Early initiation of antiretroviral therapy in HIV-infected adults and adolescents: a systematic review.

OBJECTIVES: The objective of this review was to update evidence on when to initiate antiretroviral therapy (ART) to inform revision of the 2013 WHO guidelines for ART in low and middle-income countries. DESIGN: A systematic review and meta-analysis. METHODS: We comprehensively searchescohorts. Outcomes were mortality, clinical progression, virologic failure, immunologic recover, and severe adverse events. We pooled data across studies and estimated summary effect sizes. We graded the quality of evidence from the literature for each outcome. RESULTS: We identified 24 studies; 3 were RCTs. Studies found reduced risk of mortality [1 RCT: hazard ratio 0.77, 95% confidence interval (CI) 0.34-1.76; 13 cohorts: relative risk (RR) 0.66, 95% CI 0.55-0.79], progression to AIDS or death (2 RCTs: RR 0.48, 95% CI 0.26-0.91; 9 cohorts: RR 0.70, 95% CI 0.40-1.24) and diagnosis of a non-AIDS-defining illness (1 RCT: RR 0.14, 95% CI 0.03-0.64; 1 cohort: RR 0.47, 95% CI 0.23-0.98), and an increased risk of grade 3/4 laboratory abnormalities in patients initiating ART at at least 350 cells/µl (1 RCT: RR 1.49, 95% CI 1.25-1.77). The quality of evidence was low or very low for clinical outcomes due to few events and imprecision, and high for adverse events. CONCLUSIONS: Our findings contributed to the evidence base for the revised 2013 WHO guidelines on ART, which recommend initiating ART at CD4 T-cell counts of 350-500 cells/µl, but not above 500 cells/µl compared to initiating it later when CD4 T-cell counts fall below 350 cells/µl.

Predicting treatment failure in adults and children on antiretroviral therapy: a systematic review of the performance characteristics of the 2010 WHO immunologic and clinical criteria for virologic failure.

OBJECTIVE: We systematically reviewed the performance of 2010 WHO immunologic and clinical criteria for predicting virologic failure in HIV-infected patients on antiretroviral therapy (ART). DESIGN: Systematic review. METHODS: We used Cochrane Collaboration methods. We calculated unweighted sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of immunologic and clinical criteria for predicting virologic failure. RESULTS: We identified 18 studies. Sixteen assessed immunologic criteria in adults; 12 defined virologic failure as a plasma viral load of more than 50 to more than 1000 copies/ml in adults, three as viral load at least 5000 copies/ml, and two as viral load more than 10,000 copies/ml; the sensitivity ranged from 16.8 to 54.9%, specificity from 82.9 to 95.5%, PPV from 15.0 to 38.8%, and NPV from 90.9 to 98.6%. Seven studies assessed clinical criteria to predict viral load of more than 50 to more than 1000 copies/ml; the sensitivity was 11.0%, specificity 90.5%, PPV 44.9%, and NPV 90.2%. Seven studies assessed clinical or immunologic criteria defining virologic failure as viral load of more than 50 to more than 1000 copies/ml; their sensitivity was 26.6%, specificity 85.9%, PPV 49.4%, and NPV 91.1%. Four studies assessed immunologic criteria in children; three defined virologic failure as viral load at least 5000 copies/ml and one as viral load at least 400 copies/ml. The sensitivity ranged from 4.5 to 6.3%, specificity from 97.7 to 99.3%, PPV from 20.0 to 54.9%, and NPV from 85.5 to 91.8%. CONCLUSION: The 2010 WHO clinical and immunologic criteria are insensitive and have low PPV for predicting virologic failure. These data support the strong recommendation 2013 treatment guidelines that viral load testing be used to monitor for, diagnose, and confirm ART failure.

Improving antiretroviral therapy scale-up and effectiveness through service integration and decentralization.

