Therapy In Africa Research Articles

Genetic variants association with cancers in African-based populations: A systematic review

BackgroundCancer is the single leading cause of human deaths worldwide. The highest incidence and mortality are recorded from Africa. The last two decades have witnessed extensive research which has led to emerging prognosis and new gene therapy technologies. Cancer therapy in Africa is derived with little input from African population data. While a number of cancer studies on African populations have suggested varied susceptible variant, no comprehensive review of these studies has been undertaken to assess their coverage across Africa. MethodsThis study aimed to undertake a review of all molecular genetic studies that interrogated the genetic variants of cancers in African-based populations. Our search methodology was modelled after the Cochrane systematic review protocol, which included MeSH terms and related keywords. ResultsNinety-seven articles studying 13 cancer types, were reviewed. 91 articles screened for polymorphisms using PCR-based techniques while three used SNP array, two used whole exome sequencing and one used pyrosequencing. North African (NA) countries undertook 51/97 (53 %) studies on 12/13 (92 %) cancer types while the Sub Saharan Africa (SSA) countries undertook 46/97 (47 %) studies on 7/13 (54 %) cancer types. Twelve out of these thirteen cancer type studies suggested susceptibility to their target polymorphism (p > 0.05). No study replicated or validated variants detected. ConclusionResearch on genetic determinants in African-based population cancer offers translational benefits. We recommended large scale, multi-national genome association studies using high throughput techniques. SSA needs to receive more attention due to the shortage of this type of study and data in the region.

The role and scope of occupational therapy in Africa

Purpose Occupational therapy (OT) is a global health profession that promotes participation in meaningful occupations to enhance well-being, particularly for persons with disabilities. Occupational therapy is relatively new in many African countries and there is limited research regarding the role of OT in this region. Thus, this study aims to understand the role and scope of OT in Africa by exploring its unique contribution to healthcare and cultural considerations for practicing OT in various African contexts. Methods We conducted an exploratory qualitative descriptive study involving semi-structured interviews with 15 occupational therapists from 11 African countries. Interview questions focused on participants’ work activities, rewards and challenges of their work, and perceived contribution to healthcare. We audio-recorded and transcribed interviews followed by inductive thematic analysis. Results All participants described maintaining multiple roles. Four main themes (with sub-themes) emerged: advocacy (clients and the profession), collaboration (multi-disciplinary team, professional support, and internationally), maintaining core OT principles (occupation, function, participation, empowerment, and holistic practice), and contextual considerations (community-based services, practice approaches, sustainability, cultural norms, and spirituality). Conclusions Occupational therapists working in African contexts have a unique and challenging role involving advocacy and collaboration. They need to maintain core OT values whilst addressing contextual considerations to ensure culturally relevant practice. Implications for Rehabilitation Occupational therapists have an important role in promoting health and well-being; however, practice is influenced by the cultural context. Occupational therapists in Africa maintain multiple roles, including advocacy for their clients and the profession, and collaboration within a multidisciplinary team, for professional support and internationally. African occupational therapists need to be rooted in core OT principles whilst considering their unique context to ensure culturally relevant practice.

Changes over time in creatinine clearance and comparison of emergent adverse events for HIV-positive adults receiving standard doses (300 mg/day) of lamivudine-containing antiretroviral therapy with baseline creatinine clearance of 30-49 vs ≥50 mL/min.

A retrospective analysis of the randomized controlled DART (Development of AntiRetroviral Therapy in Africa; ISRCTN13968779) trial in HIV-1-positive adults initiating antiretroviral therapy with co-formulated zidovudine/lamivudine plus either tenofovir, abacavir, or nevirapine was conducted to evaluate the safety of initiating standard lamivudine dosing in patients with impaired creatinine clearance (CLcr). Safety data collected through 96 weeks were analyzed after stratification by baseline CLcr (estimated using Cockcroft-Gault) of 30–49 mL/min (n = 168) versus ≥50 mL/min (n = 3,132) and treatment regimen. The Grade 3–4 adverse events (AEs) and serious AEs (for hematological, hepatic and gastrointestinal events), maximal toxicities for liver enzymes, serum creatinine and bilirubin and maximum treatment-emergent hematology toxicities were comparable for groups with baseline CLcr 30–49 versus CLcr≥50 mL/min. No new risks or trends were identified from this dataset. Substantial and similar increases in the mean creatinine clearance (>25 mL/min) were observed from baseline though Week 96 among participants who entered the trial with CLcr 30–49 mL/min, while no increase or smaller median changes in creatinine clearance (<7 mL/min) were observed for participants who entered the trial with CLcr ≥50 mL/min. Substantial increases (> 150 cells/ mm3) in mean CD4+ cells counts from baseline to Week 96 were also observed for participants who entered the trial with CLcr 30–49 mL/min and those with baseline CLcr ≥50 mL/min. Though these results are descriptive, they suggest that HIV-positive patients with CLcr of 30–49 mL/min would have similar AE risks in comparison to patients with CLcr ≥50 mL/min when initiating antiretroviral therapy delivering doses of 300 mg of lamivudine daily through 96 weeks of treatment. Overall improvements in CLcr were observed for patients with baseline CLcr 30–49 mL/min.

