Epidemiological Trends for HIV in Southern Africa: Implications for Reaching the Elimination Targets.

Southern Africa is the region worst affected by HIV in the world and accounts for one third of the global burden of HIV. Achieving the UNAIDS 90-90-90 target by 2020 and ending the AIDS epidemic by 2030 depend on success in this region. We review epidemiological trends in each country in southern Africa with respect to the prevalence, incidence, mortality, coverage of anti-retroviral therapy (ART) and TB notification rates, to better understand progress in controlling HIV and TB and to determine what needs to be done to reach the UNAIDS targets. Significant progress has been made in controlling HIV. In all countries in the region, the prevalence of HIV in people not on ART, the incidence of HIV, AIDS-related mortality and, in most countries, TB notification rates, are falling. In some countries, the risk of infection began to fall before biomedical interventions such as ART became widely available as a result of effective prevention measures or people's awareness of, and response to, the epidemic but the reasons for these declines remain uncertain. Some countries have achieved better levels of ART coverage than others, but all are in a position to reach the 2020 and 2030 targets if they accelerate the roll-out of ART and of targeted prevention efforts. Achieving the HIV treatment targets will further reduce the incidence of HIV-related TB, but efforts to control TB in HIV-negative people must be improved and strengthened.

The distribution of new HIV infections by mode of exposure in Morocco.

OBJECTIVES: Building on a wealth of new empirical data, the objective of this study was to estimate the distribution of new HIV infections in Morocco by mode of exposure using the modes of transmission (MoT) mathematical model. METHODS: The MoT model was implemented within a collaboration with the Morocco Ministry of Health and the Joint United Nations Programme on HIV/AIDS. The model was parameterised through a comprehensive review and synthesis of HIV and risk behaviour data in Morocco, mainly through the Middle East and North Africa HIV/AIDS Synthesis Project. Uncertainty analyses were used to assess the reliability of and uncertainty around our calculated estimates. RESULTS: Female sex workers (FSWs), clients of FSWs, men who have sex with men (MSM) and injecting drug users (IDUs) contributed 14%, 24%, 14% and 7% of new HIV infections, respectively. Two-thirds (67%) of new HIV infections occurred among FSWs, clients of FSWs, MSM and IDUs, or among the stable sexual partners of these populations. Casual heterosexual sex contributed 7% of HIV infections. More than half (52%) of HIV incidence is among females, but 71% of these infections are due to an infected spouse. The vast majority of HIV infections among men (89%) are due to high-risk behaviour. A very small HIV incidence is predicted to arise from medical injections or blood transfusions (0.1%). CONCLUSIONS: The HIV epidemic in Morocco is driven by HIV incidence in high-risk population groups, with commercial heterosexual sex being the largest contributor to incidence. There is a need to focus HIV response more on these populations, mainly through proactive and sustainable HIV surveillance, and the expansion and increased geographical coverage of services such as condom promotion among FSWs, voluntary counselling and testing, harm reduction and treatment.

Towards an improved investment approach for an effective response to HIV/AIDS.

Substantial changes are needed to achieve a more targeted and strategic approach to investment in the response to the HIV/AIDS epidemic that will yield long-term dividends. Until now, advocacy for resources has been done on the basis of a commodity approach that encouraged scaling up of numerous strategies in parallel, irrespective of their relative effects. We propose a strategic investment framework that is intended to support better management of national and international HIV/AIDS responses than exists with the present system. Our framework incorporates major efficiency gains through community mobilisation, synergies between programme elements, and benefits of the extension of antiretroviral therapy for prevention of HIV transmission. It proposes three categories of investment, consisting of six basic programmatic activities, interventions that create an enabling environment to achieve maximum effectiveness, and programmatic efforts in other health and development sectors related to HIV/AIDS. The yearly cost of achievement of universal access to HIV prevention, treatment, care, and support by 2015 is estimated at no less than US$22 billion. Implementation of the new investment framework would avert 12·2 million new HIV infections and 7·4 million deaths from AIDS between 2011 and 2020 compared with continuation of present approaches, and result in 29·4 million life-years gained. The framework is cost effective at $1060 per life-year gained, and the additional investment proposed would be largely offset from savings in treatment costs alone.

