Tuberculin sensitivity testing and treatment of latent tuberculosis remains effective for tuberculosis control in human immunodeficiency virus-infected patients in Hong Kong.

OBJECTIVE: To evaluate whether a policy to treat latent tuberculosis identified by annual tuberculin sensitivity testing is effective for tuberculosis control in human immunodeficiency virus-infected patients in Hong Kong. DESIGN: Historical cohort study. SETTING: Integrated Treatment Centre, Department of Health, Hong Kong. PATIENTS: Patients infected with human immunodeficiency virus without a history of tuberculosis were offered annual tuberculin sensitivity testing, coupled with treatment of latent tuberculosis if they tested positive. All such patients were followed for new tuberculosis. RESULTS: In all, 1154 patients on antiretroviral therapy, contributing to 5587 patient-years of observation, were analysed; 1032 patients (89%) received annual tuberculin sensitivity testing. Their baseline characteristics, including CD4 counts and other risk factors for tuberculosis, did not differ significantly from those who declined testing. The overall incidence rate of tuberculosis was 0.59 case per 100 patient-years. It was lower in those who received annual tuberculin sensitivity testing than those who did not (0.41 vs 3.85 per 100 patient-years; P<0.0001). Only a low baseline CD4 count and a history of tuberculin sensitivity testing were shown to be significant indicators of incident tuberculosis using multivariate analysis. The hazard ratio was 0.36 (95% confidence interval, 0.16-0.85; P=0.02) for those with a baseline CD4 count of 100/mm3 or above, and 0.26 (95% confidence interval, 0.08-0.77; P=0.016) for those who received annual tuberculin sensitivity testing. The incidence of tuberculosis was highest within 90 days of antiretroviral therapy initiation. CONCLUSION: The established policy continues to be effective. The high risk of tuberculosis during the early period of antiretroviral therapy supports early use of tuberculin sensitivity testing. Alternatively, the strategy of universal isoniazid preventive therapy at antiretroviral therapy initiation could be studied for those with very low baseline CD4 counts.

Treatment outcomes after early initiation of antiretroviral therapy for human immunodeficiency virus-associated tuberculosis.

OBJECTIVE: To evaluate the optimal timing for initiating antiretroviral therapy in patients with human immunodeficiency virus (HIV)-associated tuberculosis in Hong Kong. DESIGN: Historical cohort. SETTING. Tuberculosis and Chest Service and Special Preventive Programme, Public Health Service Branch, Centre for Health Protection, Department of Health, Hong Kong. PATIENTS: Consecutive patients with HIV-associated tuberculosis in a territory-wide TB-HIV registry encountered from 1996 to 2009. RESULTS: Of the 260 antiretroviral therapy-naïve patients with HIV-associated tuberculosis, 32 (12%) had antiretroviral therapy initiated within 2 months after starting anti-tuberculosis treatment (early antiretroviral therapy). Early antiretroviral therapy was associated with a more favourable outcome (cure or treatment completion without relapse) at 24 months (91% vs 67%; P=0.007) than those with antiretroviral therapy started later or not initiated, and remained an independent predictor of a favourable outcome after adjustment for potential confounders. Adverse effects from anti-tuberculosis drugs tended to occur more frequently in patients with early antiretroviral therapy (13/32 or 41%) compared with the remainder (59/228 or 26%; P=0.08). A significantly higher proportion of patients in the former group experienced immune reconstitution inflammatory syndrome than in the latter group (7/32 or 22% vs 9/228 or 4%; P<0.001). There was no death attributable to immune reconstitution inflammatory syndrome. CONCLUSIONS: Early initiation of antiretroviral therapy is associated with more favourable tuberculosis treatment outcomes in patients with HIV-associated tuberculosis with a low CD4 count (<200/µL). Drug co-toxicity and immune reconstitution inflammatory syndrome that may be increased by earlier initiation of antiretroviral therapy does not undermine tuberculosis treatment outcomes to a significant extent.

