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   Table of Contents      
SYMPOSIUM
Year : 2008  |  Volume : 56  |  Issue : 5  |  Page : 385-390

Medical management of human immunodeficiency virus infection


Department of Ophthalmology, the Department of Biostatistics and Epidemiology and the Center for Clinical Epidemiology and Biostatistics, the University of Pennsylvania, Philadelphia, Pennsylvania, USA

Date of Submission04-Jun-2007
Date of Acceptance14-Nov-2007
Date of Web Publication8-Aug-2008

Correspondence Address:
John H Kempen
Center for Preventive Ophthalmology and Biostatistics, Department of Ophthalmology, University of Pennsylvania, 3535 Market Street, Suite 700, Philadelphia, PA 19104
USA
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0301-4738.42414

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  Abstract 

The human immunodeficiency virus (HIV)/ acquired immune deficiency syndrome (AIDS) pandemic has pervasive effects on culture, economics, policy, and human development. All organs can be affected by complications of HIV/AIDS, including the eye. When sufficient resources are available and widespread antiretroviral resistance does not exist, the four available classes of antiretroviral agents - nucleoside/nucleotide reverse transcriptase inhibitors, non-nucleoside reverse transcriptase inhibitors, protease inhibitors, and fusion inhibitors - can be combined to provide highly active antiretroviral therapy (HAART). For many (not all) patients, HAART converts an inexorably fatal disease into a chronic disease with a fairly good prognosis. Use of HAART often induces partial immune recovery, which has predominantly beneficial effects on ocular complications of AIDS. However, HAART-induced immune recovery sometimes results in immune recovery inflammatory syndromes, such as immune recovery uveitis. Use of HAART is the single most useful intervention for most patients with ocular complications of AIDS. However, specific ocular therapy is also critical to avoid blindness in the early months before immune recovery can occur, or if HAART is unavailable. Increasing availability of HAART worldwide shows great promise to alleviate one of the world's greatest plagues. However, predictable secular trends in the AIDS epidemic make it likely that the number of cases of ocular complications of AIDS will increase substantially before they decrease. Ophthalmologists worldwide should be familiar with the diagnosis and management of cytomegalovirus retinitis - the most common ocular complication of AIDS - and should establish partnerships with physicians who are able to provide HAART. Research is needed to determine the optimal approach for managing cytomegalovirus retinitis in resource-constrained settings.

Keywords: Acquired immune deficiency syndrome, antiretroviral therapy, cytomegalovirus retinitis, highly active antiretroviral therapy, human immunodeficiency virus, immune recovery


How to cite this article:
Kempen JH. Medical management of human immunodeficiency virus infection. Indian J Ophthalmol 2008;56:385-90

How to cite this URL:
Kempen JH. Medical management of human immunodeficiency virus infection. Indian J Ophthalmol [serial online] 2008 [cited 2020 Oct 30];56:385-90. Available from: https://www.ijo.in/text.asp?2008/56/5/385/42414

The acquired immune deficiency syndrome (AIDS) pandemic was first recognized in 1981 in Los Angeles, California. [1] Unfortunately, human immunodeficiency virus (HIV) infection was widespread throughout the world by the time these sentinel events were recognized. The HIV/AIDS pandemic has quickly advanced to become one of the great plagues of all time, now affecting between 30.6 and 36.1 million persons worldwide, including approximately 2.5 million Indians [Figure 1]. [2],[3] More than 2.08 million persons die of HIV/AIDS per year, worldwide. [3] The pandemic has had pervasive effects on culture, economics, and policy, and has led to "the single greatest reversal in human development" in recent times. [4] The aim of the present article is to provide a review of the medical management of HIV infection.

Four treatment strategies have been shown to prolong survival of patients with HIV/AIDS: antiretroviral therapy, prophylaxis for Pneumocystis carinii , [5] prophylaxis for Mycobacterium avium [6] and care by a physician experienced in the management of HIV/AIDS. [7] Of these, only combination antiretroviral therapy, commonly called highly active antiretroviral therapy (HAART), frequently succeeds at reversing the otherwise inexorable progression of immunodeficiency, whereas P. carinii and M. avium prophylaxis prolong survival in a state of advanced immunodeficiency, during which time patients unfortunately are at increasing risk of advanced opportunistic complications of AIDS such as cytomegalovirus (CMV) retinitis. [8] The current plan for widespread introduction of inexpensive co-trimoxazole prophylaxis [9] will be of great value in improving survival, but the risk of CMV retinitis is likely to increase substantially as a result, in regions where HAART does not become widely used.

