Prevention of HIV transmission by antiretroviral therapy
Commentary by Jens Lundgren & Andrew Phillips, Lancet HIV, 30 November 2017.
Antiretroviral drugs can prevent sexual transmission of HIV. If used consistently as pre-exposure prophylaxis (PrEP) by uninfected people, the risk of becoming infected is substantially reduced (1). And when used effectively by people already infected, the risk of onward transmission is very low (2), even for condomless sex acts (3). In populations extensively and repeatedly tested for HIV, and when antiretroviral therapy (ART) is initiated immediately on testing positive, transmission risk seems to decrease(4). Models of populations of men who have sex with men suggest that epidemic control (defined as an incidence less than one per 1000 person-years) probably requires that at least 90% of those infected are on fully suppressive ART(5).
An observational study has provided support for treatment as prevention in an African setting.6 Now several randomised trials are assessing the public health benefit in African settings, characterised by high HIV prevalence and underdeveloped health-care systems. In The Lancet HIV, Collins Iwuji and colleagues report findings from one of these trials (7). In 22 communities in rural KwaZulu-Natal, South Africa, repeated HIV testing was offered to all participants; however, immediate ART was offered to only half of participants regardless of CD4 cell count (intervention group), in the control group ART was deferred to start according to national guidelines based on CD4 cell count thresholds. Disappointingly, the estimated incidence of new HIV infections in the two groups was much the same at the end of the trial. The most likely reason for this finding was that the intended increased ART coverage within the communities randomly assigned to immediate ART did not differ from that in the other communities (just over half in both groups). The substantial migration noted might also have affected the result.
Although the intended differences in the proportion of HIV positive people with viral suppression were not induced by the intervention, and hence there were no new insights provided by the primary endpoint comparison, some key results emerged that lend further support to the policy of providing ART to all patients diagnosed with HIV infection, regardless of CD4 count. That is, retention in care and viral suppression rates were just as good with universal test and treat policy as with a conservative approach.
Given the known health and transmission benefits of viral load suppression, the policy of using testing programmes to maximise the proportion of people who know their HIV status, with immediate offers of ART, is widely supported. The results from Iwuji and colleagues' trial7 do not question that. Rather, the results point to low linkage to care as the main reason for transmission not being controlled. The need for monthly clinic visits could be one factor although, once initially engaged and on ART, retention was reasonably good in the intervention group. Home-based initiation is a promising strategy for increasing ART take-up in those who test positive8 although it might be expensive. Additionally, whether retention can be maintained without home delivery of drugs is unclear.
Unlike rates of linkage to care, rates of HIV testing and diagnosis were high generally in the trial, but they were lower in men than in women, particularly younger men. Programmes must reach, test, and engage on ART for those in the community who are most likely to be the source of ongoing transmission. More extensive use of PrEP in the most vulnerable groups for infection (younger women) might supplement the benefits from use of ART. PrEP was only recommended by WHO (1) in September, 2015, and hence not studied in Iwuji and colleagues' trial (7).
Two key questions remain for ART programmes in Africa. How, sustainably and cost-effectively, to diagnose people, to initiate ART, and to retain people on ART, particularly men and those in South Africa where rates of engagement with treatment seem to be lower than elsewhere in the region? (9, 10, 11) Also, what is the target prevalence of people living with unsuppressed HIV12 that must be reached with testing and treatment to reduce incidence substantially (eg, to <1 per 1000 person-years)? In Malawi, recent data11 suggest that this prevalence of unsuppressed HIV has decreased to less than 3·5% (similar in men and women) from about 12% in 2004, and the HIV incidence, as of 2016, is just 3·7 cases per 1000 person-years compared with 21·9 cases per 1000 person-years in Iwuji and colleagues' trial(7). Sexually active men probably disproportionately contribute to prevalence, and to decrease incidence further, targeted testing and facilitation of sustained access to ART will be required.
1. WHO. HIV/AIDS: pre-exposure prophylaxis. ((accessed Nov 5, 2017).)World Health Organization, Geneva; 2015
2. Cohen, MS, Chen, YQ, McCauley, M et al. Antiretroviral therapy for the prevention of HIV-1 transmission. N Engl J Med. 2016; 375: 830?839
3. Rodger, AJ, Cambiano, V, Bruun, T et al. Sexual activity without condoms and risk of HIV transmission in serodifferent couples when the HIV-positive partner is using supportive antiretroviral therapy. JAMA. 2016; 316: 171?181
4. Brown, AE, Mohammed, H, Ogaz, D et al. Fall in new HIV diagnoses among men who have sex with men (MSM) at selected London sexual health clinics since early 2015: testing or treatment or pre-exposure prophylaxis (PrEP)?. Euro Surveill. 2017; 22: 30553
5. Phillips, AN, Cambiano, V, Miners, A et al. Potential impact on HIV incidence of higher HIV testing rates and earlier antiretroviral therapy initiation in MSM. AIDS. 2015; 29: 1855?1862
6. Tanser, F, Barnighausen, T, Grapsa, E et al. High coverage of ART associated with decline in risk of HIV acquisition in rural KwaZulu-Natal, South Africa. Science. 2013; 339: 966?971
7. Iwuji, CC, Orne-Gliemann, J, Larmarange, J et al. Universal test and treat and the HIV epidemic in rural South Africa: a phase 4, open-label, community cluster randomised trial. (published online Nov 30.)Lancet HIV. 2017;
8. MacPherson, P, Lalloo, DG, Webb, EL et al. Effect of optional home initiation of HIV care following HIV self-testing on antiretroviral therapy initiation among adults in Malawi: a randomized clinical trial. JAMA. 2014; 312: 372?379
9. Gaolathe, T, Wirth, KE, Holme, MP et al. Botswana's progress toward achieving the 2020 UNAIDS 90-90-90 antiretroviral therapy and virological suppression goals: a population-based survey. Lancet HIV. 2016; 3: e221?e230
10. Shisana, O, Rehle, T, Simbayi, LC et al. South African national HIV prevalence, incidence and behaviour survey, 2012. ((accessed Nov 5, 2017).)
11. PHIA Project. Malawi population-based HIV impact assessment. ((accessed Nov 5, 2017).)ICAP at Columbia University, New York; 2016
12. Miller, WC, Powers, KA, Smith, MK, and Cohen, MS. Community viral load as measure for assessment of HIV treatment as prevention. Lancet Infect Dis. 2013; 13: 459?464
News date: 2017-11-30
Killer cell immunoglobulin-like receptor 3DL1 variation modifies HLA-B*57 protection against HIV-1. Martin MP, Naranbhai V, Shea PR, Qi Y, Ramsuran V, Vince N, Gao X, Thomas R, Brumme ZL, Carlson JM, Wolinsky SM, Goedert JJ, Walker BD, Segal FP, Deeks SG, Haas DW, Migueles SA, Connors M, Michael N, Fellay J, Gostick E, Llewellyn-Lacey S, Price DA, Lafont BA, Pymm P, Saunders PM, Widjaja J, Wong SC, Vivian JP, Rossjohn J, Brooks AG, Carrington M, J Clin Invest. (2018), pii: 98463. doi: 10.1172/JCI98463:.