Antiretroviral treatment of HIV-1 prevents transmission of HIV-1: where do we go from here?

Abstract

Antiretroviral drugs that inhibit viral replication were expected to reduce transmission of HIV by lowering the concentration of HIV in the genital tract. In 11 of 13 observational studies, antiretroviral therapy (ART) provided to an HIV-infected index case led to greatly reduced transmission of HIV to a sexual partner. In the HPTN 052 randomised controlled trial, ART used in combination with condoms and counselling reduced HIV transmission by 96·4%. Evidence is growing that wider, earlier initiation of ART could reduce population-level incidence of HIV. However, the full benefits of this strategy will probably need universal access to very early ART and excellent adherence to treatment. Challenges to this approach are substantial. First, not all HIV-infected individuals can be located, especially people with acute and early infection who are most contagious. Second, the ability of ART to prevent HIV transmission in men who have sex with men (MSM) and people who use intravenous drugs has not been shown. Indeed, the stable or increased incidence of HIV in MSM in some communities where widespread use of ART has been established emphasises the concern that not enough is known about treatment as prevention for this crucial population. Third, although US guidelines call for immediate use of ART, such guidelines have not been embraced worldwide. Some experts do not believe that immediate or early ART is justified by present evidence, or that health-care infrastructure for this approach is sufficient. These concerns are very difficult to resolve. Ongoing community-based prospective trials of early ART are likely to help to establish the population-level benefit of ART, and-if successful-to galvanise treatment as prevention.

Figure 1. Four opportunities for HIV prevention

The four stages of infection risk are listed at the top of the figure. Potential interventions during each stage are listed within each box. The timeline for the intervention is listed in the arrows below the intervention boxes. STD = sexually transmitted diseases. ART = antiretroviral therapy. PrEP = pre-exposure prophylaxis. TDF/FTC = tenofovir disoproxil fumarate co-formulated with emtricitabine (Truvada; Gilead Sciences, Foster City, CA, USA). PEP=post-exposure prophylaxis. *TDF/FTC (Truvada) is the only ART intervention currently approved by the US Food and Drug Administration for PrEP.

Figure 2. Comparison of antiretroviral exposure at mucosal surfaces

Seminal plasma, cervicovaginal fluid, and colorectal tissue exposure is plotted as a ratio relative to matched blood plasma exposure. The Y axis is on a log scale. Y = 1 is the line of unity, at which mucosal surface exposure is similar to blood plasma. Total (protein free plus protein bound) drug concentrations were used to calculate these ratios. Ratios above the line of unity signify that drugs are concentrating at mucosal surfaces, whereas ratios below the line of unity suggest that drug concentrations are lower than blood plasma at mucosal surfaces. Semen concentration ratios are shown in white, cervicovaginal fluid in grey, and rectal tissue in blue. MRV = maraviroc. RAL = raltegravir. DTG = dolutegravir. ETR = etravirine. EFV = efavirenz. NVP = nevirapine. DLV = delavirdine. TFV = tenofovir. FTC = emtricitabine. 3TC = lamivudine. ZDV = zidovudine. ABC = abacavir. DDI = didanosine. D4T = stavudine. RTV = ritonavir. DRV = darunavir. IDV = indinavir. APV = amprenavir. ATV = atazanavir. LPV = lopinavir. NFV = nelfinavir. SQV = saquinavir. ND = not detected. Figure adapted from reference .