Ritonavir-boosted lopinavir plus nucleoside or nucleotide reverse transcriptase inhibitors versus ritonavir-boosted lopinavir plus raltegravir for treatment of HIV-1 infection in adults with virological failure of a standard first-line ART regimen (SECOND-LINE): a randomised, open-label, non-inferiority study.

BACKGROUND: Uncertainty exists about the best treatment for people with HIV-1 who have virological failure with first-line combination antiretroviral therapy of a non-nucleoside analogue (NNRTI) plus two nucleoside or nucleotide analogue reverse transcriptase inhibitors (NtRTI). We compared a second-line regimen combining two new classes of drug with a WHO-recommended regimen. METHODS: We did this 96-week, phase 3b/4, randomised, open-label non-inferiority trial at 37 sites worldwide. Adults with HIV-1 who had confirmed virological failure (plasma viral load >500 copies per mL) after 24 weeks or more of first-line treatment were randomly assigned (1:1) to receive ritonavir-boosted lopinavir plus two or three NtRTIs (control group) or ritonavir-boosted lopinavir plus raltegravir (raltegravir group). The randomisation sequence was computer generated with block randomisation (block size four). Neither participants nor investigators were masked to allocation. The primary endpoint was the proportion of participants with plasma viral load less than 200 copies per mL at 48 weeks in the modified intention-to-treat population, with a non-inferiority margin of 12%. This study is registered with ClinicalTrials.gov, number NCT00931463. FINDINGS: We enrolled 558 patients, of whom 541 (271 in the control group, 270 in the raltegravir group) were included in the primary analysis. At 48 weeks, 219 (81%) patients in the control group compared with 223 (83%) in the raltegravir group met the primary endpoint (difference 1·8%, 95% CI -4·7 to 8·3), fulfilling the criterion for non-inferiority. 993 adverse events occurred in 271 participants in the control group versus 895 in 270 participants in the raltegravir group, the most common being gastrointestinal. INTERPRETATION: The raltegravir regimen was no less efficacious than the standard of care and was safe and well tolerated. This simple NtRTI-free treatment strategy might extend the successful public health approach to management of HIV by providing simple, easy to administer, effective, safe, and tolerable second-line combination antiretroviral therapy. FUNDING: University of New South Wales, Merck, AbbVie, the Foundation for AIDS Research.

Effect of gender and race on the week 48 findings in treatment-naïve, HIV-1-infected patients enrolled in the randomized, phase III trials ECHO and THRIVE.

OBJECTIVES: A week 48 efficacy and safety analysis with respect to gender and race was conducted using pooled data from the phase III, double-blind, double-dummy efficacy comparison in treatment-naïve, HIV-infected subjects of TMC278 and efavirenz (ECHO) and TMC278 against HIV, in a once-daily regimen versus efavirenz (THRIVE) trials. METHODS: Treatment-naïve, HIV-1-infected adults were randomized to receive rilpivirine (RPV; TMC278) 25 mg once a day (qd), or efavirenz (EFV) 600 mg qd, plus tenofovir/emtricitabine (ECHO) or tenofovir/emtricitabine, zidovudine/lamivudine or abacavir/lamivudine (THRIVE). RESULTS: A total of 1368 participants (76% male and 61% White, of those with available race data) were randomized and treated. No gender-related differences in response rate (percentage of patients with HIV-1 viral load < 50 HIV-1 RNA copies/mL, using an intent-to-treat, time-to-loss-of-virological-response algorithm) were observed (RPV: men, 85%; women, 83%; EFV: men, 82%; women, 83%). Response rates were lower in Black compared with Asian and White participants (RPV: 75% vs. 95% and 85%, respectively; EFV: 74% vs. 93% and 83%, respectively); this finding was mostly a result of higher discontinuation and virological failure rates in Black patients. Safety findings were generally similar across race and gender subgroups. However, nausea occurred more commonly in women than in men in both treatment groups. In men, diarrhoea was more frequent in the EFV group, and abnormal dreams/nightmares were more frequent in men in both the EFV and RPV groups. CONCLUSIONS: Overall response rates were high for both RPV and EFV. No gender differences were observed. However, response rates were lower among Black patients, regardless of treatment group. Gender appeared to influence the incidence of gastrointestinal adverse events and abnormal dreams/nightmares for both treatments.

HIV testing uptake among the household contacts of multidrug-resistant tuberculosis index cases in eight countries.

SETTING: The household contacts (HHCs) of multidrug-resistant tuberculosis (MDR-TB) index cases are at high risk of tuberculous infection and disease progression, particularly if infected with the human immunodeficiency virus (HIV). HIV testing is important for risk assessment and clinical management. METHODS: This was a cross-sectional, multi-country study of adult MDR-TB index cases and HHCs. All adult and child HHCs were offered HIV testing if never tested or if HIV-negative >1 year previously when last tested. We measured HIV testing uptake and used logistic regression to evaluate predictors. RESULTS: A total of 1007 HHCs of 284 index cases were enrolled in eight countries. HIV status was known at enrolment for 226 (22%) HHCs; 39 (4%) were HIV-positive. HIV testing was offered to 769 (98%) of the 781 remaining HHCs; 544 (71%) agreed to testing. Of 535 who were actually tested, 26 (5%) were HIV-infected. HIV testing uptake varied by site (median 86%, range 0-100%; P < 0.0001), and was lower in children aged <18 years than in adults (59% vs. 78%; adjusted for site P < 0.0001). CONCLUSIONS: HIV testing of HHCs of MDR-TB index cases is feasible and high-yield, with 5% testing positive. Reasons for low test uptake among children and at specific sites-including sites with high HIV prevalence-require further study to ensure all persons at risk for HIV are aware of their status.