Effectiveness of structural-level needle/syringe programs to reduce HCV and HIV infection among people who inject drugs: a systematic review.

Needle-syringe programs (NSP) have been effective in reducing HIV and hepatitis C (HCV) infection among people who inject drugs (PWID). Achieving sustainable reductions in these blood-borne infections requires addressing structural factors so PWID can legally access NSP services. Systematic literature searches collected information on NSP coverage and changes in HIV or HCV infection prevalence or incidence at the population level. Included studies had to document biomarkers (HIV or HCV) coupled with structural-level NSP, defined by a minimum 50 % coverage of PWID and distribution of 10 or more needles/syringe per PWID per year. Fifteen studies reported structural-level NSP and changes in HIV or HCV infection prevalence/incidence. Nine reported decreases in HIV prevalence, six in HCV infection prevalence, and three reported decreases in HIV incidence. The results support NSP as a structural-level intervention to reduce population-level infection and implementation of NSP for prevention and treatment of HIV and HCV infection.

Mobile phone text messaging for promoting adherence to antiretroviral therapy in patients with HIV infection.

BACKGROUND: More than 34 million people are presently living with HIV infection. Antiretroviral therapy (ART) can help these people to live longer, healthier lives, but adherence to ART can be difficult. Mobile phone text-messaging has the potential to help promote adherence in these patients. OBJECTIVES: To determine whether mobile phone text-messaging is efficacious in enhancing adherence to ART in patients with HIV infection. SEARCH METHODS: Using the Cochrane Collaboration's validated search strategies for identifying randomised controlled trials and reports of HIV interventions, along with appropriate keywords and MeSH terms, we searched a range of electronic databases, including the Cochrane Central Register of Controlled Trials (CENTRAL), EMBASE, Literatura Latino-Americana e do Caribe em Ciências da Saúde (LILACS), MEDLINE (via PubMed), PsycINFO, Web of Science, and the World Health Organization (WHO) Global Index Medicus. The date range was from  01 January 1980 to 01 November 2011. There were no limits to language or publication status. SELECTION CRITERIA: Randomised controlled trials (RCTs) in which patients or their caregivers (in the case of infants and children) of any age, in any setting, and receiving ART were provided with mobile phone text messages as a means of promoting adherence to ART. DATA COLLECTION AND ANALYSIS: Two authors independently examined the abstracts of all identified trials. We initially identified 243 references. Seventeen full-text articles were closely reviewed. Both authors abstracted data independently, using a pre-designed, standardised data collection form. When appropriate, data were combined in meta-analysis. MAIN RESULTS: Two RCTs from Kenya were included in the review. One trial compared short weekly text messages against standard care. The other trial compared short daily, long daily, short weekly and long weekly messages against standard care. Both trials were with adult patients.In the trial comparing only short weekly messages to standard care, text messaging was associated with a lower risk of non-adherence at 12 months (RR 0.77, 95% CI 0.63 to 0.93) and with the non-occurrence of virologic failure at 12 months (RR 0.83, 95% CI 0.69 to 0.99).In the trial that compared different intervals and lengths for text-messaging to standard care, long weekly text-messaging was not significantly associated with a lower risk of non-adherence compared to standard care (RR 0.79, 95% CI 0.60 to 1.04). Patients receiving weekly text-messages of any length were at lower risk of non-adherence at 48 weeks than were patients receiving daily messages of any length (RR 0.79, 95% CI 0.64 to 0.99). There were no significant differences between weekly text-messaging of any length (RR 1.01, 95% CI 0.75 to 1.37) and between short or long messaging at either interval (RR 0.99, 95% CI 0.78 to 1.27). Compared to standard care, any daily text-messaging, whether short or long, did not reduce the risk for non-adherence (RR 0.99, 95% CI 0.82 to 1.20).In meta-analysis of both trials, any weekly text-messaging (i.e. whether short or long messages) was associated with a lower risk of non-adherence at 48-52 weeks (RR 0.78, 95% CI 0.68 to 0.89). The effect of short weekly text-messaging was also significant (RR 0.77, 95% CI 0.67 to 0.89). AUTHORS' CONCLUSIONS: There is high-quality evidence from the two RCTs that mobile phone text-messaging at weekly intervals is efficacious in enhancing adherence to ART, compared to standard care. There is high quality evidence from one trial that weekly mobile phone text-messaging is efficacious in improving HIV viral load suppression. Policy-makers should consider funding programs proposing to provide weekly mobile phone text-messaging as a means for promoting adherence to antiretroviral therapy. Clinics and hospitals should consider implementing such programs. There is a need for large RCTs of this intervention in adolescent populations, as well as in high-income countries.

