HIV elimination is possible... under certain conditions

In first place is the host country of the conference. Australia was able to present its excellent results for 2022 [91.1%-91.5%-97.8%], especially in New South Wales. In the Sydney region, the number of people who were told they were living with HIV fell by 88% compared to 2010. While good results have also been achieved in East and Southern Africa [92%-83%-77%], the most affected region so far, this is not the case in other parts of the world. In some regions, such as Eastern Europe and Central Asia, there has even been an increase. In 2022, 1,300,000 people were diagnosed with HIV worldwide. At 86%-76%-71%, the global HIV cascade in 2022 was still below the WHO's 2020 targets [90%-90%-90%²]. Further efforts are therefore needed to make the elimination of HIV transmission a reality. The presentations at the IAS conference show the need and the effective measures.1

In Australia, the number of men having sex with men found to be living with HIV fell by 57% within 10 years. This is particularly due to the widespread introduction of PrEP. The 2021 annual survey shows that more than 75% (69.8% in 2017) of men use an effective strategy to protect against HIV when having anal sex without a condom with casual partners, including more than 30% using PrEP (15.6% in 2010).

The framework conditions must make it possible to develop an answer to the needs of individual, community and public health.

At the international level, the elimination of HIV transmission can only be achieved if all countries achieve this individually. This means that people in low- and middle-income countries must have access to all tools, including all treatments, through international financial support and/or agreements with patent holders and manufacturers.

At the national level, countries need to develop programs that take into account local circumstances, be it in terms of epidemiology (who is at risk), social determinants (what is their living environment like) or social and health structure (who can/should intervene). To achieve this, countries must have a precise overview of their epidemiological situation to know for whom an intervention is relevant (priority). It is also essential to know the realities of life and the needs/expectations/preferences of the (particularly) vulnerable groups/individuals to develop an appropriate response [see below]. To know exactly for whom which measures should be taken (as a priority), it is crucial that as many factors as possible are taken into account in the monitoring and surveys: Gender, gender identity, sexual orientation, age, place of residence, ethnic and/or cultural affiliation, places of socialization (especially sexualized), sexual behaviour, risk and harm reduction strategies, etc. The data must be compared with each other to identify differences between subgroups of the population in concerning to one criterion or another.

Data from the annual Australian Gay Community Periodic Survey made it possible to compare the behaviour of men* who have sex with men and women (MSMW - 7% of respondents) with that of men who only have sex with men (MSMO). It was found that MSMW is more likely to have anal sex without a condom with casual male partners (50.1% vs. 42.2%), even without preventive or therapeutic HIV treatment (30.40% vs. 12.5%), more likely to have had more than 10 male sexual partners in the last 6 months (29.7% vs. 17.5%), more likely to have never had an HIV test (19.9% vs. 3%) and not to know their serostatus (20% vs. 7.6%).

* MSMW are more often trans (6.2% vs. 0.8%) and non-binary (13.1% vs. 2.5%).

Digital tools can also be a valuable instrument for the development and implementation of programs and measures. For example, artificial intelligence can enable better data analysis to identify and understand different groups/behaviours to develop tailored interventions to facilitate access to care (e.g. HIV testing and treatment) and increase retention in care (e.g. preventive or therapeutic HIV treatment). Applications (e.g. healthmpowerment.org) can also help people to take better care of their health (e.g. mental health support tools, HIV treatment management tools...) and for health services to support them where appropriate.

However, the definition and effective implementation of a program is only possible if the socio-legal context allows it. In many countries today, the HIV epidemic is concentrated in certain population groups. If these groups are stigmatized, decriminalized or even punished, it will be impossible to eliminate HIV transmission within these groups and thus in the entire population of the country. If people living with HIV are stigmatized or discriminated against, access to testing and therefore access to treatment will be made more difficult. For this reason, it is crucial to defend human rights:

• Abolition of laws that criminalize same-sex relationships and talking about homosexuality,
• Abolition of laws that criminalize sex work in any way,
• Abolition of laws that criminalize the use of substances (and possession of small amounts),
• Abolish laws that prohibit the affirmation of sex that does not correspond to the sex assigned at birth, or that impede access to and provision of sex-segregated treatment,
• Abolish laws that discriminate against people living with HIV or hepatitis and combat the discrimination they face,
• Ensure access to healthcare (information and counselling, vaccination, testing, treatment) for members of populations particularly affected by HIV and viral hepatitis (MSM, sex workers, people with a migrant background, people who use drugs, prisoners). In addition to infectious challenges, these populations also have specific or more frequent health needs that must also be addressed (gender confirmation procedures, anal health, addictions, mental health...).
• Combating systemic racism, including in prevention and healthcare facilities.

A study shows the links between the legal repression of sex between men and HIV prevalence among gay men and other MSM in sub-Saharan Africa.

The HIV prevalence among MSM is

• 5 times higher in countries where homosexuality is criminalized
• 12 times higher in countries where someone has been prosecuted for homosexuality
• 10 times higher in countries with laws against civil society organizations.

Scientific findings must be recognized and put into practice.

The role of scientific research is to expand knowledge. However, this knowledge is meaningless if it is not recognized and ineffective if it does not serve as a basis for concrete action to improve the observed reality. Denying or questioning scientific knowledge contributes to the HIV epidemic and endangers the health of those affected and public health.

• The U=U [Undetectable = Untransmissible / Indetectable = Intransmissible] concept, which has been proven for more than 10 years [Partner 1 and Partner 2], has now been confirmed by the WHO, which includes it in its new guidelines published on July 23. The WHO relies on a meta-analysis published in The Lancet, which confirms that a person living with HIV whose viral load is below 1,000 copies/mL does not transmit the virus. In practice, however, people with HIV are still stigmatized and discriminated against, be it by healthcare professionals (up to and including refusal of treatment), their relatives, their potential sexual partners, the media and thus by society as a whole. In some countries, there are still laws that criminalize the non-disclosure of HIV status, even though there is no risk of transmission.
• The efficacy of certain long-acting therapies (e.g. cabotegravir LA) has been proven or will soon be proven, both for the therapeutic treatment of people with HIV and for prevention (PrEP). The data on long-acting injection therapy show that this format is even more effective than oral treatment, as it is more discreet (no tablets at home) and less burdensome (no daily intake over a longer period of time) and transmission due to forgotten intake can be prevented. This format is particularly popular with people assigned to the female sex at birth (cisgender women, trans men and some non-binary people) who cannot take the 2+1+1 regimen orally. People should therefore have access to it. For low- and middle-income countries, the problem of drug costs must be solved. Then national authorities need to authorize these treatments as soon as possible. Regarding PrEP, several countries, notably the US, have already approved the use of CAB LA (cabotegravir long-acting), which is an important paradigm shift. Unfortunately, this is not the case in all countries, especially not in Switzerland.

Scientific innovations are still required.

The tools available today can meet most needs, but that is not enough. In some situations, the available tools are not adapted to the realities and expectations. In addition, the burden of treatment in the lives of people living with HIV is still too great.

• Research into the mechanisms of the virus and the infection must continue in order to identify new preventive and therapeutic treatment strategies that may even enable remission or even a cure.

The results of several research studies on reservoirs and control elites make it possible to define strategies for a potential cure.

• The development of antiretroviral drugs for prevention, treatment and cure must continue. Research must enable the development of new molecules and new forms of administration in order to maintain or even increase efficacy, reduce side effects and make them easier to take.            
  • Format: Oral administration, intramuscular or intradermal/subcutaneous injections, vaginal rings, implants, ingestible device,
  • Time interval: weekly, monthly, twice a quarter (every 2-3 months), semi-annually (every 6 months) or even annually (every 12 months).

First encouraging results in the development of a combination therapy with three antiretroviral drugs (tenofovir, lamivudine and dolutegravir - TLD), which is administered as an intradermal injection. This new formulation enables a long-term effect. Clinical research must now determine the possible interval between two injections.

