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SYMPOSIUM
Year : 2008  |  Volume : 56  |  Issue : 5  |  Page : 391-393

Impact of highly active antiretroviral therapy on ophthalmic manifestations in human immunodeficiency virus / acquired immune deficiency syndrome


1 Brown University Medical School, Providence, RI, USA
2 Medical Research Foundation, Sankara Nethralaya, Chennai, India
3 YRG Centre for AIDS Research and Education, VHS, Chennai, Tamil Nadu, India

Date of Submission08-Aug-2007
Date of Acceptance14-Jan-2008
Date of Web Publication8-Aug-2008

Correspondence Address:
N Kumarasamy
YRG Centre for AIDS Research and Education, Voluntary Health Services, Taramani, Chennai - 600 113
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0301-4738.42415

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  Abstract 

Highly active antiretroviral therapy (HAART) has changed the face of human immunodeficiency virus (HIV) acquired immune deficiency syndrome (AIDS) by leading to dramatic decreases in HIV-related morbidity and mortality in the developed as well as developing world. Since the introduction of HAART, the incidence of ocular opportunistic infections causing retinitis has dramatically decreased, and clinicians should be aware of changes in the clinical presentation of ocular manifestations of HIV. As studies of HIV disease after the introduction of HAART continue to become available, more thorough descriptions of treated patients with ocular opportunistic infections will include side-effects and toxicities of therapy. This review focuses on the impact of HAART on the ocular manifestations of HIV.

Keywords: Acquired immune deficiency syndrome, eye, highly active antiretroviral treatment, human immunodeficiency virus, India, ophthalmology, therapy


How to cite this article:
Venkatesh KK, Biswas J, Kumarasamy N. Impact of highly active antiretroviral therapy on ophthalmic manifestations in human immunodeficiency virus / acquired immune deficiency syndrome. Indian J Ophthalmol 2008;56:391-3

How to cite this URL:
Venkatesh KK, Biswas J, Kumarasamy N. Impact of highly active antiretroviral therapy on ophthalmic manifestations in human immunodeficiency virus / acquired immune deficiency syndrome. Indian J Ophthalmol [serial online] 2008 [cited 2020 Oct 30];56:391-3. Available from: https://www.ijo.in/text.asp?2008/56/5/391/42415

Highly active antiretroviral therapy (HAART) has changed the face of human immunodeficiency virus (HIV) acquired immunodeficiency syndrome (AIDS) by leading to dramatic decreases in HIV-related morbidity and mortality in the developed as well as developing world. [1],[2] In India, generic HAART has been shown to be safe, well-tolerated, and effective in increasing CD4 counts, and suppressing plasma viral load in patients with advanced HIV. [3],[4] The production of antiretroviral drugs by generic Indian drug manufacturers throughout the developing world has drastically reduced the price of HAART to less than one USD per day, and consequently increased access to treatment in resource-limited settings. [5] This review focuses on the impact of HAART on the ocular manifestations of HIV.

Since the introduction of HAART, the incidence of ocular opportunistic infections causing retinitis, such as cytomegalovirus (CMV), varicella zoster virus (VZV), tuberculosis, and toxoplasmosis, has dramatically decreased. [6] However, immune recovery uveitis secondary to HAART has become a major visually-threatening condition. [7],[8],[9] High rates of ocular syphilis have been documented as well among patients receiving HAART. [10] While HAART may have also decreased the incidence of other retinopathies associated with HIV, the reported incidence of these conditions was so low before the era of HAART that quantifying any changes in incidence is not feasible.

The standard HAART regimen since the late 1990s has consisted of combination therapy of three antiretroviral drugs from the three major drug categories, namely nucleoside reverse transcriptase inhibitors (NRTIs), non-nucleoside reverse transcriptase inhibitors (NNRTIs) and protease inhibitors (PIs). The goal of HAART has been to achieve sustained viral suppression, minimize drug resistance, and simplify dosage pattern. The immune recovery resulting from HAART is due to an absolute increase in CD4 cell count first through an increase in memory T cells followed by the renewed production of naοve CD4 T cells. [11] As in the developed world, the introduction of generic HAART in India has led to a dramatic reduction in the incidence of opportunistic infections. [2]