BACKGROUND: Current service delivery systems do not reach all people in need of antiretroviral therapy (ART). In order to inform the operational and service delivery section of the WHO 2013 consolidated antiretroviral guidelines, our objective was to summarize systematic reviews on integrating ART delivery into maternal, newborn, and child health (MNCH) care settings in countries with generalized epidemics, tuberculosis (TB) treatment settings in which the burden of HIV and TB is high, and settings providing opiate substitution therapy (OST); and decentralizing ART into primary health facilities and communities. DESIGN: A summary of systematic reviews. METHODS: The reviewers searched PubMed, Embase, PsycINFO, Web of Science, CENTRAL, and the WHO Index Medicus databases. Randomized controlled trials and observational cohort studies were included if they compared ART coverage, retention in HIV care, and/or mortality in MNCH, TB, or OST facilities providing ART with MNCH, TB, or OST facilities providing ART services separately; or primary health facilities or communities providing ART with hospitals providing ART. RESULTS: The reviewers identified 28 studies on integration and decentralization. Antiretroviral therapy integration into MNCH facilities improved ART coverage (relative risk [RR] 1.37, 95% confidence interval [CI] 1.05-1.79) and led to comparable retention in care. ART integration into TB treatment settings improved ART coverage (RR 1.83, 95% CI 1.48-2.23) and led to a nonsignificant reduction in mortality (RR 0.55, 95% CI 0.29-1.05). The limited data on ART integration into OST services indicated comparable rates of ART coverage, retention, and mortality. Partial decentralization into primary health facilities improved retention (RR 1.05, 95% CI 1.01-1.09) and reduced mortality (RR 0.34, 95% CI 0.13-0.87). Full decentralization improved retention (RR 1.12, 95% CI 1.08-1.17) and led to comparable mortality. Community-based ART led to comparable rates of retention and mortality. CONCLUSION: Integrating ART into MNCH, TB, and OST services was often associated with improvements in ART coverage, and decentralization of ART into primary health facilities and communities was often associated with improved retention. Neither integration nor decentralization was associated with adverse outcomes. These data contributed to recommendations in the WHO 2013 consolidated antiretroviral guidelines to integrate ART delivery into MNCH, TB, and OST services and to decentralize ART.

The accessibility of firearms and risk for suicide and homicide victimization among household members: a systematic review and meta-analysis.

BACKGROUND: Research suggests that access to firearms in the home increases the risk for violent death. PURPOSE: To understand current estimates of the association between firearm availability and suicide or homicide. DATA SOURCES: PubMed, EMBASE, the Cochrane Central Register of Controlled Trials, and Web of Science were searched without limitations and a gray-literature search was performed on 23 August 2013. STUDY SELECTION: All study types that assessed firearm access and outcomes between participants with and without firearm access. There were no restrictions on age, sex, or country. DATA EXTRACTION: Two authors independently extracted data into a standardized, prepiloted data extraction form. DATA SYNTHESIS: Odds ratios (ORs) and 95% CIs were calculated, although published adjusted estimates were preferentially used. Summary effects were estimated using random- and fixed-effects models. Potential methodological reasons for differences in effects through subgroup analyses were explored.Data were pooled from 16 [not 15] observational studies that assessed he odds of suicide or homicide, yielding pooled ORs of 3.24(95% CI, 2.41 to 4.40) and 2.00 (CI, 1.56 to 3.02) [not 1.94 (CI, .44 to 2.93)], respectively [corrected], respectively. When only studies that used interviews to determine firearm accessibility were considered, the pooled OR for suicide was 3.14 (CI, 2.29 to 4.43). LIMITATIONS: Firearm accessibility was determined by survey interviews in most studies; misclassification of accessibility may have occurred. Heterogeneous populations of varying risks were synthesized to estimate pooled odds of death. CONCLUSION: Access to firearms is associated with risk for completed suicide and being the victim of homicide. PRIMARY FUNDING SOURCE: None.

Yellow fever vaccine for patients with HIV infection.

