Home Current Issue Previous Issues Published Ahead-of-Print Collections For Authors Journal Info
Skip Navigation LinksHome > June 19, 2010 - Volume 24 - Issue 10 > Seronegative HIV-1 infection: a review of the literature
doi: 10.1097/QAD.0b013e32833ac65c
Basic Science

Seronegative HIV-1 infection: a review of the literature

Spivak, Adam M; Sydnor, Emily RM; Blankson, Joel N; Gallant, Joel E

Free Access
Article Outline
Collapse Box

Author Information

Johns Hopkins School of Medicine, Division of Infectious Diseases, Baltimore, Maryland, USA.

Received 6 January, 2010

Revised 23 March, 2010

Accepted 8 April, 2010

Correspondence to Dr Joel E. Gallant, Johns Hopkins School of Medicine, Division of Infectious Diseases, 1830 East Monument Street, 4th floor, Baltimore, MD 21287, USA. Tel: +1 410 955 7473; e-mail: jgallant@jhmi.edu

Collapse Box


HIV-1-specific antibodies can be detected in HIV-1-positive patients within weeks of primary infection. Rare cases have been reported of patients who are persistently seronegative despite evidence of HIV-1 infection. We present a retrospective review of the clinical, virologic and immunologic characteristics of 25 persistently seronegative patients whose cases have been published to date and postulate a biologic mechanism for this phenomenon.

Back to Top | Article Outline


In 1985, the US Food and Drug Administration [1] approved the first diagnostic test for HIV-1, an ELISA that detected the presence of antibodies to viral antigens in the serum. Fourth-generation ELISAs that simultaneously detect HIV-1 antibodies and p24 antigen have been developed over the last decade and are now in clinical use for HIV-1 screening in most countries [2–4]. Specimens deemed positive by ELISA should be confirmed by supplemental testing algorithms employing either alternative format screening assays, western blot, immunofloresence assays or a test to detect HIV RNA according to current Centers for Disease Control and Prevention recommendations [5]. The performance characteristics of this testing strategy have been extensively evaluated [6,7], and with a sensitivity and specificity greater than 99% [8–10], it has proven to be one of the most reliable and accurate diagnostic tests in clinical medicine.

Patients exposed to HIV-1 typically develop HIV-1-specific antibodies within several weeks of primary infection [11]. Falsely negative screening HIV-1 antibody tests have most often been attributed to a ‘window period’ prior to the development of an HIV-1-specific antibody response or infection with HIV-2 or nonclade B HIV-1 [12–17]. Several other less common phenomena can lead to falsely negative HIV-1 screening tests. In several case reports, patients treated with HAART very early in the course of disease did not develop a full HIV-1 antibody response, possibly due to HAART-induced virologic suppression and subsequent lack of antigen [18,19]. Another case report [20] describes a patient whose HIV-1 antibodies became undetectable after treatment with HAART and mycophenolate mofetil and returned once these treatments were stopped. In 2005, a case report [21] was published describing a patient with common variable immunodeficiency who lacked HIV antibodies over a 10-month period but had repeatedly detectable HIV-1 viral loads as high as 300 000 copies per milliliter. In rare cases, HIV-1-infected patients who are not receiving antiretroviral therapy (ART) or immunosuppressive medications have demonstrated persistent lack of humoral immunity to HIV-1 [22–41]. These patients tend to present with severe immunodeficiency, likely due to a combination of negative antibody-based screening tests that delay diagnosis as well as a tendency toward rapid disease progression.

Over one million people are estimated to be living with HIV-1 in the United States, and more than 16 million people are tested for HIV-1 annually [5]. According to United Nations Programme on HIV/AIDS [2] epidemiologic data, in 2008, there were 33.4 million people living with HIV/AIDS worldwide and 2.7 million incident infections. Since HIV-1 was first recognized, however, there have been only 25 published case reports of patients with confirmed HIV-1 infection who do not have detectable HIV-1 antibodies. We describe here the clinical, virologic and immunologic characteristics of these patients with seronegative HIV-1 infection.

