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: To create a retrospective cohort of all adults with HIV released from jails and prisons in Connecticut, USA (2007-14), we linked administrative custody and pharmacy databases with mandatory HIV/AIDS surveillance monitoring and case management data. We examined time to LTC (defined as first viral load measurement after release) and viral suppression at LTC. We used generalised estimating equations to show predictors of LTC within 14 days and 30 days of release.
FINDINGS: Among 3302 incarceration periods for 1350 individuals between 2007 and 2014, 672 (21%) of 3181 periods had LTC within 14 days of release, 1042 (34%) of 3064 had LTC within 30 days of release, and 301 (29%) of 1042 had detectable viral loads at LTC. Factors positively associated with LTC within 14 days of release are intermediate (31-364 days) incarceration duration (adjusted odds ratio 1·52; 95% CI 1·19-1·95), and transitional case management (1·65; 1·36-1·99), receipt of antiretroviral therapy during incarceration (1·39; 1·11-1·74), and two or more medical comorbidities (1·86; 1·48-2·36). Reincarceration (0·70; 0·56-0·88) and conditional release (0·62; 0·50-0·78) were negatively associated with LTC within 14 days. Hispanic ethnicity, bonded release, and psychiatric comorbidity were also associated with LTC within 30 days but reincarceration was not.
INTERPRETATION: LTC after release is suboptimal but improves when inmates' medical, psychiatric, and case management needs are identified and addressed before release. People who are rapidly cycling through jail facilities are particularly vulnerable to missed linkage opportunities. The use of integrated programmes to align justice and health-care goals has great potential to improve long-term HIV treatment outcomes.
FUNDING: US National Institutes of Health.
DESIGN: Sarcopenia (age-related muscle loss) causes significant morbidity to the elderly, leading to frequent hospitalizations, disability and death. Few have characterized sarcopenia in the HIV-infected who experience accelerated aging.
METHODS: Sarcopenia was defined as low muscle mass with weak grip strength and/or slow gait speed using lower 20th percentiles of controls. Multivariate logistic and linear regression analyses were used to explore risk factors and health-related outcomes associated with sarcopenia among HIV-infected individuals.
RESULTS: We recruited 315 HIV-infected individuals aged at least 25 years with at least 1-year history of undetectable viral load on treatment (HIV RNA <50 copies/ml). Percentage of sarcopenia in 315 HIV-infected was 8%. Subsequently, 153 of the 315 were paired with age, sex and ethnically matched HIV-uninfected. The percentage of sarcopenia in the HIV-infected (n = 153) compared with uninfected (n = 153) were 10 vs. 6% (P = 0.193) respectively, whereas of those at least 50 years of age among them were 17% vs. 4% (P = 0.049), respectively. Associated risk factors among the HIV-infected include education level, employment status, BMI, baseline CD4 cell count, duration on NRTIs and GGT levels. Identified negative outcomes include mortality risk scores [5.42; 95% CI 1.46-9.37; P = 0.007) and functional disability (3.95; 95% CI 1.57-9.97; P = 0.004).
CONCLUSION: Sarcopenia is more prevalent in HIV-infected at least 50 years old compared with matched controls. Our findings highlight associations between sarcopenia with loss of independence and greater healthcare burden among treated HIV-infected individuals necessitating early recognition and intervention.
METHODS: Data on children with perinatally acquired HIV aged <18 years on first-line, non-nucleoside reverse transcriptase inhibitor-based cART with viral suppression (two consecutive pVL <400 copies/mL over a six-month period) were included from a regional cohort study; those exposed to prior mono- or dual antiretroviral treatment were excluded. Frequency of pVL monitoring was determined at the site-level based on the median rate of pVL measurement: annual 0.75 to 1.5, and semi-annual >1.5 tests/patient/year. Treatment failure was defined as virologic failure (two consecutive pVL >1000 copies/mL), change of antiretroviral drug class, or death. Baseline was the date of the second consecutive pVL <400 copies/mL. Competing risk regression models were used to identify predictors of treatment failure.
RESULTS: During January 2008 to March 2015, there were 1220 eligible children from 10 sites that performed at least annual pVL monitoring, 1042 (85%) and 178 (15%) were from sites performing annual (n = 6) and semi-annual pVL monitoring (n = 4) respectively. Pre-cART, 675 children (55%) had World Health Organization clinical stage 3 or 4, the median nadir CD4 percentage was 9%, and the median pVL was 5.2 log10 copies/mL. At baseline, the median age was 9.2 years, 64% were on nevirapine-based regimens, the median cART duration was 1.6 years, and the median CD4 percentage was 26%. Over the follow-up period, 258 (25%) CLWH with annual and 40 (23%) with semi-annual pVL monitoring developed treatment failure, corresponding to incidence rates of 5.4 (95% CI: 4.8 to 6.1) and 4.3 (95% CI: 3.1 to 5.8) per 100 patient-years of follow-up respectively (p = 0.27). In multivariable analyses, the frequency of pVL monitoring was not associated with treatment failure (adjusted hazard ratio: 1.12; 95% CI: 0.80 to 1.59).