Highly active antiretroviral therapy is defined as "an antiretroviral regimen that can reasonably be expected to reduce the viral load <50 copies/mL in treatment-naοve patients". [10] A foundational advance leading to HAART was the recognition that combination antiretroviral therapy would be needed to prevent the development of viral resistance to antiretroviral agents. The HIV, an RNA virus, mutates approximately once per replication, as a result of the poor fidelity of its reverse transcriptase. [11] This property enables HIV to rapidly develop resistance to antiretroviral treatments, unless the treatment succeeds at arresting replication nearly completely. [12] Simultaneous use of multiple agents, usually three or more, attacking different aspects of HIV replication is successful because HIV would have to develop mutations simultaneously to all agents in use in order to escape control, an improbable event. However, scrupulous adherence to such therapy is extremely important for patients with HIV disease, because intermittent use of antiretroviral agents leads to the development of resistance. [13] Less than 95% adherence is associated with a 3.5-fold higher risk of treatment failure. [14]

The four classes of antiretroviral agents currently available are listed in [Table 1]. At present, available antiretroviral drugs have their effect by interfering with one of two HIV-encoded enzymes required for reproduction of the virus (reverse transcriptase, which transcribes HIV's RNA genome; or HIV protease, which is involved in the assembly and release of daughter viral particles) or by inhibiting fusion of the viral particle with the target cell.

Inhibitors of reverse transcriptase are divided into two classes: nucleoside (or nucleotide) reverse transcriptase inhibitors (NRTIs), which competitively inhibit the enzyme; and non-nucleoside reverse transcriptase inhibitors (NNRTIs), which covalently inactivate the reverse transcriptase, exerting a highly potent effect. Nucleoside inhibitors were the first effective antiretroviral drugs to be developed, beginning with zidovudine (AZT) in 1987. [15] When given as monotherapy, most of these drugs reduce the HIV load in peripheral blood on the order of 0.5 to 1.0 log 10 units, followed by the rapid development of drug resistance. The six agents in this class [Table 1] are quite useful as a component of antiretroviral combination therapies, and are widely used. Being older medications, some of them are less expensive than newer antiretroviral agents. Tenofovir is a nucleotide, rather than a nucleoside reverse transcriptase inhibitor, which circumvents a common mechanism of NRTI resistance, but otherwise works in a similar fashion to its cousins.

Non-nucleoside reverse transcriptase inhibitors are more potent than nucleoside reverse transcriptase inhibitors because they covalently inactivate reverse transcriptase. Their side-effect profile has made the three agents in this class among the most popular agents for management of HIV infection, although costs tend to limit their use worldwide. Nevertheless, they are prone to extremely rapid development of resistance if not used in appropriate combinations with a high degree of adherence to the medication schedule.

Protease inhibitors make up a third class of antiretroviral agents, the first class of "highly potent" drugs to become available, suppressing HIV load by 1.0 to 2.0 log 10 units when given as monotherapy. The HIV protease cleaves polyproteins generated by HIV-encoded mRNA; its blockade renders several essential viral enzymes inactive, resulting in production of defective HIV virions that are rapidly cleared. [16],[17] Nine such agents currently exist [Table 1]. Ideally, most are given in conjunction with ritonavir, for its "boosting" effect, which improves the pharmacokinetic profile of other protease inhibitors without incurring the extent of side-effects associated with full-dose ritonavir. Combination therapy with protease inhibitors and thymidine analog NRTIs, a highly effective antiretroviral combination, unfortunately is associated with metabolic disturbances and peripheral lipoatropy, which appear to be less common when protease inhibitors are combined with abacavir or tenofovir. [18] The latter agents are more expensive than older NRTIs.

Enfuvirtide - the first agent in a fourth class of agents, fusion inhibitors, is a 36 amino acid peptide which inhibits the function of gp41, potently inhibiting the HIV-cellular membrane fusion sequence. [19] Enfuvirtide is primarily used in wealthy countries as a salvage therapy, due to its great expense and the requirement that it be given by injection.

