Durable suppression of replication of the human immunodeficiency virus (HIV) depends on the use of potent, well-tolerated antiretroviral regimens to which patients can easily adhere.

Lopinavir is a newly developed inhibitor of human immunodeficiency virus (HIV) protease that, when formulated with ritonavir, yields mean trough plasma lopinavir concentrations that are at least 75 times as high as that needed to inhibit replication of wild-type HIV by 50 percent. We conducted a double-blind trial in which 653 HIV-infected adults who had not received antiretroviral therapy for more than 14 days were randomly assigned to receive either lopinavir–ritonavir (400 mg of lopinavir plus 100 mg of ritonavir twice daily) with nelfinavir placebo or nelfinavir (750 mg three times daily) with lopinavir–ritonavir placebo. All patients also received open-label stavudine and lamivudine. The primary efficacy end points were the presence of fewer than 400 HIV RNA copies per milliliter of plasma at week 24 and the time to the loss of virologic response through week 48. At week 48, greater proportions of patients treated with lopinavir–ritonavir than of patients treated with nelfinavir had fewer than 400 copies of HIV RNA per milliliter (75 percent vs. 63 percent, P<0.001) and fewer than 50 copies per milliliter (67 percent vs. 52 percent, P<0.001). The time to the loss of virologic response was greater in the lopinavir–ritonavir group than in the nelfinavir group (hazard ratio, 2.0; 95 percent confidence interval, 1.5 to 2.7; P<0.001). The estimated proportion of patients with a persistent virologic response through week 48 was 84 percent for patients receiving lopinavir–ritonavir and 66 percent for those receiving nelfinavir. Both regimens were well tolerated, with the rate of discontinuation related to the study drugs at 3.4 percent among patients receiving lopinavir–ritonavir and 3.7 percent among patients receiving nelfinavir. Among patients with more than 400 copies of HIV RNA per milliliter at some point from week 24 through week 48, resistance mutations in HIV protease were demonstrated in viral isolates from 25 of 76 nelfinavir-treated patients (33 percent) and none of 37 patients treated with lopinavir–ritonavir (P<0.001). For the initial treatment of HIV-infected adults, a combination regimen that includes lopinavir–ritonavir is well tolerated and has antiviral activity superior to that of a nelfinavir-containing regimen.

Background. Abacavir-lamivudine and tenofovir DF-emtricitabine fixed-dose combinations are commonly used as first-line antiretroviral therapies. Howe

Background. The pilot phase IIb VIKING study suggested that dolutegravir (DTG), a human immunodeficiency virus (HIV) integrase inhibitor (INI), would be efficacious in INI-resistant patients at the 50 mg twice daily (BID) dose. Methods. VIKING-3 is a single-arm, open-label phase III study in which therapy-experienced adults with INI-resistant virus received DTG 50 mg BID while continuing their failing regimen (without raltegravir or elvitegravir) through day 7, after which the regimen was optimized with ≥1 fully active drug and DTG continued. The primary efficacy endpoints were the mean change from baseline in plasma HIV-1 RNA at day 8 and the proportion of subjects with HIV-1 RNA <50 c/mL at week 24. Results. Mean change in HIV-1 RNA at day 8 was −1.43 log₁₀ c/mL, and 69% of subjects achieved <50 c/mL at week 24. Multivariate analyses demonstrated a strong association between baseline DTG susceptibility and response. Response was most reduced in subjects with Q148 + ≥2 resistance-associated mutations. DTG 50 mg BID had a low (3%) discontinuation rate due to adverse events, similar to INI-naive subjects receiving DTG 50 mg once daily. Conclusions. DTG 50 mg BID–based therapy was effective in this highly treatment-experienced population with INI-resistant virus. Clinical Trials Registration. www.clinicaltrials.gov (NCT01328041) and http://www.gsk-clinicalstudywww.gsk-clinicalstudyregister.com (112574).

This study describes the incidence and severity of COVID-19 among 77 590 HIV-positive patients receiving antiretroviral therapy (ART). The findings warrant further investigation of ART in HIV preex... Visual Incidence and Severity of COVID-19 in HIV-Positive Persons Receiving ART This study describes the incidence and severity of COVID-19 among 77 590 HIV-positive patients receiving ant... Background: The incidence and severity of coronavirus disease 2019 (COVID-19) among HIV-positive persons receiving antiretroviral therapy (ART) have not been characterized in large populations. Obj...