Articles tagged as "South Africa"

Ending HIV deaths in South Africa: progress made but still a long way to go

Mortality trends and differentials in South Africa from 1997 to 2012: second National Burden of Disease Study.

Pillay-van Wyk V, Msemburi W, Laubscher R, Dorrington RE, Groenewald P, Glass T, Nojilana B, Joubert JD, Matzopoulos R, Prinsloo M, Nannan N, Gwebushe N, Vos T, Somdyala N, Sithole N, Neethling I, Nicol E, Rossouw A, Bradshaw D. Lancet Glob Health. 2016 Sep;4(9):e642-53. doi: 10.1016/S2214-109X(16)30113-9.

Background: The poor health of South Africans is known to be associated with a quadruple disease burden. In the second National Burden of Disease (NBD) study, we aimed to analyse cause of death data for 1997-2012 and develop national, population group, and provincial estimates of the levels and causes of mortality.

Method: We used underlying cause of death data from death notifications for 1997-2012 obtained from Statistics South Africa. These data were adjusted for completeness using indirect demographic techniques for adults and comparison with survey and census estimates for child mortality. A regression approach was used to estimate misclassified HIV/AIDS deaths and so-called garbage codes were proportionally redistributed by age, sex, and population group population group (black African, Indian or Asian descent, white [European descent], and coloured [of mixed ancestry according to the preceding categories]). Injury deaths were estimated from additional data sources. Age-standardised death rates were calculated with mid-year population estimates and the WHO age standard. Institute of Health Metrics and Evaluation Global Burden of Disease (IHME GBD) estimates for South Africa were obtained from the IHME GHDx website for comparison.

Findings: All-cause age-standardised death rates increased rapidly since 1997, peaked in 2006 and then declined, driven by changes in HIV/AIDS. Mortality from tuberculosis, non-communicable diseases, and injuries decreased slightly. In 2012, HIV/AIDS caused the most deaths (29.1%) followed by cerebrovascular disease (7.5%) and lower respiratory infections (4.9%). All-cause age-standardised death rates were 1.7 times higher in the province with the highest death rate compared to the province with the lowest death rate, 2.2 times higher in black Africans compared to whites, and 1.4 times higher in males compared with females. Comparison with the IHME GBD estimates for South Africa revealed substantial differences for estimated deaths from all causes, particularly HIV/AIDS and interpersonal violence.

Interpretation: This study related the reversal of HIV/AIDS, non-communicable disease, and injury mortality trends in South Africa during the study period. Mortality differentials show the importance of social determinants, raise concerns about the quality of health services, and provide relevant information to policy makers for addressing inequalities. Differences between GBD estimates for South Africa and this study emphasise the need for more careful calibration of global models with local data.

Abstract   Full-text [free] access 

Editor’s notes: In South Africa in 2012, almost 500 people died every day from HIV or TB. One in every three deaths was associated with HIV or TB. Although these figures represent a substantial decline from the peak of the epidemic impact in 2006, they highlight the enormous challenge still facing this country.

South Africa is one of the few countries in Africa to have a robust civil registration system for deaths. However, there continue to be problems with misclassification of HIV-associated deaths. This analysis relied on somewhat complicated analytical methods to adjust mortality estimates. Only around half of those deaths ultimately defined as HIV associated had been originally coded as such in the registration system. The methods for adjustment differed from those used in the Global Burden of Disease (GBD) study. This explains the quite marked discrepancy in number of deaths attributed to HIV - this study estimated 40% fewer HIV-associated deaths than the GBD study.

This highlights that there is still quite a lot of uncertainty around cause-specific mortality estimates. So, although these data are useful to guide national and provincial priority setting, more fine-grain analysis is required to properly inform public health policies. There is a particular need to unpick the contribution of TB. In this respect, the recent announcement by the South African Department of Science of Technology to establish a network of health and demographic surveillance sites as a key component of the national research infrastructure is very welcome. With established verbal autopsy methods and innovations such as routine linkage to health service records, this will provide a framework to allow a deeper understanding of mortality.

South Africa
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Poor linkage to care may undermine benefits of universal test and treat

Uptake of home-based HIV testing, linkage to care, and community attitudes about ART in rural KwaZulu-Natal, South Africa: descriptive results from the first phase of the ANRS 12249 TasP cluster-randomised trial.

