Introduction: A proof-of-concept study was designed to evaluate the antiviral efficacy, safety and tolerability of a two-drug regimen with dolutegravir 50 mg once daily (QD) plus lamivudine 300 mg once daily as initial highly active antiretroviral therapy (HAART) among antiretroviral (ARV)-naive patients.Methods: PADDLE is a pilot study including 20 treatment-naive adults. To be selected, participants had no IAS-USA-defined resistance, HIV-1 RNA ≤100,000 copies/mL at screening and negative HBsAg. Plasma viral load (pVL) was measured at baseline; days 2, 4, 7, 10, 14, 21 and 28; weeks 6, 8 and 12; and thereafter every 12 weeks up to 96 weeks. Primary endpoint was the proportion of patients with HIV-1 RNA <50 copies/mL in an intention to treat (ITT)-exposed analysis at 48 weeks (the FDA snapshot algorithm).Results: Median HIV-1 RNA at entry was 24,128 copies/mL (interquartile range (IQR): 11,686–36,794). Albeit as per protocol, all patients had pVL ≤100,000 copies/mL at screening as required by inclusion criteria, four patients had ≥100,000 copies/mL at baseline. Median baseline CD4+ T-cell count was 507 per cubic millimetre (IQR: 296–517). A rapid decline in pVL was observed (median VL decay from baseline to week 12 was 2.74 logs). All patients were suppressed at week 8 onwards up to week 24. At week 48, 90% (18/20) reached the primary endpoint of a pVL <50 copies/mL. Median change in CD4 cell count between baseline and week 48 was 267 cells/mm3 (IQR: 180–462). No major tolerability/toxicity issues were observed. Nineteen patients completed 48 weeks of the study, and one patient (with undetectable VL at last visit) committed suicide. One patient presented a low-level protocol-defined confirmed virological failure at week 36, being the only observed failure. This patient had pVL <50 copies/mL at the end-of-study visit without having changed the two-drug regimen. Observed failure rate was 5%. This is the first report of integrase strand transfer inhibitor/lamivudine dual regimen in ARV-naive patients.Conclusions: This novel dual regimen of dolutegravir and lamivudine warrants further clinical research and consideration as a potential therapeutic option for ARV-therapy-naive patients.ClinicalTrials.gov Identifier: NCT02211482.
Limited information is available concerning the coexistence of COVID-19 and opportunistic infections in people living with HIV. The possible association of COVID-19 with AIDS-related respiratory diseases should be considered, particularly in patients with advance immunosuppression. We report the case of a male patient with AIDS-related disseminated histoplasmosis associated with COVID-19.
Objectives
To evaluate whether maternal HIV disease severity during pregnancy is associated with an increased likelihood of lower respiratory tract infections (LRTIs) in HIV-exposed, uninfected infants.
Methods
HIV-exposed, uninfected, singleton, term infants enrolled in the NISDI Perinatal Study, with birth weight ≥ 2500 grams were followed from birth until six months of age. LRTI diagnoses, hospitalizations, and associated factors were assessed.
Results
Of 547 infants, 103 (18.8%) experienced 116 episodes of LRTIs (incidence=0.84 LRTIs/100 child-weeks). Most (81%) episodes were bronchiolitis. Forty-nine (9.0%) infants were hospitalized at least once with an LRTI. There were 53 hospitalizations (45.7%) for 116 LRTI episodes. None of these infants were breastfed. The odds of LRTI in infants whose mothers had CD4%<14 were 4.4 times than that of those whose mothers had CD4%≥29 (p=0.003). The odds of LRTI were 16.0 times that of infants with a CD4+ count [cells/mm3] < 750 at birth compared to those with CD4+≥750 (p=0.002). Maternal CD4+ decline and Infant hemoglobin at the 6-12 week visit were associated with infant LRTIs after 6-12 weeks and before six months of age.
Conclusions
Acute bronchiolitis is common and frequently severe among HIV-exposed, uninfected infants aged six months or less. Lower maternal and infant CD4+ values were associated with a higher risk of infant LRTIs. Further understanding of the immunological mechanisms of severe LRTIs is needed.
Background Although antiretroviral regimens containing integrase inhibitors rapidly suppress HIV viral load in non-pregnant adults, few published data from randomised controlled trials have compared the safety and efficacy of any integrase inhibitor to efavirenz when initiated during pregnancy. We compared safety and efficacy of antiretroviral therapy with either raltegravir or efavirenz in late pregnancy.Methods An open-label, randomised controlled trial was done at 19 hospitals and clinics in Argentina,
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