The early phase of an HIV epidemic in a population exposed previously to HCV in the Philippines.

Human immunodeficiency virus (HIV) sentinel surveillance program for injecting drug users has been conducted in Metro Cebu, the Philippines. A low prevalence (0-0.52%) of anti-HIV-positivity had been detected in this population from 2002 to 2007. However, a 10-fold increase in HIV prevalence was detected in the 2009 national HIV sentinel surveillance program. It prompted an additional outreach program to be conducted in Metro Cebu in January 2010, which recorded the highest HIV prevalence rate ever documented in the Philippines (75%, 44/59). HIV genes from fourteen 2009 to 2010 Metro Cebu strains were clustered closely in the phylogenetic tree, but no other strain collected outside Metro Cebu and none stored in the International Nucleotide Sequence Database was allocated to the same phylogenetic cluster. All these HIV infections have emerged in the anti-hepatitis C virus (HCV)-positive population (100%, 62/62) in Metro Cebu from 2009 to 2010. The five HCV strains from the individuals harboring the closely related HIV strains were categorized into different subtypes. These results strongly suggest that HIV infections occurred recently and spread rapidly among injecting drug users, while HCV had been circulating previously among them. Considering the fact that injecting drug use was the first mode of HIV transmission in Asia, extensive monitoring of injecting drug users and associated bridging populations is necessary. Therefore, HCV-guided characterization of the spread of HIV to populations that are vulnerable to blood-borne infections could play an important role in alerting health authorities to the early phase of an HIV epidemic.

Tracking the entry routes of hepatitis C virus as a surrogate of HIV in an HIV-low prevalence country, the Philippines.

From 2002 to 2007, 1,590 individuals were enrolled in an active surveillance program conducted in Metro Cebu, Philippines, where the anti-HCV-positive rate was significantly and constantly high among injecting drug users (83%, 793/960; 71-88%), especially among those living in downtown (89%, 683/770; 87-100%), despite the extremely low percentage of anti-HIV-positives (0.34%, 3/874). Sampling areas were then enlarged nationwide and the number of samples increased to 2,645 at the end of 2007. A total of 444 samples were positive for HCV RNA. Phylogenetic analysis based on NS5B and E1-E2 regions revealed that the most dominant HCV subtype was 1a, and followed by 2b, 2a, and 1b, and that the HCV strains had the largest variety in Metro Manila and its vicinity (P < 0.01). Interestingly, subtype 1b was detected solely in Metro Manila, and four HCV strains collected in this area showed higher homology to specific foreign strains retrieved from the Genbank/EMBL/DDBJ database with bootstrap values of 68-95% comparing with other strains analyzed in this nationwide study. These data suggest that HCV strains may be introduced occasionally into the Philippines possibly through Metro Manila as a main entry point. Considering the fact that an HIV epidemic started primarily via contaminated needle sharing in Asia, the constantly high rate of HCV infections and the newly introduced foreign HCV strains in the absence of HIV epidemic warrant further investigation on HCV entry and spread for early detection of an HIV epidemic in the Philippines.

A natural inter-genotypic (2b/1b) recombinant of hepatitis C virus in the Philippines.

The prevalence study and the characterization of hepatitis C virus (HCV) was carried out in the Philippines and the sequence determination of the 5'-untranslated region (5'-UTR)-Core and the NS5B regions of HCV was carried out in this study. An HCV strain (SE-03-07-1689) collected in Metro Manila, Philippines, belonged to discordant subtypes, 2b and 1b in 5'-UTR-Core and NS5B regions, respectively. The 9.3 kb sequence of this strain including the entire open reading frame was compared with those of the reference strains retrieved from the HCV sequences database (GenBank/EMBL/DDBJ) and indicated a recombination event. The computation of the sequence similarity mapped a crossover point within the NS3 region. This is the second report on the inter-genotype recombinant of HCV and the third when an intra-genotype recombinant is included. This recombinant strain, SE-03-07-1689, is designated tentatively as RF3_2b/1b according to the suggestions used for the other two HCV recombinants.

Rapid spread of hepatitis C virus among injecting-drug users in the Philippines: Implications for HIV epidemics.

From the trends of human immunodeficiency virus (HIV) epidemics in South and Southeast Asia, it was postulated that an HIV epidemic would start as a blood-borne infection among injecting-drug users in the Philippines. In 2002, 560 individuals were recruited in Metro Cebu, Philippines and tested for HIV, hepatitis C virus (HCV), and hepatitis B virus (HBV) infections. The seroprevalence of anti-HCV among injecting-drug users (70.1%, 61/87) was significantly higher than those among inhalation drug users (16.3%, 7/43; P = 0.00; OR = 12), sex workers (0%, 0/130; P = 0.00; OR = infinity), antenatal clinic attendees (0%, 0/100; P = 0.00; OR = infinity), and students/health care workers (2%, 4/200; P = 0.00; OR = 115). The seroprevalence of HBsAg among injecting-drug users (10.3%, 9/87) was significantly higher than those among sex workers (2.3%, 3/130; P = 0.01; OR = 4.9), and antenatal clinic attendees (3%, 3/100; P = 0.04; OR = 3.7), but was not statistically different from those among inhalation drug users (9.3%, 4/43; P = 0.9) and students/health care workers (4.5%, 9/200; P = 0.06). None of the study population was reactive to anti-HIV antibody. The HCV strains obtained from the injecting-drug users belonged to either genotype 1a or 2b and the strains in each genotype clustered closely to each other. There was no dual infection with genotype 1a and 2b. These results suggest that the HCV infection in injecting-drug users may be emanating rapidly from limited number individuals in Metro Cebu, Philippines.

Randomized, double-blind, placebo-controlled trial of oromucosal low-dose interferon following prednisone withdrawal for chronic hepatitis B infection in Filipino patients.

OBJECTIVE: To evaluate the efficacy and safety of oromucosal low-dose human lymphoblastoid interferon alpha (IFN-alpha-n1 [INS]) following steroid withdrawal in Filipino patients with chronic replicative hepatitis B virus (HBV) infection. STUDY DESIGN: Randomized, double blind, placebo-controlled trial on IFN-alpha-n1 [INS], two tablets of 200 IU each or placebo, given sublingually once daily for eight months following steroid or placebo priming and withdrawal. RESULTS: A statistically significant clearance of hepatitis B e antigen (HBeAg) (50%) and seroconversion to positive antibody to HBeAg (anti-HBe) (42.9%) was noted in those given IFN-alpha-n1 [INS] compared with the placebo group. Clearance of serum HBV-DNA was not significantly different and none cleared HBsAg in both groups. More patients (57%) had normalization of ALT on IFN-alpha-n1 [INS] compared with controls (31.3%). Oromucosal IFN-alpha-n1 [INS] was devoid of any evidence of toxicity. CONCLUSION: This study conducted on a limited number of patients demonstrates the potential efficacy of oromucosal IFN-alpha-n1 [INS] in chronic HBV infection with therapeutic benefit equal to parenterally administered interferon alpha (IFNalpha) but without the side effects of myelosuppresion. Owing to the small population studied, we are unable to extrapolate these findings to the general population of patients with chronic HBV infection. A large-scale study is needed to confirm these findings.