Evaluating HIV treatment as prevention in the European context

Executive summary The goal of this project is to gather evidence regarding the population-level, and to some extent, individual-level effects of the use of antiretroviral treatment (ART) to prevent HIV infection, and to relate this to current HIV treatment guidelines. To inform the project, formal literature reviews were performed for the three main areas of interest: the effect of antiretroviral therapy in adults on preventing sexual transmission of HIV, prevention of mother-to-child transmission (pMTCT) and post exposure prophylaxis (PEP). The strongest evidence with regard to the effect of treatment of HIV positive individuals to prevent onwards sexual transmission comes from the recent randomised controlled trial (RCT), HPTN052. This study demonstrated that early versus delayed ART led to a 96% relative reduction in onwards linked transmission. Several observational studies of HIV sero-discordant heterosexual couples have also reported that transmission is rare in patients on ART, particularly in those with low HIV-RNA concentrations. However, the findings of HPTN052 and these observational studies are mainly applicable to vaginal heterosexual sex. No direct empirical evidence regarding the relationship between ART use and the risk of HIV transmission through anal intercourse is currently available. Whilst the major HIV treatment guidelines do not explicitly recommend prescribing antiretroviral treatment to prevent onwards transmission, they do not rule out individuals starting ART at a high CD4 count on a case-by-case basis. However, one must also consider the impact of earlier treatment on the HIV positive individual with regard to side effects, and development of drug resistance. Early studies showed that pMTCT regimens containing a single antiretroviral agent (short course zidovudine or single dose nevirapine) or two antiretroviral agents (zidovudine and lamivudine with or without single dose nevirapine) led to clinically important reductions in MTCT rates. However, the most substantial reductions in MTCT rates occurred when combination antiretroviral regimens (more than three antiretroviral drugs) were introduced. These regimens involve the receipt of ART before the third trimester of pregnancy, intrapartum treatment, maternal post-partum treatment and some form of neonatal treatment. There is some evidence from RCTs and extensive evidence from observational studies of the efficacy of these combination regimens, with very low rates of transmission of around 0% to 6%, in settings with no or very little breastfeeding, and 1%-9% when breastfeeding occurs. Furthermore, in settings where avoidance of breastfeeding is not possible, there are a number of studies demonstrating that receipt of maternal and/or neonatal ART during the six months after birth can reduce the risk of perinatal transmissions. All treatment guidelines recommend that HIV-positive pregnant women should receive ART to prevent MTCT, although the exact timing of when ART should begin is not always explicit. Furthermore, where mentioned, use of neonatal ART is also recommended, regardless of whether infants are breastfed. Much of the data supporting the use of PEP are based on animal models, which suggest that PEP is most efficacious if commenced as soon as possible after exposure. When considering occupational exposure to HIV, human studies are limited, as no RCTs exist for ethical reasons. Evidence for efficacy is based on one case control study which demonstrated an 81% reduction in transmission of HIV through the use of zidovudine. Other studies have demonstrated that PEP following occupational exposure is not always effective and there are cases of PEP failure. Similarly, there are also no RCTs assessing the efficacy of PEP for prevention of HIV transmission after sexual exposure, and limited evidence from observational data. Most treatment guidelines agree that PEP is not always effective and PEP policies need to emphasise the importance of risk prevention in the first place in all settings where there is a risk of HIV transmission. Side effects are not uncommon when using PEP, so it is important to consider carefully whether an individual should receive PEP and some studies have suggested that increase in availability of PEP may lead to an increase in risky sex behaviour. Antiretroviral treatment has well documented benefits in reducing transmission of HIV and, in particular, has had a major population level impact on HIV acquisition in children from HIV positive mothers. Further research is needed to help us understand how we can best use ART to prevent HIV infections through other transmission routes, and to develop evidence-based policy recommendations, particularly in the European context

Human resources needs for universal access to antiretroviral therapy in South Africa: a time and motion study