Hepatitis B Core-related Antigen: An Alternative to Hepatitis B Virus DNA to Assess Treatment Eligibility in Africa.

To eliminate hepatitis B virus (HBV) infection, it is essential to scale up testing and treatment. However, conventional tools to assess treatment eligibility, particularly nucleic acid testing (NAT) to quantify HBV DNA, are hardly available and affordable in resource-limited countries. We therefore assessed the performance of a novel immunoassay, hepatitis B core-related antigen (HBcrAg), as an inexpensive (US$ <15/assay) alternative to NAT to diagnose clinically important HBV DNA thresholds (≥2000, ≥20 000, and ≥200 000 IU/mL) and to select patients for antiviral therapy in Africa. Using a well-characterized cohort of treatment-naive patients with chronic HBV infection in The Gambia, we evaluated the accuracy of serum HBcrAg to diagnose HBV DNA levels and to indicate treatment eligibility determined by the American Association for the Study of Liver Diseases, based on reference tests (HBV DNA, hepatitis B e antigen, alanine aminotransferase, liver histopathology, and/or FibroScan). A total of 284 treatment-naive patients were included in the analysis. The area under the receiver operating characteristic curve (AUROC), sensitivity, and specificity of serum HBcrAg were 0.88 (95% confidence interval [CI], .82-.93), 83.3%, and 83.9%, respectively, to diagnose HBV DNA ≥2000 IU/mL; and 0.94 (95% CI, .88-.99), 91.4%, and 93.2% for ≥200 000 IU/mL. A simplified treatment algorithm using HBcrAg without HBV DNA showed high AUROC (0.91 [95% CI, .88-.95]) with a sensitivity of 96.6% and specificity of 85.8%. HBcrAg might be an accurate alternative to HBV DNA quantification as a simple and inexpensive tool to identify HBV-infected patients in need of antiviral therapy in low- and middle-income countries.

Need for active cardiovascular screening in HIV-infected children under antiretroviral therapy in Africa.

Unacceptably high incidence of pediatric HIV despite worldwide increased access to antiretroviral therapy. The routine management of these children includes provision of antiretroviral therapy, and periodic assessment of its results and complications. However, no systematic assessment of the nutritional status, lipid profile or screening for cardiovascular disease is done. Our study aimed at describing the occurrence of cardiovascular abnormalities in HIV-infected children under antiretroviral therapy, and at determining the vital outcomes 5 years after. A prospective observational study was implemented at a dedicated HIV center in Maputo City, where we gathered detailed socio-demographic data and performed full cardiovascular evaluation, including transthoracic cardiac ultrasound. A total of 47 children were examined (24 male) of which 10 had abnormal cardiac ultrasound: impaired systolic function (5 children); three had congenital heart defects; one had severe rheumatic aortic regurgitation and one had tuberculous pericarditis. Heart failure was present in five children. The study also uncovered the presence of malnutrition (36 patients; 80% had BMI below 18.5 kg/m2) and anemia in a considerable proportion of children. On 5 year follow up there was one death due to malária; three new cases of left ventricular dysfunction occurred among children who had normal ultrasound on recruitment. Our results support systematic cardiovascular risk profiling and disease screening in HIV-infected children on antiretroviral therapy, using cardiac ultrasound wherever possible.

Being HIV positive and staying on antiretroviral therapy in Africa: A qualitative systematic review and theoretical model.

