OBJECTIVE: The purpose of this guideline is to provide recommendations to obstetric health care providers and to minimize practice variations for HIV screening, while taking provincial and territorial recommendations into account.
OUTCOMES: The risk of transmission of HIV from mother to fetus is significant if the mother is not treated. The primary outcome of screening for and treating HIV in pregnancy is a marked decrease in the rate of vertical transmission of HIV from mother to fetus. Secondary outcomes include confirmation of HIV infection in the woman, which allows optimization of her health and long-term management.
EVIDENCE: The Cochrane Library and Medline were searched for English-language articles published related to HIV screening and pregnancy. Additional articles were identified through the references of these articles. All study types were reviewed.
RECOMMENDATIONS: None
HIV infection is a worldwide epidemic. Antiretroviral therapy has dramatically changed the outcome of the disease but there is still controversy about the best time to initiate it, especially in patients with CD4 counts over 350 cells/µL. Searching in Epistemonikos database, which is maintained by screening 30 databases, we identified two systematic reviews including four pertinent randomized controlled trials overall. We concluded early initiation of antiretroviral therapy probably reduces mortality, risk of opportunistic infections and tuberculosis, but increases the risk of important adverse effects.
IMPORTANCE: New data and antiretroviral regimens expand treatment choices in resource-rich settings and warrant an update of recommendations to treat adults infected with human immunodeficiency virus (HIV).
OBJECTIVE: To provide updated treatment recommendations for adults with HIV, emphasizing when to start treatment; what treatment to start; the use of laboratory monitoring tools; and managing treatment failure, switches, and simplification.
DATA SOURCES, STUDY SELECTION, AND DATA SYNTHESIS: An International Antiviral Society-USA panel of experts in HIV research and patient care considered previous data and reviewed new data since the 2012 update with literature searches in PubMed and EMBASE through June 2014. Recommendations and ratings were based on the quality of evidence and consensus.
RESULTS: Antiretroviral therapy is recommended for all adults with HIV infection. Evidence for benefits of treatment and quality of available data increase at lower CD4 cell counts. Recommended initial regimens include 2 nucleoside reverse transcriptase inhibitors (NRTIs; abacavir/lamivudine or tenofovir disoproxil fumarate/emtricitabine) and a third single or boosted drug, which should be an integrase strand transfer inhibitor (dolutegravir, elvitegravir, or raltegravir), a nonnucleoside reverse transcriptase inhibitor (efavirenz or rilpivirine) or a boosted protease inhibitor (darunavir or atazanavir). Alternative regimens are available. Boosted protease inhibitor monotherapy is generally not recommended, but NRTI-sparing approaches may be considered. New guidance for optimal timing of monitoring of laboratory parameters is provided. Suspected treatment failure warrants rapid confirmation, performance of resistance testing while the patient is receiving the failing regimen, and evaluation of reasons for failure before consideration of switching therapy. Regimen switches for adverse effects, convenience, or to reduce costs should not jeopardize antiretroviral potency.
CONCLUSIONS AND RELEVANCE: After confirmed diagnosis of HIV infection, antiretroviral therapy should be initiated in all individuals who are willing and ready to start treatment. Regimens should be selected or changed based on resistance test results with consideration of dosing frequency, pill burden, adverse toxic effect profiles, comorbidities, and drug interactions.
BACKGROUND: Low-cost mobile devices, such as mobile phones, tablets, and personal digital assistants, which can access voice and data services, have revolutionised access to information and communication technology worldwide. These devices have a major impact on many aspects of people's lives, from business and education to health. This paper reviews the current evidence on the specific impacts of mobile technologies on tangible health outcomes (mHealth) in low- and middle-income countries (LMICs), from the perspectives of various stakeholders.
DESIGN: Comprehensive literature searches were undertaken using key medical subject heading search terms on PubMed, Google Scholar, and grey literature sources. Analysis of 676 publications retrieved from the search was undertaken based on key inclusion criteria, resulting in a set of 76 papers for detailed review. The impacts of mHealth interventions reported in these papers were categorised into common mHealth applications.
RESULTS: There is a growing evidence base for the efficacy of mHealth interventions in LMICs, particularly in improving treatment adherence, appointment compliance, data gathering, and developing support networks for health workers. However, the quantity and quality of the evidence is still limited in many respects.
CONCLUSIONS: Over all application areas, there remains a need to take small pilot studies to full scale, enabling more rigorous experimental and quasi-experimental studies to be undertaken in order to strengthen the evidence base.