Integration of HIV/AIDS services with maternal, neonatal and child health, nutrition, and family planning services.

BACKGROUND: The integration of HIV/AIDS and maternal, neonatal, child health and nutrition services (MNCHN), including family planning (FP) is recognized as a key strategy to reduce maternal and child mortality and control the HIV/AIDS epidemic. However, limited evidence exists on the effectiveness of service integration. OBJECTIVES: To evaluate the impact of integrating MNCHN-FP and HIV/AIDS services on health, behavioral, and economic outcomes and to identify research gaps. SEARCH METHODS: Using the Cochrane Collaboration's validated search strategies for identifying reports of HIV interventions, along with appropriate keywords and MeSH terms, we searched a range of electronic databases, including the Cochrane Central Register of Controlled Trials (CENTRAL), Cumulative Index to Nursing and Allied Health Literature (CINAHL), EMBASE, MEDLINE (via PubMed), and Web of Science / Web of Social Science. The date range was from 01 January 1990 to 15 October 2010. There were no limits to language. SELECTION CRITERIA: Included studies were published in peer-reviewed journals, and provided intervention evaluation data (pre-post or multi-arm study design).The interventions described were organizational strategies or change, process modifications or introductions of technologies aimed at integrating MNCHN-FP and HIV/AIDS service delivery. DATA COLLECTION AND ANALYSIS: We identified 10,619 citations from the electronic database searches and 101 citations from hand searching, cross-reference searching and interpersonal communication. After initial screenings for relevance by pairs of authors working independently, a total of 121 full-text articles were obtained for closer examination. MAIN RESULTS: Twenty peer-reviewed articles representing 19 interventions met inclusion criteria. There were no randomized controlled trials. One study utilized a stepped wedge design, while the rest were non-randomized trials, cohort studies, time series studies, cross-sectional studies, serial cross-sectional studies, and before-after studies. It was not possible to perform meta-analysis. Risk of bias was generally high. We found high between-study heterogeneity in terms of intervention types, study objectives, settings and designs, and reported outcomes. Most studies integrated FP with HIV testing (n=7) or HIV care and treatment (n=4). Overall, HIV and MNCHN-FP service integration was found to be feasible across a variety of integration models, settings and target populations. Nearly all studies reported positive post-integration effects on key outcomes including contraceptive use, antiretroviral therapy initiation in pregnancy, HIV testing, and quality of services. AUTHORS' CONCLUSIONS: This systematic review's findings show that integrated HIV/AIDS and MNCHN-FP services are feasible to implement and show promise towards improving a variety of health and behavioral outcomes. However, significant evidence gaps remain. Rigorous research comparing outcomes of integrated with non-integrated services, including cost, cost-effectiveness, and health outcomes such as HIV and STI incidence, morbidity and mortality are greatly needed to inform programs and policy.

Sexual and reproductive health services for people living with HIV: a systematic review.

People living with HIV often have unmet needs for sexual and reproductive health (SRH) services. We present results of a systematic review of studies offering SRH services targeted to people living with HIV. Studies were selected from a broader SRH and HIV linkages review. Inclusion criteria included: (1) peer-reviewed journal articles with a pre-post or multiple-arm study design; (2) reported post-intervention evaluation data; and (3) published 1 January 1990 through 31 December 2007. Nine studies were identified with an average rigour score of 5.1 out of 9. Services included family planning (one study), sexually transmitted infection (STI) services (two studies), combined family planning and STI services (three studies) and multiple services (three studies). The review identified mostly positive effects on the outcomes measured, including condom and contraceptive use and quality of services. Yet gaps remain in the research to establish the best approaches for addressing needs and choices of people living with HIV. There is a need for high-quality intervention studies to determine the most successful and cost-effective strategies for providing SRH services to people living with HIV.

Interventions to improve adherence to antiretroviral therapy in children with HIV infection.

