health-care settings. MMWR Recomm Rep. 2006;55(RR-14):1-17. Available at http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=16988643.
  8. Pilcher CD, Christopoulos KA, Golden M. Public health rationale for rapid nucleic acid or p24 antigen tests for HIV. J Infect Dis. 2010;201 Suppl 1:S7-15. Available at http://www.ncbi.nlm.nih.gov/pubmed/20225950.
  9. Centers for Disease Control and Prevention and Association of Public Health Laboratories. Laboratory Testing for the Diagnosis of HIV Infection: Updated Recommendations. Available at http://stacks.cdc.gov/view/cdc/23447. Published June 27, 2014. Accessed March 19, 2015.
  10. Pantaleo G, Cohen OJ, Schacker T, et al. Evolutionary pattern of human immunodeficiency virus (HIV) replication and distribution in lymph nodes following primary infection: implications for antiviral therapy. Nat Med. 1998;4(3):341-345. Available at http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=9500610.
  11. Hoen B, Dumon B, Harzic M, et al. Highly active antiretroviral treatment initiated early in the course of symptomatic primary HIV-1 infection: results of the ANRS 053 trial. J Infect Dis. 1999;180(4):1342-1346. Available at http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=10479169.
  12. Lafeuillade A, Poggi C, Tamalet C, Profizi N, Tourres C, Costes O. Effects of a combination of zidovudine, didanosine, and lamivudine on primary human immunodeficiency virus type 1 infection. J Infect Dis. 1997;175(5):1051-1055. Available at http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=9129065.
  13. Lillo FB, Ciuffreda D, Veglia F, et al. Viral load and burden modification following early antiretroviral therapy of primary HIV-1 infection. AIDS. 1999;13(7):791-796. Available at http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=10357377.
  14. Malhotra U, Berrey MM, Huang Y, et al. Effect of combination antiretroviral therapy on T-cell immunity in acute human immunodeficiency virus type 1 infection. J Infect Dis. 2000;181(1):121-131. Available at http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=10608758.
  15. Smith DE, Walker BD, Cooper DA, Rosenberg ES, Kaldor JM. Is antiretroviral treatment of primary HIV infection clinically justified on the basis of current evidence? AIDS. 2004;18(5):709-718. Available at http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=15075505.
  16. Hogan CM, Degruttola V, Sun X, et al. The setpoint study (ACTG A5217): effect of immediate versus deferred antiretroviral therapy on virologic set point in recently HIV-1-infected individuals. J Infect Dis. 2012;205(1):87-96. Available at http://www.ncbi.nlm.nih.gov/pubmed/22180621.
  17. Grijsen ML, Steingrover R, Wit FW, et al. No treatment versus 24 or 60 weeks of antiretroviral treatment during primary HIV infection: the randomized Primo-SHM trial. PLoS Med. 2012;9(3):e1001196. Available at http://www.ncbi.nlm.nih.gov/pubmed/22479156.
  18. Hamlyn E, Ewings FM, Porter K, et al. Plasma HIV viral rebound following protocol-indicated cessation of ART commenced in primary and chronic HIV infection. PLoS One. 2012;7(8):e43754. Available at http://www.ncbi.nlm.nih.gov/pubmed/22952756.
  19. Strain MC, Little SJ, Daar ES, et al. Effect of treatment, during primary infection, on establishment and clearance of cellular reservoirs of HIV-1. J Infect Dis. 2005;191(9):1410-1418. Available at http://www.ncbi.nlm.nih.gov/pubmed/15809898.
  20. Rosenberg ES, Altfeld M, Poon SH, et al. Immune control of HIV-1 after early treatment of acute infection. Nature. 2000;407(6803):523-526. Available at http://www.ncbi.nlm.nih.gov/pubmed/11029005.
  21. Wawer MJ, Gray RH, Sewankambo NK, et al. Rates of HIV-1 transmission per coital act, by stage of HIV-1 infection, in Rakai, Uganda. J Infect Dis. 2005;191(9):1403-1409. Available at http://www.ncbi.nlm.nih.gov/pubmed/15809897.