The arrival of HAART has led to one of the most spectacular reversals in modern medicine, converting what is otherwise an inexorably progressive, fatal disease into a chronic disease with a fairly good prognosis for those who receive HAART and benefit from it. Use of HAART results in a much reduced risk of mortality, [20] reduced opportunistic infection risk, [21] and improved quality of life, [22] often with recovery to near-normal health. Epidemiologically, widespread use of HAART tends to result in increased prevalence of HIV/AIDS, because survival improves to a greater extent than decline in transmission of HIV infection.

Ocular complications of AIDS and their association with a patient's current immune status, as given by the CD4 + T cell count, are summarized in [Table 2]. The risk of developing CMV retinitis has declined substantially among patients receiving HAART. [23] Among patients already afflicted by CMV retinitis, use of HAART is associated with an 81% lower risk of mortality, [24] a 46% lower risk of developing retinitis in previously unaffected second eyes, [25] a 60% reduction in the risk of retinal detachment [26] and an approximate 75% reduction in the risk of loss of visual acuity. [27] Most patients who develop immune reconstitution characterized by a rise in the CD4+ T cell count to a level greater than 100 to 150 cells/L for four to six months can safely stop anti-CMV therapy, [28] with only rare exceptions. [29] Some patients also develop immune recovery uveitis (the first immune recovery inflammatory syndrome described) in which recovery of anti-CMV immunity leads to intraocular inflammation - often a vitritis - sometimes causing vision loss. [30]

Because the overall effects of immune recovery are overwhelmingly beneficial, use of HAART is the single most important intervention for patients with ocular complications of AIDS. In fact, even if substantial immune recovery never occurs, outcomes of CMV retinitis are substantially improved in patients receiving HAART with respect to those who never take HAART. [24],[25],[26],[27] However, specific ocular therapy also is critical, in order to avoid blindness in the early months before immune recovery is complete, or if antiretroviral treatment fails to restore immunity.

Unfortunately, most persons with HIV/AIDS worldwide have limited access to HAART, as a result of both economic and health infrastructure limitations. In recent years, international efforts and cost reductions, largely because of generic drugs available from Indian pharmaceutical firms, have begun improving access to HAART. Still, only 1–1.5% of patients in India receive HAART presently, and the present goal is to expand to 6–7%. [31] While it is encouraging to observe increasing use of combination antitretroviral therapy worldwide, it likely will be many years until treatment is available to the majority.

In the pre-HAART era, CMV retinitis was more than 20–fold more common than any other vision-threatening ocular complication of AIDS in the United States [32] and affected approximately 30% of all patients with AIDS at some point in their lifetime. [33] Case series from India and most parts of the world [32],[33],[34],[35],[36],[37],[38],[39],[40],[41],[42] suggest that CMV retinitis is the preeminent ocular complication of AIDS everywhere, except possibly in sub-Saharan Africa, where patients until recently have died at a stage of AIDS earlier than when CMV retinitis would be expected to occur, [43] a situation which is likely to change with improved AIDS care and infrastructure. Even if the risk of CMV retinitis is one-fourth as common worldwide as it used to be in the United States, millions of persons would be affected.

Treatment of ocular complications of AIDS is a complex topic, which I have addressed in more detail elsewhere. [44] In general, because most ocular opportunistic pathogens cannot be eradicated, their management, including the management of CMV retinitis, requires lifelong suppressive therapy except in those fortunate few in whom HAART induces sufficient recovery of endogenous immunity to control the pathogen. Management of CMV retinitis, the most common pathogen, is particularly difficult. Even with ongoing suppressive systemic anti-CMV therapy, recurrences of active retinitis occur approximately every three months, [44] due to limitations in drug delivery after restoration of the blood-retinal barrier with healing of retinitis [45] and/or the development of drug resistance, which occurs in about 27.5% by nine months. [46] The alternative of local therapy is effective, but also has its problems, with increased risk of second eye retinitis, [47] systemic CMV disease [47] and possibly mortality [24],[47],[48],[49],[50] hence the overarching need in these patients to control the underlying HIV disease and restore endogenous immunity.

