Combination prevention: new hope for stopping the epidemic.

HIV research has identified approaches that can be combined to be more effective in transmission reduction than any 1 modality alone: delayed adolescent sexual debut, mutual monogamy or sexual partner reduction, correct and consistent condom use, pre-exposure prophylaxis with oral antiretroviral drugs or vaginal microbicides, voluntary medical male circumcision, antiretroviral therapy (ART) for prevention (including prevention of mother to child HIV transmission [PMTCT]), treatment of sexually transmitted infections, use of clean needles for all injections, blood screening prior to donation, a future HIV prime/boost vaccine, and the female condom. The extent to which evidence-based modalities can be combined to prevent substantial HIV transmission is largely unknown, but combination approaches that are truly implementable in field conditions are likely to be far more effective than single interventions alone. Analogous to PMTCT, "treatment as prevention" for adult-to-adult transmission reduction includes expanded HIV testing, linkage to care, antiretroviral coverage, retention in care, adherence to therapy, and management of key co-morbidities such as depression and substance use. With successful viral suppression, persons with HIV are far less infectious to others, as we see in the fields of sexually transmitted infection control and mycobacterial disease control (tuberculosis and leprosy). Combination approaches are complex, may involve high program costs, and require substantial global commitments. We present a rationale for such investments and cite an ongoing research agenda that seeks to determine how feasible and cost-effective a combination prevention approach would be in a variety of epidemic contexts, notably that in a sub-Saharan Africa

Ensuring HIV Data Availability, Transparency and Integrity in the MENA Region Comment on “Improving the Quality and Quantity of HIV Data in the Middle East and North Africa: Key Challenges and Ways Forward”

In this commentary, we elaborate on the main points that Karamouzian and colleagues have made about HIV data scarcity in Middle Eastern and North African (MENA) countries. Without accessible and reliable data, no epidemic can be managed effectively or efficiently. Clearly, increased investments are needed to bolster capabilities to capture and interpret HIV surveillance data. We believe that this enhanced capacity can be achieved, in part, by leveraging and repurposing existing data platforms, technologies and patient cohorts. An immediate modest investment that capitalizes on available infrastructure can generate data on the HIV burden and spread that can be persuasive for MENA policy-makers to intensify efforts to track and contain the growing HIV epidemic in this region. A focus on key populations will yield the most valuable data, including among men who have sex with men (MSM), transgender women and men, persons who inject drugs (PWIDs), female partners of high risk men and female sex worker

Assessing Individual and Disseminated Effects in Network-Randomized Studies

Implementation trials often involve clustering via risk networks, where only some participants directly received the intervention. The individual effect is that among directly treated persons beyond being in an intervention network; the disseminated effect is that among persons engaged with those directly treated. We employ a causal inference framework and discuss assumptions and estimators for individual and disseminated effects and apply them to HIV Prevention Trials Network 037. HIV Prevention Trials Network 037 was a Phase III, network-level, randomized controlled HIV prevention trial conducted in the US and Thailand from 2002 to 2006 that recruited persons who injected drugs, who received either intervention or control, and their risk network members, who received no direct intervention. Combining individual and disseminated, a 35% composite rate reduction was observed in the adjusted model (95% confidence interval = 0.47, 0.90). Methodology is now available to estimate the full set of these effects enhancing knowledge gained from network-randomized trials. Although the overall effect gains validity from network randomization, we show that it will, in general, be less than the composite effect. Additionally, if only index participants benefit from the intervention, as the network size increases, the overall effect tends to the null, an unfortunate and misleading conclusion

Hepatitis B and hepatitis C in Pakistan: prevalence and risk factors

SummaryBackgroundPakistan carries one of the world’s highest burdens of chronic hepatitis and mortality due to liver failure and hepatocellular carcinomas. However, national level estimates of the prevalence of and risk factors for hepatitis B and hepatitis C are currently not available.MethodsWe reviewed the medical and public health literature over a 13-year period (January 1994–September 2007) to estimate the prevalence of active hepatitis B and chronic hepatitis C in Pakistan, analyzing data separately for the general and high-risk populations and for each of the four provinces. We included 84 publications with 139 studies (42 studies had two or more sub-studies).ResultsMethodological differences in studies made it inappropriate to conduct a formal meta-analysis to determine accurate national prevalence estimates, but we estimated the likely range of prevalence in different population sub-groups. A weighted average of hepatitis B antigen prevalence in pediatric populations was 2.4% (range 1.7–5.5%) and for hepatitis C antibody was 2.1% (range 0.4–5.4%). A weighted average of hepatitis B antigen prevalence among healthy adults (blood donors and non-donors) was 2.4% (range 1.4–11.0%) and for hepatitis C antibody was 3.0% (range 0.3–31.9%). Rates in the high-risk subgroups were far higher.ConclusionsData suggest a moderate to high prevalence of hepatitis B and hepatitis C in different areas of Pakistan. The published literature on the modes of transmission of hepatitis B and hepatitis C in Pakistan implicate contaminated needle use in medical care and drug abuse and unsafe blood and blood product transfusion as the major causal factors

The Effect of Complete Integration of HIV and TB Services on Time to Initiation of Antiretroviral Therapy: A Before-After Study.