CONCLUSIONS: Annual compared to semi-annual pVL monitoring was not associated with an increased risk of treatment failure in our cohort of virally suppressed children with perinatally acquired HIV on first-line NNRTI-based cART.
METHODS: Data from two regional cohort observational databases were analyzed for trends in median CD4 cell counts at ART initiation and the proportion of late ART initiation (CD4 cell counts <200 cells/mm(3) or prior AIDS diagnosis). Predictors for late ART initiation and mortality were determined.
RESULTS: A total of 2737 HIV-positive ART-naïve patients from 22 sites in 13 Asian countries and territories were eligible. The overall median (IQR) CD4 cell count at ART initiation was 150 (46-241) cells/mm(3). Median CD4 cell counts at ART initiation increased over time, from a low point of 115 cells/mm(3) in 2008 to a peak of 302 cells/mm(3) after 2011 (p for trend 0.002). The proportion of patients with late ART initiation significantly decreased over time from 79.1% before 2007 to 36.3% after 2011 (p for trend <0.001). Factors associated with late ART initiation were year of ART initiation (e.g. 2010 vs. before 2007; OR 0.40, 95% CI 0.27-0.59; p<0.001), sex (male vs. female; OR 1.51, 95% CI 1.18-1.93; p=0.001) and HIV exposure risk (heterosexual vs. homosexual; OR 1.66, 95% CI 1.24-2.23; p=0.001 and intravenous drug use vs. homosexual; OR 3.03, 95% CI 1.77-5.21; p<0.001). Factors associated with mortality after ART initiation were late ART initiation (HR 2.13, 95% CI 1.19-3.79; p=0.010), sex (male vs. female; HR 2.12, 95% CI 1.31-3.43; p=0.002), age (≥51 vs. ≤30 years; HR 3.91, 95% CI 2.18-7.04; p<0.001) and hepatitis C serostatus (positive vs. negative; HR 2.48, 95% CI 1.-4.36; p=0.035).
CONCLUSIONS: Median CD4 cell count at ART initiation among Asian patients significantly increases over time but the proportion of patients with late ART initiation is still significant. ART initiation at higher CD4 cell counts remains a challenge. Strategic interventions to increase earlier diagnosis of HIV infection and prompt more rapid linkage to ART must be implemented.
METHODS: We compared these regimens with respect to clinical, immunologic, and virologic outcomes using data from prospective studies of human immunodeficiency virus (HIV)-infected individuals in Europe and the United States in the HIV-CAUSAL Collaboration, 2004-2013. Antiretroviral therapy-naive and AIDS-free individuals were followed from the time they started a lopinavir or an atazanavir regimen. We estimated the 'intention-to-treat' effect for atazanavir vs lopinavir regimens on each of the outcomes.
RESULTS: A total of 6668 individuals started a lopinavir regimen (213 deaths, 457 AIDS-defining illnesses or deaths), and 4301 individuals started an atazanavir regimen (83 deaths, 157 AIDS-defining illnesses or deaths). The adjusted intention-to-treat hazard ratios for atazanavir vs lopinavir regimens were 0.70 (95% confidence interval [CI], .53-.91) for death, 0.67 (95% CI, .55-.82) for AIDS-defining illness or death, and 0.91 (95% CI, .84-.99) for virologic failure at 12 months. The mean 12-month increase in CD4 count was 8.15 (95% CI, -.13 to 16.43) cells/µL higher in the atazanavir group. Estimates differed by NRTI backbone.
CONCLUSIONS: Our estimates are consistent with a lower mortality, a lower incidence of AIDS-defining illness, a greater 12-month increase in CD4 cell count, and a smaller risk of virologic failure at 12 months for atazanavir compared with lopinavir regimens.
METHODS: We used Cox regression to analyze data of a cohort of Asian children.
RESULTS: A total of 2608 children were included; median age at cART was 5.7 years. Time-updated weight for age z score < -3 was associated with mortality (P < 0.001) independent of CD4% and < -2 was associated with immunological failure (P ≤ 0.03) independent of age at cART.
CONCLUSIONS: Weight monitoring provides useful data to inform clinical management of children on cART in resource-limited settings.
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.