In countries with substantial treatment resources, valganciclovir [51] is the most popular treatment for CMV retinitis, using a dose of 900 mg twice daily for initial control of active retinitis ("induction"), followed by 900 mg daily as suppressive ("maintenance") therapy. Valganciclovir is the only oral treatment for CMV with high bioavailability, avoiding the need for a long-term central venous catheter, with its attendant high risk of life-threatening catheter complications [52] and quality of life problems. Valganciclovir, the valine ester of ganciclovir, achieves blood ganciclovir levels similar to those with intravenous ganciclovir [53],[54],[55] and therefore can serve as a replacement for intravenous ganciclovir in most situations. Oral ganciclovir is inferior to valganciclovir because of poor oral bioavailability, and is no longer marketed in the west. Intravenous foscarnet [55],[56] is an alternative therapy for CMV disease, but requires several hours per day to administer, has significant side-effects, and is comparably expensive, making it a second-line therapy. Intravenous cidofovir is similarly effective, [57],[58] has become unpopular due to a high risk of substantial renal injury and uveitis/hypotony. [59] Local therapy with ganciclovir implants is the most effective anti-CMV treatment option in terms of time-to-retinitis relapse, and is still used in wealthy countries for immediately vision-threatening disease, [47],[49],[60],[61] generally in combination with valganciclovir to prevent systemic complications (see above). However, because of the need to treat with valganciclovir anyway, most use valganciclovir monotherapy to treat lesions that are not immediately vision-threatening, particularly if there is hope for immune recovery. Intravitreal injections of fomivirsen [62],[63] are no longer marketed because demand for the product was poor.

As the cost of all of these regimens is exceptionally high, on an order substantially higher than first-line HAART, none of them are commonly used except in wealthy countries. The most common approach to treating CMV retinitis in a large part of the world is to use intravitreal injections of ganciclovir (2.0 to −5.0 mg/0.1 cc twice weekly for three weeks, then weekly) or occasionally foscarnet (2.4 mg/0.1 cc twice weekly for three weeks, then weekly). This approach, although it has not been subjected to randomized trials, seems effective based on case series [64],[65],[66],[67] and clinical experience, but may be associated with a higher risk of second eye and systemic disease sequelae of CMV disease than a systemic treatment would be. Valganciclovir, which will not be available in generic form until 2014, may represent an improvement, particularly vis--vis systemic and second eye disease outcomes, but its cost-effectiveness as a generic drug vis--vis intravitreal injections remains to be seen.

With the anticipated widespread uptake of co-trimoxazole prophylaxis and absent full-scale implementation of HAART in most parts of the world, the number of cases of CMV retinitis, which may be already in the millions, is likely to nearly double. This substantial and increasing burden of disease calls for a more effective yet practical management strategy for CMV retinitis that can be implemented in resource-constrained settings. Ophthalmologists worldwide should be familiar with the diagnosis and management of CMV retinitis, and should establish partnerships with infectious diseases' physicians able to provide appropriate treatment for patients with ocular complications of HIV/AIDS, because antiretroviral therapy is ultimately the most effective long-term treatment for CMV retinitis and for other ocular complications of AIDS. Research is needed to determine the optimal way of managing CMV retinitis in resource-constrained settings, particularly in the window before HAART-induced immune recovery occurs, during which the risk of vision loss and other complications is substantial.

 
  References Top

1.
Centers for Disease Control. Pneumocystis pneumonia-Los Angeles. MMWR Morb Mortal Wkly Rep 1981;30:250-2.  Back to cited text no. 1
    
2.
Cohen J. HIV-AIDS. India slashes estimate of HIV-infected people. Science 2007;317:179-81.  Back to cited text no. 2
    
3.
UNAIDS Annual Report 2007: Know Your Epidemic. UNAIDS, Geneva, Switzerland. Available at: http://data.unaids.org/pub/Report/2008/jc1535_annual_report07_en.pdf (accessed July 17, 2008).  Back to cited text no. 3
    
