Challenges of scale-up to dolutegravir-based regimens in sub-Saharan Africa.

OBJECTIVE: Evaluate the potential effectiveness of the implementation of dolutegravir (DTG)-based regimens in patients on failing current antiretroviral treatment (ART) given the high levels of nucleoside reverse transcriptase inhibitor (NRTI) resistance in Togo. DESIGN: Patients on ART attending health facilities for routine follow-up visits and for whom HIV viral load test was performed were consecutively included. METHODS: Protease, reverse transcriptase and integrase fragments were sequenced and analyzed for presence of drug resistance mutations for patients with viral load more than 1000 copies/ml. RESULTS: Among 1681 patients, 320 (19.04%) had viral load more than 1000 copies/ml and 200 were tested for drug resistance mutations. Reverse transcriptase gene was successfully sequenced for 181/200 (90.5%) patients; 140/181 (77.4%) were resistant to NRTIs and non-NRTIs, 4/181 (2.2%) to NRTIs only and 18/181 (9.9%) to non-NRTIs only. Many viral strains accumulated mutations predicting resistance to NRTIs recommended in first and second-line DTG-based ART regimens. ART switch to a DTG-based regimen after viral load testing (viral load >1000 copies/ml) or blind switch without prior viral load testing to a new DTG-based first line, estimated 31% and 47.6% of patients to be potentially on functional DTG monotherapy respectively. CONCLUSION: Overall, our results predict that, at the scale of sub-Saharan Africa a significant proportion of patients could be on functional monotherapy. To achieve the third 90 of UNAIDS objectives, implementation of DTG-based regimens should be accompanied with an accelerated scaling up of access to viral load. Studies designed to quantify the implications of use of suboptimal DTG-based regimens are also needed.

[Intrathecal therapy with 1 500 UI of antitetanic serum and 1.5 g of intravenous metronidazole: prognosis of tetanus in hospitalized patients in Togo]. / Intérêt de la thérapie intrathécale à 1 500 UI de sérum antitétanique combinée à 1,5 gramme de métronidazole en intraveineux sur le pronostic du tétanos en milieu hospitalier togolais.

OBJECTIVE: To determine the effect on clinical progression and mortality during tetanus of intrathecal therapy with 1 500 IU of heterologous antitetanus serum administered with 1.5 g of intravenous metronidazole. METHOD: This prospective study took place from August 1, 2006, to June 30, 2007, and included two groups of patients randomly allocated to treatment by two different techniques. The test group of 17 patients received 1 500 IU of antitetanus heterologous immunoglobulin by the intrathecal route as well as 1.5 g of intravenous metronidazole daily. The control group of 25 patients received the standard treatment of 9 000 IU of heterologous antitetanic serum administered half (4 500 IU) cutaneously and half intramuscularly. Clinical manifestations and mortality were assessed. Mollaret's classification and the Dakar prognosis score were used to classify patients according to severity. RESULTS: Forty-two patients were treated. Their mean age was 29.44 years (standard deviation: 18.3 years) and the M/F sex ratio was 5. Skin wounds accounted for 57.1% of the portals of entry, deep wounds for 26.2%; the rest were unknown. Twenty patients (47.6%) had fever when admitted. Tetanus was generalized in all cases and 76.2% of patients were stage III. Four patients were HIV-positive. Clinical improvement, defined as a decrease in dysphagia, trismus, and paroxysm, was observed more quickly in the test group: 48 hours after treatment began, improvement was seen in more than 76% of the test group compared with 28% in the control group. In the test group, the mean hospitalization period was 7.4 days and mortality was 11.7%, compared with 19 days and a mortality rate of 52% in the control group. CONCLUSION: Prevention through vaccination appears to be the long-term solution for the eradication of tetanus. In the meantime, we can hope for a better clinical response with intrathecal therapy of 1 500 IU of heterologous antitetanus serum and 1.5 g of intravenous metronidazole daily.