BACKGROUND: Yellow fever (YF) is an acute viral haemorrhagic disease prevalent in tropical Africa and Latin America. The World Health Organization (WHO) estimates that there are 200,000 cases of YF and 30,000 deaths worldwide annually. Treatment for YF is supportive, but a live attenuated virus vaccine is effective for preventing infection. WHO recommends immunisation for all individuals > 9 months living in countries or areas at risk. However, the United States Advisory Committee on Immunization Practices (ACIP) advises that YF vaccine is contraindicated in individuals with HIV. Given the large populations of HIV-infected individuals living in tropical areas where YF is endemic, YF vaccine may be an important intervention for preventing YF in immunocompromised populations. OBJECTIVES: To assess the risk and benefits of YF immunisation for people infected with HIV. SEARCH METHODS: We used standard Cochrane methods to search electronic databases and conference proceedings with relevant search terms without limits to language. SELECTION CRITERIA: Randomised controlled trials and cohort studies of individuals with HIV infection who received YF vaccine (17DD or 17D-204). DATA COLLECTION AND ANALYSIS: Two authors screened abstracts of references identified by electronic or bibliographic searches according to inclusion and exclusion criteria as detailed in the protocol. We identified 199 references and examined 19 in detail for study eligibility. Data were abstracted independently using a standardised abstraction form. MAIN RESULTS: Three cohort studies were included in the review. They examined 484 patients with HIV infection who received YF immunisation. Patients with HIV infection developed significantly lower concentrations of neutralising antibodies in the first year post immunisation compared to uninfected patients, though decay patterns were similar for recipients regardless of HIV infection. No study patient with HIV infection suffered serious adverse events as a result of YF vaccination. AUTHORS' CONCLUSIONS: YF vaccination can produce protective levels of neutralising antibodies in HIV patients. Immunogenicity of YF vaccine is slightly less in HIV-infected patients compared to HIV-uninfected patients. No serious adverse events related to YF vaccine were observed in HIV-infected study participants. At time of immunisation, higher CD4 cell counts and lower HIV RNA levels in patients with HIV infection seem to be key determinants for development of protective titres of neutralising antibodies. The quality of the evidence for all outcomes was low to very low. YF vaccine may potentially be used safely in HIV-infected patients, although our conclusions are limited by small numbers of patients who have been reported. To assure maximum effectiveness YF vaccine should be given to HIV-infected patients after HIV replication has been suppressed.

Antiretroviral therapy for prevention of HIV transmission in HIV-discordant couples.

CLINICAL QUESTION Does treating the HIV-infected partner in a serodiscordant couple reduce the risk of HIV transmission to the uninfected partner? BOTTOM LINE Compared with serodiscordant couples without treatment, couples in which the infected partner is treated with antiretroviral therapy have a lower risk of HIV transmission.

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.

Antiretroviral therapy for prevention of HIV transmission in HIV-discordant couples.