Focusing the HIV response through estimating the major modes of HIV transmission: a multi-country analysis.

OBJECTIVE: An increasing number of countries have been estimating the distribution of new adult HIV infections by modes of transmission (MOT) to help prioritise prevention efforts. We compare results from studies conducted between 2008 and 2012 and discuss their use for planning and responding to the HIV epidemic. METHODS: The UNAIDS recommended MOT model helps countries to estimate the proportion of new HIV infections that occur through key transmission modes including sex work, injecting drug use (IDU), men having sex with men (MSM), multiple sexual partnerships, stable relationships and medical interventions. The model typically forms part of a country-led process that includes a comprehensive review of epidemiological data. Recent revisions to the model are described. RESULTS: Modelling results from 25 countries show large variation between and within regions. In sub-Saharan Africa, new infections occur largely in the general heterosexual population because of multiple partnerships or in stable discordant relationships, while sex work contributes significantly to new infections in West Africa. IDU and sex work are the main contributors to new infections in the Middle East and North Africa, with MSM the main contributor in Latin America. Patterns vary substantially between countries in Eastern Europe and Asia in terms of the relative contribution of sex work, MSM, IDU and spousal transmission. CONCLUSIONS: The MOT modelling results, comprehensive review and critical assessment of data in a country can contribute to a more strategically focused HIV response. To strengthen this type of research, improved epidemiological and behavioural data by risk population are needed.

Understanding the modes of transmission model of new HIV infection and its use in prevention planning.

The modes of transmission model has been widely used to help decision-makers target measures for preventing human immunodeficiency virus (HIV) infection. The model estimates the number of new HIV infections that will be acquired over the ensuing year by individuals in identified risk groups in a given population using data on the size of the groups, the aggregate risk behaviour in each group, the current prevalence of HIV infection among the sexual or injecting drug partners of individuals in each group, and the probability of HIV transmission associated with different risk behaviours. The strength of the model is its simplicity, which enables data from a variety of sources to be synthesized, resulting in better characterization of HIV epidemics in some settings. However, concerns have been raised about the assumptions underlying the model structure, about limitations in the data available for deriving input parameters and about interpretation and communication of the model results. The aim of this review was to improve the use of the model by reassessing its paradigm, structure and data requirements. We identified key questions to be asked when conducting an analysis and when interpreting the model results and make recommendations for strengthening the model's application in the future.

Integrated Management of Childhood Illness: efficiency of primary health in Northeast Brazil.

OBJECTIVE: The Integrated Management of Childhood Illness is a strategy designed to address major causes of child mortality. The aim of this study was to assess the impact of the strategy on the quality of child health care provided at primary facilities. METHODS: Child health quality of care and costs were compared in four states in Northeastern Brazil, in 2001. There were studied 48 health facilities considered to have had stable strategy implementation at least two years before the start of study, with 48 matched comparison facilities in the same states. A single measure of correct management of sick children was used to assess care provided to all sick children. Costs included all resources at the national, state, local and facility levels associated with child health care. RESULTS: Facilities providing strategy-based care had significantly better management of sick children at no additional cost to municipalities relative to the comparison municipalities. At strategy facilities 72% of children were correctly managed compared with 56% in comparison facilities (p=0.001). The cost per child managed correctly was US$13.20 versus US$21.05 in the strategy and comparison municipalities, respectively, after standardization for population size. CONCLUSIONS: The strategy improves the efficiency of primary facilities in Northeastern Brazil. It leads to better health outcomes at no extra cost.

Equity of antiretroviral treatment use in high HIV burden countries: Analyses of data from nationally-representative surveys in Kenya and South Africa.