BackgroundAdherence to antiretroviral therapy (ART) and long-term uninterrupted engagement in HIV care is difficult for HIV-positive people, and randomized trials of specific techniques to promote adherence often show small or negligible effects. Understanding what influences decision-making in HIV-positive people in Africa may help researchers and policy makers in the development of broader, more effective interventions and policies.MethodsWe used thematic synthesis and a grounded theory approach to generate a detailed narrative and theoretical model reflecting life with HIV in Africa, and how this influences ART adherence and engagement decisions. We included qualitative primary studies that explored perspectives, perceptions and experiences of HIV-positive people, caregivers and healthcare service providers. We searched databases from 1 January 2013 to 9 December 2016, screened all studies, and selected those for inclusion using purposeful sampling methods. Included studies were coded with Atlas.ti, and we assessed methodological quality across five domains.ResultsWe included 59 studies from Africa in the synthesis. Nine themes emerged which we grouped under three main headings. First, people who are HIV-positive live in a complicated world where they must navigate the challenges presented by poverty, competing priorities, unpredictable life events, social identity, gender norms, stigma, and medical pluralism—these influences can make initiating and maintaining ART difficult. Second, the health system is generally seen as punishing and uninviting and this can drive HIV-positive people out of care. Third, long-term engagement and adherence requires adaptation and incorporation of ART into daily life, a process which is facilitated by: inherent self-efficacy, social responsibilities, previous HIV-related illnesses and emotional, practical or financial support. These factors together can lead to a “tipping point”, a point in time when patients choose to either engage or disengage from care. HIV-positive people may cycle in and out of these care states in response to fluctuations in influences over time.ConclusionThis analysis provides a practical theory, arising from thematic synthesis of research, to help understand the dynamics of adherence to ART and engagement in HIV care. This can contribute to the design of service delivery approaches, and informed thinking and action on the part of policy makers, providers, and society: to understand what it is to be HIV-positive in Africa and how attitudes and the health service need to shift to help those with HIV lead ‘normal’ lives.

Potential latitudinal variation in orodigestive tract cancers in Africa.

Previous studies have alluded to a causal relationship between pathological entities and geographical variations, but there is a paucity of studies from Africa discussing the effect of latitudinal variation on orodigestive cancers in this region. It seems plausible that the burden of orodigestive cancer would differ as a result of variations in diet, cultural habits, climate and environmental conditions down the length of Africa. To analyse regional variations in prevalence, incidence and mortality data in the global cancer statistics database (GLOBOCAN 2012) curated by the World Health Organization and the International Agency for Research on Cancer. Basic descriptive statistical tools were used to depict regional variations in cancer morbidity and mortality. Data on 13 African countries between longitude 20⁰ and 30⁰ east and latitude 35⁰ north and 35⁰ south were examined for variation in age-standardised orodigestive cancer prevalence, incidence and mortality. Possible regional causes for orodigestive tract cancer development were investigated. Data on lip and oral cavity, oesophageal, gastric, colorectal, liver, gallbladder and pancreatic cancers in the 13 countries were compared. Our empirical findings from this preliminary study support the notion that the incidence and prevalence of orodigestive cancers vary within Africa. This effect may be due to environmental, economic, political and possibly genetic factors. Considering the heterogeneity of the above factors across Africa, disbursement of funding for cancer research and therapy in Africa should be focused in terms of regional variations to make best use of the fiscal allocation by African governments, non-governmental organisations and international agencies.

HIV-1 viral load and resistance in genital secretions in patients taking protease-inhibitor-based second-line therapy in Africa.

HIV is transmitted primarily through sexual intercourse, and the objective of this study was therefore to assess whether there is occult viral replication and resistance in genital secretions in patients on protease inhibitor (PI)-based second-line therapy. HIV-infected adults taking ritonavir-boosted lopinavir with either two nucleoside reverse transcriptase inhibitors (NRTIs), raltegravir or as monotherapy for 96 weeks, were enrolled at seven clinical sites in Uganda. Viral load (VL) was measured in cervico-vaginal secretions or semen and in a corresponding plasma sample. Genotypic resistance was assessed in genital secretion samples and plasma samples. Results were compared between compartments and with the plasma resistance profile at first-line failure. Of the 111 participants enrolled (91 female, 20 male), 16 (14%) and 30 (27%) had VL >1,000 and >40 copies/ml, respectively, in plasma; 3 (3%) and 23 (21%) had VL >1,000 copies/ml and >40 copies/ml, respectively, in genital secretions. There was 74% agreement between plasma and genital secretion VL classification above/below 40 copies/ml threshold (kappa-statistic =0.29; P=0.001). RT mutations (both NRTI and non-nucleoside reverse transcriptase inhibitor) were detected in genital secretions in four patients (similar profile to corresponding plasma sample at first-line failure) and PI mutations were detected in two (one polymorphism with no impact on resistance; one with high-level PI resistance). High level (>1,000 copies/ml) viral replication and development of new RT or PI resistance in the genital compartment were rare. The risks of transmission arising from resistance evolution in the genital compartment are likely to be low on PI-based second-line therapy.