HLA-B*5701 genetic screening among HIV-1 infected patients in Hong Kong: is this a practical approach in Han-Chinese?

Abacavir hypersensitivity is associated with the presence of human leukocyte antigen (HLA)-allele B*5701. However, the cost and workload of routine HLA-B*5701 pretreatment screening is relatively heavy. This study aimed to determine the prevalence of the HLA-B*5701 allele in the HIV-positive population under care in Hong Kong. Blood samples from 1264 HIV-1 infected patients in Hong Kong were collected between 2007 and 2011 for this study. HLA-B*5701 screening of the study group was determined by in-house polymerase chain reaction (PCR) followed by confirmation using the AlleleSEQR(®) HLA-B PCR/Sequencing Kit (Celera Corporation for Abbott, San Francisco, USA). HLA-B*5701 carriers were identified among 3% of Caucasians, 1% of non-Chinese Asians and 0.5% of Han-Chinese in Hong Kong. Our findings revealed that HLA-B*5701 pretreatment screening might not be necessary for the local Han-Chinese population due to its low prevalence.

Stable and low prevalence of transmitted HIV type 1 drug resistance despite two decades of antiretroviral therapy in Hong Kong.

Transmitted HIV resistance is of both clinical and public health importance. Baseline genotypic resistance testing was performed for HIV-1-infected treatment-naive patients who were newly diagnosed between 2003 and 2007 and attended the government HIV clinic in Hong Kong. International AIDS Society-USA mutation figures and the Stanford resistance interpretation algorithm were used to identify resistance mutations and drug susceptibility, respectively. The pattern and factors associated with resistance were examined. The presence of one or more IAS-USA resistance mutations was found in 26 (3.6%) of 731 patients over the 5-year study period. Overall, protease inhibitor (PI) resistance mutations were most common (16), followed by nucleoside reverse transcriptase inhibitors (NRTIs) (8) and nonnucleoside reverse transcriptase inhibitors (NNRTIs) (3). Resistance to drugs in one, two, and three classes was present in 25 (3.4%), 1 (0.1%), and 0, respectively. Seventy-eight (10.7%) had strains of reduced susceptibility, as predicted by the Stanford algorithm to display at least low-level resistance to one or more drugs of the three classes. Intermediate or high-level resistance was found in 1.6% overall, and in descending order for NRTIs, PIs, and NNRTIs. There was no temporal trend of increase in resistance. Sex between men, Chinese ethnicity, and lower baseline CD4 were associated with harboring resistant strains as elucidated by either method. We conclude that transmitted HIV-1 drug resistance is uncommon in up to two decades of antiretroviral therapy in Hong Kong. The situation has to be continually monitored for any change in significance.

Twenty years of clinical human immunodeficiency virus (HIV) and acquired immunodeficiency syndrome (AIDS) in Hong Kong.

OBJECTIVE: To elucidate the development of human immunodeficiency virus (HIV) clinical care and research in Hong Kong. DATA SOURCES: Articles on clinical HIV and acquired immunodeficiency syndrome (AIDS) published from 1985 to 2004 were identified through four sources: Red Ribbon Centre, Special Preventive Programme, Secretariat of the Scientific Committee on AIDS, and PubMed search. The first three are operated by the Centre for Health Protection, Department of Health, Hong Kong. STUDY SELECTION: Key words for the literature search were 'AIDS', 'HIV', and 'Hong Kong'. DATA EXTRACTION: Only papers with original local data were included. DATA SYNTHESIS: Sixty papers were identified. The contents were catalogued under seven areas: clinical epidemiology, HIV disease course and presentation, specific complications or organ-based manifestations, immunological evaluation and other monitoring, antiretroviral therapy, HIV/AIDS mortality, and HIV in specific groups. Prevalence of HIV has remained low in Hong Kong but new infections continue to occur together with a significant number of late presenters. Three published AIDS patients' series, up to the first 200 reported cases, identified Pneumocystis carinii pneumonia as the most common AIDS-defining illness in Hong Kong. Penicillium marneffei and Mycobacterium tuberculosis were two important specific infections studied most; uniqueness of the former in patients of South-East Asia was evident. Local studies of Kaposi's sarcoma and HIV-associated lymphoma have also been reported. Research on CD4 counts has revealed that it is lower in healthy and HIV-infected Chinese than their western counterparts. Children, pregnant women, and haemophiliac patients infected with HIV are among the specific groups of patients studied. Survival of patients with advanced disease has greatly improved over the years, particularly after the advent of highly active antiretroviral therapy. CONCLUSION: The clinical presentation and outcome of HIV/AIDS patients in Hong Kong are a mixture of those of western and developing countries. Research on clinical HIV/AIDS in Hong Kong is not only beneficial to the planning of patient care, but also enables the formulation of treatment guidelines and provides a reference for other countries.