OBJECTIVE: To assess changes and equity in antiretroviral therapy (ART) use in Kenya and South Africa. METHODS: We analysed national population-based household surveys conducted in Kenya and South Africa between 2007 and 2012 for factors associated with lack of ART use among people living with HIV (PLHIV) aged 15-64 years. We considered ART use to be inequitable if significant differences in use were found between groups of PLHIV (e.g. by sex). FINDINGS: ART use among PLHIV increased from 29.3% (95% confidence interval [CI]: 22.8-35.8) to 42.5% (95%CI: 37.4-47.7) from 2007 to 2012 in Kenya and 17.4% (95%CI: 14.2-20.9) to 30.3% (95%CI: 27.2-33.6) from 2008 to 2012 in South Africa. In 2012, factors independently associated with lack of ART use among adult Kenyan PLHIV were rural residency (adjusted odds ratio [aOR] 1.98, 95%CI: 1.23-3.18), younger age (15-24 years: aOR 4.25, 95%CI: 1.7-10.63, and 25-34 years: aOR 5.16, 95%CI: 2.73-9.74 versus 50-64 years), nondisclosure of HIV status to most recent sex partner (aOR 2.41, 95%CI: 1.27-4.57) and recent recreational drug use (aOR 2.50, 95%CI: 1.09-5.77). Among South African PLHIV in 2012, lack of ART use was significantly associated with younger age (15-24 years: aOR 4.23, 95%CI: 2.56-6.70, and 25-34 years: aOR 2.84, 95%CI: 1.73-4.67, versus 50-64 years), employment status (aOR 1.61, 95%CI: 1.16-2.23 in students versus unemployed), and recent recreational drug use (aOR 4.56, 95%CI: 1.79-11.57). CONCLUSION: Although we found substantial increases in ART use in both countries over time, we identified areas needing improvement including among rural Kenyans, students in South Africa, and among young people and drug users in both countries.

Global epidemiology of HIV-AIDS.

Although intravenous drug use is the major route of transmission in several countries, sexual transmission is the dominant mode of HIV spread globally, with a concomitant epidemic in infants borne to HIV-infected mothers. The HIV epidemic varies substantially from one geographic area to another, and three broad epidemic categories describe the diversity of features observed globally: low epidemic settings, centrzated epidemics, and generalized epidemics. The introduction of highly active antiretroviral therapy in industrialized countries has transformed AIDS from an inevitably fatal condition to a chronic, treatable condition, but this goal has yet to be realized in most resource-constrained settings that bear a disproportionate burden of infection. This article describes the modes of HIV transmission, geographic distribution of the evolving AIDS pandemic, and case studies of each of the three types of HIV epidemics, and presents global trends in AIDS and mortality.

Global and regional distribution of HIV-1 genetic subtypes and recombinants in 2004.

OBJECTIVE: To estimate the global and regional distribution of HIV-1 subtypes and recombinants in 2004. DESIGN: A study was conducted in which molecular epidemiological data on HIV-1 subtype distribution in individual countries were combined with country-specific estimates of the number of people living with HIV. METHODS: HIV-1 subtype data were collected for 23 874 HIV-1 samples from 70 countries, which together accounted for 89% of all people living with HIV worldwide in 2004. The proportions of HIV-1 infections due to various subtypes detected in each country were combined with the number of HIV infected people in the respective countries to generate regional and global HIV-1 subtype distribution estimates. RESULTS: Subtype C accounted for 50% of all infections worldwide in 2004. Subtypes A, B, D and G accounted for 12%, 10%, 3% and 6%, respectively. The subtypes F, H, J and K together accounted for 0.94% of infections. The circulating recombinant forms CRF01_AE and CRF02_AG each were responsible for 5% of cases, and CRF03_AB for 0.1%. Other recombinants accounted for the remaining 8% of infections. All recombinant forms taken together were responsible for 18% of infections worldwide. CONCLUSION: Combining data on HIV-1 subtype distribution in individual countries with country-specific estimates of the number of people living with HIV provided a good method to generate estimates of the global and regional HIV-1 genetic diversity in 2004. The results could serve as an important resource for HIV scientists, public health officials and HIV vaccine developers.

