Thus, expansion of treatment for those who need it for their own health is likely to have substantial benefit for them in terms of prevention of HIV and TB-related morbidity and mortality and decreased HIV incidence among their HIV-uninfected partners and potentially protecting their families, households, and communities from risk of TB. Clearly, expansion of TasP to those at earlier stages of HIV disease is an important frontier for further research and implementation.
Enthusiasm for TasP must be tempered by acknowledging that it is not a panacea but rather its success is dependent on a multiplicity of other complementary and necessary interventions.54 Behavioral, biomedical, and structural interventions are required to ensure that various components of the HIV care cascade are optimized to achieve the ultimate goal of TasP. Achieving higher coverage with ART for those in need will require expansion of HIV testing, using innovative approaches such as provider-initiated testing and counseling, household testing, and community-focused approaches.55,56 It will also require attention to maximize every step of the HIV care cascade from linkage of those found to be HIV positive to retention in care, prompt determination of ART eligibility, and initiation of ART with provision of adherence support.54 Without attention to the HIV care cascade, the promise of TasP as an intervention for both HIV treatment and HIV prevention will fail to be realized57 (Figure 1). Two meta-analyses from sub-Saharan Africa demonstrated that less than a third of persons testing HIV positive remain in care until ART initiation.58,59 Results are similar in the United States, where 19%–29% of persons with HIV infection are estimated to achieve viral load suppression.60–62
In reality, it may be difficult to achieve the magnitude of coverage with ART for all individuals with HIV in a community as presumed in many of the modeling studies, supporting the need for other HIV and TB prevention interventions. As noted in Figure 1, HIV testing is the foundation of all prevention interventions. Although, for those individuals found to be HIV infected, TasP is an important prevention intervention when combined with supportive interventions, those found to be HIV-uninfected should also be candidates for HIV prevention interventions. They need to be linked to appropriate prevention interventions such as voluntary medical male circumcision (VMMC) and preexposure prophylaxis (PrEP), with ongoing counseling and adherence support, as needed, and repeat HIV testing. Despite substantial evidence in support of the efficacy of VMMC for prevention of HIV transmission,63–65 its implementation and scale-up has been suboptimal in some settings.66 Availability of new nonoperative methods for male circumcision that do not require anesthesia and can be performed by nurses holds great promise.67,68 A recent study demonstrated that expansion of VMMC is cost effective and may have a substantial effect on decreasing the number of new HIV infections in the short term, with TasP demonstrating substantial effect in the long term.8 PrEP using antiretroviral drugs in HIV-uninfected individuals is also a promising intervention shown to be efficacious in several studies,2,4 whereas conflicting results have been noted in other studies where adherence with PrEP was compromised.69,70 That a significant proportion of transmissions in couples in HPTN 052 and other discordant couple studies were unlinked highlights the potential importance of PrEP if monogamy among couples is not assured. PrEP may also be appropriate for individuals at high risk who are unaware of their partner’s HIV status or in settings where an HIV-infected partner is unwilling or unable to take ART for prevention.
Enthusiasm for the potential effect of ART on TB incidence should not divert resources from other TB control strategies, including the “three I’s,” ie, intensified case finding, IPT, and infection control, in addition assuring provision of directly observed therapy for those diagnosed with TB.71,72 A comprehensive public health approach that includes these strategies is needed to control the TB epidemic, particularly among HIV-infected individuals. HIV-infected individuals on ART remain at an increased risk for TB when compared with HIV-uninfected individuals, even when their CD4+ counts are high.73,74 With the increase in survival associated with ART, the lifetime risk of TB in HIV-infected persons in the absence of other interventions is likely to remain high. IPT and ART prevent TB via complementary mechanisms,75 and evidence supports an additive protective benefit from concomitant IPT use among individuals on ART.36,37 To provide IPT safely, it must be implemented in the context of intensified case finding, to prevent the development of drug resistance from inadvertently prescribing monotherapy to individuals with undiagnosed TB. Implementation of infection control measures is also essential to prevent nosocomial transmission of TB in health care settings where ART is provided.
There is an urgent need for empiric data to evaluate the effectiveness of TasP at a population level. Two studies are planned to address this question, the HPTN 071 (PopART) Study in South Africa and Zambia and the Mochudi Study in Botswana.76 In addition, there is a paucity of data regarding whether ART use will be an efficacious intervention for prevention of HIV transmission in key populations, particularly among men who have sex with men and injection drug users.49
There is also an urgent need to obtain empiric data to assess the potential benefits and risks associated with use of ART for individuals at higher CD4+ counts, who are largely the target group of current considerations for TasP.77 Few data exist with regard to this issue in patients with CD4+ count >350 cell/μL from resource-limited settings, supporting the need for clinical trials to inform this question.47 The ongoing START study is aiming to address this question largely in developed countries,78 whereas the TEMPRANO study in Cote d’Ivoire (ANRS12136) may provide some insights on this question. However, neither study will provide definitive answers to the question of the benefits and risks of early versus deferred ART in terms of key outcomes including mortality, TB incidence, and hospitalizations in resource-limited countries.47
There is the need for implementation research that aims at examining the “how” with regard to implementation of TasP and its scale-up, if found to be effective at population level.
Expanded use of ART holds great promise for saving lives and enhancing the health and well being of persons living with HIV and for the prevention of HIV and TB. The evidence for TasP should serve to further energize efforts to reach all those who need ART for their own health as an important priority. Aspiration for TasP should not distract attention from the quality of HIV programming, the effectiveness of the HIV care cascade, and the need for inclusion of other HIV prevention interventions and other TB prevention measures. Important questions that remain to be answered include which population to prioritize, what other interventions to use, how to integrate TasP in the health system, how best to use ART for the benefit of individuals and society, and how to measure its effectiveness and impact at population level.
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