Iwuji CC, Orne-Gliemann J, Larmarange J, Okesola N, Tanser F, Thiebaut R, Rekacewicz C, Newell ML, Dabis F. PLoS Med. 2016 Aug 9;13(8):e1002107. doi: 10.1371/journal.pmed.1002107. eCollection 2016.

Background: The 2015 WHO recommendation of antiretroviral therapy (ART) for all immediately following HIV diagnosis is partially based on the anticipated impact on HIV incidence in the surrounding population. We investigated this approach in a cluster-randomised trial in a high HIV prevalence setting in rural KwaZulu-Natal. We present findings from the first phase of the trial and report on uptake of home-based HIV testing, linkage to care, uptake of ART, and community attitudes about ART.

Methods and findings: Between 9 March 2012 and 22 May 2014, five clusters in the intervention arm (immediate ART offered to all HIV-positive adults) and five clusters in the control arm (ART offered according to national guidelines, i.e., CD4 count ≤ 350 cells/µl) contributed to the first phase of the trial. Households were visited every 6 mo. Following informed consent and administration of a study questionnaire, each resident adult (≥16 y) was asked for a finger-prick blood sample, which was used to estimate HIV prevalence, and offered a rapid HIV test using a serial HIV testing algorithm. All HIV-positive adults were referred to the trial clinic in their cluster. Those not linked to care 3 mo after identification were contacted by a linkage-to-care team. Study procedures were not blinded. In all, 12 894 adults were registered as eligible for participation (5790 in intervention arm; 7104 in control arm), of whom 9927 (77.0%) were contacted at least once during household visits. HIV status was ever ascertained for a total of 8233/9927 (82.9%), including 2569 ascertained as HIV-positive (942 tested HIV-positive and 1627 reported a known HIV-positive status). Of the 1177 HIV-positive individuals not previously in care and followed for at least 6 mo in the trial, 559 (47.5%) visited their cluster trial clinic within 6 mo. In the intervention arm, 89% (194/218) initiated ART within 3 mo of their first clinic visit. In the control arm, 42.3% (83/196) had a CD4 count ≤350 cells/µl at first visit, of whom 92.8% initiated ART within 3 mo. Regarding attitudes about ART, 93% (8802/9460) of participants agreed with the statement that they would want to start ART as soon as possible if HIV-positive. Estimated baseline HIV prevalence was 30.5% (2028/6656) (95% CI 25.0%, 37.0%). HIV prevalence, uptake of home-based HIV testing, linkage to care within 6 mo, and initiation of ART within 3 mo in those with CD4 count ≤350 cells/µl did not differ significantly between the intervention and control clusters. Selection bias related to noncontact could not be entirely excluded.

Conclusions: Home-based HIV testing was well received in this rural population, although men were less easily contactable at home; immediate ART was acceptable, with good viral suppression and retention. However, only about half of HIV-positive people accessed care within 6 mo of being identified, with nearly two-thirds accessing care by 12 mo. The observed delay in linkage to care would limit the individual and public health ART benefits of universal testing and treatment in this population.

Trial registration: NCT01509508.

Abstract  Full-text [free] access 

Editor’s notes: The UNAIDS treatment target set for 2020 aim for at least 90 percent of all people living with HIV to be diagnosed, at least 90 percent of people diagnosed to receive antiretroviral therapy, and for treatment to be effective and consistent enough in at least 90 percent of people on treatment to suppress the virus. This would result in about 73% of all HIV-positive people being virally suppressed. 

This paper describes the key process indicators (such as uptake of initial and repeat home-based HIV testing, linkage to care, uptake of ART, and viral suppression) along the treatment cascade during the two-year initial phase of a trial evaluating a treatment as prevention package in a rural South African setting. Although the investigators were unable to contact one-quarter of the potential key population - especially men - they found good acceptance of home-based HIV testing.

However, they found disappointingly low rates of linkage to care. Only about half of HIV-positive participants not yet in care attended a clinic within six months of diagnosis. This increased to two-thirds after 12 months, partly due the efforts of a linkage-to-care team. They contacted those not linked to care three months after an HIV-positive test. Among people who did present to the clinics, the rates of ART uptake, retention in care and viral suppression were high.