Studies have shown that early ART initiation in TB/HIV co-infected patients lowers mortality. One way to implement earlier ART commencement could be through integration of TB and HIV services, a more efficient model of care than separate, vertical programs. We present a model of full TB/HIV integration and estimate its effect on time to initiation of ART

HIV-prevention science at a crossroads: advances in reducing sexual risk.

Purpose of review—We review the current state of evidence-based prevention strategies for reducing sexual transmission of HIV. The combined programmatic and scientific efforts through 2008 to reduce sexual transmission of HIV have failed to reduce substantially the global pandemic. Recent findings—Prevention interventions to reduce HIV infection target behavioral, biomedical, and structural risk factors. Some of these prevention strategies have been evaluated in randomized clinical trials (RCTs) with HIV seroincidence endpoints. When RCTs are not feasible, a variety of observational and quasiexperimental research approaches can provide insight as to program effectiveness of specific strategies. Only five RCTs have demonstrated a notable decrease in sexually acquired HIV incidence. These include the Mwanza study of syndromic management of sexually transmitted diseases and three male circumcision trials in East Africa; a microbicide trial reported in 2009 shows substantial promise for the efficacy of PRO 2000 (0.5% gel). Summary—The combined programmatic and scientific efforts to reduce sexual transmission of HIV have made incremental progress. New prevention tools are needed to stem the continued spread of HIV, though microbicides and vaccines will take many more years to develop, test, and deploy. Combination strategies of existing modalities should be tested to evaluate the potential for more proximate prevention benefits

Achieving Pregnancy Safely in HIV-Affected Individuals and Couples: An Important Strategy to Eliminate HIV Transmission From Mother-To-Child and Between Sexual Partners

HIV-infected individuals are living longer, more productive lives. HIV-affected individuals and couples experience personal and social desires to reproduce for all the same reasons as uninfected individuals and couples,1 and thus require safe reproductive options. HIV prevention interventions often do not consider the childbearing desires of HIV-affected individuals or couples, especially in low- and middle-income countries (LMICs). Failure to assist women with desired fertility can contribute to continued HIV transmission and must be addressed within national elimination of mother-to-child transmission (eMTCT) strategies. A human rights perspective suggests that HIV-affected couples* should have the same ability to choose if and when to have children as HIV-unaffected couples, including access to pre-pregnancy counseling, contraceptives, and, when needed, abortion services. This holistic view includes assistance in mitigating HIV transmission risk when children are desired. In high-income countries, HIV-affected individuals and couples have access to an array of options: (1) treatment of the HIV-infected partner as prevention of transmission to the uninfected partner in conjunction with timed condomless intercourse2**; (2) preexposure prophylaxis (PrEP) for the uninfected partner3; (3) assisted reproductive services, including timed vaginal insemination and sperm washing with intrauterine insemination or in-vitro fertilization4,5 4,5; (4) sperm donation; and (5) adoption.1,6 1,6 In contrast, access to methods of becoming pregnant in LMICs are limited by cost, availability, and sometimes a lack of appreciation by policymakers of the desires and rights of HIV-affected individuals/couples to have children safely. Simple fertility methods may not be discussed as a component of routine HIV care and treatment counseling due to a lack of awareness or knowledge about their safety, affordability, or efficacy.7 To enhance the armamentarium of HIV prevention and reproductive services to achieve zero perinatal and sexual transmission, “safer conception”, and fertility services should be integrated into existing PMTCT strategies. The existing four-pronged prevention of mother-to-child transmission (PMTCT) strategy, developed by the World Health Organization (WHO), includes (1) prevention of HIV in women of reproductive age; (2) prevention of unintended pregnancy in women with HIV; (3) prevention of HIV transmission from mother to child; and (4) the provision of ongoing care and support to mothers, their children, and their families.8 All four prongs are rooted in prevention of sexual and perinatal HIV transmission, HIV testing, use of ART for mothers and infants, exclusive breastfeeding, and access to contraceptive services. The continuum of care services are included within the third WHO prong, including antenatal, intrapartum, and postpartum/postnatal health care services (Fig. 1). However, provision of education and clinical services for achieving pregnancy safely is not uniquely addressed in the current WHO eMTCT strategy,8 and we believe that they should be included within the continuum of care services of the third prong of the strategy that addresses: “prevention of HIV transmission from mother to child.