Back to Top | Article Outline


Literature review

We performed a literature review using the online search engine of the United States National Library of Medicine (http://www.ncbi.nlm.nih.gov/sites/entrez?db=pubmed) by searching for English language case reports and reviews under the medical subheading (MeSH term) ‘HIV seronegativity.’ Articles were screened to ensure that they reported a case or cases of HIV-positive patients whose plasma screening tests were negative at the time of diagnosis and remained antibody negative for prolonged periods or progressed to clinical AIDS and died without seroconversion. Data from these publications was reviewed and collated by the authors.

Back to Top | Article Outline


Case inclusion

Twenty-five cases were identified that described patients with evidence of seronegative HIV-1 infection. All were confirmed to have seronegative HIV-1 infection by a combination of consistently negative results on two or more HIV-1 screening ELISA assays, and virologic evidence for HIV-1 infection by plasma HIV-1 RNA, p24 antigen assays, positive DNA PCR, recovery of virus from culture or all. These patients were found to be HIV-1 antibody negative at two or more time points (range 2–39) from independent samples. Patients that lacked evidence of serial antibody testing or definitive evidence of HIV-1 infection by any of the methods above were excluded, as were patients of HIV-2 infection.

Back to Top | Article Outline
Demographic characteristics

Of the 25 seronegative patients who have been reported, the majority were in their third or fourth decade at the time of diagnosis. The mean age at diagnosis was 27 years. The youngest patient reported was an infant (age 2 months at the time of presentation); the oldest patient was 59 years old. Fourteen patients were male and 10 were female; in one patient, sex was not reported. None of the patients described had a medical condition that would predispose them to an attenuated immune response (Table 1).

Table 1
Table 1
Image Tools
Back to Top | Article Outline
Clinical features

The mode of virus acquisition was unknown or not reported in eight of 25 patients. Suspected parenteral exposure is described in one patient, and vertical transmission occurred in two patients. The remaining 14 patients were ascribed to sexual transmission. Pneumocystis jiroveci pneumonia, globally the most common AIDS-defining opportunistic infection [42], was present at the time of diagnosis in 12 of 25 patients. Other reported opportunistic infections at the time of diagnosis included esophageal candidiasis, tuberculosis, bacillary angiomatosis and cryptococcosis. Only four patients had CD4+ T-cell counts above 200 cells/μl (all of whom met criteria for AIDS through presentations with opportunistic infection), whereas 11 had counts below 50 cells/μl. Viral loads were not reported for seven patients. Among the remaining 18 patients, 16 had viral loads greater than 100 000 copies/ml. Six patients had viral loads that exceeded the upper limit of the assays used. Every patient met criteria for symptomatic AIDS.

In four patients, the time from primary infection to presentation could be determined; one patient was enrolled in a serodiscordant couples study [27] and received close serologic monitoring to identify incident HIV infection, one patient was followed closely because of high-risk behavior and had serial viral load and HIV-1 antibody testing [31] and two patients acquired HIV-1 infection as a result of vertical transmission [29,34]. All four of these patients progressed from primary infection to AIDS within 5 months. Although the exact time of primary infection could not be determined in the remainder of patients, there is clinical evidence for both high morbidity and rapid progression to AIDS (Table 1).

Back to Top | Article Outline
Virologic evaluation

Viral clade or subtype was not reported for eight patients. Eleven patients had subtype B virus, one had subtype C, one had subtype A, one had subtype A2, two had a circulating recombinant form AG (CRF02-AG) and one had a circulating recombinant form BG (CRF14-BG). Of the eight patients reporting viral tropism, four were found to have dual-tropic virus (R5/X4) and four had R5-tropic virus. Eleven of 25 patients reported an evaluation for drug resistance mutations; all were negative, showing evidence of wild-type drug susceptible virus. Six cases reported phylogenetic analyses that linked the virus isolated from the index patient to virus from the HIV-infected source individual identified by history. In all of these cases, the source patient had a positive antibody response to HIV-1 (Table 2).