Significant progress is being made in the global scale-up of prevention of mother-to-child transmission of HIV (PMTCT), including in high burden and resource-limited settings. For the first time, the elimination of mother-to-child transmission of HIV (MTCT) is now considered a realistic public health goal and an important part of the campaign to achieve the millennium development goals. In the light of the global effort, it is critically important to provide the best evidence-based interventions to reduce the risk of transmission from an HIV-infected mother to her newborn child, while at the same time promoting the health of both the mother and the child. Since WHO issued revised guidelines in 2006, important new evidence has emerged on the use of antiretroviral (ARV) prophylaxis to prevent MTCT, including during breastfeeding, on the optimal time to initiate antiretroviral therapy (ART) in individuals who need treatment, and on safe feeding practices for HIV-exposed infants. This evidence forms the basis for the new recommendations contained in these 2010 revised guidelines and summarized in preliminary form in the 2009 Rapid Advice: Use of antiretroviral drugs for treating pregnant women and preventing HIV infection in infants. The Rapid Advice gives a list of the key recommendations whereas the full guidelines document presents in detail the scientific evidence and rationale supporting these recommendations. The detailed guidelines document provides the necessary information for countries to adapt the WHO recommendations to their local settings. The 2010 guidelines are developed to provide international standards, primarily for low- and middle-income settings, in support of the global scale-up of more effective interventions aimed at preventing MTCT in resource-limited settings. Once implemented, these recommendations could reduce the risk of MTCT to less than 5% (or even lower) in breastfeeding populations from a background risk of 35%, and to less than 2% in non-breastfeeding populations from a background risk of 25%, and will ensure increased maternal and child survival. The 2010 revision of the WHO guidelines on PMTCT complies with the recently updated WHO guidelines development process, which requires systematic review of new evidence for key questions and recommendations, as well as a consideration of programme feasibility and the cost implications of potential new recommendations. WHO has simultaneously revised guidelines for adult ART as well as HIV and infant feeding. All three sets of guidelines were updated in a harmonized fashion.
UNLABELLED: Darunavir is an oral nonpeptidic HIV-1 protease inhibitor (PI) that is used, together with a low boosting dose of ritonavir, as part of an antiretroviral therapy (ART) regimen in treatment-experienced and -naive patients with HIV-1 infection. Compared with early-generation PIs, boosted darunavir has a high genetic barrier to resistance and is active against multidrug-resistant HIV isolates. In clinical trials in treatment-experienced patients with HIV-1 infection receiving an optimized background regimen (OBR), twice-daily boosted darunavir was more effective than investigator-selected ritonavir-boosted control PIs (CPIs) or ritonavir-boosted lopinavir. In clinical trials in treatment-naive patients with HIV-1 infection receiving a fixed background regimen, once-daily boosted darunavir was noninferior to boosted lopinavir at 48 weeks and more effective than boosted lopinavir at 96weeks. Boosted darunavir was generally well tolerated in patients with HIV-1 infection in clinical trials. It was associated with a lower incidence of diarrhoea than CPIs or lopinavir in treatment-experienced or -naive patients, and fewer lipid abnormalities than lopinavir in treatment-naive patients. Thus, for the management of treatment-experienced or -naive patients with HIV-1 infection, a ritonavir-boosted darunavir-based ART regimen is a valuable treatment option. PHARMACOLOGICAL PROPERTIES: Darunavir is an oral nonpeptidic HIV-1 PI that selectively inhibits the cleavage of HIV gag and gag-pol polyproteins, thereby preventing viral maturation. Darunavir is highly potent against laboratory strains and clinical isolates of wild-type and multidrug-resistant HIV and has limited cytotoxicity. In an in vitro study in MT-2 cells, the potency of darunavir was greater than that of saquinavir, amprenavir, nelfinavir, indinavir, lopinavir and ritonavir. Darunavir binds with high affinity to HIV-1 protease, including multidrug-resistant proteases, and retains potency against multidrug-resistant HIV-1 strains. Although some potential may exist for cross-resistance with amprenavir, darunavir did not display cross-resistance with other PIs in vitro. In a 24-week analysis of pooled data from the POWER 1 and 2 studies in treatment-experienced patients, 11 protease mutations associated with a reduced response to boosted darunavir were identified (V11I, V32I, L33F, I47V, I50V, I54L/M, G73S, L76V, I84V and L89V). The presence of at least three darunavir resistance-associated mutations (prevalent in approximately 7-9% of treatment-experienced patients) together with a high number of protease resistance-associated mutations were required to confer darunavir resistance. In the 48-week analysis of treatment-experienced patients with virological failure in the the TITAN study, fewer in the boosted darunavir group than in the boosted lopinavir group developed additional mutations or lost susceptibility to PIs compared with baseline. In