<p>Background - Although access to life-saving treatment for patients infected with HIV in South Africa has improved substantially since 2004, treating all eligible patients (universal access) remains elusive. As the prices of antiretroviral drugs have dropped over the past years, availability of human resources may now be the most important barrier to achieving universal access to HIV treatment in Africa. We quantify the number of HIV health workers (HHWs) required to be added to the current HIV workforce to achieve universal access to HIV treatment in South Africa, under different eligibility criteria.</p> <p>Methods - We performed a time and motion study in three HIV clinics in a rural, primary care-based HIV treatment program in KwaZulu-Natal, South Africa, to estimate the average time per patient visit for doctors, nurses, and counselors. We estimated the additional number of HHWs needed to achieve universal access to HIV treatment within one year.</p> <p>Results - For universal access to HIV treatment for all patients with a CD4 cell count of ≤350 cells/μl, an additional 2,200 nurses, 3,800 counselors, and 300 doctors would be required, at additional annual salary cost of 929 million South African rand (ZAR), equivalent to US$141 million. For universal treatment (‘treatment as prevention’), an additional 6,000 nurses, 11,000 counselors, and 800 doctors would be required, at an additional annual salary cost of ZAR 2.6 billion (US$ 400 million).</p> <p>Conclusions - Universal access to HIV treatment for patients with a CD4 cell count of ≤350 cells/μl in South Africa may be affordable, but the number of HHWs available for HIV treatment will need to be substantially increased. Treatment as prevention strategies will require considerable additional financial and human resources commitments.</p&gt

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. Evidence for Action was a 5-year, multidisciplinary research programme, which ran from 2006 to 2011, with partners in India, Malawi, Uganda, Zambia and the United Kingdom.The primary aim of this supplement is to stimulate reflection and provide guidance on what should be in the package of HIV treatment and care systems, as national programmes look to maintain the major advances of the past decade and scale-up treatment to the other 50% of people in need of it

Cohort profile: the Right to Care Clinical HIV Cohort, South Africa

PURPOSE: The research objectives of the Right to Care Clinical HIV Cohort analyses are to: (1) monitor treatment outcomes (including death, loss to follow-up, viral suppression and CD4 count gain among others) for patients on antiretroviral therapy (ART); (2) evaluate the impact of changes in the national treatment guidelines around when to initiate ART on HIV treatment outcomes; (3) evaluate the impact of changes in the national treatment guidelines around what ART regimens to initiate on drug switches; (4) evaluate the cost and cost-effectiveness of HIV treatment delivery models; (5) evaluate the need for and outcomes on second-line and third-line ART; (6) evaluate the impact of comorbidity with non-communicable diseases on HIV treatment outcomes and (7) evaluate the impact of the switch to initiating all patients onto ART regardless of CD4 count. PARTICIPANTS: The Right to Care Clinical HIV Cohort is an open cohort of data from 10 clinics in two provinces within South Africa. All clinics include data from 2004 onwards. The cohort currently has data on over 115 000 patients initiated on HIV treatment and patients are followed up every 3–6 months for clinical and laboratory monitoring. FINDINGS TO DATE: Cohort data includes information on demographics, clinical visit, laboratory data, medication history and clinical diagnoses. The data have been used to identify rates and predictors of first-line failure, to identify predictors of mortality for patients on second-line (eg, low CD4 counts) and to show that adolescents and young adults are at increased risk of unsuppressed viral loads compared with adults. FUTURE PLANS: Future analyses will inform national models of HIV care and treatment to improve HIV care policy in South Africa

Uptake of home-based voluntary HIV testing in sub-Saharan Africa: a systematic review and meta-analysis

Improving access to HIV testing is a key priority in scaling up HIV treatment and prevention services. Home-based voluntary counselling and testing (HBT) as an approach to delivering wide-scale HIV testing is explored here