Exploring attitudes and perceptions of patients and staff towards an after-hours co-pay clinic supplementing free HIV services in Kampala, Uganda

BackgroundThere has been a rapid scale up of HIV services and access to anti-retroviral therapy in Africa over the last 10 years as a result of multilateral donor funding mechanisms. However, in order to continue to expand and to sustain these services it is important that “in country” options are explored. This study sought to explore attitudes and perceptions of people living with HIV (PLHIV) and health care staff towards using a fee-based “after hours” clinic (AHC) at the Infectious Diseases Institute (IDI) in Kampala, Uganda.MethodsA cross-sectional study design, using qualitative methods for data collection was used. A purposeful sample of 188 adults including PLHIV accessing care at IDI and IDI staff were selected. We conducted 14 focus group discussions and 55 in-depth interviews. Thematic content analysis was conducted and Nvivo Software Version 10 was used to manage data.ResultsFindings suggested that some respondents were willing to pay for consultation, brand-name drugs, laboratory tests and other services. Many were willing to recommend the AHC to friends and/or relatives. However, there were concerns expressed of a risk that the co-pay model may lead to reduction in quality or provision of the free service. Respondents agreed that, as a sign of social responsibility, fees for service could help underprivileged patients.ConclusionThe IDI AHC clinic is perceived as beneficial to PLHIV because it provides access to HIV services at convenient times. Many PLHIV are willing to pay for this enhanced service. Innovations in HIV care delivery such as quality private-public partnerships may help to improve overall coverage and sustain quality HIV services in Uganda in the long term.

The state of gene therapy research in Africa, its significance and implications for the future.

Gene therapy has made impressive recent progress and has potential for treating a wide range of diseases, many of which are important to Africa. However, as a result of lack of direct public funding and skilled personnel, direct research on gene therapy in Africa is currently limited and resources to support the endeavor are modest. A strength of the technology is that it is based on principles of rational design, and the tools of gene therapy are now highly versatile. For example gene silencing and gene editing may be used to disable viral genes for therapeutic purposes. Gene therapy may thus lead to cure from infections with HIV-1, hepatitis B virus and Ebola virus, which are of significant public health importance in Africa. Although enthusiasm for gene therapy is justified, significant challenges to implementing the technology remain. These include ensuring efficient delivery of therapeutic nucleic acids to target cells, limiting unintended effects, cost and complexity of treatment regimens. In addition, implementation of effective legislation that will govern gene therapy research will be a challenge. Nevertheless, it is an exciting prospect that gene therapy should soon reach the mainstream of medical management. Participation of African researchers in the exciting developments is currently limited, but their involvement is important to address health problems, develop capacity and enhance economic progress of the continent.

HIV Task Sharing Between Nurses and Physicians in Nigeria: Examining the Correlates of Nurse Self-Efficacy and Job Satisfaction

A global shortfall of 12.9 million health care workers has been predicted to occur in the next two decades. Task sharing between physicians and nurses, a method used to help compensate for provider shortages, was shown to improve access to antiretroviral therapy in Africa, but led to nurses performing beyond their scopes of practice. We surveyed 508 nurses in task-shifted roles in Nigeria. Respondents (n=399) provided information on age, years in practice, gender, registration status, employment site, and access to task-sharing training and mentoring. Years in practice negatively influenced task-sharing self-efficacy. Positive correlates of job satisfaction were years in practice, older age, male gender, single licensure, employment at a tertiary hospital, mentoring, and duration of training. System challenges and employment in faith-based and nontertiary hospitals increased likelihood of job dissatisfaction. Supportive practice and policy interventions are needed to minimize negative effects of disparities in job satisfaction across facilities.

Is 90-90-90 achievable?