Table 2
Table 2
Image Tools
Back to Top | Article Outline
Immunologic evaluation

All patients by definition had multiple negative HIV-1 ELISAs. Western blot results were not reported for two patients. Fifteen patients had no bands present on western blot. Seven patients had a p24 band, four had a p17 band, one had p31 and p51 and one patient had faint gp160 and gp41 bands. All but two cases included an evaluation of humoral responses and quantitative immunoglobulin levels. Sixteen patients reported quantitative immunoglobulin levels, all of which were in the normal range. The two case reports of vertically infected infants describe normal immunoglobulin panels at 10 months of age. Several cases report antibody responses to common antigens or vaccines. Four patients were found to have immunoglobulin G (IgG) antibodies to hepatitis B and one to hepatitis C. Ten patients were reported to have antibodies to human herpesviruses (HHVs), including cytomegalovirus, Epstein–Barr virus, herpes simplex virus (HSV)-1, HSV-2 and HHV8.

The results from all patients demonstrate an inadequate humoral response that appears isolated to HIV-1 infection, as quantitative immunoglobulins and specific IgG responses to other pathogens or immunogens were normal in all patients. Although T-cell responses to HIV-1 infection appear to be central to the initial partial immune control of viral replication [43,44], comparatively little has been reported regarding the presence of cellular immunity in these patients. In a recent case report [39] describing two patients with rapid progression to AIDS (included here as patients #22 and 23), an interferon-gamma ELISPOT assay was used to detect cellular immune responses to HIV-1. No T-cell responses were found to HIV-1 in either patient. In patient number 25, our group demonstrated a reproducible T-cell response to two Gag epitopes [41]. Despite the development of a broad antibody response to HIV-1 several months after the initiation of ART and immune reconstitution in this patient, the T-cell response remained limited to these two Gag epitopes.

Four case reports describe human leukocyte antigen (HLA) analysis. One patient was found to be homozygous for HLA class II alleles associated with high viral loads and rapid progression (HLA-DR1*0101 and HLA-DR1*0103) [45]. HLA-B*3503, another allele associated with rapid progression [46], was identified in another patient. Our group identified the presence of the HLA-B*5802 allele in patient number 25, who has also been associated with rapid disease progression [47,48]. In one of the cases in which an HIV-1-positive source patient was identified by history and confirmed by viral phylogenetics, HLA typing was performed on both the index and source patients. This transmission pair was found to have matched HLA supertypes for 3 of 4 HLA-A and HLA-B alleles. Autologous viral epitopes did not induce a T-cell response in the index patient, suggesting that rapid progression in this patient may have occurred due to transmission of viral cytotoxic T-lymphocyte (CTL) escape mutants (Table 3).

Table 3
Table 3
Image Tools
Back to Top | Article Outline
Treatment and outcomes

There is high mortality among the reported cases of seronegative HIV-1 infection. Of the 17 patients reporting outcomes, there were 10 deaths occurring within a mean of 8 months of diagnosis (range = 2 days to 33 months). Eleven of 17 patients received some form of antiretroviral therapy, with nine receiving HAART. Three of these treated patients died, six seroconverted with positive ELISA and western blot assays after a mean of 3 months on treatment (range = 1–9 months), one patient had a viral load reported to be less than 1000 copies/ml without seroconversion at 16 months and one patient did not have an outcome reported after the initiation of HAART (Table 4).

Table 4
Table 4
Image Tools
Back to Top | Article Outline


The 25 patients discussed here indicate that seronegative HIV-1 infection is associated with high viral loads, rapid disease progression and significant mortality. It remains unclear whether this clinical presentation is a cause or an effect of the absence of a humoral response. The common causes of falsely negative HIV-1 antibody tests described above (‘window period’ testing, screening assays that do not detect nonclade-B virus, early ART and hypogammaglobulinemia) do not appear to be playing a role in these patients.

No patient is reported to have spontaneously seroconverted; however, several developed positive ELISAs and western blots after administration of ART and immune reconstitution. A similar phenomenon has been described in a patient coinfected with HIV and hepatitis C virus (HCV) [49]. This patient had persistently detectable HCV viremia without hepatitis C antibodies (serosilent HCV infection) for a period of 13 months. Treatment with ART and anti-HCV therapy was followed shortly by the development of detectable HCV antibodies.

None of the patients reported here provide evidence of viral attenuation or mutation as a cause of the lack of antibody response. Case reports describing HIV-1-infected transmission pairs in which one partner exhibits an expected disease course (including positive HIV-1 antibody screening tests) and the other is HIV-1 seronegative with rapid disease progression (patients #5, 6, 7, 18 and 23) strengthen the conclusion that the host, not the virus, is responsible for this phenomenon.