4.
United Nations Development Programme. Human Development Report 2005. 2005.  Back to cited text no. 4
    
5.
Fischl MA, Dickinson GM, La Voie L. Safety and efficacy of sulfamethoxazole and trimethoprim chemoprophylaxis for Pneumocystis carinii pneumonia in AIDS. JAMA 1988;259:1185-9.  Back to cited text no. 5
[PUBMED]    
6.
Pierce M, Crampton S, Henry D, Heifets L, LaMarca A, Montecalvo M, et al . A randomized trial of clarithromycin as prophylaxis against disseminated Mycobacterium avium complex infection in patients with advanced acquired immunodeficiency syndrome. N Engl J Med 1996;335:384-91.  Back to cited text no. 6
[PUBMED]  [FULLTEXT]  
7.
Kitahata MM, Koepsell TD, Deyo RA, Maxwell CL, Dodge WT, Wagner EH. Physicians' experience with the acquired immunodeficiency syndrome as a factor in patients' survival. N Engl J Med 1996;334:701-6.  Back to cited text no. 7
[PUBMED]  [FULLTEXT]  
8.
Hoover DR, 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. 8
[PUBMED]  [FULLTEXT]  
9.
World Health Organization. Guidelines on co-trimoxazole prophylaxis for HIV-related infections among children, adolescents and adults. Recommendations for a public health approach. 2006. p. 1-66.  Back to cited text no. 9
    
10.
Bartlett JG, Gallant JE. Medical management of HIV infection. 2000.  Back to cited text no. 10
    
11.
Lukashov VV, Goudsmit J. HIV heterogeneity and disease progression in AIDS: A model of continuous virus adaptation. AIDS 1998;12:S43-52.  Back to cited text no. 11
    
12.
Coffin JM. HIV population dynamics in vivo : Implications for genetic variation, pathogenesis and therapy. Science 1995;267:483-9.  Back to cited text no. 12
[PUBMED]  [FULLTEXT]  
13.
Parienti JJ, Massari V, Descamps D, Vabret A, Bouvet E, Larouze B, et al . Predictors of virologic failure and resistance in HIV-infected patients treated with nevirapine- or efavirenz-based antiretroviral therapy. Clin Infect Dis 2004;38:1311-6.  Back to cited text no. 13
    
14.
Ickovics JR, Cameron A, Zackin R, Bassett R, Chesney M, Johnson VA, et al . Consequences and determinants of adherence to antiretroviral medication: Results from Adult AIDS Clinical Trials Group protocol 370. Antivir Ther 2002;7:185-93.  Back to cited text no. 14
[PUBMED]    
15.
Fischl MA, Richman DD, Grieco MH, Gottlieb MS, Volberding PA, Laskin OL, et al . The efficacy of azidothymidine (AZT) in the treatment of patients with AIDS and AIDS-related complex: A double-blind, placebo-controlled trial. N Engl J Med 1987;317:185-91.  Back to cited text no. 15
    
16.
Deeks SG, Smith M, Holodniy M, Kahn JO. HIV-1 protease inhibitors: A review for clinicians. JAMA 1997;277:145-53.  Back to cited text no. 16
[PUBMED]    
17.
Flexner C. HIV-protease inhibitors. N Engl J Med 1998;338:1281-92.  Back to cited text no. 17
[PUBMED]  [FULLTEXT]  
18.
Moyle GJ, Sabin CA, Cartledge J, Johnson M, Wilkins E, Churchill D, et al . A randomized comparative trial of tenofovir DF or abacavir as replacement for a thymidine analogue in persons with lipoatrophy. AIDS 2006;20:2043-50.  Back to cited text no. 18
[PUBMED]  [FULLTEXT]  
19.
Jamjian MC, McNicholl IR. Enfuvirtide: First fusion inhibitor for treatment of HIV infection. Am J Health Syst Pharm 2004;61:1242-7.  Back to cited text no. 19
[PUBMED]  [FULLTEXT]  
20.
Krentz HB, Kliewer G, Gill MJ. Changing mortality rates and causes of death for HIV-infected individuals living in Southern Alberta, Canada from 1984 to 2003. HIV Med 2005;6:99-106.  Back to cited text no. 20
[PUBMED]  [FULLTEXT]  
21.
Palella FJ Jr, Delaney KM, Moorman AC, Loveless MO, Fuhrer J, Satten GA, et al . Declining morbidity and mortality among patients with advanced human immunodeficiency virus infection. N Engl J Med 1998;338:853-60.  Back to cited text no. 21
[PUBMED]  [FULLTEXT]  
22.
Nieuwkerk PT, Reijers MH, Weigel HM, Lange JM, Sprangers MA. Quality of life in maintenance vs prolonged induction therapy for HIV. JAMA 2000;284:178-9.  Back to cited text no. 22
[PUBMED]  [FULLTEXT]  
23.
Jabs DA, Bartlett JG. AIDS and ophthalmology: A period of transition. Am J Ophthalmol 1997;124:227-33.  Back to cited text no. 23
[PUBMED]    
24.
Kempen JH, Jabs DA, Wilson LA, Dunn JP, West SK, Tonascia J. Mortality risk for patients with cytomegalovirus retinitis and acquired immune deficiency syndrome. Clin Infect Dis 2003;37:1365-73.  Back to cited text no. 24
[PUBMED]  [FULLTEXT]  
25.
Kempen JH, Jabs DA, Wilson LA, Dunn JP, West SK. Incidence of cytomegalovirus (CMV) retinitis in second eyes of patients with the acquired immune deficiency syndrome and unilateral CMV retinitis. Am J Ophthalmol 2005;139:1028-34.  Back to cited text no. 25
[PUBMED]  [FULLTEXT]  
26.
Kempen JH, Jabs DA, Dunn JP, West SK, Tonascia J. Retinal detachment risk in cytomegalovirus retinitis related to the acquired immunodeficiency syndrome. Arch Ophthalmol 2001;119:33-40.  Back to cited text no. 26
[PUBMED]    
27.
Kempen JH, Jabs DA, Wilson LA, Dunn JP, West SK, Tonascia JA. Risk of vision loss in patients with cytomegalovirus retinitis and the acquired immunodeficiency syndrome. Arch Ophthalmol 2003;121:466-76.  Back to cited text no. 27
[PUBMED]    
28.
Masur H, Kaplan JE, Holmes KK. Guidelines for preventing opportunistic infections among HIV-infected persons-2002. Recommendations of the U.S. Public Health Service and the Infectious Diseases Society of America. Ann Intern Med 2002;137:435-78.  Back to cited text no. 28
    