The main study (reported at the AIDS 2016 conference in Durban) did not demonstrate an effect of offering immediate ART on HIV incidence at population level, mainly due the low rates of linkage to care following HIV diagnosis. 

These results suggest that systems to improve linkage to care will be necessary if the individual and public health benefits of universal testing and treatment are to be maximised.

South Africa
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Systematic review finds that the evidence for the impact of HCT on HIV acquisition is limited but scale-up remains vital to facilitate other proven interventions

The effect of HIV counselling and testing on HIV acquisition in sub-Saharan Africa: a systematic review.

Rosenberg NE, Hauser BM, Ryan J, Miller WC. Sex Transm Infect. 2016 Aug 16. pii: sextrans-2016-052651. doi: 10.1136/sextrans-2016-052651. [Epub ahead of print]

Objectives: Annually, millions of people in sub-Saharan Africa (SSA) receive HIV counselling and testing (HCT), a service designed to inform persons of their HIV status and, if HIV uninfected, reduce HIV acquisition risk. However, the impact of HCT on HIV acquisition has not been systematically evaluated. We conducted a systematic review to assess this relationship in SSA.

Methods: We searched for articles from SSA meeting the following criteria: an HIV-uninfected population, HCT as an exposure, longitudinal design and an HIV acquisition endpoint. Three sets of comparisons were assessed and divided into strata: sites receiving HCT versus sites not receiving HCT (Strata A), persons receiving HCT versus persons not receiving HCT (Strata B) and persons receiving couple HCT (cHCT) versus persons receiving individual HCT (Strata C).

Results: We reviewed 1635 abstracts; eight met all inclusion criteria. Strata A consisted of one cluster randomised trial with a non-significant trend towards HCT being harmful: incidence rate ratio (IRR): 1.4. Strata B consisted of five observational studies with non-significant unadjusted IRRs from 0.6 to 1.3. Strata C consisted of two studies. Both displayed trends towards cHCT being more protective than individual HCT (IRRs: 0.3-0.5). All studies had at least one design limitation.

Conclusions: In spite of intensive scale-up of HCT in SSA, few well-designed studies have assessed the prevention impacts of HCT. The limited body of evidence suggests that individual HCT does not have a consistent impact on HIV acquisition, and cHCT is more protective than individual HCT.

Abstract access  

Editor’s notes: Although it is plausible that knowing that you are HIV-negative might be an incentive for safer behaviour and thus reduce the risk of HIV acquisition, previous studies have not been conclusive.  HIV counselling and testing (HCT) is an integral part of other prevention and treatment activities (e.g. voluntary medical male circumcision (VMMC) or pre-exposure prophylaxis (PreP)). The findings from this systematic review suggest that with the available evidence individual HCT does not consistently have a protective or harmful effect on HIV acquisition. Couples’ HCT may be protective but the authors caution against a simplistic interpretation, reminding us of limited evidence including imprecise estimates and possibilities of bias. There were just two studies on couples’ HCT and convincing evidence of benefit was only seen in the study which compared couples’ HCT with individual HCT. There could be systematic differences between people who sought couples’ versus individual HCT (who may be unable or unwilling to take up a couples programme). While couples’ HCT may be suited to some people and be protective for them, the wider applicability may be more limited. The authors describe the methodological challenges of measuring the impact of an HCT activity on HIV acquisition, including the fact that large cohorts need to be effectively followed for long periods. In addition, randomised comparisons with no HCT are not possible because of ethical barriers to withholding HCT. Another challenge the authors cite is that both the primary exposure (HCT) and the primary outcome (HIV acquisition) require an HIV test. Arguably, this could be circumvented by offering anonymised remote (eg laboratory) HIV testing to determine HIV acquisition, rather than point-of-care tests where results would be immediately available. The final message from this paper is that although convincing evidence for reduction in HIV acquisition from HCT is not apparent, it’s scale-up must continue. HCT is the gateway to other proven activities for both prevention and treatment.

HIV testing
Rwanda, South Africa, Uganda, Zimbabwe
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South Africa’s major cascade gap is between testing and treatment

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

Jean K, Puren A, Cutler E, Singh B, Bouscaillou J, Rain-Taljaard R, Taljaard D, Gouws E, Lissouba P, Lewis DA, Peytavin G, Auvert B. AIDS. 2016 Aug 24;30(13):2107-16. doi: 10.1097/QAD.0000000000001155.