It is tempting to ascribe a direct causal relationship between the lack of HIV-1-specific antibodies in this patient cohort and their rapid disease progression and high mortality. Scant immunologic evidence exists to support this concept however. In an SIV animal model, depletion of antibody-producing cells with the anti-CD20 mAb rituximab in SIV-infected primates did not significantly alter their viral loads or survival time when compared with SIV-infected primates who did not receive rituximab and retained SIV-specific neutralizing antibody titers [50,51]. In studies of elite suppressors (patients infected with HIV-1 with stable CD4+ T-cell counts who maintain viral loads <50 copies/ml without ART), low titers of neutralizing antibodies have been found and the highest levels of neutralizing antibodies to autologous virus were seen in patients with progressive disease [52,53].

Although the presence of HIV-1-specific neutralizing antibodies does not appear to be associated with control of viral replication, CTL response and the presences of specific major histocompatibility complex class I alleles do appear to correlate with viral load set points and the tempo of disease progression [43,44,54–56]. A subset of the patients described above underwent evaluation for T-cell function and HLA alleles. There appeared to be absent [39] or deficient T-cell responses to HIV-1 epitopes in these patients, which interestingly did not change after immune reconstitution and seroconversion [41]. Several patients had HLA alleles known to be associated with rapid disease progression. In one case, the HLA supertypes between the seronegative patient described and the HIV-1-positive source patient were found to be identical, suggesting the possibility of transmission of viral species that had already mutated to evade the donor's cellular immunity.

The absence of an HIV-1-specific humoral response seen in the group of persistently seronegative patients described here may represent a downstream effect that begins with ineffective cellular immunity, leading to unimpeded viral replication and rapid CD4+ T-cell loss. As B cells require CD4+ T-cell signaling to become activated and produce antibodies in the setting of acute infection, profound and sudden CD4+ lymphopenia may lead to a lack of detectable antibody production. This inference is supported by the observation that in several of the patients described above, antibody production to HIV-1 antigens develops with restoration of CD4+ T cells after initiation of ART. The presence of normal immunoglobulin levels and detectable serum antibodies to common pathogens in the patients described here suggests that the defective humoral immune response may be unique to HIV-1 due to rapid depletion of HIV-1-specific CD4+ T-cell during primary infection [57].

If the clinical and immunologic responses of elite suppressors to HIV-1 infection exist at one end of a spectrum, seronegative HIV-1 patients such as the ones described here are at the other end. Further understanding of the interplay between the virus and development of adaptive immunity is needed to better understand the accelerated and dramatic clinical course among these patients, and has significant implications for diagnostics as well as therapeutic vaccine design.

Back to Top | Article Outline


All authors (A.M.S., E.R.M.S., J.N.B. and J.E.G.) contributed to evaluation, selection and data abstraction of the publications evaluated in this manuscript.

There are no conflicts of interest.

Back to Top | Article Outline


1. United States Food and Drug Administration. HIV/AIDS historical time line 1981–1990. http://www.fda.gov/oashi/aids/miles81.html; 2009. [Accessed 17 March 2009]

2. Joint United Nations Programme on HIV/AIDS (UNAIDS) and World Health Organization (WHO). 2009 AIDS epidemic update [UNAIDS/09.36E/JC1700E, English original]. www.unaids.org; November 2009.

3. van Binsbergen J, Siebelink A, Jacobs A, Keur W, Bruynis F, van de Graaf M, et al. Improved performance of seroconversion with a 4th generation HIV antigen/antibody assay. J Virol Methods 1999; 82:77–84.

4. World Health Organization. Guidance on provider-initiated HIV testing and counselling in health facilities. www.unaids.org; 2007.

5. Branson BM, Handsfield HH, Lampe MA, Janssen RS, Taylor AW, Lyss SB, et al. Revised recommendations for HIV testing of adults, adolescents, and pregnant women in health-care settings. MMWR Recomm Rep 2006; 55:1–17, quiz CE1–4.

6. Gurtler L. Difficulties and strategies of HIV diagnosis. Lancet 1996; 348:176–179.

7. Sloand EM, Pitt E, Chiarello RJ, Nemo GJ. HIV testing. State of the art. JAMA 1991; 266:2861–2866.

8. Mylonakis E, Paliou M, Lally M, Flanigan TP, Rich JD. Laboratory testing for infection with the human immunodeficiency virus: established and novel approaches. Am J Med 2000; 109:568–576.