29.
Jabs DA, Van Natta ML, Kempen JH, Reed Pavan P, Lim JI, Murphy RL, et al . Characteristics of patients with cytomegalovirus retinitis in the era of highly active antiretroviral therapy. Am J Ophthalmol 2002;133:48-61.  Back to cited text no. 29
[PUBMED]  [FULLTEXT]  
30.
Kempen JH, Min YI, Freeman WR, Holland GN, Friedberg DN, Dieterich DT, et al . Risk of immune recovery uveitis in patients with AIDS and cytomegalovirus retinitis. Ophthalmology 2006;113:684-94.  Back to cited text no. 30
[PUBMED]  [FULLTEXT]  
31.
Steinbrook R. HIV in India-the challenges ahead. N Engl J Med 2007;356:1197-201.  Back to cited text no. 31
[PUBMED]  [FULLTEXT]  
32.
Jabs DA. Ocular manifestations of HIV infection. Trans Am Ophthalmol Soc 1995;93:623-83.  Back to cited text no. 32
[PUBMED]  [FULLTEXT]  
33.
Hoover DR, Peng Y, Saah A, Semba R, Detels RR, Rinaldo CR Jr, et al . Occurrence of cytomegalovirus retinitis after human immunodeficiency virus immunosuppression. Arch Ophthalmol 1996;114:821-7.  Back to cited text no. 33
[PUBMED]    
34.
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. 34
[PUBMED]  Medknow Journal  
35.
Biswas J, Madhavan HN, George AE, Kumarasamy N, Solomon S. Ocular lesions associated with HIV 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. 35
[PUBMED]  [FULLTEXT]  
36.
Jabs DA. Ocular manifestations of AIDS. 1998. p. 123-36.  Back to cited text no. 36
    
37.
Lim SA, Heng WJ, Lim TH, Leo YS, Wong SY. Ophthalmic manifestations in human immunodeficiency virus infection in Singapore. Ann Acad Med Singapore 1997;26:575-80.  Back to cited text no. 37
[PUBMED]    
38.
Mesaric B, Begovac J, Ugrinovic N, Babic K, Lisic M. Cytomegalovirus retinitis in patients with human immunodeficiency virus infection. Lijec Vjesn 1998;120:106-10.  Back to cited text no. 38
    
39.
Muccioli C, Belfort R Jr, Lottenberg C, Lima J, Santos P, Kim M, et al . Ophthalmological manifestations in AIDS: Evaluation of 445 patients in one year. Rev Assoc Med Bras 1994;40:155-8.  Back to cited text no. 39
    
