Continuation of emtricitabine/lamivudine within combination antiretroviral therapy following detection of the M184V/I HIV-1 resistance mutation.

OBJECTIVES: The aim of the study was to investigate whether lamivudine (3TC) or emtricitabine (FTC) use following detection of M184V/I is associated with better virological outcomes. METHODS: We identified people with viruses harbouring the M184V/I mutation in UK multicentre data sets who had treatment change/initiation within 1 year. We analysed outcomes of viral suppression (< 200 HIV-1 RNA copies/mL) and appearance of new major drug resistance mutations (DRMs) using Cox and Poisson models, with stratification by new drug regimen (excluding 3TC/FTC) and Bayesian implementation, and estimated the effect of 3TC/FTC adjusted for individual and viral characteristics. RESULTS: We included 2597 people with the M184V/I resistance mutation, of whom 665 (25.6%) were on 3TC and 458 (17.6%) on FTC. We found a negative adjusted association between 3TC/FTC use and viral suppression [hazard ratio (HR) 0.84; 95% credibility interval (CrI) 0.71-0.98]. On subgroup analysis of individual drugs, there was no evidence of an association with viral suppression for 3TC (n = 184; HR 0.94; 95% CrI 0.73-1.15) or FTC (n = 454; HR 0.99; 95% CrI 0.80-1.19) amongst those on tenofovir-containing regimens, but we estimated a reduced rate of viral suppression for people on 3TC amongst those without tenofovir use (n = 481; HR 0.71; 95% CrI 0.54-0.90). We found no association between 3TC/FTC and detection of any new DRM (overall HR 0.92; 95% CrI 0.64-1.18), but found inconclusive evidence of a lower incidence rate of new DRMs (overall incidence rate ratio 0.69; 95% CrI 0.34-1.11). CONCLUSIONS: We did not find evidence that 3TC or FTC use is associated with an increase in viral suppression, but it may reduce the appearance of additional DRMs in people with M184V/I. 3TC was associated with reduced viral suppression amongst people on regimens without tenofovir.

Predictors of CD4 cell recovery following initiation of antiretroviral therapy among HIV-1 positive patients with well-estimated dates of seroconversion.

OBJECTIVES: To investigate factors that predict speed of recovery and long-term CD4 cell count in HIV-1 seroconverters initiating combination antiretroviral therapy (cART), and to quantify the influence of very early treatment initiation. We make use of all pre-treatment CD4 counts, because analyses using only a single observation at initiation may be subject to biases. METHODS: We used data from the CASCADE (Concerted Action on SeroConversion to AIDS and Death in Europe) multinational cohort collaboration of HIV-1 seroconverters. We analysed pre- and post-treatment data of patients with seroconversion dates estimated January 2003-March 2014 (n = 7600 for primary analysis) using a statistical model in which the characteristics of recovery in CD4 counts are determined by multiple predictive factors. Secondary analyses were performed incorporating uncertainty in the exact timing of seroconversion to allow more precise estimation of the benefit of very early treatment initiation. RESULTS: 'True' CD4 count at cART initiation was the strongest predictor of CD4 count beyond 3 years on cART. Allowing for lack of complete certainty in the date of seroconversion, CD4 recovery was more rapid for patients in whom treatment was initiated within 4 months. For a given CD4 count, higher viral load (VL) at initiation was strongly associated with higher post-treatment CD4 recovery. For other patient and drug characteristics, associations with recovery were statistically significant but small in magnitude. CONCLUSIONS: CD4 count at cART initiation is the most important factor in predicting post-treatment recovery, but VL provides substantial additional information. If cART is initiated in the first 4 months following seroconversion, recovery of CD4 counts appears to be more rapid.

Fetal growth reference ranges in twin pregnancy: analysis of the Southwest Thames Obstetric Research Collaborative (STORK) multiple pregnancy cohort.

OBJECTIVE: To generate reference charts for expected fetal growth in dichorionic diamniotic (DCDA) and monochorionic diamniotic (MCDA) twin pregnancies and to compare these with those from singleton pregnancies. METHODS: This was a retrospective study of biometric measurements from serial ultrasound examinations of twin pregnancies in the second and third trimesters, from 14 weeks' gestation to term, collected by nine hospitals over a 10-year period. The measurements obtained in each fetus at each examination included head circumference (HC), biparietal diameter (BPD), abdominal circumference (AC) and femur length (FL). Multilevel mixed effects statistical models were used to evaluate growth in each biometric variable in relation to gestational age, taking account of the serial examinations and the association between the two fetuses in each pregnancy, with separate models constructed for DCDA and MCDA pregnancies. RESULTS: The final dataset for analysis included a total of 9866 second- and third-trimester ultrasound examinations in 1802 DCDA and 323 MCDA twin pregnancies, with a median of five (range, 1-14) scans per pregnancy. For each variable, the mean value for DCDA twins was close to the reported value in singletons at 20-30 weeks and showed a decrease relative to singletons beyond 30 weeks. The differences were greater for AC and HC, for which the mean in twins was approximately equivalent to the 30th percentile in singletons at 18 weeks, the 35th percentile at 25 weeks and the 30th percentile at 35 weeks. Fetuses in MCDA twin pregnancies displayed lower mean measurements than did those in DCDA pregnancies throughout the gestational age range considered. CONCLUSIONS: Ultrasound biometry shows a small but statistically significant reduction in fetal growth in twin pregnancies relative to that in singletons, particularly in the third trimester, with a more marked difference for MCDA than for DCDA pregnancies.