  Changes in ocular manifestations of HIV in the pre- and post-HAART eras Top


There have been dramatic changes in the incidence of ocular manifestations of HIV between the pre- and post-HAART era. In the era prior to HAART, our center described the first two cases, one patient with CMV retinitis and the other with endogenous endophthalmitis, of ocular involvement of HIV in India in 1995. [12] Before the introduction of HAART, CMV retinitis affected 30–40% of HIV-infected individuals, [13] with visual loss primarily due to CMV involvement of the posterior retina and retinal detachment; [14] it was also suggested that upon careful examination, 30% of patients with CD4 cell counts below 50 cells/l would be harboring CMV retinitis. [15] At that time a study from our center documented CMV retinitis and cotton-wool spots caused by HIV-related microvasculopathy as the most frequently encountered ocular lesions. A lower prevalence (45.7%) of ocular involvement was observed in HIV infection among Indian patients than other regional settings. [16],[17] Additionally, a study conducted at our center in Indian children infected with HIV found a high prevalence of ocular and systemic lesions, most commonly anterior uveitis followed by CMV retinitis. [18]

In the HAART era, it has been suggested that there has been an estimated 80% decrease in the incidence of CMV retinitis; [1],[19] however, there is evidence that suggests that this decrease has now been leveled off as patients continue to present with CMV retinitis after initiating HAART. [19],[20] It has also been reported that the clinical picture and level of intraocular pressure are similar in the pre-HAART and post-HAART era. [21] Highly active antiretroviral therapy induces at least partial immune restoration and improves the long-term outcome of CMV retinitis. [6] However, after the initiation of HAART, a relapse of CMV retinitis as vitritis has been reported. [8] Recurrences of CMV can be due to progressive immune dysfunction, inadequate intraocular drug levels, and drug resistance. By studying CMV retinitis, physicians can investigate whether the rejuvenated immune system resulting from HAART can effectively control opportunistic infections caused by AIDS.


  Treatment options for CMV and associated complications in the era of HAART Top


Treatment of CMV has changed since the introduction of HAART. Prior to HAART, patients had to remain on maintenance anti-CMV regimens to decrease rates of recurrence. However, HAART has led to low levels of CMV recurrence, even when anti-CMV regimens are stopped. [6],[22] It has been suggested that patients who can sustain an elevated CD4 cell count due to HAART on two consecutive measurements three months apart and whose CMV retinitis remains regressed on anti-CMV therapy for more than four months may discontinue anti-CMV therapy with close clinical monitoring for reactivation. [23] The conventionally used definition of immune recovery is a CD4 cell count >100 cells/l, which has been used as a guideline for discontinuation of anti-CMV therapy. [24] Despite the marked increase in CD4+ cell counts, it may be advisable to not discontinue anti-CMV medications during the first few months of initiating HAART. [25] Due to the small number of cases reported and the variable periods of follow-up, the relapse rate of CMV retinitis among patients who discontinue anti-CMV treatment remains unclear.

Since the advent of HAART, immune recovery uveitis (IRU) has become an ocular manifestation described in patients with inactive CMV retinitis. [8],[26] The reported incidence of IRU has been shown to vary widely and limited data is available of possible risk factors. [27],[28],[29] Some HIV-infected individuals experience clinical deterioration after initiating antiretroviral therapy that is believed to be a result of the restored immune system to mount an exuberant inflammatory response. Immune reconstitution syndrome can cause posterior segment inflammation in CMV retinitis and can lead to visual morbidity in patients with AIDS. [29] We have reported a case of immune reconstitution in an HIV-infected Indian male receiving HAART with CMV retinitis who developed panuveitis with hypopyon, which was related to immune recovery mediated by combination protease inhibitors-based antiretroviral therapy. [30]


  Conclusion: future clinical trajectories of treating ocular manifestations of HIV Top


Clinicians should be aware of changes in the clinical presentation of ocular manifestations of HIV since the introduction of HAART. Among patients with CMV in the HAART era, immune recovery may be associated with a greater number of inflammatory complications, including macular edema and epiretinal membrane formation. [21] Given the range of ocular manifestations of HIV, routine ocular examinations and screening for visual loss is recommended in patients with CD4 counts <50 cells/l. [31] As studies on HIV disease after the introduction of HAART continue to become available, more thorough descriptions of treated patients with ocular opportunistic infections will include side-effects and toxicities on therapy. As increasing number of HIV-infected individuals present with treatment failure in resource-limited settings such as India, the risk of ophthalmic complications may increase. Further research is needed to study the effects of the restored immune system following HAART on the eye and to identify the best therapeutic approach for HIV-infected patients.[32]

 
  References Top

1.
Palella F, Delaney KM, Moorman AC, Loveless MO, Fuhrer J, Satten GA, et al . Declining morbidity and mortality among patients with advanced human immunodeficiency virus infection: HIV Outpatient Study Investigators. N Engl J Med 1998;338:853-60.  Back to cited text no. 1
    
