HIV

Abstract

Getting to zero: zero new HIV infections, zero deaths from AIDS-related illness, zero discrimination is the theme of World AIDS Day 2012. Given the spread of the epidemic today, getting to zero may sound difficult, but significant progress is underway. The total annual loss for the entire country due to HIV is 7% of GDP, which exceeds India’s annual health expenditure in 2004. The additional loss due to loss of labor income and increased medical expenditure as measured by the external transfers, account for 5% of the country’s health expenditure and 0.23% of GDP. Given that the HIV incidence rate is only 0.27% in India, these losses are quite staggering. Despite the remarkable achievements in development of anti-retroviral therapies against HIV and the recent advances in new prevention technologies, the rate of new HIV infections continue to outpace efforts on HIV prevention and control. Thus, the development of a safe and effective vaccine for prevention and control of AIDS remains a global public health priority and the greatest opportunity to eventually end the AIDS pandemic.

Keywords: :

• immunity
• HIV
• research
• vaccine
• virus

Introduction

The Human Immunodeficiency Virus (HIV) targets the immune system and weakens people's surveillance and defense systems against infections and cancers. As the virus destroys and impairs the function of immune cells, infected individuals gradually become immune-deficient. Immune function is typically measured by CD4 cell count. It is possible to be co-infected by more than one strain of HIV—a condition known as HIV superinfection. The most advanced stage of HIV infection is AIDS, which can take ~2–15 y to develop depending on the individual. Since the identification of HIV as the cause of AIDS in the early 1980s, the march of HIV has been unparalleled and it continues to plague mankind. AIDS was first recognized in the United States in 1981 in homosexual men in Los Angeles and New York.¹ HIV is transmitted by three main routes: sexual contact, exposure to infected body fluids or tissues, and from mother to child during pregnancy or delivery or breastfeeding (vertical transmission). There is no risk of acquiring HIV if exposed to feces, nasal secretions, saliva, sputum, sweat, tears, urine, or vomit unless these are contaminated with blood.² According to the NACO report, the main route of transmission is through heterosexual contact (87%). Parent-to-child transmission is next most frequent (5%), while the other routes (injected drugs, homosexual, blood and blood products) constitute the rest of the cases. According to studies, the average per-act risk of getting HIV by exposure to an infected source varies from blood transfusion (90%)³ to penile–vaginal intercourse (0.01–0.4%).⁴ Promising development has been seen in recent years in global efforts to address the AIDS epidemic, including increased access to effective treatment and prevention programs, but HIV continues to be a major global public health issue due to its enormous death toll, thus assuming the dubious tag of a modern pandemic. In terms of morbidity and mortality, the HIV pandemic may be worse than the Black Death (plague) of the 14th century.

Global and Regional Overview

The HIV pandemic has attained enormous proportions, having claimed more than 25 million lives over the past three decades. According to the UNAIDS report 2011, ~34 million people globally are living with HIV, of which ~50% are women. There were ~2.5 million new infections in 2011 with mortality of almost 1.7 million. The magnitude of the problem can be fathomed from the fact that for every person who gains access to anti-retroviral drugs, two people are newly infected with HIV. Sub-Saharan Africa remains the most affected region, with nearly 5% of adults living with HIV. The situation in India is far from rosy, having the third highest number of estimated people living with HIV, behind South Africa and Nigeria (UNAIDS Report on the Global AIDS epidemic 2010). But the silver lining is the situation has improved dramatically in recent years. Based on the HIV Estimation 2012, India has achieved an annual reduction of 57% in new HIV infections (among adults) from 2.74 to 1.16 per 100 000 in 2011, reflecting the impact of various interventions and scaled-up prevention strategies under the National AIDS Control Program. Adult HIV prevalence has decreased from 0.41% in 2001 to 0.27% in 2011. The estimated number of people living with HIV also has decreased from 24.1 in 2000 to 20.9 per 100 000 in 2011.⁵ The total annual loss for the entire country due to HIV is 7% of GDP, which exceeds India’s annual health expenditure in 2004. This huge magnitude of cost is not surprising given that it includes private valuation of one’s own life as well as loss from stigma. The additional loss of labor income and increased medical expenditure as measured by the external transfers account for 5% of the country’s health expenditure and 0.23% of GDP. Given that the HIV incidence rate is only 0.27% in India, these losses are quite staggering.⁶

