METHODS: Prospectively collected longitudinal data from patients in Thailand, Hong Kong, Malaysia, Japan, Taiwan, and South Korea were provided for analysis. Covariates included demographics, hepatitis B and C coinfections, baseline CD4 T lymphocyte count, and plasma HIV-1 RNA levels. Clinical deterioration (a new diagnosis of Centers for Disease Control and Prevention category B/AIDS-defining illness or death) was assessed by proportional hazards models. Surrogate endpoints were 12-month change in CD4 cell count and virologic suppression post therapy, evaluated by linear and logistic regression, respectively.
RESULTS: Of 1105 patients, 1036 (93.8%) infected with CRF01_AE or subtype B were eligible for inclusion in clinical deterioration analyses and contributed 1546.7 person-years of follow-up (median: 413 days, interquartile range: 169-672 days). Patients >40 years demonstrated smaller immunological increases (P = 0.002) and higher risk of clinical deterioration (hazard ratio = 2.17; P = 0.008). Patients with baseline CD4 cell counts >200 cells per microliter had lower risk of clinical deterioration (hazard ratio = 0.373; P = 0.003). A total of 532 patients (48.1% of eligible) had CD4 counts available at baseline and 12 months post therapy for inclusion in immunolgic analyses. Patients infected with subtype B had larger increases in CD4 counts at 12 months (P = 0.024). A total of 530 patients (48.0% of eligible) were included in virological analyses with no differences in response found between genotypes.
CONCLUSIONS: Results suggest that patients infected with CRF01_AE have reduced immunologic response to therapy at 12 months, compared with subtype B-infected counterparts. Clinical deterioration was associated with low baseline CD4 counts and older age. The lack of differences in virologic outcomes suggests that all patients have opportunities for virological suppression.
DESIGN: A molecular epidemiology study was conducted among HIV-1 seropositive patients attending the University Malaya Medical Center (UMMC) from July 2003 to June 2004.
METHODS: Protease (PR) and reverse transcriptase (RT) gene sequences were derived from drug resistance genotyping assay of 100 newly diagnosed or antiretroviral-naive patients. These were phylogenetically analysed to determine the subtypes and recombination breakpoint analyses were performed on intersubtype recombinants to estimate the recombination breakpoint(s).
RESULTS: CRF01_AE predominated in Kuala Lumpur with 65% in both PR and RT genes. B subtype was detected at 14% and 12% in PR and RT genes, respectively. C subtype was present at 1% in both genes. Overall, the concordance of PR and RT genes in discriminating subtypes/circulating recombinant forms (CRF) was high at 96%. In this study, novel CRF01_AE/B intersubtype recombinants were detected at high prevalence (22%), including those isolates with subtype discordance. Thai variants of CRF01_AE and B subtype were involved in the genesis of these unique recombinant forms (URF). Interestingly, 19 CRF01_AE/B intersubtype recombinant isolates shared similar recombination breakpoints in both PR and RT genes. Several distinct URF were also identified.
CONCLUSION: PR and RT genes can be utilized for subtype/CRF assessment with high degree of agreement, allowing concurrent surveillance of circulating HIV-1 subtypes with antiretroviral drug resistance genotyping tests. The emergence of highly identical CRF01_AE/B intersubtype recombinants suggests the possibility of the appearance of a new circulating recombinant form in Kuala Lumpur.
METHODS: PLHIV enrolled in the Therapeutics, Research, Education and AIDS Training in Asia (TREAT Asia) HIV Observational Database (TAHOD) who initiated ART with a CD4 count 1 year were censored at 12 months. Competing risk regression was used to analyse risk factors with loss to follow-up as a competing risk.
RESULTS: A total of 1813 PLHIV were included in the study, of whom 74% were male. With 73 (4%) deaths, the overall first-year mortality rate was 4.27 per 100 person-years (PY). Thirty-eight deaths (52%) were AIDS-related, 10 (14%) were immune reconstituted inflammatory syndrome (IRIS)-related, 13 (18%) were non-AIDS-related and 12 (16%) had an unknown cause. Risk factors included having a body mass index (BMI) 100 cells/μL: SHR 0.12; 95% CI 0.05-0.26) was associated with reduced hazard for mortality compared to CD4 count ≤ 25 cells/μL.
CONCLUSIONS: Fifty-two per cent of early deaths were AIDS-related. Efforts to initiate ART at CD4 counts > 50 cell/μL are associated with improved short-term survival rates, even in those with late stages of HIV disease.
KEY FINDINGS: Among ARVs, the most common drugs employed from the class of entry inhibitors are maraviroc (MVC), which is a CCR5 receptor antagonist. Other entry inhibitors like emtricitabine (FTC) and tenofovir (TFV) are also used. Rilpivirine (RPV) and dapivirine (DPV) are the most common drugs employed from the Non-nucleoside reverse transcriptase inhibitor (NNRTIs) class, whereas, tenofovir disoproxil fumarate (TDF) is primarily used in the Nucleoside Reverse Transcriptase Inhibitor (NRTIs) class. Cabotegravir (CAB) is an analog of dolutegravir, and it is an integrase inhibitor. Some of these drugs are also used in combination with other drugs from the same class.
SUMMARY: Some of the most common pre-exposure prophylactic strategies employed currently are the use of inhibitors, namely entry inhibitors, non-nucleoside reverse transcriptase inhibitors, nucleoside reverse transcriptase inhibitors, integrase and protease inhibitors. In addition, we have also discussed on the adverse effects caused by ART in PrEP, pharmacoeconomics factors and the use of antiretroviral prophylaxis in serodiscordant couples.
METHODS: Factors associated with survival and failure were analyzed using Cox proportional hazards and discrete time conditional logistic models.
RESULTS: TDR, found in 60 (4.1%) of 1471 Asian treatment-naive patients, was one of the significant predictors of failure. Patients with TDR to >1 drug in their regimen were >3 times as likely to fail compared to no TDR.
CONCLUSIONS: TDR was associated with failure in the context of non-fully sensitive regimens. Efforts are needed to incorporate resistance testing into national treatment programs.