2.
Kumarasamy N, Solomon S, Chaguturu SK, Cecelia AJ, Vallabhaneni S, Flanigan TP, et al . The changing natural history of HIV disease: Before and after the introduction of generic antiretroviral therapy in southern India. Clin Infect Dis 2005;41:1525-8.  Back to cited text no. 2
[PUBMED]  [FULLTEXT]  
3.
Kumarasamy N, Solomon S, Chaguturu SK, Mahajan AP, Flanigan TP, Balakrishnan P, et al . The safety, tolerability and effectiveness of generic antiretroviral drug regimens for HIV-infected patients in south India. AIDS 2003;17:2265-71.  Back to cited text no. 3
    
4.
Kumarasamy N, Vallabhaneni S, Flanigan TP, Balakrishnan TP, Cecelia A, Carpenter CJ, et al . Rapid viral load suppression following generic highly active antiretroviral therapy in Southern Indian HIV-infected patients. AIDS 2005;19:625-7.  Back to cited text no. 4
    
5.
Kumarasamy N. Generic antiretroviral drugs-will they be the answer to HIV in the developing world? Lancet 2004;364:3-4.  Back to cited text no. 5
[PUBMED]  [FULLTEXT]  
6.
Whitcup S, Fortin E, Nussenblatt RB, Polis MA, Muccioli C, Belfort R. Therapeutic effect of combination antiretroviral therapy on cytomegalovirus retinitis. J Am Med Assoc 1997;277:1519-20.  Back to cited text no. 6
    
7.
Boyraz-Ikiz H, Witmer JP, Frissen PH. Cytomegalovirus (re)activation plays no role in the ocular vitritis observed after initiation of highly active antiretroviral therapy. AIDS 1999;13:867.  Back to cited text no. 7
    
8.
Karavellas M, Plummer DJ, Macdonald JC, Torriani FJ, Shufelt CL, Azen SP, et al . Incidence of immune recovery vitritis in cytomegalovirus retinitis patients following institution of successful highly active antiretroviral therapy. J Infect Dis 1999;179:697-700.  Back to cited text no. 8
    
9.
Jacobson M, Zegans M, Pavan PR, O'Donnell JJ, Sattler F, Rao N, et al . Cytomegalovirus retinitis after initiation of highly active antiretroviral therapy. Lancet 1997;349:1443-5.  Back to cited text no. 9
    
10.
Balba G, Kumar PN, James AN, Malani A, Palestine AG, Welch JN, et al . Ocular syphilis in HIV-positive patients receiving highly active antiretroviral therapy. J Med 2006;119:21-5.  Back to cited text no. 10
    
11.
Autran B, Carcelain G, Li TS, Blanc C, Mathez D, Tubiana R, et al . Positive effects of combined antiretroviral therapy on CD4+ T cell homeostasis and function in advanced HIV disease. Science 1997;277:112-6.  Back to cited text no. 11
[PUBMED]  [FULLTEXT]  
12.
Biswas J, Madhavan HN, Badrinath SS. Ocular lesions in AIDS: A report of first two cases in India. Indian J Ophthalmol 1995;43:69-72.  Back to cited text no. 12
[PUBMED]  Medknow Journal  
13.
Hoover D, Saah AJ, Bacellar H, Phair J, Detels R, Anderson R, et al . Clinical manifestations of AIDS in the era of pneumocystis prophylaxis: Multicenter AIDS Cohort Study. N Engl J Med 1993;329:1922-6.  Back to cited text no. 13
    
14.
Holbrook J, Jabs DA, Weinberg DV, Lewis RA, Davis MD, Friedberg D, et al . Visual loss in patients with cytomegalovirus retinitis and acquired immunodeficiency syndrome before widespread availability of highly active antiretroviral therapy. Arch Ophthomol 2003;121:99-107.  Back to cited text no. 14
    
15.
Kuppermann B, Petty JG, Richman DD, Mathews WC, Fullerton SC, Rickman LS, et al . Correlation between CD4+ counts and prevalence of cytomegalovirus retinitis and human immunodeficiency virus-related noninfectious retinal vasculopathy in patients with acquired immunodeficiency syndrome. Am J Ophthalmol 1993;115:575-82.  Back to cited text no. 15
    
16.
Biswas J, Joseph A, Raizada S, Kumarasamy N, Solomon S. Ophthalmic manifestations of human immunodeficiency virus (HIV) infection in India. Indian J Ophthalmol 1999;47:87-93.  Back to cited text no. 16
  Medknow Journal  
17.
Biswas J, Madhavan HN, George AN, Kumarasamy N, Solomon S. Ocular lesions associated with HIUV infection in India: A series of 100 consecutive patients evaluated at a referral center. Am J Ophthalmol 2000;129:9-15.  Back to cited text no. 17
    
