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Few HIV-Positive People Can Control Disease Progression Without Antiretrovirals

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Published: Mar 5, 2012 2:59 pm
Few HIV-Positive People Can Control Disease Progression Without Antiretrovirals

Results from a United Kingdom-based study suggest that fewer than one in 1,000 HIV-positive individuals can control HIV/AIDS disease progression naturally without antiretroviral therapy.

The authors of the study, however, cautioned that this number could be an underestimation. They noted that some natural HIV controllers, people who can control HIV without antiretrovirals, may not have gotten themselves checked for HIV due to the absence of symptoms.

Results also showed that among slow HIV progressors, people whose HIV progresses to AIDS but more slowly than usual, those with lower amounts of HIV in the blood were more likely to show minimal immune system loss over time. In addition, in most cases, controllers and non-progressors did eventually progress to AIDS.

“Studying these patients could form the basis for the design of novel strategies to prevent immune deterioration in HIV-infected individuals,” said Dr. Nesrina Imami, a medical statistician in Immunology at Imperial College, London and senior author of the study, in correspondence with The AIDS Beacon. She added that understanding how the immune systems in these individuals control HIV could lead to therapeutic options that target the virus.

“Regrettably our findings indicate that [such individuals] are in limited numbers, and that even controllers and non-progressors eventually do progress,” said Dr. Imami.

She noted that the findings from this study also emphasized the need to initiate antiretroviral treatment well before deterioration of the immune system, even in individuals who control viral replication, have stable CD4 (white blood cell) counts, and show no signs of progression.

Previous studies have shown that once people are infected with HIV, the rate of disease progression varies considerably from person to person. There are some individuals who can maintain stable CD4 counts and stay asymptomatic for several years after HIV infection, without the use of antiretroviral medications (see related AIDS Beacon news). Such individuals are referred to as long-term non-progressors (LTNP).

Some LTNP also naturally show undetectable levels of HIV in their blood; they are called HIV controllers.

In the current study, researchers from the United Kingdom aimed to estimate the number of LTNP and HIV controllers by analyzing data from a database of people with HIV who had visited HIV clinics in Chelsea and Westminster between 1988 and 2010. The authors also investigated the time at which LTNP and HIV controllers eventually progressed. In addition, they compared the characteristics of infection and the immune system in these groups of individuals with those of the general HIV-infected population.

Results showed that of the 14,227 HIV-positive people in the database, about 2 percent had had HIV for more than seven years, had never taken antiretroviral drugs, and had never had an opportunistic infection (infections that do not usually occur in people with a healthy immune system). Among these individuals, 17 percent showed stable (non-declining) CD4 counts from the time of diagnosis to the end of the study.

If a participant’s CD4 count had never dipped below the normal range (450 to 1,650 cells per microliter of blood), even temporarily, the researchers classified such individuals as LTNP. In total, 0.09 percent of the individuals in the study were classified as LTNP.

Among these individuals, 0.007 percent also showed undetectable levels of virus in the blood and were classified as HIV controllers.

If a participant’s stable CD4 count had dipped below the normal range at least once, the researchers classified such individuals as having ‘long-term stable low CD4 counts’. In all, 0.3 percent of individuals in the study fell into this category; 0.02 percent of study participants also had undetectably low viral levels in the blood.

According to the study authors, their results confirm the notion that LTNP and HIV controllers are relatively rare among the HIV-positive population.

The authors also compared disease parameters among people who had had HIV for at least seven years but were asymptomatic without antiretroviral therapy. They found that individuals who showed a declining CD4 count over time had a three-fold higher median peak viral load (amount of HIV in the blood) than those with stable CD4 counts.

Among those with stable CD4 counts, there were fewer Caucasians in the group whose counts remained in the normal range (58 percent) than in the group whose counts had dipped below the normal range at least once (69 percent).

Those whose CD4 counts remained in the normal range had an estimated 9.1 years before experiencing clinical disease progression, as compared to 7.3 years in those whose counts had dipped below the normal range at least once.

The authors found no significant differences between LTNP and the ‘long-term stable low CD4 count’ group in gender, ethnicity, or age. However, duration since HIV diagnosis, lowest CD4 count recorded since diagnosis (nadir CD4 count), and recent CD8 counts (a type of immune cell) were higher in LTNP.

For more information, please refer to the study in PLoS One.

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  • Loreen Willenberg said:

    Have Mandalia et al contributed to the vast body of knowledge of LTNPs/HIV Controllers, or have they merely found that LTNPs/HCs within their cohort “inevitably progressed” to AIDS? Indeed, in this paper, the investigators admit that “due to the small numbers of individuals in the LTNP and long-term stable CD4+ T cell count groups, power to detect a statistical significance (of biological markers of progression) was low.” (Mandalia, p.7). They also state, “Furthermore, the infecting clade of HIV-1 and the geographic origin of infection are likely to impact the course of HIV-1 disease progression…Of the 13 patients identified as LTNPs, clade information was available for 5. Of these, 3 were infected with clade B, and 2 with clade C virus, while the infecting viral clade for the remaining 8 LTNP has not yet been tested.” (Mandalia, p. 7). The test results for all LTNP subjects would have been of interest in this case. In the many years I have been following (and participating in)LTNP/HC clinical studies, this is the first time an investigating team has, to my knowledge, managed to utilize the rarity of LTNPs/HCs within a small class of study subjects to serve as evidence that “ultimate progression” to AIDS is inevitable in the entire general population of LTNPs and HIV Controllers.