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.

Abstract access  

Editor’s notes: The efficacy of antiretroviral treatment (ART) in preventing HIV transmission from HIV-positive to HIV-negative people is clearly established. However, HIV incidence remains stubbornly high in many settings, and the challenge is to find ways to implement ART at sufficient scale, in combination with other effective programmes, to make an impact on HIV incidence at community level.

In this study, the authors surveyed a representative sample of adults in a community near Johannesburg, South Africa, where HIV prevalence is high and ART has been widely available since 2005. A trial of voluntary male medical circumcision (VMMC) was run in this location between 2002 to 2004, and a programme of incentivised VMMC and community mobilisation have been in place since 2008. The proportion of adults who had ever tested for HIV was nearly 80% among women and 60% among men, similar to that reported at national level in South Africa. Among survey participants with detectable ART agents in their blood, 94% had an HIV viral load below 1000 copies per ml, 92% below 400 copies per ml and 78% below 50 copies per ml. However, because ART programmes were sub-optimal at the time of the study, only 24% of all HIV-positive people in the survey had an HIV viral load below 400 copies per ml.

This study presents data from a real-world setting in South Africa. During the time of the study (2005-2012) treatment programmes were still sub-optimal (using the WHO 2006 treatment guidelines) but it shows that for all people on ART, significant levels of viral suppression were obtained. Of critical importance for treatment programmes will be to make sure that people have access to testing services and that testing and treatment programmes are linked. 

South Africa
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Pregnancy and intimate partner violence among women living with HIV

Intimate partner violence experienced by HIV-infected pregnant women in South Africa: a cross-sectional study.

Bernstein M, Phillips T, Zerbe A, McIntyre JA, Brittain K, Petro G, Abrams EJ, Myer L. BMJ Open. 2016 Aug 16;6(8):e011999. doi: 10.1136/bmjopen-2016-011999.

Objectives: Intimate partner violence (IPV) during pregnancy may be common in settings where HIV is prevalent but there are few data on IPV in populations of HIV-infected pregnant women in Southern Africa. We examined the prevalence and correlates of IPV among HIV-infected pregnant women.

Setting: A primary care antenatal clinic in Cape Town, South Africa.

Participants: 623 consecutive HIV-infected pregnant women initiating lifelong antiretroviral therapy.

Measures: IPV, depression, substance use and psychological distress were assessed using the 13-item WHO Violence Against Women questionnaire, the Edinburgh Postnatal Depression Scale (EPDS), Alcohol and Drug Use Disorders Identification Tests (AUDIT/DUDIT) and the Kessler 10 (K-10) scale, respectively.

Results: The median age in the sample was 28 years, 97% of women reported being in a relationship, and 70% of women reported not discussing and/or agreeing on pregnancy intentions before conception. 21% of women (n=132) reported experiencing ≥1 act of IPV in the past 12 months, including emotional (15%), physical (15%) and sexual violence (2%). Of those reporting any IPV (n=132), 48% reported experiencing 2 or more types. Emotional and physical violence was most prevalent among women aged 18-24 years, while sexual violence was most commonly reported among women aged 25-29 years. Reported IPV was less likely among married women, and women who experienced IPV were more likely to score above threshold for substance use, depression and psychological distress. In addition, women who reported not discussing and/or not agreeing on pregnancy intentions with their partner prior to conception were significantly more likely to experience violence.

Conclusions: HIV-infected pregnant women in the study reported experiencing multiple forms of IPV. While the impact of IPV on maternal and child health outcomes in the context of HIV infection requires further research attention, IPV screening and support services should be considered within the package of routine care for HIV-infected pregnant women.

Trial registration number: NCT01933477.

Abstract  Full-text [free] access 

Editor’s notes: Intimate partner violence among women in sub-Saharan Africa is >30%. There is limited research examining intimate partner violence among women living with HIV. Research is important as intimate partner violence may impact on a woman’s ability to adhere to antiretroviral therapy. Among pregnant women, this includes during pregnancy and post-partum. This study describes the prevalence of recent intimate partner violence, and examines associations between recent intimate partner violence and demographic, relationship and psychological variables.