By 2010, the results of observational studies had suggested that high coverage of antiretroviral therapy (ART) is associated with decreased HIV transmission at a population level. 1 Anglemyer A Rutherford GW Egger M Siegfried N Antiretroviral therapy for prevention of HIV transmission in HIV-discordant couples. Cochrane Database Syst Rev. 2011; 5 (CD009153) Google Scholar In 2011, the first reports from the randomised controlled trial HPTN 052 were published, 2 Cohen MS Chen YQ McCauley M et al. Prevention of HIV-1 infection with early antiretroviral therapy. N Engl J Med. 2011; 365: 493-505 Crossref PubMed Scopus (5409) Google Scholar which definitively showed that ART reduces the risk of sexually transmitted HIV for serodiscordant couples. Findings from HPTN 052 have been extended, 3 Cohen MS Chen YQ McCauley M et al. Antiretroviral therapy for the prevention of HIV-1 transmission. N Engl J Med. 2016; 375: 830-839 Crossref PubMed Scopus (978) Google Scholar and similarly compelling data have emerged from the TEMPRANO trial. 4 The TEMPRANO ANRS 12136 Study GroupA trial of early antiretrovirals and isoniazid preventive therapy in Africa. N Engl J Med. 2015; 373: 808-822 Crossref PubMed Scopus (860) Google Scholar On the basis of these and other data, UNAIDS in 2014, 5 UNAIDS90-90-90. An ambitious target to help end the AIDS epidemic. Joint United Nations Programme on HIV/AIDS, Geneva2014 Google Scholar and WHO in 2015, 6 WHOGuideline on when to start antiretroviral therapy and pre-exposure prophylaxis for HIV. World Health Organization, Geneva2015 Google Scholar launched aggressive new policies to diagnose and to treat all patients with HIV infection worldwide to achieve plasma viral loads of under 1000 copies per mL in at least 73%. This policy has been framed as the HIV care and treatment cascade, in which 90% of people with HIV infection worldwide are diagnosed, 90% of those diagnosed start ART, and 90% of those taking ART achieve virological suppression. 7 WHOConsolidated strategic information guidelines for HIV in the health sector. World Health Organization, Geneva2015 Google Scholar The mathematical models 8 Granich RM Gilks CF Dye C De Cock KM Williams BG Universal voluntary HIV testing with immediate antiretroviral therapy as a strategy for elimination of HIV transmission: a mathematical model. Lancet. 2009; 373: 48-57 Summary Full Text Full Text PDF PubMed Scopus (1524) Google Scholar that led to this new policy suggested that this prevalence of suppression will be associated with a fall in the basic reproductive number, R0, to below 1·0 and the gradual extinction of the HIV epidemic as a major public health problem by 2030. From HIV infection to therapeutic response: a population-based longitudinal HIV cascade-of-care study in KwaZulu-Natal, South AfricaHIV programmes should focus on linkage to care as the most important bottleneck in the cascade. Cascade estimation should be longitudinal rather than cross-sectional and start with the population stages preceding clinical care. Full-Text PDF

SAT-150 - Development and validation of a simple score to select HBV-infected patients for antiviral therapy in Africa

SAT-150 - Development and validation of a simple score to select HBV-infected patients for antiviral therapy in Africa

Microalbuminuria in Diabetic Patients in the Bamenda Health District

Diabetic nephropathy (DN) is the most common cause of end stage renal disease (ESRD) and it accounts for one third of all patients requiring renal replacement therapy in Africa. Diabetic patients with microalbuminuria (MA) have an increased risk of progression to macroalbuminuria and later to ESRD. So detecting MA which is a marker of DN helps to alert the clinician to intervene at a time when future renal damage is still preventable. The main goal of this study was to determine the prevalence of MA in diabetic patients at the Bamenda Regional Hospital. This study was a prospective cross sectional study involving diabetic patients at the Bamenda Regional Hospital. A random (spot) or first morning urine specimen was collected and MA was measured by a semi quantitative dipstick method using the URS-14H urine test strips. The prevalence of MA in the present study was 34.6%, which is high but similar to the results of other studies done in sub-Saharan Africa. Although MA was more common (50%) in individuals with diabetes more than 16 years, a high proportion (42.85%) of patients with MA had a duration of diabetes of ≤ 5years. There was no significant difference in the occurrence of MA with respect to age, gender and duration of diabetes. This study showed a high prevalence of MA in the diabetic population presenting at the Bamenda Regional Hospital. Consequently, measures of glycemic control should be enhanced in this population to prevent the progression to macroalbuminuria and ESRD.

