The Epidemic Emergence of HIV: What Novel Enabling Factors Were Involved?

Figures & data

Figure 1. The process of simian immunodeficiency virus adaptation by serial transmission.

In a typical cross-species transmission of SIV the virus is suppressed after acute infection initially (A); with serial transmission through sequential acute-stage infections, the virus gradually adapts to the new host and acquires the ability to sustain substantial viral load past acute infection (B). The time course of the viral load in the individual infections is shown in red (X-axis is time since infection, Y-axis is viral load).

SIV: Simian immunodeficiency virus.

For color figures please see www.tandfonline.com/doi/full/10.2217/fvl-2017-0042

Figure 2. Progression of healthcare in Central and West Africa.

The progression of the number of treated patients (excluding vaccinations) for any condition (TP) and the number of smallpox vaccinations in the three African colonies more relevant to HIV-1 and HIV-2 origins.

Based on colonial reports (Sousa JD, Unpublished Database).

Table 1. Factors potentially contributing to HIV adaptation.

Factors potentially contributing to biological adaptation of SIV to humans	Estimated temporal pattern of factor	Prediction for temporal distribution of epidemic HIV origins if the factor alonewas sufficient to Stage 5 transition	Other arguments	Consistent with evidence
Present in precolonial era (before 1885)
1. SIV preadaptation Some SIVs are more preadapted to human infection than others, e.g., within SIVcpz, the ancestors of HIV-1-M are more preadapted than other strains [1,3]	Pattern not expected to differ since millennia	Multiple emergences during millennia		No
2. Individual host genetic factors	Pattern not expected to differ since millennia	Depending on frequency of the specific host genetic factor, potential emergence stable during millennia		No
3. Viral diversity transmitted Experiments suggest it can be relevant [47–49]	Relatively common during exposure to bushmeat; likely repeatedly during millennia	Multiple emergences during millennia		No
4. Serial sexual transmission in absence of GUD Serial passage experiments suggest it can be relevant [35,59]	Pattern not expected to differ since millennia	Emergence during millennia with a frequency depending on the likelihood of short chains of transmission	Simulations show that even short chains are rare without GUD [40]	No
Combinations of factors 1–4 e.g., 1 + 2, 1 + 2 + 3, 1 + 2 + 4, etc.	Pattern not expected to differ since millennia	Depending on the likelihoodof the required combination of factors, occasional emergence during millennia	It cannot be excluded that occasional short-lived HIV epidemics might have taken place in the past	Unlikely
Present in colonial and postcolonial era (after 1885)
5. Serial transmission through unsafe injections Serial passage experiments suggest it can be relevant [35,59]	Injections 2 orders of magnitude more common in late 1950s than in 1920s; sterilization standards worse after ∼1960	Many more Stage 5 emergences starting in mid 20th century than in early 20th century – the opposite is observed		Unlikely
6. Serial transmission through transfusions Serial passage experiments suggest it can be relevant [35,59]	Transfusions rare before 1950	Same as in 5	Tranfusions allow maximal viral diversity transmitted	Unlikely
7. Parenteral outbreak generating dozens of infections (e.g., in hospital or clinic) Multiplication of infections could favor adaptation	Hospital entries: in late 1950s, Ten-times higher than in 1930, 50-times higher than in 1915; amount of injections in hospitals probably proportional to hospital entries	Same as in 5		Unlikely
8. Massive parenteral transmission	Same as in 5	Same as in 5	Injection intensity of rural campaigns much lower than in IVDUs [41]	Unlikely
Combinations of factors 1–8 e.g., 1 + 5, 1 + 3 + 5, 1 + 3 + 6, etc.	Far more common after 1950	Same as in 5		Unlikely
9. Sexual serial transmission enhanced by GUD Serial passage experiments suggest it can be relevant [35,59]	GUD almost absent before 1885; far more common in colonial cities in the period 1900–1935; 2 orders of magnitude less common in late 1950s	More Stage 5 emergences starting in early 20th century, as is observed	These chains may have been common and HIVs are rare	Less likely
10. Long chain of sexual transmission, enhanced by sex work, with GUD rare	More brothels and high turnover sex workers after 1960 [38]	Same as in 5	Simulations suggest sex work less important than GUD [40]	Less likely
11. Long chain of sexual transmission, enhanced by GUD	Same as in 9	Same as in 9	Simulations show this is possible even with ill-adapted HIV [40]	Yes
Combinations including 11 e.g., 1 + 2 + 10 + 11, 1 +3 + 5 + 11, 1 + 3 + 6 + 11, 1 + 3 + 9 + 10 + 11, etc.	Peak in 1910–1935 if GUD was the crucial factor	Same as in 9	Several factors other than GUD (e.g., factor 1 probably played a role [1,3])	Yes

GUD: Genital ulcer disease; IVDU: Intravenous drug user; SIV: Simian immunodeficiency virus.

In the leftmost column, we list the factors/combinations of factors that could have contributed to SIV/HIV adaptation to the human host, with references supporting a possible role in adaptation. In the second column, we list their temporal patterns. In the third column we list what would be the temporal pattern of Stage 5 HIV emergences observed if that factor/combination alone was sufficient to let HIV transition to Stage 5. In the fourth column we add other relevant arguments. The rightmost column contains our evaluation of the plausibility of each factor/combination alone having been sufficient for epidemic emergence and thus being consistent with the observed pattern of origins of the four Stage 5 HIVs.

Figure 3. A three-step model for HIV adaptation and emergence.

The three panels illustrate our proposed three steps in HIV adaptation and emergence. In Step 1, there is a simian-to-human transfer of SIV genetically suitable to adapt to humans. In Step 2, we outline several alternative (not mutually exclusive) processes potentially generating rough HIV adaptation. In Step 3, enhanced heterosexual transmission involving GUD produces a Stage 5 capable HIV strain.

GUD: Genital ulcer disease; SIV: Simian immunodeficiency virus.

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