BACKGROUND: Antiretroviral drugs have been shown to reduce risk of mother-to-child transmission of human immunodeficiency virus (HIV) and are also widely used for post-exposure prophylaxis for parenteral and sexual exposures. Sexual transmission may be lower in couples in which one partner is infected with HIV and the other is not and the infected partner is on antiretroviral therapy (ART). OBJECTIVES: To determine if ART use in an HIV-infected member of an HIV-discordant couple is associated with lower risk of HIV transmission to the uninfected partner compared to untreated discordant couples. SEARCH METHODS: We used standard Cochrane methods to search electronic databases and conference proceedings with relevant search terms without limits to language. SELECTION CRITERIA: Randomised controlled trials (RCT), cohort studies and case-control studies of HIV-discordant couples in which the HIV-infected member of the couple was being treated or not treated with ART DATA COLLECTION AND ANALYSIS: Abstracts of all trials identified by electronic or bibliographic scanning were examined independently by two authors. We initially identified 3,833 references and examined 87 in detail for study eligibility. Data were abstracted independently using a standardised abstraction form. MAIN RESULTS: One RCT and nine observational studies were included in the review. These ten studies identified 2,112 episodes of HIV transmission, 1,016 among treated couples and 1,096 among untreated couples. The rate ratio for the single randomised controlled trial was 0.04 [95% CI 0.00, 0.27]. All index partners in this study had CD4 cell counts at baseline of 350-550 cells/µL. Similarly, the summary rate ratio for the nine observational studies was 0.58 [95% CI 0.35, 0.96], with substantial heterogeneity (I(2)=64%). After excluding two studies with inadequate person-time data, we estimated a summary rate ratio of 0.36 [95% CI 0.17, 0.75] with substantial heterogeneity (I(2)=62%). We also performed subgroup analyses among the observational studies to see if the effect of ART on prevention of HIV differed by the index partner's CD4 cell count. Among couples in which the infected partner had ≥350 CD4 cells/µL, we estimated a rate ratio of 0.12 [95% CI 0.01, 1.99]. In this subgroup, there were 247 transmissions in untreated couples and 30 in treated couples. AUTHORS' CONCLUSIONS: ART is a potent intervention for prevention of HIV in discordant couples in which the index partner has ≤550 CD4 cells/µL. A recent multicentre RCT confirms the suspected benefit seen in earlier observational studies and reported in more recent ones. Questions remain about durability of protection, the balance of benefits and adverse events associated with earlier therapy, long-term adherence and transmission of ART-resistant strains to partners. Resource limitations and implementation challenges must also be addressed.Counselling, support, and follow up, as well as mutual disclosure, may have a role in supporting adherence, so programmes should be designed with these components. In addition to ART provision, the operational aspects of delivering such programmes must be considered.

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.

Using GRADE methodology for the development of public health guidelines for the prevention and treatment of HIV and other STIs among men who have sex with men and transgender people.

BACKGROUND: The World Health Organization (WHO) Department of HIV/AIDS led the development of public health guidelines for delivering an evidence-based, essential package of interventions for the prevention and treatment of HIV and other sexually transmitted infections (STIs) among men who have sex with men (MSM) and transgender people in the health sector in low- and middle-income countries. The objective of this paper is to review the methodological challenges faced and solutions applied during the development of the guidelines. METHODS: The development of the guidelines followed the WHO guideline development process, which utilizes the GRADE approach. We identified, categorized and labeled the challenges identified in the guidelines development process and described the solutions through an interactive process of in-person and electronic communication. RESULTS: We describe how we dealt with the following challenges: (1) heterogeneous and complex interventions; (2) paucity of trial data; (3) selecting outcomes of interest; (4) using indirect evidence; (5) integrating values and preferences; (6) considering resource use; (7) addressing social and legal barriers; (8) wording of recommendations; and (9) developing global guidelines. CONCLUSION: We were able to successfully apply the GRADE approach for developing recommendations for public health interventions. Applying the general principles of the approach while carefully considering specific challenges can enhance both the process and the outcome of guideline development.

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.

Population-based biomedical sexually transmitted infection control interventions for reducing HIV infection.