9. Kleinman S, Busch MP, Hall L, Thomson R, Glynn S, Gallahan D, et al. False-positive HIV-1 test results in a low-risk screening setting of voluntary blood donation. Retrovirus Epidemiology Donor Study. JAMA 1998; 280:1080–1085.

10. Owen SM, Yang C, Spira T, Ou CY, Pau CP, Parekh BS, et al. Alternative algorithms for human immunodeficiency virus infection diagnosis using tests that are licensed in the United States. J Clin Microbiol 2008; 46:1588–1595.

11. Burin des Roziers N, Sotto A, Arnaud A, Saissi G, Nasar O, Jourdan J. Kinetics of detection of antibodies to HIV-1 and plasma p24 antigens during a severe primary HIV-1 infection. AIDS 1995; 9:528–529.

12. Busch MP, Lee LL, Satten GA, Henrard DR, Farzadegan H, Nelson KE, et al. Time course of detection of viral and serologic markers preceding human immunodeficiency virus type 1 seroconversion: implications for screening of blood and tissue donors. Transfusion 1995; 35:91–97.

13. Zouhair S, Roussin-Bretagne S, Moreau A, Brunet S, Laperche S, Maniez M, et al. Group o human immunodeficiency virus type 1 infection that escaped detection in two immmunoassays. J Clin Microbiol 2006; 44:662–665.

14. Loussert-Ajaka I, Ly TD, Chaix ML, Ingrand D, Saragosti S, Courouce AM, et al. HIV-1/HIV-2 seronegativity in HIV-1 subtype O infected patients. Lancet 1994; 343:1393–1394.

15. Markovitz DM. Infection with the human immunodeficiency virus type 2. Ann Intern Med 1993; 118:211–218.

16. Schable C, Zekeng L, Pau CP, Hu D, Kaptue L, Gurtler L, et al. Sensitivity of United States HIV antibody tests for detection of HIV-1 group O infections. Lancet 1994; 344:1333–1334.

17. Simon F, Mauclere P, Roques P, Loussert-Ajaka I, Muller-Trutwin MC, Saragosti S, et al. Identification of a new human immunodeficiency virus type 1 distinct from group M and group O. Nat Med 1998; 4:1032–1037.

18. Kassutto S, Johnston MN, Rosenberg ES. Incomplete HIV type 1 antibody evolution and seroreversion in acutely infected individuals treated with early antiretroviral therapy. Clin Infect Dis 2005; 40:868–873.

19. Hare CB, Pappalardo BL, Busch MP, Karlsson AC, Phelps BH, Alexander SS, et al. Seroreversion in subjects receiving antiretroviral therapy during acute/early HIV infection. Clin Infect Dis 2006; 42:700–708.

20. Jurriaans S, Sankatsing SU, Prins JM, Schuitemaker H, Lange J, Van Der Kuyl AC, et al. HIV-1 seroreversion in an HIV-1-seropositive patient treated during acute infection with highly active antiretroviral therapy and mycophenolate mofetil. AIDS 2004; 18:1607–1608.

21. Padeh YC, Rubinstein A, Shliozberg J. Common variable immunodeficiency and testing for HIV-1. N Engl J Med 2005; 353:1074–1075.

22. Soriano V, Dronda F, Gonzalez-Lopez A, Chaves F, Bravo R, Gutierrez M, et al. HIV-1 causing AIDS and death in a seronegative individual. Vox Sang 1994; 67:410–411.

23. Oka S, Ida S, Shioda T, Takebe Y, Kobayashi N, Shibuya Y, et al. Genetic analysis of HIV-1 during rapid progression to AIDS in an apparently healthy man. AIDS Res Hum Retroviruses 1994; 10:271–277.

24. Wegner S, Ohl C, DeNobile J, Mascola J, Carr J, Skillman D, et al. Case Report of a woman with seronegative HIV-1 infection [abstract #173]. AIDS Res Hum Retroviruses 1995; 11(Suppl 1):S107.