Rescuing artemisinin combination therapy in Africa.

Rescuing artemisinin combination therapy in Africa.

Effects of a multicomponent intervention to streamline initiation of antiretroviral therapy in Africa: a stepped-wedge cluster-randomised trial

In Africa, up to 30% of HIV-infected patients who are clinically eligible for antiretroviral therapy (ART) do not start timely treatment. We assessed the effects of an intervention targeting prevalent health systems barriers to ART initiation on timing and completeness of treatment initiation. In this stepped-wedge, non-blinded, cluster-randomised controlled trial, 20 clinics in southwestern Uganda were randomly assigned in groups of five clinics every 6 months to the intervention by a computerised random number generator. This procedure continued until all clinics had crossed over from control (standard of care) to the intervention, which consisted of opinion-leader-led training and coaching of front-line health workers, a point-of-care CD4 cell count testing platform, a revised counselling approach without mandatory multiple pre-initiation sessions, and feedback to the facilities on their ART initiation rates and how they compared with other facilities. Treatment-naive, HIV-infected adults (aged ≥18 years) who were clinically eligible for ART during the study period were included in the study population. The primary outcome was ART initiation 14 days after first clinical eligibility for ART. This study is registered with ClinicalTrials.gov, number NCT01810289. Between April 11, 2013, and Feb 2, 2015, 12 024 eligible patients visited one of the 20 participating clinics. Median CD4 count was 310 cells per μL (IQR 179-424). 3753 of 4747 patients (weighted proportion 80%) in the intervention group had started ART by 2 weeks after eligibility compared with 2585 of 7066 patients (38%) in the control group (risk difference 41·9%, 95% CI 40·1-43·8). Vital status was ascertained in a random sample of 208 patients in the intervention group and 199 patients in the control group. Four deaths (2%) occurred in the intervention group and five (3%) occurred in the control group. A multicomponent intervention targeting health-care worker behaviour increased the probability of ART initiation 14 days after eligibility. This intervention consists of widely accessible components and has been tested in a real-world setting, and is therefore well positioned for use at scale. National Institute of Allergy and Infectious Diseases (NIAID) and the President's Emergency Fund for AIDS Relief (PEPFAR).

Neurocognitive Function at the First-Line Failure and on the Second-Line Antiretroviral Therapy in Africa: Analyses From the EARNEST Trial.

To assess neurocognitive function at the first-line antiretroviral therapy failure and change on the second-line therapy. Randomized controlled trial was conducted in 5 sub-Saharan African countries. Patients failing the first-line therapy according to WHO criteria after >12 months on non-nucleoside reverse transcriptase inhibitors-based regimens were randomized to the second-line therapy (open-label) with lopinavir/ritonavir (400 mg/100 mg twice daily) plus either 2-3 clinician-selected nucleoside reverse transcriptase inhibitors, raltegravir, or as monotherapy after 12-week induction with raltegravir. Neurocognitive function was tested at baseline, weeks 48 and 96 using color trails tests 1 and 2, and the Grooved Pegboard test. Test results were converted to an average of the 3 individual test z-scores. A total of 1036 patients (90% of those >18 years enrolled at 13 evaluable sites) had valid baseline tests (58% women, median: 38 years, viral load: 65,000 copies per milliliter, CD4 count: 73 cells per cubic millimeter). Mean (SD) baseline z-score was -2.96 (1.74); lower baseline z-scores were independently associated with older age, lower body weight, higher viral load, lower hemoglobin, less education, fewer weekly working hours, previous central nervous system disease, and taking fluconazole (P < 0.05 in multivariable model). Z-score was increased by mean (SE) of +1.23 (0.04) after 96 weeks on the second-line therapy (P < 0.001; n = 915 evaluable), with no evidence of difference between the treatment arms (P = 0.35). Patients in sub-Saharan Africa failing the first-line therapy had low neurocognitive function test scores, but performance improved on the second-line therapy. Regimens with more central nervous system-penetrating drugs did not enhance neurocognitive recovery indicating this need not be a primary consideration in choosing a second-line regimen.

Let's treat everyone with HIV now: what happens next?