BACKGROUND: Achieving and maintaining high levels of medication adherence are required to achieve the full benefits of antiretroviral therapy (ART), yet suboptimal adherence among children is common in both developed and developing countries. OBJECTIVES: To conduct a systematic review of the literature of evaluations of interventions for improving paediatric ART adherence. SEARCH METHODS: We created a comprehensive search strategy in order to identify all studies relevant to this topic. In July 2010, we searched the following electronic databases: EMBASE, MEDLINE, PsycINFO, Cochrane Central Register of Controlled Trials (CENTRAL), CINAHL, LILACS, Web of Science, Web of Social Science, NLM Gateway (supplemented by a manual search of the most recent abstracts not included in the Gateway database). We searched abstracts from the International AIDS Conference from 2002 to 2010, the International AIDS Society Conference on Pathogenesis, Treatment and Prevention from 2003 to 2009, and from the Conference on Retroviruses and Opportunistic Infections from 1997 to 2010. We used search strategies determined by the Cochrane Review Group on HIV/AIDS. We also contacted researchers who work in this field and checked reference lists of related systematic reviews and of all included studies. SELECTION CRITERIA: Randomised and non-randomised controlled trials of interventions to improve adherence to ART among children and adolescents (age ≤18 years) were included. Studies had to report adherence to ART as an outcome. DATA COLLECTION AND ANALYSIS: After one author performed an initial screening to exclude citations that did not meet the inclusion criteria, two authors did a second screening of those citations that likely met the criteria. For all articles that passed the second screening, full articles were pulled in order to make a final determination. Two authors then extracted data and graded methodological quality independently. Differences were resolved through discussion. MAIN RESULTS: Four studies met the inclusion criteria. No single intervention was evaluated by more than one trial. Two studies were conducted in low-income countries. Two studies were randomised controlled trials (RCT), and two were non-randomised trials. An RCT of a home-based nursing programme showed a positive effect of the intervention on knowledge and medication refills (p=.002), but no effect on CD4 count and viral load. A second RCT of caregiver medication diaries showed that the intervention group had fewer participants reporting no missed doses compared to the control group (85% vs. 92%, respectively), although this difference was not statistically significant (p=.08). The intervention had no effect on CD4 percentage or viral load. A non-randomised trial of peer support group therapy for adolescents demonstrated no change in self-reported adherence, yet the percentage of participants with suppressed viral load increased from 30% to 80% (p=.06). The second non-randomised trial found that the percentage of children achieving >80% adherence was no different between children on a lopinavir-ritonavir (LPV/r) regimen compared to children on a non-nucleoside reverse transcriptase regimen (p=.781). However, the proportion of children achieving virological suppression was significantly greater for children on the LPV/r regimen than for children on the NNRTI-containing regimen (p=.002). AUTHORS' CONCLUSIONS: A home-based nursing intervention has the potential to improve ART adherence, but more evidence is needed. Medication diaries do not appear to have an effect on adherence or disease outcomes. Two interventions, an LPV/r-containing regimen and peer support therapy for adolescents, did not demonstrate improvements in adherence, yet demonstrated greater viral load suppression compared to control groups, suggesting a different mechanism for improved health outcomes. Well-designed evaluations of interventions to improve paediatric adherence to ART are needed.

Interventions for preventing late postnatal mother-to-child transmission of HIV.

BACKGROUND: Worldwide, mother-to-child transmission (MTCT) of human immunodeficiency virus type 1 (HIV) represents the most common means by which children acquire HIV infection. Efficacious and effective interventions to prevent in utero and intrapartum transmission of HIV infection have been developed and implemented. However, a large proportion of MTCT of HIV occurs postnatally, through breast milk transmission. OBJECTIVES: The objectives of this systematic review were to collate and assess the evidence regarding interventions to decrease late postnatal MTCT of HIV, and to determine the efficacy of such interventions in decreasing late postnatal MTCT of HIV, increasing overall survival, and increasing HIV-free survival. SEARCH STRATEGY: Electronic searches were undertaken using PubMed, EMBASE and other databases for 1980-2008. Hand searches of reference lists of pertinent reviews and studies, as well as abstracts from relevant conferences, were also conducted. Experts in the field were contacted to locate any other studies. The search strategy was iterative. SELECTION CRITERIA: Randomized clinical trials assessing the efficacy of interventions to prevent MTCT of HIV through breast milk were included in the analysis. Other trials and intervention cohort studies with relevant data also were included, but only when randomization was not feasible due to the nature of the intervention (i.e., infant feeding modality). DATA COLLECTION AND ANALYSIS: Data regarding HIV infection status and vital status of infants born to HIV-infected women, according to intervention, were extracted from the reports of the studies. MAIN RESULTS: Six randomized clinical trials and one intervention cohort study were included in this review. Two trials addressed the issue of shortening the duration of (or eliminating) exposure to breast milk. In a trial of breastfeeding versus formula feeding, formula feeding was efficacious in preventing MTCT of HIV (the cumulative probability of HIV infection at 24 months was 36.7% in the breastfeeding arm and 20.5% in the formula arm [p = 0.001]), but the mortality and malnutrition rates during the first two years of life were similar in the two groups. In a trial of early cessation of breastfeeding, HIV-free survival was similar between those children who ceased breastfeeding around four months of age and those who continued breastfeeding. Another trial addressing vitamin supplementation found more cases of HIV infection among children of mothers in the vitamin A arm. Efficacy for other vitamin supplements was not shown. An intervention cohort study evaluated the risk of MTCT according to infant feeding modality, and found increased risks of MTCT among breastfed children who also received solids (hazard ratio = 10.87, p = 0.018) as well as higher 3-month mortality rates (hazard ratio = 2.06) among infants given non- breast milk feedings (instead of exclusive breastfeeding). Three trials evaluated antiretroviral prophylaxis to breastfeeding infants. One trial found that breastfeeding with zidovudine prophylaxis (transmission rate = 9.0%) was not as effective as formula feeding (transmission rate 5.6%) in preventing late postnatal HIV transmission (p = 0.04). Breastfeeding with zidovudine prophylaxis and formula feeding had comparable HIV-free survival rates at 18 months (p = 0.60). Two trials of extended nevirapine prophylaxis demonstrated efficacy. In the first (data combined from trials conducted in three different countries), a six-week course of nevirapine resulted in a lower risk of HIV transmission by six weeks of age (p=0.009), but not at six months of age (p = 0.016). In the second, nevirapine administration until 14 weeks of age (5.2%) or nevirapine with zidovudine until 14 weeks of age (6.4%) resulted in significantly lower risks of MTCT of HIV by 9 months of age than a control regimen of peripartum prophylaxis (10.6%) (p < 0.001). HIV-free survival was significantly better through the age of 9 months in both extended prophylaxis groups, and through the age of 15 months in the extended nevirapine group. AUTHORS' CONCLUSIONS: Complete avoidance of breastfeeding is efficacious in preventing MTCT of HIV, but this intervention has significant associated morbidity (e.g., diarrheal morbidity if formula is prepared without clean water). If breastfeeding is initiated, two interventions 1). exclusive breastfeeding during the first few months of life; and 2) chronic antiretroviral prophylaxis to the infant (nevirapine alone, or nevirapine with zidovudine) are efficacious in preventing transmission.