The results for various drugs and combinations were presented:

• Doravirin + islatravir as effective as Biktarvy (TAF/BIC/FTC)
• Islatravir + lenacapavir weekly orally (Phase II)
• Lenacapavir + monoclonal antibodies every six months (phase I)

Lenacapavir (Purpose) is also being tested for use in prevention by subcutaneous injection every 6 months.

The HPTN084 study investigated the preferences of cisgender women with regard to PrEP. The results show that a large majority (78%) of those assigned to the female sex at birth preferred PrEP by intramuscular injection (CAB LA) over oral. Some who chose one model later preferred to switch to the other. The preference for PrEP injection is mainly based on the desire for discretion (no drug in the house) and convenience (1 injection every 2 months vs. daily use).

The HPTN084-01 study confirms these results. 92% of young women who had started PrEP with intramuscular injection (CAB LA) opted to continue PrEP, while some of the participants opted for oral PrEP.

• The search for new therapeutic approaches must be continued. The results presented on broadly neutralizing HIV antibodies (bNab) are inspiring. Research in this field must continue in order to develop vaccines and treatments that can have a preventive, therapeutic or even remitting or curative effect.

The therapeutic benefits of bNAbs are:

• BnAbs do not generate resistance, as is the case with antiretroviral therapies.
• BnAbs have a long-lasting effect (several weeks to 2 months).
• BnAbs have stable pharmacokinetics in all population groups.
• BnAbs do not induce hepatic cytochromes and therefore do not alter the pharmacokinetics of other drugs (no interaction).
• BnAbs are not toxic.
• BnAbs have a high therapeutic index. Therefore, if large differences in blood concentrations are possible, this will not affect clinical efficacy or increase toxicity.
• BnAbs provide beneficial immunomodulation, benefiting cytotoxic CD8+ T cells that can eliminate HIV reservoir cells (which is a prerequisite for a cure).

It has been shown that antibodies can be used due to their virucidal activity, but also due to their simple suppression of replication. It is therefore possible to consider remission without synthetic antiretroviral therapy (ARV) by immunotherapies that combine several bNAbs, bNAbs and antiretroviral therapy (with a long duration of action) or vaccination that elicits bNAbs antibodies. It is also being considered to develop monoclonal antibodies in the laboratory that are tri-specific, i.e. that target three different epitopes simultaneously with the same antibody molecule. As a reminder, an antibody molecule normally targets the same epitope twice.

• Research into other STIs must be continued.
  • The data on protection against gonorrhea of the meningitis B vaccine(Bexsero)³ [Edit from May 15, 2023 - the final analysis of the results has called this efficacy into question] show partial but not negligible cross-protection [40-66%]. For adults, however, there is no data on the duration of efficacy and thus on the need for booster vaccinations and their intervals. This should encourage further research in this area in the future, but also raise the question of whether it makes sense to give particularly vulnerable people access to this vaccine in order to prevent outbreaks.
  • The first results on the use of an antibiotic as post-exposure treatment (PEP)⁴. Taking 200 mg of doxycycline, ideally within 24 hours (and up to 72 hours) after sexual intercourse without a condom, shows significant efficacy in preventing syphilis and chlamydia in individuals assigned to the male sex at birth (cis men, trans women and certain non-binary individuals). However, DoxyPEP was ineffective for individuals assigned to the female sex at birth (cis women, trans men and certain non-binary individuals) and for gonorrhea. The impact on the development of antibiotic resistance (AMR) [to doxycycline and tetracyclines] in gonorrhea and other sexually transmitted diseases [Chlamydia suis with risk of transmission to C. trachomatis; syphilis; Mycoplasma genitalium...] is a cause for concern. is a cause for concern. Similarly, the effects on other pathogens, particularly those of the intestinal microbiota, are not yet sufficiently known [Staphylococcus aureus; Escherichia coli...]. However, given the epidemiological situation in certain population groups, implementation could be considered for particularly vulnerable people, provided that regular screening for STIs and, in the event of a diagnosis, a post-treatment confirmation test (test of cure) and monitoring of antibiotic resistance [phenotype and genotype of the pathogens] are introduced. This applies in particular to MSM and especially to a proportion of those who take PrEP (25% of MSM who take PrEP are responsible for 75% of diagnosed STIs). In this group, adherence is remarkable with an average of 7 intakes per month.