Impact of early-stage HIV transmission on treatment as prevention

Timely HIV treatment improves health (1) and reduces transmission (2). These individual- level benefits of HIV treatment for both clinical and preventive purposes are well established, but several questions remain about the population-level impact of HIV treatment as prevention (3). In PNAS, Eaton and Hallett (4) use a mathematical model to address one such question: Does the proportion of transmission during early HIV infection affect the impact of HIV treatment on HIV incidence

Comparative assessment of structures and treatment processes in public and private hiv treatment centres in port harcourt, rivers state

Background: HIV treatment centres use the WHO standard policies and guidelines to conduct HIV testing services, and anti-retroviral treatment to people living with HIV. The purpose of the study was to assess and compare structures and treatment processes in public and private HIV treatment centres in Port Harcourt, Rivers State. Materials and Methods: This was a comparative cross-sectional study carried out in both public and private HIV treatment centres in Port Harcourt, Rivers State. The sample size of 10 public and 10 private HIV treatment centres were used for this study. A stratified sampling method was used to randomly select ten public and ten private HIV treatment centres from existing forty-six (46) public and forty (40) private ART facilities in Port Harcourt metropolis, Rivers State. Public and private HIV treatment centres included in the study were all that had existed for 6 months, still functional and render HIV treatment to a minimum of 5 patients per week. Other treatment facilities that did not meet this criteria were excluded. The study tool was pretested in other HIV treatment centres that were not selected for the main study. The tool was validated by performing Cronbach’s alpha (α) using 24 items tool for measuring the structure and 10 items tool for measuring the process; hence 0.902 and 0.736 were obtained for structure and treatment process respectively. A semi-structured interviewer checklist was used to assess structures of the treatment centres and evaluate the treatment process. The assessment the structure and evaluation of HIV treatment process was completed in a period of eight (8) weeks. Data was entered into the Statistical Package for Social Sciences (SPSS) software version 21 in numeric codes and analyzed using SPSS version 21. Comparative analysis for public and private HIV treatment centres were done. Ethical clearance for the study was obtained from the Research and Ethics Committee of the University of Port-Harcourt. Written permission from Rivers State Primary Health Management Board, Department of Planning, Research and Statistics (DPRS) and Rivers state Ministry of Health was obtained to cover the various health facilities used. Verbal permission/ consent were obtained from the directors of the private treatment centres. Result: A total of 20 facility assessment checklists were used to assess the public and private HIV treatment centres. The result indicated that public versus private structures of facilities had median scores of 11 versus 6.5 for utilities, 30.5 versus 22.5 for equipment, 24 versus 18.5 for commodities and the overall structural score of 65 versus 46. There was a statistically significant difference between the various structural domains and the health facility type: Utilities (5.60; p=0.02); Equipment (10.08; p=0.002); Commodities (6.27; p=0.01); Overall Structural scores (7.02; p=0.01). Also, (public versus private facilities) had median scores of (39 versus 34.5) with interquartile range of 39-46 for public facilities and (30-37) for private facilities. A statistically significant association was observed between HIV treatment process in public and private facilities (10.87; p=0.001).The HIV treatment process in public versus private facilities had median scores of (39 versus 34.5) with interquartile range of 39-46 for public facilities and (30-37) for private facilities. Conclusion: Based on findings in this study, the researchers conclude that the public HIV treatment centres had good structures in offering HIV service delivery. The public HIV treatment centers had a better HIV treatment process than the private HIV treatment centres. The non-governmental organizations should be encouraged to take responsibility of equipping private facilities with the needed structure which in turn will enhance HIV treatment process

Timeliness of Clinic Attendance is a good predictor of Virological Response and Resistance to Antiretroviral drugs in HIV-infected patients

Ensuring long-term adherence to therapy is essential for the success of HIV treatment. As access to viral load monitoring and genotyping is poor in resource-limited settings, a simple tool to monitor adherence is needed. We assessed the relationship between an indicator based on timeliness of clinic attendance and virological response and HIV drug resistance