The potential impact of male circumcision on HIV in Sub-Saharan Africa.

BACKGROUND: A randomized controlled trial (RCT) has shown that male circumcision (MC) reduces sexual transmission of HIV from women to men by 60% (32%-76%; 95% CI) offering an intervention of proven efficacy for reducing the sexual spread of HIV. We explore the implications of this finding for the promotion of MC as a public health intervention to control HIV in sub-Saharan Africa. METHODS AND FINDINGS: Using dynamical simulation models we consider the impact of MC on the relative prevalence of HIV in men and women and in circumcised and uncircumcised men. Using country level data on HIV prevalence and MC, we estimate the impact of increasing MC coverage on HIV incidence, HIV prevalence, and HIV-related deaths over the next ten, twenty, and thirty years in sub-Saharan Africa. Assuming that full coverage of MC is achieved over the next ten years, we consider three scenarios in which the reduction in transmission is given by the best estimate and the upper and lower 95% confidence limits of the reduction in transmission observed in the RCT. MC could avert 2.0 (1.1-3.8) million new HIV infections and 0.3 (0.1-0.5) million deaths over the next ten years in sub-Saharan Africa. In the ten years after that, it could avert a further 3.7 (1.9-7.5) million new HIV infections and 2.7 (1.5-5.3) million deaths, with about one quarter of all the incident cases prevented and the deaths averted occurring in South Africa. We show that a) MC will increase the proportion of infected people who are women from about 52% to 58%; b) where there is homogenous mixing but not all men are circumcised, the prevalence of infection in circumcised men is likely to be about 80% of that in uncircumcised men; c) MC is equivalent to an intervention, such as a vaccine or increased condom use, that reduces transmission in both directions by 37%. CONCLUSIONS: This analysis is based on the result of just one RCT, but if the results of that trial are confirmed we suggest that MC could substantially reduce the burden of HIV in Africa, especially in southern Africa where the prevalence of MC is low and the prevalence of HIV is high. While the protective benefit to HIV-negative men will be immediate, the full impact of MC on HIV-related illness and death will only be apparent in ten to twenty years.

Level of viral suppression and the cascade of HIV care in a South African semi-urban setting in 2012.

OBJECTIVE: In 2012, 7 years after the introduction of antiretroviral treatment (ART) in the South African township of Orange Farm, we measured the proportion of HIV-positive people who were virally suppressed, especially among high-risk groups (women 18-29 years and men 25-34 years). DESIGN: A community-based cross-sectional representative survey was conducted among 3293 men and 3473 women. METHODS: Study procedures included a face-to-face interview and collection of blood samples that were tested for HIV, 11 antiretroviral drugs and HIV-viral load. RESULTS: HIV prevalence was 17.0% [95% confidence interval: 15.7-18.3%] among men and 30.1% [28.5-31.6%] among women. Overall, 59.1% [57.4-60.8%] of men and 79.5% [78.2-80.9%] of women had previously been tested for HIV. When controlling for age, circumcised men were more likely to have been tested compared with uncircumcised men (66.1 vs 53.6%; P < 0.001). Among HIV+, 21.0% [17.7-24.6%] of men and 30.5% [27.7-33.3%] of women tested positive for one or more antiretroviral drugs. Using basic calculations, we estimated that, between 2005 and 2012, ART programs prevented between 46 and 63% of AIDS-related deaths in the community. Among antiretroviral-positive, 91.9% [88.7-94.3%] had viral suppression (viral load <400 copies/ml). The proportion of viral suppression among HIV+ was 27.0% [24.3-29.9%] among women and 17.5% [14.4-20.9%] among men. These proportions were lower among the high-risk groups: 15.6% [12.1-19.7%] among women and 8.4% [5.0-13.1%] among men. CONCLUSION: In Orange Farm, between 2005 and 2012, ART programs were suboptimal and, among those living with HIV, the proportion with viral suppression was still low, especially among the young age groups. However, our study showed that, in reality, antiretroviral drugs are highly effective in viral suppression at an individual level.