A positive holistic approach to health that focuses on people's needs is required.

Destigmatization / decolonization

It is important for the elimination of HIV that the most vulnerable people have access to medical care. However, in many countries, members of key populations do not have access to information and counseling, testing, prevention (PrEP) or treatment.

Indeed, analysis of PEPFAR program data from 2019 to 2022 shows that 70% of MSM and TDS did not start PrEP during this period. Of the 1,371,984 people who started PrEP in one of the 40 participating countries, only 38% were men who have sex with men, trans women, sex workers or injecting drug users.

According to the models presented, at least 50% of the key population should take PrEP in high-prevalence countries (15% in low-prevalence countries). To achieve this, the social and legal framework would need to be less oppressive for these populations [see above] and specific measures would need to be taken [see below].

It is crucial that research/programs/strategies/measures/actions are defined and implemented with local stakeholders to meet their needs and expectations. Community participation can also ensure that development and implementation takes into account the stigma/discrimination that communities also face in health facilities [racism, heterosexism, bisexism, validism ... systemic]. The decolonial approach is particularly promoted in the field of HIV (research, care, health policy).

The social and communication sciences also show that a negative risk approach (very common in the medical field, especially in HIV prevention) is ineffective or even counterproductive. Positive communication based on the motivation to take care of oneself and one's health [bio-psycho-social] proves to be far more effective (self-care).

Diversification / demedicalization

The surveys among the key populations show that the realities and therefore the needs are very different. Accordingly, the answers to these questions must be just as varied in terms of the instruments, access options, personnel for implementation, etc.

In a vision of person-centred care, the range of public and private (including community), general and specialized (including primary care) health services must be diversified and defined according to the needs of the people to be reached. Secondly, an implmentation should be as integrated as possible (one-stop store model): one place, one time, one staff member for a maximum of possible services (information and counseling; vaccinations; HIV and other STI testing and hepatitis; preventive, emergency and therapeutic HIV treatment; hepatitis treatment; mental and psychosocial health services; gender-specific services; cancer screening; general health...).

An inspiring example of a health center by and for trans people in Thailand: Tangerine's services have been gradually expanded according to the needs/requests of trans people (gender-specific hormone treatments, HIV and other STI tests, preventive and therapeutic HIV treatment) and continue to be expanded (project for gender-specific surgeries or hair implants). Most of the center's team members are trans people themselves.

In Nigeria, the integration of hepatitis C testing into facilities providing antiretroviral therapy for HIV has led to a significant increase in testing rates and the prospect of micro-elimination of viral hepatitis in people living with HIV.

Community and/or de-medical services are one way of reaching particularly marginalized population groups that are far removed from health services. Convincing examples were presented at the conference:

• Community screening through self-tests (HIV, syphilis, viral hepatitis) and self-sampling (HIV, HPV, gonorrhea, chlamydia)
• Introduction and monitoring of PrEP in pharmacies
• Community provision of antiretroviral drugs for preventive and therapeutic HIV treatment

A research project has been conducted in Bangkok, Thailand, which aims to reduce the number of people who are lost from sight (20%) when they are tested for HIV in the community. Men who have sex with men and trans people who find out they have HIV can start HIV treatment directly on the day of diagnosis. The study, conducted from October 2021 to March 2023, enabled 587 people (72.1% MSM and 7.3% trans women) who were relatively young (average age 25) to start their treatment in the community, half of them on the day of diagnosis. The retention rate after 6 months was 87% and after 12 months still 84.6%. At the end of the study, 94.2% of those treated had an undetectable viral load.

In Brazil, a similar project has been developed for young men who have sex with men and transgender people.

Decentralization / dematerialization

As far as possible, access points should be diversified to be close to the people to be reached, be it in terms of geographical location, opening hours, access conditions or the subjective perceptions of the people to be reached.

In Tanzania, a collaboration has been developed so that many private pharmacies can initiate and monitor PrEP. Interested people can fill out an assessment questionnaire online. They can then visit one of the participating pharmacies, where a rapid HIV test is carried out. If the test is negative, PrEP is dispensed.