  22. Cohen MS, Chen YQ, McCauley M, et al. Prevention of HIV-1 infection with early antiretroviral therapy. N Engl J Med. 2011;365(6):493-505. Available at http://www.ncbi.nlm.nih.gov/pubmed/21767103.
  23. Mehandru S, Poles MA, Tenner-Racz K, et al. Primary HIV-1 infection is associated with preferential depletion of CD4+ T lymphocytes from effector sites in the gastrointestinal tract. J Exp Med. 2004;200(6):761-770. Available at http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=15365095.
  24. Guadalupe M, Reay E, Sankaran S, et al. Severe CD4+ T-cell depletion in gut lymphoid tissue during primary human immunodeficiency virus type 1 infection and substantial delay in restoration following highly active antiretroviral therapy. J Virol. 2003;77(21):11708-11717. Available at http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=14557656.
  25. Panel on Treatment of HIV-Infected Pregnant Women and Prevention of Perinatal Transmission. Recommendations for use of antiretroviral drugs in pregnant HIV-1-infected women for maternal health and interventions to reduce perinatal HIV transmission in the United States. 2014. Available at http://aidsinfo.nih.gov/contentfiles/lvguidelines/PerinatalGL.pdf. Accessed April 3, 2015.
  26. Wheeler WH, Ziebell RA, Zabina H, et al. Prevalence of transmitted drug resistance associated mutations and HIV-1 subtypes in new HIV-1 diagnoses, U.S.-2006. AIDS. 2010;24(8):1203-1212. Available at http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=20395786.
  27. Kim D, Wheeler W, Ziebell R, al e. Prevalence of transmitted antiretroviral drug resistance among newly-diagnosed HIV-1-infected persons, U.S., 2007. Presented at: 17th Conference on Retroviruses and Opportunistic Infections. 2010. San Francisco, CA.
  28. Wensing AM, van de Vijver DA, Angarano G, et al. Prevalence of drug-resistant HIV-1 variants in untreated individuals in Europe: implications for clinical management. J Infect Dis. 2005;192(6):958-966. Available at http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=16107947.
  29. Yanik EL, Napravnik S, Hurt CB, et al. Prevalence of transmitted antiretroviral drug resistance differs between acutely and chronically HIV-infected patients. J Acquir Immune Defic Syndr. 2012;61(2):258-262. Available at http://www.ncbi.nlm.nih.gov/pubmed/22692092.
  30. Grant RM, Lama JR, Anderson PL, et al. Preexposure chemoprophylaxis for HIV prevention in men who have sex with men. N Engl J Med. 2010;363(27):2587-2599. Available at http://www.ncbi.nlm.nih.gov/pubmed/21091279.
  31. Baeten JM, Donnell D, Ndase P, et al. Antiretroviral prophylaxis for HIV prevention in heterosexual men and women. N Engl J Med. 2012;367(5):399-410. Available at http://www.ncbi.nlm.nih.gov/pubmed/22784037.
  32. Thigpen MC, Kebaabetswe PM, Paxton LA, et al. Antiretroviral preexposure prophylaxis for heterosexual HIV transmission in Botswana. N Engl J Med. 2012;367(5):423-434. Available at http://www.ncbi.nlm.nih.gov/pubmed/22784038.
  33. El-Sadr WM, Lundgren J, et al with the Strategies for Management of Antiretroviral Therapy Study Group. CD4+ count-guided interruption of antiretroviral treatment. N Engl J Med. 2006;355(22):2283-2296. Available at http://www.ncbi.nlm.nih.gov/pubmed/17135583.
  34. Kuller LH, Tracy R, Belloso W, et al. Inflammatory and coagulation biomarkers and mortality in patients with HIV infection. PLoS Med. 2008;5(10):e203. Available at http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=18942885.

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