40.
Nagata Y, Fujino Y, Matsumoto S, Nishi M, Ono A, Mochizuki M, et al . Ocular manifestations in Japanese patients with human immunodeficiency virus infection. Jpn J Ophthalmol 1993;37:275-81.  Back to cited text no. 40
[PUBMED]    
41.
Tanterdtam J, Suwannagool S, Namatra C, Singalavanija A. A study of ocular manifestations in HIV patients. Thai J Ophthalmol 2002;10:11-20.  Back to cited text no. 41
    
42.
Wong KH, Lee SS, Lo YC, Li PC, Ho HF, Sitt WH, et al . Profile of opportunistic infections among HIV-1 infected people in Hong Kong. Zhonghua Yi Xue Za Zhi (Taipei) 1995;55:127-36.  Back to cited text no. 42
[PUBMED]    
43.
Kestelyn P. The epidemiology of CMV retinitis in Africa. Ocul Immunol Inflamm 1999;7:173-7.  Back to cited text no. 43
[PUBMED]    
44.
Kempen JH, Jabs DA. Ocular complications of HIV infection, 2 nd ed. 2003. p. 318-40.  Back to cited text no. 44
    
45.
Arevalo JF, Gonzalez C, Capparelli EV, Kirsch LS, Garcia RF, Quiceno JI, et al . Intravitreous and plasma concentrations of ganciclovir and foscarnet after intravenous therapy in patients with AIDS and cytomegalovirus retinitis. J Infect Dis 1995;172:951-6.  Back to cited text no. 45
[PUBMED]    
46.
Jabs DA, Enger C, Dunn JP, Forman M; CMV Retinitis and Viral Resistance Study Group. Cytomegalovirus retinitis and viral resistance: Ganciclovir resistance. J Infect Dis 1998;177:770-3.  Back to cited text no. 46
    
47.
Musch DC, Martin DF, Gordon JF, Davis MD, Kuppermann BD. Treatment of cytomegalovirus retinitis with a sustained-release ganciclovir implant: The Ganciclovir Implant Study Group. N Engl J Med 1997;337:83-90.  Back to cited text no. 47
[PUBMED]  [FULLTEXT]  
48.
Binquet C, Saillour F, Bernard N, Rougier MB, Leger F, Bonnal F, et al . Prognostic factors of survival of HIV-infected patients with cytomegalovirus disease: Aquitaine Cohort, 1986-1997. Eur J Epidemiol 2000;16:425-32.  Back to cited text no. 48
[PUBMED]  [FULLTEXT]  
49.
Martin DF, Kuppermann BD, Wolitz RA, Palestine AG, Li H, Robinson CA, et al . Oral ganciclovir for patients with cytomegalovirus retinitis treated with a ganciclovir implant. N Engl J Med 1999;340:1063-70.  Back to cited text no. 49
    
50.
Skiest DJ, Chiller T, Chiller K, Park A, Keiser P. Protease inhibitor therapy is associated with markedly prolonged time to relapse and improved survival in AIDS patients with cytomegalovirus retinitis. Int J STD AIDS 2001;12:659-64.  Back to cited text no. 50
[PUBMED]  [FULLTEXT]  
51.
Martin DF, Sierra-Madero J, Walmsley S, Wolitz RA, Macey K, Georgiou P, et al . A controlled trial of valganciclovir as induction therapy for cytomegalovirus retinitis. N Engl J Med 2002;346:1119-26.  Back to cited text no. 51
[PUBMED]  [FULLTEXT]  
52.
Thorne JE, Jabs DA, Vitale S, Miller T, Dunn JP, Semba RD. Catheter complications in AIDS patients treated for cytomegalovirus retinitis. AIDS 1998;12:2321-7.  Back to cited text no. 52
[PUBMED]  [FULLTEXT]  
53.
Collaborative DHPG Treatment Study Group. Treatment of serious cytomegalovirus infections with 9-(1,3-dihydroxy-2-propoxymethyl)guanine in patients with AIDS and other immunodeficiencies. N Engl J Med 1986;314:801-5.  Back to cited text no. 53
[PUBMED]    
54.
Spector SA, Weingeist T, Pollard RB, Dieterich DT, Samo T, Benson CA, et al . A randomized, controlled study of intravenous ganciclovir therapy for cytomegalovirus peripheral retinitis in patients with AIDS. J Infect Dis 1993;168:557-63.  Back to cited text no. 54
[PUBMED]    
55.
Studies of Ocular Complications of AIDS Research Group in collaboration with the AIDS Clinical Trials Group. Foscarnet-Ganciclovir Cytomegalovirus Retinitis Trial 4: Visual outcomes. Ophthalmology 1994;101:1250-61.  Back to cited text no. 55
[PUBMED]    
56.
Palestine AG, Polis MA, De S, Baird BF, Falloon J, Kovacs JA, et al . A randomized, controlled trial of foscarnet in the treatment of cytomegalovirus retinitis in patients with AIDS. Ann Intern Med 1991;115:665-73.  Back to cited text no. 56
    