The study was set in a township in Cape Town, South Africa, where the majority of residents have low socio-economic status and HIV infection among women is approximately 30%. Some 21% percent of 623 participants reported any recent intimate partner violence in the past 12 months.  Fifteen percent reported emotional violence, 15% physical violence (7% severe physical) and two percent sexual violence. Recent violence was associated with hazardous alcohol use, psychological distress and depression. It was more likely among unmarried women, and among women who had not discussed/agreed pregnancy prior to conception. There was no evidence to suggest intimate partner violence was elevated among women newly diagnosed with HIV.

These data suggest significant intimate partner violence experience among pregnant women living with HIV, living in this township. This study adds to the limited literature, examining intimate partner violence in the context of pregnancy and HIV. Longitudinal studies, and studies which examine the impact of intimate partner violence on ART uptake and adherence, including during pregnancy and post-partum, are necessary. 

South Africa
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Updated evidence that DMPA increases HIV risk among women

Update on hormonal contraceptive methods and risk of HIV acquisition in women: a systematic review of epidemiological evidence, 2016.

Polis CB, Curtis KM, Hannaford PC, Phillips SJ, Chipato T, Kiarie JN, Westreich DJ, Steyn PS. AIDS. 2016 Aug 5. [Epub ahead of print]

Objective and design: Some studies suggest that specific hormonal contraceptive (HC) methods (particularly depot medroxyprogesterone acetate [DMPA]) may increase women's HIV acquisition risk. We updated a systematic review to incorporate recent epidemiological data.

Methods: We searched for articles published between 1/15/2014-1/15/2016, and hand-searched reference lists. We identified longitudinal studies comparing users of a specific HC method against either (1) non-users of HC, or (2) users of another specific HC method. We added newly identified studies to those in the previous review, assessed study quality, created forest plots to display results, and conducted a meta-analysis for data on DMPA versus no HC.

Results: We identified ten new reports: five were considered "unlikely to inform the primary question". We focus on the other five reports, along with 9 from the previous review, considered "informative but with important limitations". The preponderance of data for oral contraceptive pills, injectable norethisterone enanthate (NET-EN), and levonorgestrel implants do not suggest an association with HIV acquisition, though data for implants are limited. The new, higher-quality studies on DMPA (or non-disaggregated injectables), which had mixed results in terms of statistical significance, had hazard ratios (HR) between 1.2 and 1.7, consistent with our meta-analytic estimate for all higher-quality studies of HR 1.4.

Conclusions: While confounding in these observational data cannot be excluded, new information increases concerns about DMPA and HIV acquisition risk in women. If the association is causal, the magnitude of effect is likely ≤HR 1.5. Data for other hormonal contraceptive methods, including NET-EN, are largely reassuring.

Abstract access

Editor’s notes: For several years there has been debate about whether the risk of HIV acquisition in women may be increased by the use of hormonal contraception. A systematic review published in 2014 included a meta-analysis of data from 22 studies, and this paper adds 10 new studies to the analysis. While these new papers carried some of the previous review’s limitations which cannot be ignored, the new data also lends further strength to the evidence and renewed analysis. The authors found some encouraging results which suggest that there is no significant increased risk of HIV with the use of oral contraceptives and the NET-EN injectable. However, this analysis does suggest that there is an increased risk of 1.4-1.5 of HIV with the use of DMPA. This is particularly concerning given the widespread use of this product throughout the world, and especially in areas where high rates of new HIV infections continue to persist, such as sub-Saharan Africa. Studies continue to explore this association of risk, and will hopefully produce evidence in the near future to definitively provide guidance as to how clinicians should direct the use of DMPA in women at risk of HIV. 

Africa, Northern America
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Challenges in assessing quality in HIV outpatient care

Structure and quality of outpatient care for people living with an HIV infection.

Engelhard EA, Smit C, Nieuwkerk PT, Reiss P, Kroon FP, Brinkman K, Geerlings SE. AIDS Care. 2016 Aug;28(8):1062-72. doi: 10.1080/09540121.2016.1153590. Epub 2016 Mar 13.