BACKGROUND: The transmission of sexually transmitted infections (STIs) is closely related to the sexual transmission of human immunodeficiency virus (HIV). Similar risk behaviours, such as frequent unprotected intercourse with different partners, place people at high risk of HIV and STIs, and there is clear evidence that many STIs increase the likelihood of HIV transmission. STI control, especially at the population or community level, may have the potential to contribute substantially to HIV prevention.This is an update of an existing Cochrane review. The review's search methods were updated and its inclusion and exclusion criteria modified so that the focus would be on one well-defined outcome. This review now focuses explicitly on population-based biomedical interventions for STI control, with change in HIV incidence being an outcome necessary for a study's inclusion. OBJECTIVES: To determine the impact of population-based biomedical STI interventions on the incidence of HIV infection. SEARCH STRATEGY: We searched PubMed, EMBASE, the Cochrane Central Register of Controlled Trials (CENTRAL), Web of Science/Social Science, PsycINFO, and Literatura Latino Americana e do Caribe em Ciências da Saúde (LILACS), for the period of 1 January1980 - 16 August 2010. We initially identified 6003 articles and abstracts. After removing 776 duplicates, one author (TH) removed an additional 3268 citations that were clearly irrelevant. Rigorously applying the inclusion criteria, three authors then independently screened the remaining 1959 citations and abstracts. Forty-six articles were chosen for full-text scrutiny by two authors. Ultimately, four studies were included in the review.We also searched the Aegis database of conference abstracts, which includes the Conference on Retroviruses and Opportunistic Infections (CROI), the International AIDS Conference (IAC), and International AIDS Society Conference on HIV Pathogenesis, Treatment and Prevention (IAS) meetings from their inception dates (1993, 1985 and 2001, respectively) through 2007. We manually searched the web sites of those conferences for more recent abstracts (up to 2010, 2010 and 2009, respectively)  In addition to searching the clinical trials registry at the US National Institutes of Health, we also used the metaRegister of Controlled Trials.We checked the reference lists of all studies identified by the above methods. SELECTION CRITERIA: Randomised controlled trials involving one or more biomedical interventions in general populations (as opposed to occupationally or behaviourally defined groups, such as sex workers) in which the unit of randomisation was either a community or a treatment facility and in which the primary outcome was incident HIV infection. The term "community" was interpreted to include a group of villages, an arbitrary geographical division, or the catchment population of a group of health facilities. DATA COLLECTION AND ANALYSIS: Three authors (BN, LB, TH) independently applied the inclusion criteria to potential studies, with any disagreements resolved by discussion. Trials were examined for completeness of reporting. Data were abstracted independently using a standardised abstraction form. MAIN RESULTS: We included four trials. One trial evaluated mass treatment of all individuals in a particular community. The other three trials evaluated various combinations of improved syndromic STI management in clinics, STI counselling, and STI treatment.In the mass treatment trial in rural southwestern Uganda, after three rounds of treatment of all community members for STIs, the adjusted rate ratio (aRR) of incident HIV infection was 0.97 (95% CI 0.81 - 1.2), indicating no effect of the intervention. The three STI management intervention studies were all conducted in rural parts of Africa. One study, in northern Tanzania, showed that the incidence of HIV infection in the intervention groups (strengthened syndromic management of STIs in primary care clinics) was 1.2% compared with 1.9% in the control groups (aRR = 0.58, 95% CI 0.42 - 0.79), corresponding to a 42% reduction (95% CI 21.0% - 58.0%) in HIV incidence in the intervention group. Another study, conducted in rural southwestern Uganda, showed that the aRR of behavioural intervention and STI management compared to control on HIV incidence was 1.00 (95% CI 0.63 - 1.58). In the third STI management trial, in eastern Zimbabwe, there was no effect of the intervention on HIV incidence (aRR = 1.3, 95% CI 0.92 - 1.8). These are consistent with data from the mass treatment trial showing no intervention effect. Overall, pooling the data of the four studies showed no significant effect of any intervention (rate ratio [RR] = 0.97, 95% CI 0.78 - 1.2).Combining the mass treatment trial and one of the STI management trials, we find that there is a significant 12.0% reduction in the prevalence of syphilis for those receiving a biomedical STI intervention (RR 0.88, 95% CI 0.80 - 0.96). For gonorrhoea, we find a statistically significant 51.0% reduction in its prevalence in those receiving any of these interventions (RR 0.49, 95% CI 0.31 - 0.77). Finally, for chlamydia, we found no significant difference between any biomedical intervention and control (RR 1.03, 95% CI 0.77 - 1.4). AUTHORS' CONCLUSIONS: We failed to confirm the hypothesis that STI control is an effective HIV prevention strategy. Improved STI treatment services were shown in one study to reduce HIV incidence in an environment characterised by an emerging HIV epidemic (low and slowly rising prevalence), where STI treatment services were poor and where STIs were highly prevalent; Incidence was not reduced in two other settings. There is no evidence for substantial benefit from a presumptive treatment intervention for all community members. There are, however, other compelling reasons why STI treatment services should be strengthened, and the available evidence suggests that when an intervention is accepted it can substantially improve quality of services provided.

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.