25. Martin-Rico P, Pedersen C, Skinhoj P, Nielsen C, Lindhardt BO. Rapid development of AIDS in an HIV-1-antibody-negative homosexual man. AIDS 1995; 9:95–96.

26. Reimer L, Mottice S, Schable C, Sullivan P, Nakashima A, Rayfield M, et al. Absence of detectable antibody in a patient infected with human immunodeficiency virus. Clin Infect Dis 1997; 25:98–100.

27. Montagnier L, Brenner C, Chamaret S, Guetard D, Blanchard A, de Saint Martin J, et al. Human immunodeficiency virus infection and AIDS in a person with negative serology. J Infect Dis 1997; 175:955–959.

28. Michael NL, Brown AE, Voigt RF, Frankel SS, Mascola JR, Brothers KS, et al. Rapid disease progression without seroconversion following primary human immunodeficiency virus type 1 infection: evidence for highly susceptible human hosts. J Infect Dis 1997; 175:1352–1359.

29. Quinonez JM, Begue RE, Steele RW. HIV seronegativity in an infant with the acquired immunodeficiency syndrome. South Med J 1998; 91:879–881.

30. Sullivan PS, Schable C, Koch W, Do AN, Spira T, Lansky A, et al. Persistently negative HIV-1 antibody enzyme immunoassay screening results for patients with HIV-1 infection and AIDS: serologic, clinical, and virologic results. Seronegative AIDS Clinical Study Group. AIDS 1999; 13:89–96.

31. Rice PS, Cybulska B, Parry JV, Rowland-Jones S, Daniels RS. Reappearance of HIV antibody in an infected, seronegative individual after treatment with highly active antiretroviral therapy. AIDS 1999; 13:729–731.

32. Ellenberger DL, Sullivan PS, Dorn J, Schable C, Spira TJ, Folks TM, et al. Viral and immunologic examination of human immunodeficiency virus type 1-infected, persistently seronegative persons. J Infect Dis 1999; 180:1033–1042.

33. Candotti D, Adu-Sarkodie Y, Davies F, Baldrich-Rubio E, Stirrups K, Lee H, et al. AIDS in an HIV-seronegative Ghanaian woman with intersubtype A/G recombinant HIV-1 infection. J Med Virol 2000; 62:1–8.

34. De Rossi A, Giaquinto C, Del Mistro A, Zamarchi R, Chieco-Bianchi L. Onset of HIV-1 antibody production after highly active antiretroviral therapy in a seronegative HIV-1-infected child. AIDS 2000; 14:1284–1286.

35. Cardoso AR, Goncalves C, Pascoalinho D, Gil C, Ferreira AF, Bartolo I, et al. Seronegative infection and AIDS caused by an A2 subsubtype HIV-1. AIDS 2004; 18:1071–1074.

36. Monkemuller K, Fry LC, Decker JM, Rickes S, Smith PD. Severe gastrointestinal disease due to HIV-1-seronegative AIDS. Z Gastroenterol 2007; 45:706–709.

37. Chin BS, Lee SH, Kim GJ, Kee MK, Suh SD, Kim SS. Early identification of seronegative human immunodeficiency virus type 1 infection with severe presentation. J Clin Microbiol 2007; 45:1659–1662.

38. Novitsky V, Gaolathe T, Woldegabriel E, Makhema J, Essex M. A seronegative case of HIV-1 subtype C infection in Botswana. Clin Infect Dis 2007; 45:e68–e71.

39. Dalmau J, Puertas MC, Azuara M, Marino A, Frahm N, Mothe B, et al. Contribution of immunological and virological factors to extremely severe primary HIV type 1 infection. Clin Infect Dis 2009; 48:229–238.

40. Bartolo I, Camacho R, Barroso H, Bezerra V, Taveira N. Rapid clinical progression to AIDS and death in a persistently seronegative HIV-1 infected heterosexual young man. AIDS 2009; 23:2359–2362.

41. Spivak AM, Brennan T, O'Connell K, Sydnor E, Williams TM, Siliciano RF, et al. A case of seronegative HIV-1 infection. J Infect Dis 2010; 201:341–345.

42. Jain MK, Skiest DJ, Cloud JW, Jain CL, Burns D, Berggren RE. Changes in mortality related to human immunodeficiency virus infection: comparative analysis of inpatient deaths in 1995 and in 1999–2000. Clin Infect Dis 2003; 36:1030–1038.