Need for Vaccine

Despite the remarkable achievements in development of anti-retroviral therapies and recent advances in new prevention technologies, the rate of new HIV infections continues to outpace efforts on prevention and control. Thus, the development of a safe and effective vaccine for prevention and control of AIDS remains a global public health priority and the greatest opportunity to eventually end the AIDS pandemic.

There is a renaissance in HIV vaccine development due mainly to the first demonstration of vaccine-induced protection, albeit modest, in a human efficacy trial, a generation of improved vaccine candidates advancing in the clinical pipeline, and newly defined viral targets for broadly neutralizing antibodies.⁷ The search for an HIV vaccine was seen as the logical solution to the burgeoning epidemic soon after the discovery of HIV, but early enthusiasm became muted as the realities of the challenge became evident.^8-10

Nevertheless, there are scientific reasons why there is hope that an HIV vaccine will be developed. First, studies of non-human primates that were given candidate vaccines based on HIV or SIV (simian immunodeficiency virus) have shown either complete or partial protection against infection with wild-type virus.¹¹ Second, vaccines have been identified against other retroviruses.¹² Third, almost all humans develop some form of immune response to HIV infection, with some exposed people remaining uninfected or developing immune responses that are protective or that are able to control the viral infection over long periods of time.¹³ Scientists believe that an HIV vaccine candidate will provide robust protection against HIV infection only if it engages both arms of the adaptive immune system, i.e., cell-mediated and antibody-based. Although multiple vaccine approaches have been developed over the last three decades, including peptides, proteins, nucleic acid, viral vectors, and prime–boost combination regimens, only three vaccine approaches have completed human efficacy trials. The first was a recombinant protein (HIV gp120) adjuvant with alum, but this candidate failed to prevent or control HIV infection in men who have sex with other men and in injected-drug users.

The second, a recombinant adenovirus type-5 vaccine containing HIV gag, pol, and nef genes and aimed at stimulating cellular immunity to control infection, also failed to provide efficacy in preventing or controlling HIV in men who have sex with men. One concerning observation from this clinical trial was that more HIV infections occurred among vaccine recipients who were uncircumcised and had pre-existing immunity against the vaccine vector compared with placebo recipients with the same characteristics, for reasons that still are not completely understood. A prime-boost strategy (RV144), utilizing canarypox vector prime + monomeric gp120 boost, has had the only positive clinical efficacy data to date for prevention of infection, albeit with a modest 31% efficacy in heterosexuals at moderate risk for infection.⁷ The regimen was a heterologous prime-boost, i.e., 4 doses of one vaccine was boosted by 2 doses containing both vaccines. Although this result is not enough to qualify the vaccine for licensure, RV144 has provided very useful pointers for a way forward. Several trials are planned incorporating lessons learned from RV144. If sufficient efficacy can be shown for any of the vaccines in these trials, an HIV vaccine could become available by ~2020.¹⁴

Will an effective vaccine ever be developed? The answer to this million-dollar question is still ambiguous—depending on a complex interplay of research, economic constraints, political will, and above all the appropriate technology and breakthroughs in the study of HIV’s mysterious behavior. Every day >7000 people are infected with HIV and ~5000 die from AIDS. Simpler and more affordable treatment and prevention are urgently needed.¹⁵ The development of an affordable, appropriate, and effective HIV vaccine might be in reach within 7–10 y. Vaccines are the only beacon of hope for the control of HIV infection, as was the case with smallpox and polio, which have been fully or partially eliminated by global vaccination programs.

10.4161/hv.26243