Policy-makers and clinicians are faced with a gap of evidence to guide policy on standards for HIV outpatient care. Ongoing debates include which settings of care improve health outcomes, and how many HIV-infected patients a health-care provider should treat to gain and maintain expertise. In this article, we evaluate the studies that link health-care facility and care provider characteristics (i.e., structural factors) to health outcomes in HIV-infected patients. We searched the electronic databases MEDLINE, PUBMED, and EMBASE from inception until 1 January 2015. We included a total of 28 observational studies that were conducted after the introduction of combination antiretroviral therapy in 1996. Three aspects of the available research linking the structure to quality of HIV outpatient care were evaluated: (1) assessed structural characteristics (i.e., health-care facility and care provider characteristics); (2) measures of quality of HIV outpatient care; and (3) reported associations between structural characteristics and quality of care. Rather than scarcity of data, it is the diversity in methodology in the identified studies and the inconsistency of their results that led us to the conclusion that the scientific evidence is too weak to guide policy in HIV outpatient care. We provide recommendations on how to address this heterogeneity in future studies and offer specific suggestions for further reading that could be of interest for clinicians and researchers.

Abstract access

Editor’s notes: The availability of antiretroviral therapy has resulted in remarkable decreases in HIV-associated mortality.  Complexity in the management of HIV infection has however grown along with these advances in treatment. Health-care providers are confronted with challenges associated with antiretroviral therapy including toxicities; drug-drug interactions and drug resistance; and comorbidities and aging among the population living with HIV. In order to achieve optimal health outcomes, care for people living with HIV should be provided at health-care facilities and by care providers with sufficient expertise. A variety of different delivery models have been attempted to achieve this. There are a growing number of studies assessing care delivery models and programmes in outpatient HIV care.  In this article the authors provide an overview of the scientific literature linking health-care facility and care provider characteristics to the quality of HIV outpatient care.

The authors conducted a systematic review of articles that reported an original observational research study with an adult population living with HIV, were conducted after 1996, and that did not focus exclusively on interventions.

The authors acknowledge the limitations of their research. These included a disproportionate number of studies based in the USA and sub-Saharan Africa (thus limited generalisability); diversity in the definition of structural variables; a wide scope of measures of quality of care used in studies; and limited inclusion of peoples’ healthcare experiences. The authors summarise two main implications of their research.  First, they note that their findings suggest that health-care provider experience improves outcomes among people living with HIV although they are unable to make recommendations regarding facility volume requirements for outpatient care. Second, they advocate for the need for research to extend to regions outside the USA and sub-Saharan Africa.  They also note the need for researchers to align their methods of measuring quality including by going beyond HIV-associated morbidity in the evaluation of health outcomes.  Peoples’ preferences and retention in care should also play an important role in the evaluation of the quality of care.

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Antiretroviral therapy dramatically reduces transmission of HIV to sexual partners

Antiretroviral therapy for the prevention of HIV-1 transmission.

Cohen MS, Chen YQ, McCauley M, Gamble T, Hosseinipour MC, Kumarasamy N, Hakim JG, Kumwenda J, Grinsztejn B, Pilotto JH, Godbole SV, Chariyalertsak S, Santos BR, Mayer KH, Hoffman IF, Eshleman SH, Piwowar-Manning E, Cottle L, Zhang XC, Makhema J, Mills LA, Panchia R, Faesen S, Eron J, Gallant J, Havlir D, Swindells S, Elharrar V, Burns D, Taha TE, Nielsen-Saines K, Celentano DD, Essex M, Hudelson SE, Redd AD, Fleming TR. N Engl J Med. 2016 Jul 18. [Epub ahead of print]

Background: An interim analysis of data from the HIV Prevention Trials Network (HPTN) 052 trial showed that antiretroviral therapy (ART) prevented more than 96% of genetically linked infections caused by human immunodeficiency virus type 1 (HIV-1) in serodiscordant couples. ART was then offered to all patients with HIV-1 infection (index participants). The study included more than 5 years of follow-up to assess the durability of such therapy for the prevention of HIV-1 transmission.

Methods: We randomly assigned 1763 index participants to receive either early or delayed ART. In the early-ART group, 886 participants started therapy at enrollment (CD4+ count, 350 to 550 cells per cubic millimeter). In the delayed-ART group, 877 participants started therapy after two consecutive CD4+ counts fell below 250 cells per cubic millimeter or if an illness indicative of the acquired immunodeficiency syndrome (i.e., an AIDS-defining illness) developed. The primary study end point was the diagnosis of genetically linked HIV-1 infection in the previously HIV-1-negative partner in an intention-to-treat analysis.