43. Borrow P, Lewicki H, Hahn BH, Shaw GM, Oldstone MB. Virus-specific CD8+ cytotoxic T-lymphocyte activity associated with control of viremia in primary human immunodeficiency virus type 1 infection. J Virol 1994; 68:6103–6110.

44. Koup RA, Safrit JT, Cao Y, Andrews CA, McLeod G, Borkowsky W, et al. Temporal association of cellular immune responses with the initial control of viremia in primary human immunodeficiency virus type 1 syndrome. J Virol 1994; 68:4650–4655.

45. Mann DL, Murray C, Yarchoan R, Blattner WA, Goedert JJ. HLA antigen frequencies in HIV-1 seropositive disease-free individuals and patients with AIDS. J Acquir Immune Defic Syndr 1988; 1:13–17.

46. Itescu S, Mathur-Wagh U, Skovron ML, Brancato LJ, Marmor M, Zeleniuch-Jacquotte A, et al. HLA-B35 is associated with accelerated progression to AIDS. J Acquir Immune Defic Syndr 1992; 5:37–45.

47. Ngumbela KC, Day CL, Mncube Z, Nair K, Ramduth D, Thobakgale C, et al. Targeting of a CD8 T cell env epitope presented by HLA-B*5802 is associated with markers of HIV disease progression and lack of selection pressure. AIDS Res Hum Retroviruses 2008; 24:72–82.

48. Lazaryan A, Lobashevsky E, Mulenga J, Karita E, Allen S, Tang J, et al. Human leukocyte antigen B58 supertype and human immunodeficiency virus type 1 infection in native Africans. J Virol 2006; 80:6056–6060.

49. Bernardin F, Stramer SL, Rehermann B, Page-Shafer K, Cooper S, Bangsberg DR, et al. High levels of subgenomic HCV plasma RNA in immunosilent infections. Virology 2007; 365:446–456.

50. Gaufin T, Gautam R, Kasheta M, Ribeiro R, Ribka E, Barnes M, et al. Limited ability of humoral immune responses in control of viremia during infection with SIVsmmD215 strain. Blood 2009; 113:4250–4261.

51. Gaufin T, Pattison M, Gautam R, Stoulig C, Dufour J, MacFarland J, et al. Effect of B-cell depletion on viral replication and clinical outcome of simian immunodeficiency virus infection in a natural host. J Virol 2009; 83:10347–10357.

52. Bailey JR, Lassen KG, Yang HC, Quinn TC, Ray SC, Blankson JN, et al. Neutralizing antibodies do not mediate suppression of human immunodeficiency virus type 1 in elite suppressors or selection of plasma virus variants in patients on highly active antiretroviral therapy. J Virol 2006; 80:4758–4770.

53. Hatano H, Delwart EL, Norris PJ, Lee TH, Dunn-Williams J, Hunt PW, et al. Evidence for persistent low-level viremia in individuals who control human immunodeficiency virus in the absence of antiretroviral therapy. J Virol 2009; 83:329–335.

54. Goulder PJ, Watkins DI. Impact of MHC class I diversity on immune control of immunodeficiency virus replication. Nat Rev Immunol 2008; 8:619–630.

55. Fellay J, Shianna KV, Ge D, Colombo S, Ledergerber B, Weale M, et al. A whole-genome association study of major determinants for host control of HIV-1. Science 2007; 317:944–947.

56. Limou S, Le Clerc S, Coulonges C, Carpentier W, Dina C, Delaneau O, et al. Genomewide association study of an AIDS-nonprogression cohort emphasizes the role played by HLA genes (ANRS Genomewide Association Study 02). J Infect Dis 2009; 199:419–426.

57. Douek DC, Brenchley JM, Betts MR, Ambrozak DR, Hill BJ, Okamoto Y, et al. HIV preferentially infects HIV-specific CD4+ T cells. Nature 2002; 417:95–98.


acute seroconversion; HIV diagnosis; HIV seronegativity; rapid HIV progression

© 2010 Lippincott Williams & Wilkins, Inc.


Search for Similar Articles
You may search for similar articles that contain these same keywords or you may modify the keyword list to augment your search.