The molecular epidemiology of HIV in the Philippines has changed from subtype B, with the more aggressive CRF01_AE now being the predominant subtype. This is according to a study that was “done to better characterize the Philippines’ HIV epidemic,” shared to Outrage Magazine by Edsel Maurice Salvaña, MD, FIDSA, one of the people behind the study. “Since 2006, the number of new HIV cases has been growing exponentially, and so we wanted to know if there was any change in the character of the virus that could help explain the surge.”
Doing the study with Salvaña were Brian Schwem, PhD; Jill Itable, MD; Patrick Ching, MD; Sharie Ganchua; Marissa Alejandria, MD; Jodor Lim, MD; and Raul Destura, MD.
For Salvaña, their findings should be a cause of concern.
“It shows that the strain of HIV in the Philippines has changed to a potentially more aggressive (faster time to AIDS) and more transmissible variant,” Salvaña said. “It also means that it is more likely a local epidemic due to the predominance of one genotype because multiple genotypes would be more likely if most of the HIV cases were imported from different parts of the world.”
INCREASING RATES
For Salvaña, the “finding of the study at least partially explain the unprecedented increase in the number of cases.”
In April of this year alone, over 500 (to be exact: 560) new HIV cases were reported in the country, according to the Department of Health (DOH). The 560 new cases are 42% higher than the 393 cases reported in April 2014. Earlier – in March – the figure was higher, with 667 new HIV cases reported; this was the highest figure ever recorded since the first case of HIV was reported in the country in 1984.
As such, the Philippines is not only one of only nine countries globally with rapidly increasing rates of HIV infection; it is, in fact, the country with the highest infection rates. An average of 20 new HIV cases are being reported every day since the start of 2015, compared with an average of 17 HIV cases a day and an average of nine in 2012.
With the numbers from April, the number of people living with HIV in the Philippines for the first four months of the year alone reached 2,409. The figure includes 65 deaths. In total – since 1984 – the number of HIV cases in the country reached 24,936, with 2,213 of these progressing to AIDS, and 1,183 ending in death.
While sexual transmission still accounts for over 95% of HIV cases in the Philippines, a major shift from a heterosexual to men who have sex with men (MSM) transmission has been noted. In March, for instance, 547 of the new cases were transmitted through sex, particularly among men who have sex with men (MSM), who accounted for 477 (87%) of the cases. Particularly, 295 of the cases were through homosexual contact, while 182 were through bisexual contact.
WORRYING CHANGE
The shift (in the molecular composition of HIV in the Philippines) may have occurred beginning in 2006. However, as per Salvaña, “if we look at published data for HIV genotypes in the Philippines, there is a big gap between 2003 and 2013 in terms of molecular characterization of HIV genotypes.”
For this study, 81 newly-diagnosed, treatment-naive HIV-positive patients at the Philippine General Hospital (PGH) were interviewed and underwent genotyping of HIV RT and PR genes using World Health Organization (WHO) approved protocols for HIV genotyping. Generated sequences were analyzed using the Stanford Drug Resistance Database. Demographics, sexual habits and CD4 counts at presentation were collected.
The study’s participants only included MSM, which was “not intentional,” Salvaña said. But “during the period of enrolment, very few women tested positive and we were unable to capture them during the recruitment process. This is consistent with the current national statistics of the epidemic, where over 90% of newly diagnosed cases are men.”
However, “we can look at that kind of data in two ways: that there really are more cases of HIV in men, or that men are more likely to get tested due to their own perceived need for testing (e.g. risk, employment for abroad, et cetera). The DOH estimates that only 12% of the at-risk population has been tested, and so we certainly do not have the complete picture. But it is better to have some of the picture than not to have any of it, it is just harder to make more widely applicable conclusions.”
The cohort had an average age of 29 years (range 19-51 years), CD4 count of 254 cells/mm3 (2-744 cells), and self-reported acquisition time of 2.42 years (0.17-8.17 years). All were male, and 79 were MSM. Genotype distribution was CRF01_AE (75%), B (22%), C (1%), and CRF01_AE/K (1%).
According to the study, pooled analysis of published data from samples collected from 1985-2000 showed that the majority of Philippine HIV infections were previously caused by subtype B (71%, N=100), followed by subtype CRF01_AE (20%). Comparison with this newer study’s cohort shows a highly significant shift in subtype (p<0.001 by Chi-square).
Comparison of CD4 counts at presentation between CRF01_AE and B showed a significantly lower count (233 cells/mm3 versus 350 cells/mm3, p=0.03 by T-test) despite no difference in age (p=0.15), and self-reported time to acquisition (p=0.66).
As per the study: “This is consistent with previous reports that CRF01_AE is more aggressive, with faster progression to AIDS. While no viral loads were available for this cohort, CRF01_AE has been reported to have a higher rate of transmission. “
For this study – and again – “these two factors may partly explain the explosive increase in the number of new infections.”
CHANGING FACE OF HIV?
HIV continues to be a source of worry; but this news is even more worrisome, particularly when taken following the news about the new, aggressive HIV strain that was discovered in Cuba. In a study conducted by researchers from the University of Leuven in Belgium, several HIV-infected people in Cuba developed AIDS in less than three years, which is faster than the usual 10 years it typically takes. All patients infected with CRF19, a recently-discovered strain of the HIV virus, had higher levels of it in their body.
A major difference – and this is worth highlighting – is that the Cuban strain is a new variant of HIV which may be more aggressive in time to AIDS. “It wasn’t the predominant strain there, only that it was discovered there in a small pool of samples,” Salvaña said.
The Philippine study actually had more samples (n=80) than the one in Cuba (n=73). But “we need to be very careful in interpreting these kinds of data because strong evidence is needed to support conclusions and most of what is available is typically done retrospectively (reviewing case files) and in uncontrolled situations. The data can be influenced by bias and other confounders. There seems to be at least some evidence to suggest that this strain is more virulent, but whether this is borne out in the future in bigger and more stringent prospective studies remains to be seen.”
Salvaña added: “HIV is a very complex virus in that it mutates very fast and gives rise to multiple variations which also recombine. The original virus likely originated from at least five different transmission events from apes, and more will likely be found. The nature of this virus is to constantly change, and that is why it took so long to find appropriate treatment using a three-drug combination that suppressed the mutations, and it is taking even longer to find a durable cure. We need to stay on top of this virus by starting everyone on treatment (which prevents it from mutating further and decreases the risk of transmitting it to others), educating the public on protecting themselves from infection, and supporting research that is looking for an effective vaccine and a cure.
STRENGTHENING RESPONSES
Salvaña sees the need to work together to fight HIV.
Academic institutions, for instance, can take part by helping in characterizing the epidemic and watching out for more aggressive variants. As such, however, “funding more studies like ours helps keep an eye on the emergence of these new strains.”
The media, meanwhile, “has a key role to play in spreading the word, educating the public, and helping people understand how they can make a difference in the fight against HIV and AIDS.”
And with HIV continuing to be a major concern, “the government and others working on HIV eradication should redouble their efforts in controlling the spread of HIV in the country,” Salvaña ended.