Results: Index participants were followed for 10,031 person-years; partners were followed for 8509 person-years. Among partners, 78 HIV-1 infections were observed during the trial (annual incidence, 0.9%; 95% confidence interval [CI], 0.7 to 1.1). Viral-linkage status was determined for 72 (92%) of the partner infections. Of these infections, 46 were linked (3 in the early-ART group and 43 in the delayed-ART group; incidence, 0.5%; 95% CI, 0.4 to 0.7) and 26 were unlinked (14 in the early-ART group and 12 in the delayed-ART group; incidence, 0.3%; 95% CI, 0.2 to 0.4). Early ART was associated with a 93% lower risk of linked partner infection than was delayed ART (hazard ratio, 0.07; 95% CI, 0.02 to 0.22). No linked infections were observed when HIV-1 infection was stably suppressed by ART in the index participant.

Conclusions: The early initiation of ART led to a sustained decrease in genetically linked HIV-1 infections in sexual partners. (Funded by the National Institute of Allergy and Infectious Diseases; HPTN 052 number, NCT00074581.).

Abstract access

Editor’s notes: The HPTN 052 trial has been a landmark study in establishing antiretroviral therapy as a strategy for preventing onward transmission of HIV. It was a study of more than 800 couples. More than half of the couples were in African countries. In each couple, one sexual partner was HIV positive and the other HIV negative.  The participants living with HIV were randomised either to receive immediate antiretroviral therapy or to delay until their CD4 count fell to 350, an approved approach at that time. The HIV negative partners were then monitored for acquisition of HIV.  When new HIV infections occurred, the virus was studied for genetic similarity to the virus of the known positive partner. The interim analysis was published in 2011.  It illustrated the programme to be so effective that the randomisation was ended and all the participants living with HIV were offered antiretroviral therapy. 

This article presents data after five years of follow-up, and if anything the results are even more remarkable. In more than 10 000 person-years of follow up, there were only eight transmissions of genetically linked virus from participants receiving antiretroviral therapy. Of these transmissions, four occurred early in treatment when the viral load would not be expected to be suppressed.  The other four occurred after treatment failure. In this enormous study, there were therefore no linked transmissions from participants who were stable on treatment without detectable viraemia. The study provides powerful support for the UNAIDS 90-90-90 treatment target.  The widest possible effective use of antiretroviral therapy will not only improve the health of people treated but could have a dramatic effect on new HIV infections.

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Identifying important proximal epidemiological parameters for HIV prevention

Prospects for HIV control in South Africa: a model-based analysis.

Johnson LF, Chiu C, Myer L, Davies MA, Dorrington RE, Bekker LG, Boulle A, Meyer-Rath G. Glob Health Action. 2016 Jun 8;9:30314. doi: 10.3402/gha.v9.30314. eCollection 2016.

Background: The goal of virtual elimination of horizontal and mother-to-child HIV transmission in South Africa (SA) has been proposed, but there have been few systematic investigations of which interventions are likely to be most critical to reducing HIV incidence.

Objective: This study aims to evaluate SA's potential to achieve virtual elimination targets and to identify which interventions will be most critical to achieving HIV incidence reductions.

Design: A mathematical model was developed to simulate the population-level impact of different HIV interventions in SA. Probability distributions were specified to represent uncertainty around 32 epidemiological parameters that could be influenced by interventions, and correlation coefficients (r) were calculated to assess the sensitivity of the adult HIV incidence rates and mother-to-child transmission rates (2015-2035) to each epidemiological parameter.

Results: HIV incidence in SA adults (ages 15-49) is expected to decline from 1.4% in 2011-2012 to 0.29% by 2035 (95% CI: 0.10-0.62%). The parameters most strongly correlated with future adult HIV incidence are the rate of viral suppression after initiating antiretroviral treatment (ART) (r=-0.56), the level of condom use in non-marital relationships (r=-0.40), the phase-in of intensified risk-reduction counselling for HIV-positive adults (r=0.29), the uptake of medical male circumcision (r=-0.24) and the phase-in of universal ART eligibility (r=0.22). The paediatric HIV parameters most strongly associated with mother-to-child transmission rates are the relative risk of transmission through breastfeeding when the mother is receiving ART (r=0.70) and the rate of ART initiation during pregnancy (r=-0.16).

