Deep Sequencing Reveals Central Nervous System Compartmentalization in Multiple Transmitted/Founder Virus Acute HIV-1 Infection.

HIV-1 disseminates to a broad range of tissue compartments during acute HIV-1 infection (AHI). The central nervous system (CNS) can serve as an early and persistent site of viral replication, which poses a potential challenge for HIV-1 remission strategies that target the HIV reservoir. CNS compartmentalization is a key feature of HIV-1 neuropathogenesis. Thus far, the timing of how early CNS compartmentalization develops after infection is unknown. We examined whether HIV-1 transmitted/founder (T/F) viruses differ between CNS and blood during AHI using single-genome sequencing of envelope gene and further examined subregions in pol and env using next-generation sequencing in paired plasma and cerebrospinal fluid (CSF) from 18 individuals. Different proportions of mostly minor variants were found in six of the eight multiple T/F-infected individuals, indicating enrichment of some variants in CSF that may lead to significant compartmentalization in the later stages of infection. This study provides evidence for the first time that HIV-1 compartmentalization in the CNS can occur within days of HIV-1 exposure in multiple T/F infections. Further understanding of factors that determine enrichment of T/F variants in the CNS, as well as potential long-term implications of these findings for persistence of HIV-1 reservoirs and neurological impairment in HIV, is needed.

Ketoconazole is inferior to ritonavir as an alternative booster for saquinavir in a once daily regimen in Thai HIV-1 infected patients.

OBJECTIVE: To improve the pharmacokinetics of protease inhibitors, boosting with low-dose ritonavir is performed. However, toxicity, storage conditions and high costs of antiretroviral treatment may necessitate interruption of ritonavir. Ketoconazole was investigated as a potential booster of once-daily (o.d.) saquinavir. METHODS: In a single-group, two-period design, 25 virologically and immunologically stable patients on saquinavir/ritonavir 2000/100 mg o.d. were switched to saquinavir/ketoconazole 2000/400 mg o.d. for 2 weeks. Two steady-state pharmacokinetic curves were recorded at both periods. RESULTS: Fourteen females and 11 male patients were included. Median age was 34 years [interquartile range (IQR), 32-42 years], body weight 54 kg (IQR, 47-59 kg) and body mass index 21 kg/m (19-23 kg/m). The mean saquinavir area under the curve (AUC) during boosting with ritonavir was 57.93 +/- 27.96 mg/h/l, maximum observed concentration (Cmax) was 7.50 +/- 3.45 mg/l and concentration at 24 h (Cmin) was 0.35 +/- 0.30 mg/l. When ketoconazole was used, the saquinavir AUC, Cmax, and Cmin were 12.00 +/- 6.97 mg/h/l, 2.43 +/- 1.35 mg/l and 0.03 +/- 0.04 mg/l, respectively. CONCLUSION: Boosting with ketoconazole resulted in 80% lower exposure to saquinavir. Although saquinavir AUC might still be adequate for treatment, concentrations at 24 h reached levels below the recommended trough concentrations of 0.1 mg/l, which may result in selection of resistant HIV-1 viral strains. Therefore, boosting of saquinavir by ketoconazole is not recommended.

Low incidence of HIV infection in an anonymous HIV counselling and testing clinic cohort in Bangkok, Thailand despite high HIV prevalence and self-report of high-risk behaviour.

BACKGROUND: HIV counselling and testing (HCT) clinics have the potential to be entry points for recruiting populations at high risk for HIV infection for HIV prevention and treatment studies. Cohort data from key populations are crucial for HIV study site selection. METHOD: This cohort study recruited clients at an HCT clinic in Bangkok, Thailand. HIV prevalence was assessed along with demographics, perception of risk and behavioural risk factors. Participants who were HIV negative at baseline were followed up every 4 months for up to 1 year to measure HIV incidence and changes in risk behaviour. RESULTS: A total of 992 subjects enrolled; median age was 30 years, 27% were men who have sex with men (MSM) and 8% were commercial sex workers (CSW). Baseline HIV prevalence was 10%. Factors positively associated with HIV infection were age >30 years, lower educational status and being MSM. Factors negatively associated with HIV infection were self-perception of minimal or moderate risk. Overall dropout rate was 49%, with 24% not returning after enrolment. HIV incidence was lower than expected at 0.50 per 100 person-years overall and 1.95 per 100 person-years for MSM. CONCLUSIONS: This HCT population had a high baseline HIV prevalence but a low incidence rate on follow-up. Overall retention in the cohort was poor and may have resulted from suboptimal reminders and characteristics of high-risk clients who use anonymous HIV testing services. MSM had higher HIV incidence and better retention than other high-risk groups.