HIV and the eye: a global perspective

Evolution of HIV treatment: a success story of modern medicine?

In the early 1980s, the world was confronted with the advent of HIV and AIDS. However, there is growing evidence that HIV and AIDS have been present in Central Africa for almost 100 years [1]. During the last 30 years, many millions have been infected with the virus (∼33 million in 2007) and still, millions die of the disease every year. In this issue of Expert Review of Ophthalmology, Alay Banker and colleagues give an excellent and concise overview of HIV and opportunistic eye diseases [2].

In the early years of the HIV epidemic, cytomegalovirus (CMV) retinitis was one of the most common and dreadful AIDS-related opportunistic ocular infections and developed in approximately 50% of AIDS patients in North America and Europe.

In the 1990s in the USA, where the AIDS disease complex was described for the first time, the number of people diagnosed with AIDS-defining opportunistic infections and AIDS-related malignancies started to decrease, thanks to the introduction of highly active antiretroviral therapy (HAART). This has revolutionized the treatment of HIV, increasing patient survival for many years and, potentially, even decades.

Advances have also been made in the treatment of opportunistic infections. Instead of frequent intravitreal injections or long-term systemic treatment, CMV retinitis can be treated today by intraocular sustained-release implants, which emit ganciclovir for up to 6 months. This treatment modality markedly improves quality of life and decreases ocular morbidity.

Today, in richer countries, the focus often lies on the side effects of treatment (e.g., immune recovery uveitis), resistances, maintenance or reintroduction of therapy. The fight against AIDS and HIV has been a great success story of modern medicine and biomedical research. However, as long as millions of HIV patients have only limited or even no access to modern treatment for HIV and its complications, there remains a bitter taste.

Sub-Saharan Africa sustains just 10% of the world’s population, but is home to almost 65% of all people living with HIV: 26–28 million. In 2007, an estimated 3.2 million people in the region became newly infected, while 2.4 million adults and children died of AIDS.

In contrast to Europe and North America, the vast majority of HIV in Africa is transmitted among heterosexuals, with women at higher risk of infection [3].

The incidence and prevalence of HIV-related ocular complications is different from that in the Western world. HIV patients in Africa, due to comorbidity and starvation, often die at CD4⁺ cell counts over 100 and, thus, develop CMV less frequently than in the Western world. However, in contrast to Sub-Saharan Africa, CMV retinitis is the most common ocular manifestation of AIDS in India [4].

High frequency of ocular surface squamous neoplasia in HIV patients seems to be unique to Africa

The severe effect of the HIV epidemic has changed the incidence and prevalence of certain ocular malignancies in many Sub-Saharan African countries in a manner that seems to be unique to the continent. A dramatic increase of ocular surface squamous neoplasia (OSSN) and other AIDS-related malignancies, such as non-Hodgkin’s lymphoma and Kaposi’s sarcoma, have been observed in Sub-Saharan African countries, with OSSN being the most common by far [5,6]. There are numerous reports suggesting a strong association of OSSN with HIV infection in Sub-Saharan Africa [7,8]. OSSN includes a spectrum of diseases, which range in severity from mild dysplasia to carcinoma in situ and, ultimately, to invasive carcinoma. In the northern hemisphere, OSSN usually occurs in patients older than 60 years, progresses slowly and, most often, has a favorable prognosis. Traditionally, risk factors for this disease have included UV light exposure, petroleum products, heavy smoking and, more recently, human papillomavirus infection [10]. In Sub-Saharan Africa, by contrast, the majority of patients with OSSN seem to be younger (aged 20–50 years), the disease seems to be more aggressive and HIV has been identified as the major risk factor. Often, OSSN may be the only clinically evident sign of HIV infection [10].

The exact etiological role of HIV in OSSN remains unclear. Important cofactors in HIV-associated OSSN may be UV light-induced DNA damage and human papillomavirus infection. Sunlight-related mutations of p53, a protein that has a crucial role in tumor suppression and cell cycle control, have been identified with high frequency in HIV-positive patients with OSSN [11].

Although it has been stated that the prevalence of OSSN does not rank very high in the overall clinical presentation of HIV, it seems to be one of the most (or maybe even the most) frequently seen ocular complications of HIV in Sub-Saharan Africa, where lymphomas and Kaposi’s sarcoma are encountered less frequently than in Europe or North America [8]. The treatment of HIV-associated OSSN in Africa is often limited to surgical excision, as most healthcare facilities in Africa do not have access to adjunctive therapy, such as topical mitomycin C or IFN-α. However, current clinical practice in the treatment of squamous cell carcinoma of the conjunctiva associated with HIV/AIDS rests on rather weak evidence [12].

Antiretroviral therapy may have a beneficial role as an adjunctive therapy in the treatment of patients with HIV-associated OSSN, as more and more patients in Sub-Saharan Africa get access to free or low-cost antiretroviral therapy. However, so far, there is still only one case report supporting this hypothesis [13]. Moreover, another obstacle for the use of HAART as an adjunctive therapy for OSSN might be that, currently, a positive HIV test and a conjunctival neoplasia as the only clinically detectable abnormality does not qualify patients for free antiretroviral treatment in many African countries.

Although CMV retinitis seems to be rarer in Africa [14] and other regions of the so-called developing world, the prevalence of CMV retinitis seems to have increased as patients survive longer, thanks to the treatment of other opportunistic infections. However, this impression may also be due to the fact that poorer countries are often under-researched with respect to the prevalence of retinal diseases. CMV retinitis is often a major threat to vision and the quality of life of patients with HIV in poorer countries. Patients often present late and most healthcare facilities lack adequate medication for the treatment of CMV retinitis. One example is Malawi, where only frequent intravitreal ganciclovir injections or intravenous ganciclovir treatment are currently available. This makes successful treatment of CMV retinitis often very difficult because patients must frequently travel long distances to reach an eye care facility and, therefore, cannot return for follow-up visits.

During the last few years, the benefits of HAART have also been made available to many African patients, improving the survival of HIV patients on the continent tremendously. However, there remains much to be done, including optimizing the treatment of ocular complications of HIV in poorer countries. The global fight against HIV can only be won if this plague of the 21st century suffers more defeats in its alleged home – Africa.

Financial & competing interests disclosure

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

No writing assistance was utilized in the production of this manuscript.