By Philip R. Fischer, MD, DTM&H

Professor of Pediatrics, Department of Pediatric and Adolescent Medicine, Mayo Clinic, Rochester, MN

Dr. Fischer reports no financial relationships relevant to this field of study.

SYNOPSIS: Several strategies have proven effective in reducing transmission of HIV, including access to confidential testing and counseling, early introduction of HIV medications, and male circumcision. Three new studies show what actually affects the spread of HIV in populations, and results vary between different African settings.

SOURCES: Makhema J, Wirth KE, Pretorius Holme M, et al. Universal testing, expanded treatment, and incidence of HIV infection in Botswana. N Engl J Med 2019;381:230-242.

Havlir DV, Balzer LB, Charlebois ED, et al. HIV testing and treatment with the use of a community health approach in rural Africa. N Engl J Med 2019;381:219-229.

Hayes RJ, Donnell D, Floyd S, et al; HPTN 071 (PopART) Study Team. Effect of universal testing and treatment on HIV incidence – HPTN 071 (PopART). N Engl J Med 2019;381:207-218.

Last month, a single issue of the New England Journal of Medicine included three articles from different groups in Africa that dealt with population-level means of reducing the incidence and spread of HIV infection. Outcomes varied, presumably related to background situations in the different study settings.

Makhema and colleagues randomized villages in Botswana to receive either standard care or additional interventions, including HIV testing and counseling, ready access to care, antiretroviral treatment started earlier (higher CD4 counts) than is typical, and availability of male circumcision. The study ran from 2013 to 2018, and individual participants were followed for 29 months. In 2016, all HIV-positive patients in the country were offered antiretroviral treatment, whether the viral load was elevated or not and whether the CD4 count was low or not. Thirty villages were included, and approximately 20% of households were invited to participate; 12,600 individual participants were included.

At study entry, 29% of participants were HIV positive, and 83% of those knew they were HIV positive. Of those who knew they were positive, 87% were on antiretroviral treatment, and 96% of those had achieved viral suppression. A total of 4,487 HIV-negative individuals were enrolled and followed to determine HIV incidence with and without the added testing and treatment interventions. The annualized incidence of contracting HIV infection was 0.59% in the intervention group and 0.92% in the standard care (control) group (P = 0.05). HIV viral suppression was greater in the intervention group, as was the use of circumcision (from 30% at baseline to 40% with the intervention). Declining incidence of HIV infection and increasing viral suppression in infected individuals suggest that the interventions were significantly beneficial. The authors suspected that recruiting infected individuals in communities in socially accepted manners that facilitated treatment initiation made the difference.

Havlir and colleagues studied 32 rural communities in Uganda and Kenya. They offered routine/standard care to the “control” villages. They provided annual HIV testing, access to antiretroviral therapy for all infected individuals, and patient-centered care to the intervention communities. Their study began in 2013 and went through 2017. Follow-up of patients continued for three years. After 2015, universal antiretroviral treatment became available in control communities as well. Baseline HIV positivity varied from 4% to 19% in the three geographic regions where the study took place. Circumcision rates in men varied from 14% to 46% in the various regions included. Approximately 150,000 individuals were included. With the intervention, HIV-positive individuals were more likely to begin antiretroviral treatment and were more likely to achieve viral suppression (79% in the treatment group vs. 68% in the control communities). The three-year cumulative incidence of new HIV infection in the intervention group was 0.77%, as compared to 0.81% in the control group (not statistically significantly different). However, death was less common among HIV-positive individuals in the intervention group than in the control group.

Hayes and colleagues randomized 21 urban and peri-urban communities in Zambia and South Africa to either standard treatment (control group) or to a bundle of interventions (home HIV testing, linkage to HIV care, and personalized treatment follow-up) with or without universal antiretroviral treatment for all HIV-positive individuals. The study was conducted from 2013 through 2018. In the intervention groups, uncircumcised males were encouraged to seek circumcision, and pregnant women were advised to seek prenatal care. Starting in 2016, universal antiretroviral treatment was provided for all HIV-positive individuals, regardless of initial treatment group. A total of 48,301 individuals were enrolled in the study. Baseline HIV positivity was 21-22% in the three groups. At baseline, a bit less than half of HIV-positive individuals had achieved viral suppression. The incidence of new HIV infections was 30% lower in the treatment groups than in the control group. Interestingly, universal antiretroviral treatment did not add benefit over standard treatment, perhaps because of limited rates of viral suppression.

COMMENTARY

Each of these three studies demonstrated favorable results with multifaceted HIV prevention interventions. Despite demographic differences (different countries and cultures, urban vs. rural settings, higher vs. lower baseline HIV incidence), the combination of personalized care (encouraging confidential testing and facilitating treatment adherence) and antiretroviral treatment reduced the spread of infection and/or reduced the death rate in the various intervention groups.

Single interventions are less likely than are multifaceted interventions to reduce the spread of HIV. It is likely that the personalized attention (and encouragement toward reducing risky behaviors and improving medication adherence) was a key part in the favorable outcomes of these studies. Simply making medication available in pharmacies likely is much less effective than connecting medication availability with trusted health workers who provide patient-centered care in the context of multidisciplinary teams. An editorial accompanying the three New England Journal of Medicine papers emphasized the challenge of overcoming denial of HIV risk and the stigma of seeking care.1

The need for trusted multidisciplinary care was reiterated the following week in the New England Journal of Medicine’s report about the ongoing Ebola outbreak in the Democratic Republic of Congo. Despite great gains, the incidence of Ebola started rising in February 2019 related to militia attacks on medical workers and growing distrust of the Ebola response teams.2 False beliefs and fear can compromise medical efforts — whether they are related to the stigma of seeking HIV care or anger at Ebola vaccination teams.

One of the three HIV studies included advice about condom use. Another group of authors speculated that their explanation about universal treatment might have prompted study participants to show less restraint with new sexual contacts. The urban study pointed out the risk of migration of sexual contacts into and out of the study population. Personal behaviors and population mixing still can affect the results of attempts at population-based interventions.

The three HIV studies remind us of the importance of ongoing attention to HIV infection, since prevalence rates were up to 29% in one study area. And they remind us of the value of multidisciplinary teams providing multifaceted interventions to combat complex problems on a population level.

REFERENCES

  1. Abdool Kareem SS. HIV-1 epidemic control — insights from test-and-treat trials. N Engl J Med 2019;381:286-288.
  2. Ilunga Kalenga O, Moeti M, Sparrow A, et al. The ongoing Ebola epidemic in the Democratic Republic of Congo, 2018-2019. N Engl J Med 2019;381:373-383.