18.
Biswas J, Kumar AA, George AE, Madhavan HN, Kumarasamy N, Mothi SN, et al . Ocular and systemic lesions in children with HIV. Indian J Pediatr 2000;67:721-4.  Back to cited text no. 18
    
19.
Jacobson M, Stanley H, Holtzer C, Margolis TP, Cunningham ET. Natural history and outcome of new AIDS-related cytomegalovirus retinitis diagnosed in the era of highly active antiretroviral therapy. Clin Infect Dis 2000;30:231-3.  Back to cited text no. 19
    
20.
Jabs D, Van Natta ML, Holbrook JT, Kempen JH, Meinert CL, Davis MD, et al . Longitudinal study of the ocular complications of AIDS: 1, Ocular diagnoses at enrollment. Ophthalmology 2007;114:780-6.  Back to cited text no. 20
    
21.
Jabs D, Van Natta ML, Holbrook JT, Kempen JH, Meinert CL, Davis MD, et al . Longitudinal study of the ocular complications of AIDS: 2, Ocular examination results at enrollment. Ophthalmology 2007;114:787-93.  Back to cited text no. 21
    
22.
Jabs D, Bolton SG, Dunn JP, Palestine AG. Discontinuing anticytomegalovirus therapy in patients with immune reconstitution after combination antiretroviral therapy. Am J Ophthalmol 1998;126:817-22.  Back to cited text no. 22
    
23.
Macdonald J, Karavellas MP, Torriani FJ, Morse LS, Smith IL, Reed JB, et al . Highly active antiretroviral therapy-related immune recovery in AIDS patients with cytomegalovirus retinitis. Ophthalmology 2000;107:877-81.  Back to cited text no. 23
    
24.
Guidelines for preventing opportunistic infections among HIV-infected persons-2002. Recommendations of the US Public Health Service and the Infectious Diseases Society of America. MMWR Recomm Rep 2002;51:1-52.  Back to cited text no. 24
    
25.
Biswas J, Fogla R, Gopal L, Narayana KM, Banker AS, Kumarasamy N, et al . Current approaches to diagnosis and management of ocular lesions in human immunodeficiency virus positive patients. Indian J Ophthalmol 2002;50:83-6.  Back to cited text no. 25
[PUBMED]  Medknow Journal  
26.
Song M, Karavellas MP, MacDonald JC, Plummer DJ, Freeman WR. Characterization of reactivation of cytomegalovirus retinitis in patients healed after treatment with highly active antiretroviral therapy. Retina 2000;20:151-5.  Back to cited text no. 26
    
27.
Karavellas M, Azen SP, MacDonald JC, Shufelt CL, Lowder CY, Plummer DJ, et al . Immune recovery vitritis and uveitis in AIDS: Clinical predictors, sequelae and treatment outcomes. Retina 2001;21:1-9.  Back to cited text no. 27
    
28.
Kempen J, Min YI, Freeman WR, Holland GN, Friedberg DN, Dieterich DT, et al . Risk of immune recovery uveitis in patients with AIDS and cytomegalovirus retinitis. Am J Ophthalmol 2006;113:684-94.  Back to cited text no. 28
    
29.
Nguyen Q, Kempen JH, Bolton SG, Dunn JP, Jabs DA. Immune recovery uveitis in patients with AIDS and cytomegalovirus retinitis after highly active antiretroviral therapy. Am J Ophthalmol 2000;129:634-9.  Back to cited text no. 29
    
30.
Biswas J, Choudhry S, Kumarasamy N, Solomon S. Immune recovery vitritis presenting as panuveitis following therapy with protease inhibitors. Indian J Ophthalmol 2000;48:313-5.  Back to cited text no. 30
[PUBMED]  Medknow Journal  
31.
Kumarasamy N, Vallabhaneni S, Flanigan TP, Mayer KH, Solomon S. Clinical profile of HIV in India. Indian J Med Res 2005;121:377-94.  Back to cited text no. 31
[PUBMED]  Medknow Journal  
32.
Kumarasamy N, Vallabhaneni S, Cecelia AJ, Yepthomi T, Balakrishnan P, Saghayam S, et al . Reasons for modification of generic highly active antiretroviral therapeutic regimens among patients in southern India. J Acquir Immune Deficiency Syndrome 2006;41:53-8.  Back to cited text no. 32
    



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