Linking sexual and reproductive health and HIV interventions: a systematic review.

BACKGROUND: The international community agrees that the Millennium Development Goals will not be achieved without ensuring universal access to both sexual and reproductive health (SRH) services and HIV/AIDS prevention, treatment, care and support. Recently, there has been increasing awareness and discussion of the possible benefits of linkages between SRH and HIV programmes at the policy, systems and service delivery levels. However, the evidence for the efficacy of these linkages has not been systematically assessed. METHODS: We conducted a systematic review of the evidence for interventions linking SRH and HIV. Structured methods were employed for searching, screening and data extraction. Studies from 1990 to 2007 reporting pre-post or multi-arm evaluation data from SRH-HIV linkage interventions were included. Study design rigour was scored on a nine-point scale. Unpublished programme reports were gathered as "promising practices". RESULTS: Of more than 50,000 citations identified, 185 studies were included in the review and 35 were analyzed. These studies had heterogeneous interventions, populations, objectives, study designs, rigour and measured outcomes. SRH-HIV linkage interventions were generally considered beneficial and feasible. The majority of studies showed improvements in all outcomes measured. While there were some mixed results, there were very few negative findings. Generally, positive effects were shown for key outcomes, including HIV incidence, sexually transmitted infection incidence, condom use, contraceptive use, uptake of HIV testing and quality of services. Promising practices (n = 23) tended to evaluate more recent and more comprehensive programmes. Factors promoting effective linkages included stakeholder involvement, capacity building, positive staff attitudes, non-stigmatizing services, and engagement of key populations. CONCLUSIONS: Existing evidence provides support for linkages, although significant gaps in the literature remain. Policy makers, programme managers and researchers should continue to advocate for, support, implement and rigorously evaluate SRH and HIV linkages at the policy, systems and service levels.

International collaboration in conducting systematic reviews: the Cochrane Collaborative Review Group on HIV Infection and AIDS.

To make sound health care decisions, policy makers, providers and researchers need access to relevant research findings. The role of systematic reviews is increasingly acknowledged as an important contribution in evidence-based health care decision making, and several review efforts, including that of the international Cochrane Collaboration, are under way. The Cochrane Collaborative Review Group on HIV Infection and AIDS (CRG on HIV/AIDS), conducts systematic reviews on the prevention and the treatment of HIV infection and AIDS and is guided by the Cochrane Collaboration's principles, which include minimizing potential bias, ensuring quality in the review process, keeping reviews up to date, and enhancing collaboration. The CDC HIV/AIDS Prevention Research Synthesis (PRS) project is working closely with the CRG on HIV/AIDS to produce Cochrane reviews of behavioral prevention interventions and on development and maintenance of a centralized, cumulative electronic database of HIV/AIDS behavioral prevention studies. Systematic reviews can play an important role in advancing evidence-based policy and practice in HIV/AIDS prevention and care.