"Well, not me, but other women do not register because..."- Barriers to seeking antenatal care in the context of prevention of mother-to-child transmission of HIV among Zimbabwean women: a mixed-methods study.

Background: While barriers to uptake of antenatal care (ANC) among pregnant women have been explored, much less is known about how integrating prevention of mother-to-child transmission (PMTCT) programmes within ANC services affects uptake. We explored barriers to uptake of integrated ANC services in a poor Zimbabwean community.

Methods: A cross-sectional survey was conducted among post-natal women at Mbare Clinic, Harare, between September 2010 and February 2011.

Cohort Profile: Collaboration of Observational HIV Epidemiological Research Europe (COHERE) in EuroCoord.

Many questions about the long-term effects of combination antiretroviral therapy (cART) on clinical outcomes in people living with HIV (PLWH) and their impact on health systems remain unanswered. The Collaboration of Observational HIV Epidemiological Research Europe (COHERE) was formed in 2005 to pool and harmonize existing longitudinal data on people living with HIV in Europe, to answer key research questions that could not be addressed adequately by individual cohorts. Key research questions include long-term prognosis, rare outcomes, and variations across patient groups, settings and health systems.

Manuscript title: Facilitators and barriers to cotrimoxazole prophylaxis among HIV exposed babies: a qualitative study from Harare, Zimbabwe.

Background: Implementation of cotrimoxazole prophylaxis (CTX-p) among HIV-exposed infants (HEI) is poor in southern Africa. We conducted a study to investigate barriers to delivery of CTX-p to HEI in Zimbabwe at each step of the care cascade. Here we report findings of the qualitative component designed to investigate issues related to adherence conducted among women identified as HIV positive whose babies were started on CTX-p postnatally.

The magnitude of loss to follow-up of HIV-exposed infants along the prevention of mother-to-child HIV transmission continuum of care: a systematic review and meta-analysis.

Introduction: Although prevention of mother-to-child HIV transmission (PMTCT) programs are widely implemented, many children do not benefit from them because of loss to follow-up (LTFU). We conducted a systematic review to determine the magnitude of infant/baby LTFU along the PMTCT cascade.

Methods: Eligible publications reported infant LTFU outcomes from standard care PMTCT programs (not intervention studies) at any stage of the cascade.

Evidence for Action on HIV Treatment and Care Systems in low and middle-income countries: background and introduction.

Despite the unprecedented scale-up of treatment for HIV in low and middle-income countries over the past decade, 49% of adults and 77% of children in need of HIV treatment still do not have access to it. ART programmes that were initially set up as an emergency response now need to be adapted to ensure that they include all the essential components and are well integrated with other health services; meet the needs of special groups, including children, adolescents, pregnant women and older people; address the mental health needs of HIV-positive people; and monitor as well as report their impact in valid and comparable ways.This supplement is an output from the Evidence for Action on HIV Treatment and Care Systems research programme consortium.

HIV treatment and care systems: the way forward.

This article summarizes the conclusions and recommendations from the articles in this supplement. It presents a call for greater clarity of thinking related to projections of future need for HIV treatment and care. The demands placed on HIV treatment and care services will increase for the foreseeable future while the resources available for this are likely to remain constant or to decline.

Evaluating the systems used to monitor HIV populations accessing therapy and care in low-income and lower-middle-income countries.

Objectives: The scale-up of delivery of antiretroviral therapy (ART) in low-income and middle-income countries has been coupled with the collection of data aimed at monitoring the welfare of the HIV-positive and treated populations in those countries. We aimed to compare the data items collected and reported and the degree of harmonization achieved following the publication of WHO tools for collection and reporting of these data in 2006, and of two United Nations General Assembly Special Session (UNGASS) indicators relating to the health of patients on ART in 2008.

Design: Retrospective examination of monitoring tools used in four countries in 2008 and 2010.

Common inherited mitochondrial DNA mutations and nucleoside reverse transcriptase inhibitor-induced severe hyperlactataemia in HIV-infected adults: an exploratory study.

Background: Genetic predisposition to dideoxynucleoside-induced mitochondrial dysfunction might be related to mitochondrial DNA (mtDNA) polymorphisms. Severe hyperlactataemia is probably the best model to assess such a predisposition.

Methods: For this exploratory study in White European and Black African HIV-infected adults, hypervariable region 1 of mtDNA samples from peripheral blood mononuclear cells or buccal smears of patients who have developed confirmed severe hyperlactataemia was sequenced.

Does trimethoprim-sulfamethoxazole prophylaxis for HIV induce bacterial resistance to other antibiotic classes? Results of a systematic review.

Background: Trimethoprim-sulfamethoxazole (TMP-SMX) prophylaxis has long been recommended for immunosuppressed HIV-infected adults and children born to HIV-infected women. Despite this, many resource-limited countries have not implemented this recommendation, partly because of fear of widespread antimicrobial resistance not only to TMP-SMX, but also to other antibiotics. We aimed to determine whether TMP-SMX prophylaxis in HIV-infected and/or exposed individuals increases bacterial resistance to antibiotics other than TMP-SMX.