The effectiveness of antiretroviral therapy (ART) in the treatment and prevention of HIV infection has been firmly established and is no longer subject to debate. The earliest possible ART preserves immune function, 1 Le T Wright EJ Smith DM et al. Enhanced CD4+ T-cell recovery with earlier HIV-1 antiretroviral therapy. N Engl J Med. 2013; 368: 218-230 Crossref PubMed Scopus (272) Google Scholar prevents infection and neoplasms, 2 Danel C Moh R Gabillard D et al. A trial of early antiretrovirals and isoniazid preventive therapy in Africa. N Engl J Med. 2015; 373: 808-822 Crossref PubMed Scopus (851) Google Scholar , 3 Lundgren JD Babiker AG Gordin F et al. Initiation of antiretroviral therapy in early asymptomatic HIV infection. N Engl J Med. 2015; 373: 795-807 Crossref PubMed Scopus (2) Google Scholar and prevents the sexual transmission of HIV. 4 Cohen MS Chen YQ McCauley M et al. Prevention of HIV-1 infection with early antiretroviral therapy. N Engl J Med. 2011; 365: 493-505 Crossref PubMed Scopus (5382) Google Scholar Almost all HIV treatment guidelines now recommend ART initiation at the time of diagnosis, 5 WHOGuideline on when to start antiretroviral therapy and on pre-exposure prophylaxis for HIV. World Health Organisation, Geneva2015http://apps.who.int/iris/bitstream/10665/186275/1/9789241509565_eng.pdf Google Scholar and UNAIDS 6 UNAIDS90-90-90 An ambitious treatment target to help end the AIDS epidemic. Joint United Nations Programme on HIV/AIDS, Geneva2014 Google Scholar and the 2015 US National HIV/AIDS Strategy (NHAS) 7 White House Office of National AIDS PolicyNational HIV/AIDS Strategy for the United States. https://www.whitehouse.gov/sites/default/files/uploads/NHAS.pdfDate: 2015 Google Scholar have described plans to detect and treat 85–90% of people with HIV infection, regardless of disease stage. Effect of the US National HIV/AIDS Strategy targets for improved HIV care engagement: a modelling studyAchievement of NHAS progress indicators for screening, linkage, and particularly improving retention in care, can substantially reduce the burden of HIV in the USA, but continued and increased financial investment will be required. Full-Text PDF

Third-line antiretroviral therapy in Africa: effectiveness in a Southern African retrospective cohort study.

Background An increasing number of patients in Africa are experiencing virologic failure on second-line antiretroviral therapy (ART) and those who develop resistance to protease inhibitors (PI) will require third-line ART, but no data on the outcomes of third-line are available from the region. We assessed the virologic outcomes and survival of patients started on salvage ART in a Southern African private sector disease management programme.Methods Retrospective observational cohort study with linkage to the national death register. Adults (≥18 years) who started salvage ART between July 2007 and December 2011 were included. Salvage ART was defined by inclusion of darunavir or tipranavir in an ART regimen after having failed another PI. For Kaplan–Meier (KM) analysis, patients were followed up until event, or censored at death (only for virologic outcomes), leaving the programme, or April 2014.Results152 patients were included. Subtype was known for 113 patients: 111 (98 %) were infected with subtype C. All 152 had a genotype resistance test demonstrating major PI resistance mutations. Salvage drugs included were: darunavir/ritonavir (n = 149), tipranavir/ritonavir (n = 3), raltegravir (n = 58), and etravirine (n = 8). Median follow-up was 2.5 years (IQR = 1.5–3.3). 82.9 % achieved a viral load ≤400 copies/ml and 71.1 % ≤50 copies/ml. By the end of the study 17 (11.2 %) of the patients had died. The KM estimate of cumulative survival was 87.2 % at 2000 days.ConclusionsVirologic suppression was comparable to that demonstrated in clinical trials and observational studies of salvage ART drugs conducted in other regions. Few deaths occurred during short term follow-up. Third-line regimens for patients with multidrug resistant subtype C HIV in Africa are virologically and clinically effective.

In HIV-1, immediate vs deferred antiretroviral therapy and isoniazid vs no isoniazid reduced severe illness at 30 mo

Source Citation TEMPRANO ANRS 12136 Study Group, Danel C, Moh R, et al. A trial of early antiretrovirals and isoniazid preventive therapy in Africa. N Engl J Med. 2015;373:808-22. 26193126