Measuring the quality of child health care at first-level facilities.

Sound policy and program decisions require timely information based on valid and relevant measures. Recent findings suggest that despite the availability of effective and affordable guidelines for the management of sick children in first-level health facilities in developing countries, the quality and coverage of these services remains low. We report on the development and evaluation of a set of summary indices reflecting the quality of care received by sick children in first-level facilities. The indices were first developed through a consultative process to achieve face validity by involving technical experts and policymakers. The definition of evaluation measures for many public health programs stops at this point. We added a second phase in which standard statistical techniques were used to evaluate the content and construct validity of the indices and their reliability, drawing on data sets from the multi-country evaluation of integrated management of childhood illness (MCE) in Brazil, Tanzania and Uganda. The statistical evaluation identified important conceptual errors in the indices arising from the theory-driven expert review. The experts had combined items into inappropriate indicators resulting in summary indices that were difficult to interpret and had limited validity for program decision making. We propose a revised set of summary indices for the measurement of child health care in developing countries that is supported by both expert and statistical reviews and that led to similar programmatic insights across the three countries. We advocate increased cross-disciplinary research within public health to improve measurement approaches. Child survival policymakers, program planners and implementers can use these tools to improve their monitoring and so increase the health impact of investments in health facility care.

Changing patterns of knowledge, reported behaviour and sexually transmitted infections in a South African gold mining community.

BACKGROUND: In 1998, a major HIV intervention project was started in a mining community in Carletonville, South Africa. This included community-based peer education, condom distribution, syndromic management of sexually transmitted infections (STI), and presumptive STI treatment for sex workers. OBJECTIVES: To investigate changes in sexual behaviour and the prevalence of STI before and 2 years after the start of the HIV prevention programme. METHODS: Cross-sectional surveys were carried out in 1998 and 2000 among mine workers, sex workers and adults in the community. Demographic and behavioural factors were recorded and participants were tested for syphilis, gonorrhoea and chlamydial infection and, at the start of the intervention, for HIV. RESULTS: In 1998, the prevalence of HIV among men and women in the general population, mine workers, and sex workers, was 20%, 37%, 29% and 69%, respectively. In 2000, syphilis, gonorrhoea and chlamydial infection had increased among mine workers; chlamydial infection had increased among men and women, and syphilis had increased among women. There was evidence of positive behaviour change but this was not substantial or universal. Knowledge of HIV/AIDS and awareness of the epidemic were high but condom use remained low. CONCLUSION: There was little evidence of significant behaviour change and the prevalence of curable STI increased. The prevention programme had had less impact than expected. Reasons for the reduced impact, and the lessons for future intervention projects are discussed. There is a need for further monitoring of the HIV epidemic especially as its impact increases.

GB virus type C coinfection in HIV-infected African mothers and their infants, KwaZulu Natal, South Africa.

GB virus type C (GBV-C) infection was studied in a convenience sample of 75 antiretroviral (ART)-naive African mothers with human immunodeficiency virus infection and their infants. GBV-C RNA was extracted from serum and amplified by reverse-transcriptase polymerase chain reaction. Twenty-seven (36%) of these 75 HIV-infected women tested positive for GBV-C RNA. To study transmission dynamics, we chose a random subsample of 20 of these women and their infants. In this cohort, there was evidence of postnatal transmission of GBV-C; however, it was not possible to demonstrate evidence of in utero or intrapartum transmission. In this pilot observational study, transmission of HIV from mother-to-infant occurs independently of the GBV-C infection status of the mother. The immunological indices measured tend to suggest an association with protection and or delayed progression of HIV disease in GBV-C-infected mothers.

Estimates of world-wide distribution of child deaths from acute respiratory infections.