Risk factors for fatality in HIV-infected patients with dideoxynucleoside-induced severe hyperlactataemia or lactic acidosis.

Background: Lactic acidosis (LA) and severe hyperlactataemia (HL) are infrequent but serious complications of antiretroviral therapy that have been associated with a high fatality rate.

Methods: In a multinational retrospective cohort study, LA was defined as arterial blood pH<7.35, bicarbonate <20 mmol/l and lactate above normal, and HL as confirmed blood lactate >5 mmol/l.

An appraisal of indicators used to monitor the treated population in antiretroviral programmes in low-income countries.

Monitoring the progress of HIV programmes is vital, as services are scaled up to include increasing numbers in need of care. Globally, the presence of multiple donors at all levels of HIV care has produced vast monitoring systems. Within HIV-treatment programmes in low and middle-income countries, directly assessing long-term outcomes such as survival is problematic, so indicators are used to monitor the progress of the treated population.

Risk of myocardial infarction in patients with HIV infection exposed to specific individual antiretroviral drugs from the 3 major drug classes: the data collection on adverse events of anti-HIV drugs (D:A:D) study.

BACKGROUND. The risk of myocardial infarction (MI) in patients with human immunodeficiency virus (HIV) infection has been assessed in 13 anti-HIV drugs in the Data Collection on Adverse Events of Anti-HIV Drugs (D:A:D) study. METHODS.

The risk of developing peripheral neuropathy induced by nucleoside reverse transcriptase inhibitors decreases over time: evidence from the Delta trial.

Background: Peripheral neuropathy (PN) in HIV-infected individuals is thought be due to a toxic effect on mitochondria induced by some nucleoside reverse transcriptase inhibitors (NRTI).

Methods: A time-to-event analysis was performed using data from the Delta trial to study the incidence of PN in HIV-infected individuals receiving zidovudine (AZT) alone or in combination with didanosine (ddl) or zalcitabine (ddC). In an on-treatment analysis, changes in the incidence of PN by duration of treatment were directly estimated using a flexible parametric survival model.

Use of nucleoside reverse transcriptase inhibitors and risk of myocardial infarction in HIV-infected patients enrolled in the D:A:D study: a multi-cohort collaboration.

Background: Whether nucleoside reverse transcriptase inhibitors increase the risk of myocardial infarction in HIV-infected individuals is unclear. Our aim was to explore whether exposure to such drugs was associated with an excess risk of myocardial infarction in a large, prospective observational cohort of HIV-infected patients.

Methods: We used Poisson regression models to quantify the relation between cumulative, recent (currently or within the preceding 6 months), and past use of zidovudine, didanosine, stavudine, lamivudine, and abacavir and development of myocardial infarction in 33 347 patients enrolled in the D:A:D study.

A new approach for 'deep salvage' trials in advanced HIV infection.

One of the most difficult problems in HIV care today is the management of individuals infected with multidrug-resistant viruses. Well-controlled, carefully designed clinical trials have recently resulted in the approval of several new antiviral agents for the treatment of drug-resistant HIV. The design of these trials has come at the cost of the predictable emergence of drug-resistant viruses among individuals randomly assigned to receive a suboptimal revised treatment regimen.

Monocyte derived dendritic cells from HIV-1 infected individuals partially reconstitute CD4 T-cell responses.

Objectives: The study tests the hypothesis that monocyte derived dendritic cells from HIV-1 infected individuals are normal and can restore impaired CD4 T-cell antigen specific responses.

Design: Monocyte derived dendritic cells were isolated from individuals at three different stages of HIV-1 infection with a wide spectrum of viral load and CD4 T-cell counts, and from healthy volunteers. The cell surface phenotype and allogeneic stimulatory potential of these dendritic cells was documented.

HIV drug resistance testing: is the evidence really there?

Objectives: To assess the strength of evidence supporting the routine use of HIV drug resistance testing.

Design: A critical review of all studies relating to the clinical utility of HIV resistance testing, with a focus on randomized trials.

Results: Two cohort studies found no evidence of a difference in virological response in patients who had resistance testing compared with matched controls.

Drug-resistant HIV-1 in the semen of men receiving antiretroviral therapy with acute sexually transmitted infections.

Sexually transmitted infections may enhance the sexual transmission of HIV-1. It is possible that loss of virological control in patients with such infections receiving antiretroviral therapy (ART) may even facilitate the transmission of drug-resistant HIV. We have recently demonstrated that in those on maximally suppressive ART this effect is reduced.

Polyphenotypic expression of mitochondrial toxicity caused by nucleoside reverse transcriptase inhibitors.

An HIV-infected man taking long-term zidovudine and didanosine presented with a polyphenotypic expression of nucleoside reverse transcriptase inhibitor (NRTI)-induced mitochondrial toxicity. Clinical features included lactic acidosis, myopathy, Fanconi-type proximal tubulopathy, pancreatic dysfunction, pseudo-obstruction, mega-oesophagus, peripheral sensory neuropathy and osteoporosis. A muscle biopsy showed morphologically abnormal mitochondria and respiratory chain biochemistry revealed marked reductions in the activity of respiratory chain enzymes containing mitochondrial DNA-encoded subunits.