treatment-naive patients, no primary PI-resistance-associated mutations developed in patients with an available genotype at baseline and endpoint during 96 weeks of treatment with boosted darunavir or boosted lopinavir. Oral darunavir, boosted with low-dose ritonavir, is rapidly absorbed, generally reaching peak plasma concentrations within 2.5-4 hours. The bioavailability of oral darunavir is increased by about 30% when taken with food. Darunavir is primarily metabolized by the hepatic cytochrome P450 (CYP) enzymes, primarily CYP3A. The 'boosting' dose of ritonavir acts an an inhibitor of CYP3A, thereby increasing darunavir bioavailability. Drug interactions can result when darunavir is coadministered with other drugs that are inducers or inhibitors of, or act as substrates for, CYP3A. The mean elimination half-life of boosted darunavir is approximately 15 hours. THERAPEUTIC EFFICACY: In treatment-experienced patients with HIV-1 infection, the therapeutic efficacy of oral twice-daily darunavir 600 mg, boosted with ritonavir 100 mg, versus that of investigator selected boosted CPIs (POWER studies) or versus twice-daily boosted lopinavir (administered as a fixed dose combination of lopinavir/ritonavir 400/100 mg) [TITAN study] has been evaluated in phase IIb and III studies. All patients received concurrent treatment with an OBR. Significantly more patients receiving boosted darunavir achieved a viral load reduction from baseline of >or=1 log(10) copies/mL (primary endpoint) than boosted CPI recipients at all timepoints, up to and including the final efficacy analysis at 144 weeks, in the combined analyses of POWER 1 and 2. The efficacy of boosted darunavir was noninferior to that of boosted lopinavir at 48 weeks, and was significantly better than boosted lopinavir at 48 and 96 weeks in the TITAN study, as determined by significantly more patients in the darunavir group than in the lopinavir group achieving a viral load of <400 copies/mL (primary endpoint). In the ARTEMIS study in treatment-naive patients with HIV-1 infection receiving a fixed background regimen of tenofovir and emtricitabine, once-daily boosted darunavir 800 mg was noninferior to boosted lopinavir 800 mg/day at 48 weeks. At 96 weeks, boosted darunavir was found to be more effective than boosted lopinavir, as determined by significantly more patients in the darunavir group than in the lopinavir group achieving a confirmed plasma viral load of <50 copies/mL (primary endpoint).
TOLERABILITY: Boosted darunavir was generally well tolerated in patients with HIV-1 infection in clinical trials, with most events being mild to moderate in severity. At 48-week analyses, the most common adverse events associated with once- or twice-daily boosted darunavir in treatment-experienced or -naive patients were diarrhoea, nausea, headache, upper respiratory tract infection and nasopharyngitis. The most common boosted darunavir-related grade 2-4 laboratory abnormalities in treatment-experienced patients included increased triglycerides and increased total cholesterol. Overall, boosted darunavir was associated with less diarrhoea than CPIs or boosted lopinavir in treatment-experienced and -naive patients, and a lower incidence of grade 2-4 elevations in triglycerides and total cholesterol than boosted lopinavir in treatment-naive patients. Treatment discontinuation because of adverse events occurred in 3% of boosted darunavir recipients and 7% of boosted lopinavir recipients during 48 weeks of therapy in treatment-naive patients. PHARMACOECONOMIC CONSIDERATIONS: Healthcare costs in the UK and US were estimated to be lower with boosted darunavir than with investigator-selected CPIs in treatment-experienced patients with HIV-1 infection in two 1-year cost analyses conducted from the perspective of a healthcare provider and using predicted costs based on CD4+ cell counts and clinical data from the POWER studies. The higher acquisition cost of boosted darunavir compared with CPIs was more than offset by the better efficacy of darunavir. In modelled cost-effectiveness analyses, boosted darunavir was predicted to be cost effective compared with other boosted CPIs in heavily pretreated adults from a healthcare payer perspective in Europe and from a societal perspective in the US. In a further model of a subgroup of patients with at least one primary International AIDS Society-USA PI mutation, boosted darunavir was predicted to be cost effective compared with boosted lopinavir from a healthcare payer perspective in Europe. The incremental costs per quality-adjusted life-year gained were within commonly accepted thresholds in all cost-effectiveness analyses.
The purpose of this guideline is to provide recommendations to obstetric health care providers and to minimize practice variations for HIV screening, while taking provincial and territorial recommendations into account.
OUTCOMES:
The risk of transmission of HIV from mother to fetus is significant if the mother is not treated. The primary outcome of screening for and treating HIV in pregnancy is a marked decrease in the rate of vertical transmission of HIV from mother to fetus. Secondary outcomes include confirmation of HIV infection in the woman, which allows optimization of her health and long-term management.
EVIDENCE:
The Cochrane Library and Medline were searched for English-language articles published related to HIV screening and pregnancy. Additional articles were identified through the references of these articles. All study types were reviewed.