Acute respiratory infections (ARI) are among the leading causes of childhood mortality. Estimates of the number of children worldwide who die from ARI are needed in setting priorities for health care. To establish a relation between deaths due to ARI and all-cause deaths in children under 5 years we show that the proportion of deaths directly attributable to ARI declines from 23% to 18% and then 15% (95% confidence limits range from +/- 2% to +/- 3%) as under-5 mortality declines from 50 to 20 and then to 10/1000 per year. Much of the variability in estimates of ARI in children is shown to be inherent in the use of verbal autopsies. This analysis suggests that throughout the world 1.9 million (95% CI 1.6-2.2 million) children died from ARI in 2000, 70% of them in Africa and southeast Asia.

Measurement of trends in childhood malaria mortality in Africa: an assessment of progress toward targets based on verbal autopsy.

Reduction of deaths associated with malaria in children is a primary goal of malaria control programmes in Africa, but there has been little discussion about how changes in mortality will be measured. This paper assesses recent historical changes in the contribution of malaria to child survival in Africa by examining data from demographic surveillance systems (DSS) in 25 mainly rural settings. The data were adjusted for the varying sensitivity and specificity of verbal autopsies (VA) in different ranges of malaria mortality and for varying parasite prevalences. Average malaria mortality in the DSS sites in west Africa was 7.8 per 1000 child-years between 1982 and 1998; the rate did not change significantly over this period. In the sites in east and southern Africa combined, malaria mortality was 6.5 per 1000 child-years between 1982 and 1989, but it increased to 11.9 per 1000 child-years between 1990 and 1998. All-cause child mortality and non-malaria mortality, by contrast, decreased significantly over time in both regions; consequently, the proportion of deaths due to malaria rose from 18% to 23% in west African sites and from 18% to 37% in east and southern African sites between 1982-89 and 1990-98. If malaria mortality fell at a rate consistent with the Roll Back Malaria target of halving malaria mortality by the year 2010, an individual DSS of a total population of 63 500 could with adequate VA adjustment detect this reduction after 7 years.

Pediatric mortality in Africa: plasmodium falciparum malaria as a cause or risk?

The disability adjusted life year (DALY) approach of defining cause-specific health burdens is becoming the benchmark for international disease control prioritization. For malaria, this categorical approach may not fully capture its burden that includes chronic anemia, low birth weight, and enhancement of the severity of other childhood diseases. We investigated the extent to which malaria acts as a risk factor for all-cause mortality in African children less than five years of age from 1) ecologic associations between Plasmodium falciparum infection prevalence (PR) and under-five mortality, and 2) reductions in all-cause under-five mortality achieved in malaria intervention trials. Across 48 demographic surveillance studies, when adjusted for secular trends, PR more than doubled all-cause mortality (P = 0.0001). Trials of insecticide-treated mosquito nets generally found smaller population-attributable fractions of pediatric mortality to malaria infection, which may relate to their imperfect coverage and efficacy. In conclusion, the disability and death burden due to malaria in African children could be higher than that detectable from cause-specific DALY estimations.

Effect of Integrated Management of Childhood Illness (IMCI) on health worker performance in Northeast-Brazil.

A multi-country evaluation is being carried out in Brazil and four other countries to determine the effectiveness, cost, and impact of the Integrated Management of Childhood Illness (IMCI). We examine the effect of IMCI on the quality of health care provided to children under five visiting health facilities. A health facility survey was conducted at 24 facilities (12 with IMCI) in each of four States in the Northeast. We assessed the quality of care provided to children between 2 months and 5 years attending the facilities. Health workers trained in IMCI provided significantly better care than those not trained. Significant differences between health workers who were trained or not trained in IMCI were found in the assessment of the child, disease classification, treatment, and caretaker communication. Nurses trained in IMCI performed as well as, and sometimes better than, medical officers trained in IMCI. We conclude that while there is room for further improvement, IMCI case management training significantly improves health worker performance, and that parts of Brazil that have not yet introduced IMCI should be encouraged to do so.