57.
Lalezari JP, Stagg RJ, Kuppermann BD, Holland GN, Kramer F, Ives DV, et al . Intravenous cidofovir for peripheral cytomegalovirus retinitis in patients with AIDS: A randomized, controlled trial. Ann Intern Med 1997;126:257-63.  Back to cited text no. 57
[PUBMED]  [FULLTEXT]  
58.
Studies of Ocular Complications of AIDS Research Group in collaboration with the AIDS Clinical Trials Group. Parenteral cidofovir for cytomegalovirus retinitis in patients with AIDS: The HPMPC peripheral cytomegalovirus retinitis trial: A randomized, controlled trial. Ann Intern Med 1997;126:264-74.  Back to cited text no. 58
[PUBMED]  [FULLTEXT]  
59.
Studies of Ocular Complications of AIDS Research Group in collaboration with the AIDS Clinical Trials Group. Long-term follow-up of patients with AIDS treated with parenteral cidofovir for cytomegalovirus retinitis: The HPMPC Peripheral Cytomegalovirus Retinitis Trial. AIDS 2000;14:1571-81.  Back to cited text no. 59
[PUBMED]  [FULLTEXT]  
60.
Martin DF, Parks DJ, Mellow SD, Ferris FL, Walton RC, Remaley NA, et al . Treatment of cytomegalovirus retinitis with an intraocular sustained-release ganciclovir implant: A randomized controlled clinical trial. Arch Ophthalmol 1994;112:1531-9.  Back to cited text no. 60
[PUBMED]    
61.
Martin DF, Dunn JP, Davis JL, Duker JS, Engstrom RE Jr, Friedberg DN, et al . Use of the ganciclovir implant for the treatment of cytomegalovirus retinitis in the era of potent antiretroviral therapy: Recommendations of the International AIDS Society-USA panel. Am J Ophthalmol 1999;127:329-39.  Back to cited text no. 61
[PUBMED]  [FULLTEXT]  
62.
Vitravene Study Group. A randomized controlled clinical trial of intravitreous fomivirsen for treatment of newly diagnosed peripheral cytomegalovirus retinitis in patients with AIDS. Am J Ophthalmol 2002;133:467-74.  Back to cited text no. 62
[PUBMED]  [FULLTEXT]  
63.
Vitravene Study Group. Randomized dose-comparison studies of intravitreous fomivirsen for treatment of cytomegalovirus retinitis that has reactivated or is persistently active despite other therapies in patients with AIDS. Am J Ophthalmol 2002;133:475-83.  Back to cited text no. 63
[PUBMED]  [FULLTEXT]  
64.
Baudouin C, Chassain C, Caujolle C, Gastaud P. Treatment of cytomegalovirus retinitis in AIDS patients using intravitreal injections of highly concentrated ganciclovir. Ophthalmologica 1996;210:329-35.  Back to cited text no. 64
[PUBMED]    
65.
Cochereau-Massin I, LeHoang P, Lautier-Frau M, Zazoun L, Marcel P, Robinet M, et al . Efficacy and tolerance of intravitreal ganciclovir in cytomegalovirus retinitis in acquired immune deficiency syndrome. Ophthalmology 1991;98:1348-53.  Back to cited text no. 65
[PUBMED]    
66.
Young S, Morlet N, Besen G, Wiley CA, Jones P, Gold J, et al . High-dose (2000-microgram) intravitreous ganciclovir in the treatment of cytomegalovirus retinitis. Ophthalmology 1998;105:1404-10.  Back to cited text no. 66
[PUBMED]    
67.
Diaz-Llopis M, Espana E, Munoz G, Navea A, Chipont E, Cano J, et al . High dose intravitreal foscarnet in the treatment of cytomegalovirus retinitis in AIDS. Br J Ophthalmol 1994;78:120-4.  Back to cited text no. 67
    


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