METHODS: Children enrolled in the TREAT Asia Pediatric HIV Observational Database who had SM (weight-for-height or body mass index-for-age Z score less than -3) at ART initiation were analyzed. Generalized estimating equations were used to investigate poor weight recovery (weight-for-age Z score less than -3) and poor CD4% recovery (CD4% <25), and competing risk regression was used to analyze mortality and toxicity-associated treatment modification.
RESULTS: Three hundred fifty-five (11.9%) of 2993 children starting ART had SM. Their median weight-for-age Z score increased from -5.6 at ART initiation to -2.3 after 36 months. Not using trimethoprim-sulfamethoxazole prophylaxis at baseline was associated with poor weight recovery [odds ratio: 2.49 vs. using; 95% confidence interval (CI): 1.66-3.74; P < 0.001]. Median CD4% increased from 3.0 at ART initiation to 27.2 after 36 months, and 56 (15.3%) children died during follow-up. More profound SM was associated with poor CD4% recovery (odds ratio: 1.78 for Z score less than -4.5 vs. -3.5 to less than -3.0; 95% CI: 1.08-2.92; P = 0.023) and mortality (hazard ratio: 2.57 for Z score less than -4.5 vs. -3.5 to less than -3.0; 95% CI: 1.24-5.33; P = 0.011). Twenty-two toxicity-associated ART modifications occurred at a rate of 2.4 per 100 patient-years, and rates did not differ by malnutrition severity.
CONCLUSION: Trimethoprim-sulfamethoxazole prophylaxis is important for the recovery of weight-for-age in severely malnourished children starting ART. The extent of SM does not impede weight-for-age recovery or antiretroviral tolerability, but CD4% response is compromised in children with a very low weight-for-height/body mass index-for-age Z score, which may contribute to their high rate of mortality.
OBJECTIVE: To identify the optimal CD4 cell count at which cART should be initiated.
DESIGN: Prospective observational data from the HIV-CAUSAL Collaboration and dynamic marginal structural models were used to compare cART initiation strategies for CD4 thresholds between 0.200 and 0.500 × 10(9) cells/L.
SETTING: HIV clinics in Europe and the Veterans Health Administration system in the United States.
PATIENTS: 20, 971 HIV-infected, therapy-naive persons with baseline CD4 cell counts at or above 0.500 × 10(9) cells/L and no previous AIDS-defining illnesses, of whom 8392 had a CD4 cell count that decreased into the range of 0.200 to 0.499 × 10(9) cells/L and were included in the analysis.
MEASUREMENTS: Hazard ratios and survival proportions for all-cause mortality and a combined end point of AIDS-defining illness or death.
RESULTS: Compared with initiating cART at the CD4 cell count threshold of 0.500 × 10(9) cells/L, the mortality hazard ratio was 1.01 (95% CI, 0.84 to 1.22) for the 0.350 threshold and 1.20 (CI, 0.97 to 1.48) for the 0.200 threshold. The corresponding hazard ratios were 1.38 (CI, 1.23 to 1.56) and 1.90 (CI, 1.67 to 2.15), respectively, for the combined end point of AIDS-defining illness or death.
LIMITATIONS: CD4 cell count at cART initiation was not randomized. Residual confounding may exist.
CONCLUSION: Initiation of cART at a threshold CD4 count of 0.500 × 10(9) cells/L increases AIDS-free survival. However, mortality did not vary substantially with the use of CD4 thresholds between 0.300 and 0.500 × 10(9) cells/L.
METHODS: Prospective study of predominantly white HIV-infected participants receiving suppressive ART for at least 12 months. We analysed the CD14 SNPs C-260T and the TLR4 SNPs A+896G, C+1196T. We also determined the levels of LPS and soluble CD14 in plasma samples collected pre-ART and post-ART initiation. CD4 T-cell recovery was assessed by linear mixed models.
RESULTS: Following ART, individuals with a TT genotype compared with a CT or CC genotype for CD14 C-260T SNP showed higher levels of soluble CD14 (P = 0.008 and 0.003, respectively). The CC genotype for the CD14 C-260T SNP, compared with CT or TT, and the TLR4 SNP (AC/GT), compared with the homozygous genotype (AA/CC), were both independently associated with enhanced long-term CD4 T-cell recovery (>3 months; P
METHODS: A prospective cohort study among ALHIV and matched HIV-uninfected controls aged 12-18 years was conducted at 9 sites in Malaysia, Thailand, and Vietnam from July 2013 to March 2017. Participants completed an audio computer-assisted self-interview at weeks 0, 48, 96, and 144. Virologic failure (VF) was defined as ≥1 viral load (VL) measurement >1000 copies/mL. Generalized estimating equations were used to identify predictors for VF.
RESULTS: Of 250 ALHIV and 59 HIV-uninfected controls, 58% were Thai and 51% females. The median age was 14 years at enrollment; 93% of ALHIV were perinatally infected. At week 144, 66% of ALHIV were orphans vs. 28% of controls (P < 0.01); similar proportions of ALHIV and controls drank alcohol (58% vs. 65%), used inhalants (1% vs. 2%), had been sexually active (31% vs. 21%), and consistently used condoms (42% vs. 44%). Of the 73% of ALHIV with week 144 VL testing, median log VL was 1.60 (interquartile range 1.30-1.70) and 19% had VF. Over 70% of ALHIV had not disclosed their HIV status. Self-reported adherence ≥95% was 60% at week 144. Smoking cigarettes, >1 sexual partner, and living with nonparent relatives, a partner or alone, were associated with VF at any time.
CONCLUSIONS: The subset of ALHIV with poorer adherence and VF require comprehensive interventions that address sexual risk, substance use, and HIV-status disclosure.
METHODS: Patient data from 2003-2017 were obtained from the Therapeutics, Research, Education and AIDS Training in Asia (TREAT Asia) HIV Observational Database (TAHOD). We included patients on antiretroviral therapy (ART) with > 1 day of follow-up. Cumulative incidences were plotted for CVD-related, AIDS-related, non-AIDS-related, and unknown CODs, and any CVD (i.e. fatal and nonfatal). Competing risk regression was used to assess risk factors of any CVD.
RESULTS: Of 8069 patients with a median follow-up of 7.3 years [interquartile range (IQR) 4.4-10.7 years], 378 patients died [incidence rate (IR) 6.2 per 1000 person-years (PY)], and this total included 22 CVD-related deaths (IR 0.36 per 1000 PY). Factors significantly associated with any CVD event (IR 2.2 per 1000 PY) were older age [sub-hazard ratio (sHR) 2.21; 95% confidence interval (CI) 1.36-3.58 for age 41-50 years; sHR 5.52; 95% CI 3.43-8.91 for ≥ 51 years, compared with < 40 years], high blood pressure (sHR 1.62; 95% CI 1.04-2.52), high total cholesterol (sHR 1.89; 95% CI 1.27-2.82), high triglycerides (sHR 1.55; 95% CI 1.02-2.37) and high body mass index (BMI) (sHR 1.66; 95% CI 1.12-2.46). CVD crude IRs were lower in the later ART initiation period and in lower middle- and upper middle-income countries.
CONCLUSIONS: The development of fatal and nonfatal CVD events in our cohort was associated with older age, and treatable risk factors such as high blood pressure, triglycerides, total cholesterol and BMI. Lower CVD event rates in middle-income countries may indicate under-diagnosis of CVD in Asian-Pacific resource-limited settings.
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.