Universal decline in mortality in patients with advanced HIV-1 disease in various demographic subpopulations after the introduction of HAART in Hong Kong, from 1993 to 2002.

OBJECTIVE: Reductions in HIV/AIDS mortality associated with highly active antiretroviral therapy (HAART) have mainly been reported from Western countries. We studied the impact on survival of patients with advanced HIV disease after the introduction of HAART in Hong Kong. METHODS: The mortality pattern in a government clinic cohort of 511 adult HIV-1-infected patients with AIDS or CD4 count <200 cells/microL from 1993 to 2002 was examined. The number of deaths, the crude mortality rate (CMR) and the death rate per 1000 person-months were recorded. RESULTS: Despite an increase in the patient population, 36 deaths occurred in the HAART era (1997-2002) as compared with 56 deaths in the pre-HAART era (1993-1996). The overall annual CMR fell significantly from a high, fluctuating level of 10.8-30.4 per 100 mid-year patient population pre-HAART to a low, steady level of 0.8-6.9 per 100 mid-year population in the HAART era (P=0.004, 1996 vs 1998; P<0.001, 1996 vs 2000; P<0.001, 1996 versus 2002). A fall in CMR was observed in all demographic subpopulations, categorized by sex, ethnicity, HIV exposure risk and age (P ranged from 0.012 to<0.001). Longitudinal tracking until mid-2003 revealed a death rate of 9.2 events/1000 person-months (52 deaths with 5661.5 person-months follow up) among patients first diagnosed as having advanced disease during 1993-1996, and a lower death rate of 2.4 events/1000 person-months (25 deaths with 10551.8 person-months follow up) in patients first diagnosed as having advanced disease during 1997-2001 (rate ratio 3.9; 95% confidence interval 2.4-6.2). CONCLUSION: There was dramatic temporal decline in mortality in patients with advanced HIV disease in all demographic subpopulations with the advent of HAART. Notwithstanding confounding variables, one reason for the universal decline may be that there was no major disparity in access to HIV care across community groups.

Effects of single nucleotide polymorphisms in the RANTES promoter region in healthy and HIV-infected indigenous Chinese.

We determined the occurrence of the single nucleotide polymorphisms (SNPs) -403A/G and -28C/G in the promoter region of RANTES in 1082 Chinese blood donors from northern and southern China and 249 HIV patients from southern China. Compared to healthy adults, Chinese AIDS patients had a significantly higher frequency of the -403G allele and haplotype I, -403G/-28C (P < 0.05), and a lower frequency of the -403A/A genotype (P < 0.01). Symptomatic patients had a higher frequency of the -28G allele and a lower frequency of the -28C/C genotype (P < or = 0.01). The plasma RANTES level was significantly lower in blood donors homozygous for haplotype I than in those who were homozygous for haplotypes II and III (P < 0.05). The frequency of the -403G allele was found to be higher in Chinese than in indigenous Africans, but lower than in Caucasians, Hispanics, and African Americans. The frequency of the -28G allele was comparable in Chinese and Japanese; this allele is rare in other ethnic groups. Results suggest that -403G may be associated with increased susceptibility to HIV infection, while -28G may be associated with advanced disease progression. The impact of SNPs on HIV infection appears to be unique in Chinese.