Switch to second-line ART in West African routine care: incidence and reasons for switching.

In sub-Saharan Africa, while antiretroviral therapy (ART) becomes widely available, access to biological measurements to monitor patients under ART remains scarce, making the management of ART difficult. We described the management of switching to second-line ART where HIV care is provided mainly in secondary health-care structures, in the region of Segou, Mali. Of 865 patients, followed under ART for a median time of 15 months, 40 switched to second-line ART (3.3 switches/100 person years). Reason for switching was failure in 18 patients (after 21 months in median) and severe intolerance in 13 (after three months in median). Switching to second-line ART occurred earlier when motivated by intolerance than by failure. The low rate of switch compares well with other studies, but was low compared to the expected rate of failure, and may indicate that physicians are reluctant to switch ART when treatment options are limited.

Resistance-associated mutations to etravirine (TMC-125) in antiretroviral-naïve patients infected with non-B HIV-1 subtypes.

Susceptibility to etravirine (ETR), an expanded-spectrum nonnucleoside reverse transcriptase inhibitor (NNRTI), is dependent on the type and number of NNRTI resistance-associated mutations (RAMs). Studies have shown that some HIV-1 subtypes may have natural polymorphisms described as ETR RAMs. This study addresses the prevalence of ETR RAMs in treatment-naïve patients infected with HIV-1 non-B subtypes and its potential impact on ETR susceptibility. The prevalence of ETR RAMs in 726 antiretroviral-naïve patients infected with non-B HIV-1 subtypes was studied. ETR genotypic resistance was interpreted according to Agence Nationale de Recherches sur le SIDA and Stanford algorithms. NNRTI phenotypic susceptibilities of samples with at least one ETR RAM were measured. Overall, 75 (10.3%) of 726 sequences harbored at least one ETR RAM: sequences from 72 patients (10%) each had one ETR RAM, and sequences from 3 patients (0.4%) each had two ETR RAMs (V90I and Y181C in one case and V90I and A98G in two cases). None of the viruses had three or more ETR RAMs, and none were consequently classified as resistant to ETR. All sequences with two ETR RAMs belonged to subtype CRF02_AG. The presence of one ETR RAM was statistically more frequent in subtype CRF02_AG than in other non-B subtypes (P=0.004). Three new mutation profiles (E138A and V179I, Y181C and H221Y, and V90I and Y181C) showing decreased ETR phenotypic susceptibility were identified. In conclusion, although the prevalence of ETR RAMs in treatment-naïve patients infected with non-B HIV-1 subtypes was 10%, in most cases this had no significant impact on ETR susceptibility. However, the transmission of drug-resistant viruses with Y181C in a non-B genetic background has a potential for impact on ETR susceptibility.

Incidence of lipodystrophy and metabolic disorders in patients starting non-nucleoside reverse transcriptase inhibitors in Benin.

BACKGROUND: The incidence and risk factors for lipodystrophy and metabolic disorders among patients in Africa on first-line combined antiretroviral treatment (cART) mostly containing non-nucleoside reverse transcriptase inhibitors is poorly documented. METHODS: This prospective cohort study recruited 88 HIV-infected patients initiating cART between October 2004 and June 2005 in Cotonou, Benin. Patients were followed for 24 months. The main outcomes were incidence of lipodystrophy and metabolic disorders. Multivariate Cox proportional hazards regression models were used to describe factors associated with progression to lipodystrophy. RESULTS: After a median follow-up of 23.2 months (interquartile range 22.3-23.7), 24 (30%) patients developed lipodystrophy (lipoatrophy 9%, lipohypertrophy 24% and mixed pattern 2.5%). The incidence rate for lipodystrophy was estimated to 1.72 per person-month (95% confidence interval [CI] 1.15-2.56) occurring after a median time of 11 months on cART. Metabolic syndrome (International Diabetes Federation definition) appeared in 10 (13%) patients after a median of 15 months with an estimated incidence rate of 0.62 per person-month (95% CI 0.33-1.16). It was more common in women (19.2% versus 3.1% in men; P=0.043). Diabetes (8%) and hypercholesterolaemia (35%) were also observed. After adjustment, gender, young age (hazard ratio [HR] 0.45 [95% CI 0.22-0.90]; P=0.025), high BMI at inclusion (HR 1.53 [95% CI 1.28-1.83]; P<0.0001) and smoking (HR 28.0 [95% CI 2.5-307.4]; P=0.006) were significantly associated with lipohypertrophy. CONCLUSIONS: Lipodystrophy and metabolic syndrome were commonly and rapidly observed in this cohort of sub-Saharan patients initiating cART.

Evolution of genetic diversity and drug resistance mutations in HIV-1 among untreated patients from Mali between 2005 and 2006.

OBJECTIVES: To describe HIV-1 variants circulating in Mali and to estimate the rate of transmission of HIV-1 drug resistance in 2006. PATIENTS AND METHODS: Viral reverse transcriptase (RT) and protease (PR) genes from 198 antiretroviral (ARV)-naive patients diagnosed HIV-1 positive in May 2006 in Bamako and Segou were sequenced. RESULTS: Although CRF02_AG was always the predominant HIV-1 subtype observed (72%), a higher genetic diversity than that in 2005 was observed. The overall prevalence of primary resistance is 11.5% in Mali in 2006, according to the 2007 IAS-USA list of mutations [nucleoside RT inhibitor (NRTI): 1.5%, non-NRTI (NNRTI): 9% and PI: 1%], and 2.5% (NRTI: 1%, NNRTI: 1.5% and PI: 0%), according to the Stanford list of mutations. There was no significant difference between 2005 and 2006 in the overall primary resistance prevalence or in the prevalence of mutations in the different ARV classes. Resistance mutations found in RT and PR genes are in agreement with the highly active antiretroviral therapy regimen available in Mali, except for V90I, V106I and A98G mutations which are associated with etravirine resistance, but polymorphic in non-B subtypes. CONCLUSIONS: HIV-1 genetic diversity seems increased in Mali, but the overall HIV-1 primary resistance prevalence remains low. This is consistent with the findings from other West African countries where prevalence rates are lower than 5%. However, considering the large scaling up of ARV use in this country, it is necessary to regularly monitor the development of primary resistance in Mali.

Costing universal access of highly active antiretroviral therapy in Benin.

The study aimed to estimate costs of provision and access to highly active antiretroviral therapy (HAART) in order to assist in planning and resource allocation regarding scaling up and sustainable access to HAART in Benin. A prospective study was carried out to collect data on costs of provision of care at the Outpatient Treatment Centre (OTC) of the National University hospital in Cotonou, Benin and on costs borne by people living with HIV/AIDS (PLWHA) and their families in accessing care. We used an Excel model, a macro costing approach and WHO guidelines for costing health services. Annual costs were subsequently extrapolated from a societal perspective over a 10-year time horizon. Sensitivity analysis was conducted on major cost categories. The study population was mostly of middle age (median age of 38, IQR 34-42), married (65%), working class (60%) with low literacy (70% primary education level or less). The main drivers of costs of HAART service provision were drugs (73%), biological monitoring (15%) and personnel (8%). Annual costs of provision of HAART and household costs borne by PLWHA and families in seeking care amounted to 1160 USD and 111 USD per PLWHA respectively. These household costs are respectively 40% and 14% of household health and education related costs and may represent catastrophic health expenditures for patients and families. The provision of drugs and biological monitoring, and household costs in accessing care, remain by far the main barriers to ensuring universal access to HAART.