Conclusions: The virtual elimination target of a 0.1% incidence rate in adults will be difficult to achieve. Interventions that address the infectiousness of patients after ART initiation will be particularly critical to achieving long-term HIV incidence declines in South Africa.

Abstract  Full-text [free] access 

Editor’s notes: Despite substantial progress in controlling HIV in South Africa, incidence rates remain very high. There is a continued need to identify and prioritise HIV prevention programmes to improve the impact of existing programmes. A deterministic compartmental model was used to simulate the impact of HIV programmes in South Africa. The modeling study aimed at identifying proximal epidemiological parameters that are important in reducing HIV incidence. The authors of this paper also aimed to evaluate the possibility of achieving the ‘virtual elimination’ targets that have been suggested for both heterosexual and mother-to-child transmission and the UNAIDS 90-90-90 treatment target. The model was parameterised using behavioural and demographic data for South Africa.  The results from the study suggest that for the purpose of preventing heterosexual and mother-to-child transmission of HIV in South Africa, the most important proximal epidemiological parameter to focus on is the infectiousness of people receiving antiretroviral therapy. The model predicts that the virtual elimination target of a 0.1% incidence rate in adults will be difficult to achieve. The authors emphasized on the need to scale-up existing HIV prevention and treatment programmes in order to reduce HIV incidence in South Africa.

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Demand-side activities are essential for achieving population level impact of HIV prevention tools

Interventions to strengthen the HIV prevention cascade: a systematic review of reviews.

Krishnaratne S, Hensen B, Cordes J, Enstone J, Hargreaves JR. Lancet HIV. 2016 Jul;3(7):e307-17. doi: 10.1016/S2352-3018(16)30038-8.

Background: Much progress has been made in interventions to prevent HIV infection. However, development of evidence-informed prevention programmes that translate the efficacy of these strategies into population effect remain a challenge. In this systematic review, we map current evidence for HIV prevention against a new classification system, the HIV prevention cascade.

Methods: We searched for systematic reviews on the effectiveness of HIV prevention interventions published in English from Jan 1, 1995, to July, 2015. From eligible reviews, we identified primary studies that assessed at least one of: HIV incidence, HIV prevalence, condom use, and uptake of HIV testing. We categorised interventions as those seeking to increase demand for HIV prevention, improve supply of HIV prevention methods, support adherence to prevention behaviours, or directly prevent HIV. For each specific intervention, we assigned a rating based on the number of randomised trials and the strength of evidence.

Findings: From 88 eligible reviews, we identified 1964 primary studies, of which 292 were eligible for inclusion. Primary studies of direct prevention mechanisms showed strong evidence for the efficacy of pre-exposure prophylaxis (PrEP) and voluntary medical male circumcision. Evidence suggests that interventions to increase supply of prevention methods such as condoms or clean needles can be effective. Evidence arising from demand-side interventions and interventions to promote use of or adherence to prevention tools was less clear, with some strategies likely to be effective and others showing no effect. The quality of the evidence varied across categories.

Interpretation: There is growing evidence to support a number of efficacious HIV prevention behaviours, products, and procedures. Translating this evidence into population impact will require interventions that strengthen demand for HIV prevention, supply of HIV prevention technologies, and use of and adherence to HIV prevention methods.

Abstract  Full-text [free] access

Editor’s notes: Demand, supply and use of programmes are crucial for the uptake and effective use of HIV prevention strategies. This paper presents an impressive undertaking in which the authors conducted a review of systematic reviews on the evidence for the effectiveness of HIV prevention programmes across the multiple steps in an HIV prevention cascade. This particular prevention cascade allocates programmes into demand-side, supply-side, adherence, and direct HIV prevention technologies. This was published in a separate paper in conjunction with this review. The review found that there is strong evidence with regards to which direct HIV prevention technologies are efficacious, as well as maps where adherence and supply-side programmes have been effective. A primary gap was noted on the demand-side of the cascade (e.g. information, education and communication, and peer-based activities to increase demand for medical male circumcision) where studies have not resulted in reducing HIV incidence or prevalence. There remains a need to understand why, despite supply, there is low uptake of some HIV prevention strategies, and for evaluation of novel activities to increase demand.  

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