Digitalization is an instrument to overcome the challenges of distance and anticipate discrimination and condemnation. Several projects use digital tools to reach members of key populations and provide them with access to tools (information and counseling, screening, preventive and therapeutic HIV treatment).

E-PrEPPY is a research campaign to provide PrEP to men who have sex with men and trans people through the community-based NGO LoveYourself in the Philippines. An online platform allows people to answer an evaluation questionnaire. Based on the answers, online counseling is provided by a community worker. An HIV self-test is then sent out. If the result is negative, the first month of PrEP is sent together with a second self-test. The same procedure is carried out two months later and then every three months for as long as the test is negative. If the test is reactive, the person is referred to a health service. The PrEP+self-test kits can be sent to any postal address, in one of the many stores of a commercial partner or by a courier service of the project.

For more information on the presentations and posters: (2023), Abstract Supplement Abstracts from IAS 2023, the 12th IAS Conference on HIV Science, July 23 - 26, Brisbane, Australia & Virtual. J Int AIDS Soc, 26: e26134. doi.org/10.1002/jia2.26134

Sources

^{1, 2}
95% des personnes vivant avec le VIH (PvVIH) connaissent leur statut sérologique.
95% des PvVIH connaissant leur statut ont accès à un traitement.
95% des PvVIH sous traitement ont une charge virale indétectable.

³
Nouvelles données d’efficacité d’un vaccin contre le méningocoque B et d’un antibiotique préventif pour réduire le risque d'IST bactériennes et efficacité démontrée du vaccin MVA-BN contre mpox. Communiqué de presse de l'ANRS, du 23 février 2023
Communiqué de presse de l’ANRS
Edit: l’analyse finale est susceptible de modifier les résultats intermédiaires de l’essai évaluant l’efficacité de la vaccination contre le méningocoque B pour la prévention des infections à gonocoques Communiqué de presse de l’ANRS du 15 mai 2023

⁴
Molina JM, Charreau I, Chidiac C et al.Post-exposure prophylaxis with doxycycline to prevent sexually transmitted infections in men who have sex with men: an open-label randomised substudy of the ANRS IPERGAY trial.Lancet Infect Dis., 2018; 18(3): 308-17. doi: 10.1016/S1473-3099(17)30725-9

Luetkemeyer A, Dombrowski J, Cohen S et al.Doxycycline post-exposure prophylaxis for STI prevention among MSM and transgender women on HIV PrEP or living with HIV: high efficacy to reduce incident STI’s in a randomized trial. The 24th International AIDS Conference, Montreal, Canada, 2022.

San Francisco Department of Public Health. Health Update - Doxycycline Post-Exposure Prophylaxis Reduces Incidence of Sexually Transmitted Infections. San Francisco Department of Public Health, October 20, 2022.

Molina JM, Bercot B, Assoumou L et al. ANRS 174 DOXYVAC: an open-label randomized trial to prevent STI in MSM on PrEP. Conference on Retroviruses and Opportunistic Infections (CROI), 19-22 Février 2023, Seattle, Washington (voir extraits de la présentation dans Roncier C. DOXYVAC confirme l’efficacité de la doxycycline et du vaccin anti méningocoque B en PEP ainsi que celle du vaccin anti-variolique chez les prépeurs. vih.org, 23 février 2023)

Cornelisse VJ, Ong JJ, Ryder N et al.Interim position statement on doxycycline post-exposure prophylaxis (Doxy-PEP) for the prevention of bacterial sexually transmissible infections in Australia and Aotearoa New Zealand - the Australasian Society for HIV, Viral Hepatitis and Sexual Health Medicine (ASHM). Sexual Health, 2023. doi: 10.1071/SH23011

Kenyon C, Baetselier ID, Wouters K. Screening for STIs in PrEP cohorts results in high levels of antimicrobial consumption.Int J STD AIDS, 2020; 31(12): 1215-1218. doi:10.1177/0956462420957519

Photo: ias2023.smugmug.com